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The Viagra, Regitina and Uprima Secret X FILE !!!!
El Expediente Secreto X de la
Viagra, Regitina y Uprima.
Data-Medicos
Dermagic/Express No. 4-(3) X file)
15 Agosto 2.002 / 15 August 2.002
COMENTARIOS ESPAÑOL:
==========================
Hola amigos de la red, DERMAGIC de nuevo con ustedes, en esta
ocasión con una interesante revision sobre las TRES pastillas mas utilizadas para tratar la
disfunción ERÉCTIL: VIAGRA (Sildenafil), REGITINA (Mesilato de Fentolamina) y UPRIMA (Apomorfina).
Considero esta evision un EXPEDIENTE SECRETO porque quizá muchos de ustedes no CONOCEN ALGUNAS COSAS DE ESTAS
PÍLDORAS las cuales revelare hoy.
Yo PERSONALMENTE probé las tres drogas y puedo HABLAR con propiedad de lo que experimente con ellas y los efectos que produjeron en mi cuerpo..
VIAGRA: (Pfizer)
--------------------------
En el año de Marzo de 1998 el mundo se vio conmocionado por la
aparición de una PÍLDORA MILAGROSA la cual lograba levantar de manera INUSITADA " PENES MUERTOS" por causa de la edad o enfermedades secundarias que
impedían la correcta erección.
La droga estaba siendo PROBADA COMO un hipotensor y se
descubrió casualmente que facilitaba las erecciones en las personas
que las tomaban, como hipotensor fracaso, pero emergió como la MARAVILLA SEXUAL.
La explicación de como la VIAGRA
actúa, es que ella incrementa el oxido nítrico, un químico natural del cuerpo que dilata los vasos
sanguíneos, provocando un aumento del flujo al pene.
La viagra También bloquea una enzima (substancia) producida en el pene que causa que el hombre pierda la
erección.
Pocas semanas después de liberada al mercado la VIAGRA, se reportaron los primeros MUERTOS ASOCIADOS al uso de la MISMA, entre marzo y noviembre de ese año ya se
habían REPORTADO 130 MUERTOS a la FDA.
Para Marzo del año del 2.000 ya se han reportado mas de 522 muertes asociados AL VIAGRA, muchos de ellos con antecedentes de lesiones cardiacas o
tomando medicación para el corazón (nitratos).
Pero ese mismo mes de marzo del año 2.000 se reporta un estudio donde se DEMUESTRA QUE LA VIAGRA ESTA ASOCIADA A MUERTE EN PERSONAS que no
tenían ANTECEDENTES DE daño cardiaco y en HOMBRES JÓVENES TAMBIÉN, sin antecedentes de enfermedad cardiaca.
He leído muchos de los artículos sobre la viagra y la
mayoría de LAS PERSONAS murieron poco tiempo después de tomada LA
PÍLDORA MILAGROSA, en un acto sexual, donde la misma PROVOCA sus efectos secundarios. Los mas importantes los cuales describo a
continuación:
1.) Muerte
2.) Infarto al miocardio.
3.) Arritmias cardiacas.
4.) Insuficiencia Cardiaca
5.) Nauseas.
6.) Dolor de Cabeza.
7.) Flushing (enrojecimiento del cuerpo)
8.) Diarrea.
9.) Rinitis
10.) Dispepsia
11.) Disturbios visuales (objetos se ven azules)
12.) Insomnio.
13.) Palpitaciones.
14.) Erecciones prolongadas (priapismo)
Como les dije, hace 2 años tome la viagra, en 2 ocasiones, tengo mas de 40 años, no sufro del corazon, y no soy hipertenso, hago deportes semanales, y describo lo que experimente. NO sufro de
disfunción eréctil, pero muchos PACIENTES ME PREGUNTABAN como actuaba la pastilla y si era verdad que funcionaba. Me tome 25 mgrs en la primera
ocasión (media pastilla) y realmente el efecto se produjo a la hora. Luego me tome 15 mgrs y logre los mismos efectos: SOY ALTAMENTE SENSIBLE A ESTA DROGA..
La píldora no actúa como afrodisiaco, tiene que haber estimulo sexual. El efecto fue bueno pero LOS EFECTOS SECUNDARIOS QUE EXPERIMENTE me hicieron pensar en NO PROBAR MAS ESTA DROGA, ellos fueron:
1.) Fluishing (enrojecimiento del torax) cara y orejas)
2.) Conjuntivas oculares rojas
3.) Taquicardia.
4.) Insomnio: ESTUVE 14 HORAS SEGUIDAS SIN DORMIR.
CONSIDERO finalmente QUE ESTA
PÍLDORA ES DE CUIDADO Y PARA TOMARLA HAY QUE ESTAR 100 % sano del
corazón, aun así corres el BENEFICIO Y RIESGO de tener una gran
relación SEXUAL, pero PUEDE QUE SEA TU ULTIMA, pues te mueres de UN INFARTO
ASÍ DE FÁCIL
LA REGITINA (Novartis)
-------------------------------
EL mesilato de fentolamina es una droga vieja utilizada como hipotensor, hace años es utilizada inyectada en el pene exitosamente provocando buenas erecciones sola o en
combinación con otras 2 drogas, papaverina (bimix) y prostaglandina E (trimix). La
presentación es ampollas de 10 mgrs.
Poco tiempo después del éxito de la VIAGRA. la casa
farmacéutica Zonagen se planteo la producción de una fentolamina de uso oral para tratar la
disfunción eréctil, ya sabiendo que inyectada en el pene funcionaba. Algunos creyeron que el producto NO iba a funcionar, y
todavía HOY día se discute si es efectiva o no, pero SI FUNCIONA
La fentolamina actúa bloqueando la adrenalina y causando una vasodilatación en el pene que provoca la
erección. La fentolamina salió al mercado para tratar la disfunción
eréctil bajo el nombre de REGITINA en tabletas de 40 mgrs para el año de 1.999. con un porcentaje de efectividad del 40 %
EFECTOS ADVERSOS
-----------------------------------:
1,) Agudos y prolongados estados hipotensivos.
2.) Arritmias cardiacas.
3,) Debilidad.
4.) Mareos.
5.) Hipotensión ortostatica
6.) Congestión nasal.
7.) Nauseas.
8.) Vómitos.
9.) Diarreas
Particularmente YO TAMBIÉN probé la FENTOLAMINA, y
conseguí los mismos efectos que la VIAGRA, pro hubo una GRAN DIFERENCIA: No hubo taquicardia, no flushing, no ojos rojos y pude dormir esa noche. El
único efecto adverso que note fue CONGESTIÓN nasal pasajera.
Pienso que EL MESILATO DE FENTOLAMINA ES MAS SEGURO QUE LA VIAGRA, Y no hay MUERTES REPORTADAS por su uso desde que
salió al MERCADO.
UPRIMA (Abbott)
--------------------------
La UPRIMA, (apomorfina), es la ultima de estas tres drogas en aparecer en el mercado, PERO TAMBIEN ES UNA droga de viejo uso. La apomorfina ha sido utilizada previamente como tratamiento oral en pacientes para tratar LOS
SÍNTOMAS DE LA ENFERMEDAD DE PARKINSON, como emético en envenenamientos, como SEDANTE para tratar problemas de comportamiento, y en pacientes
ALCOHÓLICOS para tratar problemas de conducta.
Y se descubrio CASUALMENTE en estos pacientes CON PARKINSON que provocaba y mejoraba la
erección.
La apomorfina a diferencia de la VIAGRA Y LA REGITINA
ACTÚA a nivel central. Farmacológicamente es un receptor agonista para la dopamina, induciendo una selectiva
activación en el núcleo para-ventricular que conlleva a producir señales
erectogénicas al pene. En otras palabras no actúa directamente en el pene, sino a nivel del cerebro.
A pesar de la GRAN CANTIDAD de efectos secundarios REPORTADOS en los estudios realizados con la UPRIMA
decidí tomar 2 mgrs, (la dosis mínima requerida) para observar que efectos
producía en mi cuerpo. No me gusto el hecho de tener que esperar unos 10 minutos a que la pastilla se disolviera en mi boca (se utiliza sublingual)
Los efectos obtenidos NO FUEROS SUPERIORES A LOS DE LA VIAGRA NI A LOS DE LA REGITINA que previamente
había experimentado. El único efecto adverso que note fue nauseas.
EFECTOS ADVERSOS:
-----------------------------------
La UPRIMA (apomorfina) fue lanzada al mercado en el año 2.001, como una NUEVA ALTERNATIVA PARA tratar la
disfunción eréctil, PERO REALMENTE ES UNA VIEJA DROGA USADA DURANTE
DÉCADAS para tratar la enfermedad de PARKINSON.
Tiene muchos efectos adversos y para no ser SUBJETIVO LOS INVITO A LEER LAS REFERENCIAS 35 Y 36 DE estos EXPEDIENTES SECRETOS X, las cuales PROCEDEN DE LA FDA, su efectividad es de un 30 a 40%.
A pesar de ello, LA UPRIMA, al igual que la REGITINA no han sido reportadas MUERTES por su uso.
CONCLUSIONES:
-----------------------------
Pienso en mi propia experiencia y de acuerdo a las REFERENCIAS BIBLIOGRÁFICAS que de estas 3 PÍLDORAS para mejorar la disfuncion erectil, la que tiene menos riesgos es la REGITINA (Novartis) la MAS POTENTE es LA VIAGRA (Pfizer) pero la MAS RIESGOSA, pues ha causado numerosas muertes. En cuanto a la UPRIMA (Abbott) tiene una gran desventaja: Han sido reportado numerosos casos de sincope
hipotensión y nauseas en los estudios de prueba y su efecto es a nivel central, pienso que mejor es el efecto directamente en el pene como la VIAGRA Y REGITINA.
Para finalizar recomiendo a TODA PERSONA QUE antes de experimentar con estas "PÍLDORAS DEL SEXO" consulte a un
cardiólogo y tenga una evaluación previa del funcionamiento de su corazón,
tensión y estado físico. Porque en una PRUEBA DE ESTAS puede que tenga su ULTIMA
RELACIÓN SEXUAL y deje el planeta tierra para ir a formar filas en el CIELO.
VIAGRA PARA MUJERES:
-------------------------------------
No quiero OLVIDAR A LAS MUJERES, quienes también quieren SU VIAGRA. De estas tres PÍLDORAS, LA
ÚNICA QUE HA SIDO UTILIZADA con relativo éxito en mejorar la calidad de la
relación sexual en las MUJERES es la REGITINA, (fentolamina)
DEMOSTRÁNDOSE en algunos estudios que mejora la LUBRICACIÓN Y sensaciones placenteras en la vagina. DE la VIAGRA SE HABLA MUCHO sobre esto, pero
todavía no se concluye nada AL RESPECTO, de la UPRIMA TAMPOCO.
VIACREME, LA CREMA DEL AMOR:
----------------------------------------------------
PERO para aquellas DAMAS QUE NO QUIEREN TOMAR la REGITINA, por temor, ya los científicos inventaron una "CREMA" que colocada en la
región genital de la mujer, provoca un mejoramiento increíble del COMPORTAMIENTO SEXUAL. Se denomina VIACREME o la CREMA DEL AMOR, esta compuesta por mentol y L ARGININA, un
aminoácido..
El efecto inmediato de la VIACREME es que causa un efecto irritante que provoca un aumento de la
lubricación vaginal y también incrementa los niveles de testosterona en la mujer aumentando la LIBIDO.
En otras PALABRAS las mujeres también TIENEN su VIAGRA para mejorar la calidad de sus relaciones sexuales, en 2 opciones: la FENTOLAMINA oral (REGITINA) y la VIACREME de uso local... QUE TAL ??? " Totalmente
APOCALÍPTICO ".
NOTA: 1 año después de la publicación de este
articulo, en el 2003, salieron al mercados dos nuevas PÍLDORAS para tratar
la disfunción ERÉCTIL.
1.) LA LEVITRA: o VARDENAFIL
en tabletas de 5, 10 y 20 mgr; y
2.) LA CIALIS: o
TADALAFIL, también en tabletas de 2,5, 5, 10 y 20 mgrs, y
también 40 mgr los genéricos.
Ambas también son ALTAMENTE
EFECTIVAS en la disfunción ERÉCTIL, siendo la mas utilizada hoy día 2025
el TADALAFILO, por poseer menos efectos secundarios que el SILDENAFIL
(VIAGRA), y tener mayor durabilidad en su efecto.
En las referencias los hechos.
Saludos a todos
Dr. José Lapenta R.
ENGLISH COMMENTS:
=====================
Hello friends of the net, DERMAGIC again with you, in this occasion with an interesting revision on the THREE pills but used to treat the ERECTILE dysfunction: VIAGRA (Sildenafil), REGITINA (Mesylate of phentolamine) and UPRIMA (Apomorphine).
I consider this revision a SECRET X FILES because many of you don't maybe KNOW SOME THINGS OF THESE PILLS which I will reveal today.
I PERSONALLY proved the three drugs and I can SPEAK correctly of what experiences with them and the effects that took place in my body.
VIAGRA: (Pfizer)
----------------------
In the year of March of 1998 the world was shocked by the appearance of a MIRACULOUS PILL which was able to "wake up" in UNUSUAL way "DEAD PENISES" by reason of the age (older people) or secondary illnesses that impeded the correct erection.
The drug was BEING PROVEN AS a hipotensor and he was discovered accidentally that it facilitated the erections in the people that they took them; as hipotensor fail, but it emerged as the SEXUAL MARVEL.
The explanation on how Viagra works is that it increases nitric oxide, a natural body chemical that dilates blood vessels, to get more blood flowing to the penis. Also Viagra blocks an enzyme produced in the penis that causes men to lose an erection.
Few weeks after having released to the market the VIAGRA, the first DEADS ASSOCIATED to the use of the SAME one they were reported, between March and November of that year 130 DEADS had already BEEN REPORTED by the FDA. For March of the year of the 2.000 they have already been reported but of 522 deaths associated TO THE VIAGRA, many of them with antecedents of heart lesions or taking medication for the heart (nitrates).
But that same month of March of the year 2.000 are reported a study where it is DEMONSTRATED THAT THE VIAGRA IS ASSOCIATED TO DEATH IN PEOPLE that didn't have ANTECEDENTS OF heart damage and in YOUNG MEN ALSO without cardiac antecedents.
I have read many of the articles on the viagra and most of PEOPLE died little time after having taken THE MIRACULOUS PILL, in a sexual act, where the same one CAUSES their secondary effects,
which I describe next:
1.) Death
2.) Myocardial infarction.
3.) Heart arrhythmias.
4.) Heart Failure
5.) Nauseas.
6.) Headache.
7.) Flushing.
8.) Diarrhea.
9.) Rhinitis
10.) Dyspepsia
11.) visual disturbances (blue/green-tinted vision)
12.) Insomnia.
13.) Hypotension and cardiac dysrhythmia.
14.) Prolongated erections.
As I told you I has taken the viagra 2 years ago, in 2 occasions, I have but of 40 years, I don't suffer of the heart, and I am not hipertensive man, I make weekly sports, and I describe what experiences. I don't suffer of erectile dysfunction, but many PACIENTES they ASKED ME the way the pill acted and if it was true that worked. I take 25 mgrs in the first oacasion (half pill) and really the effects in a hour presented. Then take 15 mgrs and achieve the same effects: I am HIGHLY SENSITIVE TO THIS DRUG.
The pill doesn't act as aphrodisiac, it has to exist sexual stimulation.
The effect was good, but THE SECONDARY EFFECTS THAT I EXPERIENCES made me think NOT PROVING IT MORE and they were these:
1.) Fluishing.
2.) Red ocular Conjunctive
3.) Tachycardia
4.) insomnia: I was 14 FOLLOWED HOURS WITHOUT SLEEPING.
I CONSIDER finally THAT THIS PILL is OF CARE AND to TAKE IT it is necessary 100 healthy% of the heart to BE, even so you run the BENEFIT AND RISK of having a great SEXUAL relationship, but it CAN BE the LAST ONE, because you COULD die SO EASY from MYOCARDIAL INFARCTION or heart failure.
REGITINA (Novartis)
---------------------------------
The meshylate of phentolamine is an old drug used as hipotensor, it has been used for years injected successfully in the penis causing good erections alone or in combination with other 2 drugs, papaverine (bimix) and prostaglandin E-1 (trimix). The presentation is vial of 10 and 25 mgrs.
Little time after the success of the VIAGRA. the pharmaceutical house Zonagen outlines the production of a Phentolamine of oral use to treat the erectile dysfunction, already knowing that injected in the penis it worked. Some believed that the product will not work, and still discusses nowadays if it is effective or not, but yes, it really WORKS.
The phentolamine works by blocking adrenaline and causing penile blood vessels to dilates that causes the erection. The phentolamine came out to the market to treat the erectile dysfunction under the name of REGITINA in pills of 40 mgrs for the year of 1.999. with a percentage of effectiveness of 40%
ADVERSE EFFECTS:
-------------------------------------
1.) Acute and prolonged hypotensive episodes
2.) tachycardia
3.) cardiac arrhythmias
4.) weakness
5.) dizziness
6.) flushing
7.) orthostatic hypotension
8.) nasal stuffiness
9.) nauseas
10.) vomiting
11.) diarrhea
Particularly I ALSO proved the PHENTOLAMINE, and I got the same effects that the VIAGRA,
but had a GREAT DIFFERENCE: There was not tachycardia, non flushing, red eyes and I could
sleep that night. The only adverse effect that I notice was nasal stuffiness.
I think that THE MESYLATE OF PHENTOLAMINE is MORE secure than THE VIAGRA,
AND there are not REPORTED DEATHS for its use since it left to the MARKET.
UPRIMA (Abbott)
--------------------------
The UPRIMA, (apomorphine), it is the last of these three drugs in appearing in the market, BUT it is
ALSO A drug of old use. The apomorphine has been used previously as oral treatment in patients to
treat THE SYMPTOMS OF THE PARKINSON'S DISEASE, as emetic, in poisonings, to
SEDATIVE for behavioral disturbances, and also to behavior-altering agent for
ALCOHOLIC patients. And she was discovered ACCIDENTALLY in these patients WITH
PARKINSON were this drug improved the erection.
The apomorphine contrary to the VIAGRA AND THE REGITINA ACTS at central level. The
pharmacology of the UPRIMA: it acts as agonist receptor for the dopamine, inducing a selective
activation in the nucleus paraventricularis leading to erectogenic signals to the penis. In other words it
doesn't act directly in the penis, it really acts in the brain.
In spite of the GREAT QUANTITY of REPORTED secondary effects in the studies carried out
with the UPRIMA I decided to take 2 mgrs (the required minimum dose) to observe the effects on
my body. I dislike the fact of having to wait about 10 minutes to the pill was dissolved in my mouth
(is used sublingual)
The effects obtained WAS NOT SUPERIOR TO THOSE OF THE VIAGRA NEITHER THOSE
OF THE REGITINA that previously had experienced. The only adverse effect that I notice was
nauseas.
ADVERSE EFFECTS:
--------------------------------
The UPRIMA (apomorphine) it was thrown to the market in the year 2.001, like a NEW
ALTERNATIVE to treat the dysfunction erectil, BUT it is REALLY AN OLD DRUG USED
DURING DECADES to treat the PARKINSON'S disease. She has many of adverse effects and
for not being SUBJECTIVE I INVITE YOU to READ THE REFERENCES 35 AND 36 OF
THESE SECRET X FILES, which COME FROM THE FDA, their effectiveness is from 30 to
40%.
In spite of it, the UPRIMA as the REGITINA has not been reported DEATHS for their USE.
CONCLUSIONS:
------------------------
I think of my own experience and according to the bibliographical references that of these 3 PILLS
to improve the erectile dysfunction, the one that has less risks is the REGITINA (Novartis), the BUT
POTENT it is THE VIAGRA (Pfizer) but the BUT RISKY, because it has caused numerous
deaths. As for the UPRIMA(Abbott) she has a great disadvantage: Numerous cases have been
reported of syncope hipotension and nauseas in the trial studies, and their effect is at central level, I
think that better it is directly the effect in the penis like the VIAGRA AND REGITINA.
To conclude I recommend ALL PERSON THAT consults to a cardiologist before experiencing with
these "PILLS OF THE SEX" and have a previous evaluation of the function of their heart, tension
and physical state. Because PROVING OF THESE DRUGS can has their FINAL SEXUAL
RELATIONSHIP and leave the planet earth, and go to form lines in the SKY.
VIAGRA FOR WOMEN:
----------------------------------
I don't want to FORGET TO THE WOMEN who THEIR VIAGRA also wants. Of these three
PILLS, THE ONLY one THAT has BEEN USED with relative success in improving the quality of
the sexual relationship in the WOMEN is the REGITINA, (phentolamine) being
DEMONSTRATED in some studies that it improves the LUBRICATION AND pleasurable
sensations in the vagina. Of the VIAGRA has been spoken a lot OF THIS, but doesn't still conclude
anything in this respect, neither of the UPRIMA
VIACREME, THE CREAM OF THE LOVE;
--------------------------------------------------------------
BUT for those LADIES THAT don't WANT to TAKE the REGITINA, for fear, the scientists
already invented a "CREAM " that placed in the woman's genital region, it causes an incredible
improvement of the SEXUAL BEHAVIOR. it is denominated VIACREME or the CREAM OF
LOVE, IT is compound one for menthol and L ARGININE, an amino acid.
The immediate effect of the VIACREME is that it causes an irritating effect that causes an increase
of the vaginal lubrication and it also increases the testosterone levels in the woman increasing the
LIBIDO.
In other words the women also they HAVE their VIAGRA to improve the quality of their sexual
relationships, in 2 options: the oral PHENTOLAMINE (REGITINA) and the VIACREME of local
use. .... SO SO ??? " Completely APOCALYPTIC."
NOTE: One year after this article was published, in 2003, two new pills
for treating erectile dysfunction came onto the market.
1.)
LEVITRA: or VARDENAFIL in 5, 10, and 20 mg tablets; and
2.) CIALIS: or
TADALAFIL, also in 2.5, 5, 10, and 20 mg tablets, and the generic version
is 40 mg.
Both are also HIGHLY EFFECTIVE for erectile dysfunction,
with the most commonly used pill today, 2025, being TADALAFIL, as it has
fewer side effects than SILDENAFIL (VIAGRA) and has a longer-lasting
effect.
In the references the facts:
Greetings to all
Dr José Lapenta R
================================================================
DERMAGIC/EXPRESS 4-(3) X-Files
================================================================
REFERENCIAS BIBLIOGRÁFICAS /
BIBLIOGRAPHICAL REFERENCES
================================================================
================================================================
THE VIAGRA SECRET X FILES
================================================================
1.) FDA Issues New Viagra Warnings
2.) Postmarketing Safety of Sildenafil Citrate (Viagra)
3.) Summary of Reports of Death in Viagra Users Received from Marketing (late March) through mid-November 1998
4.) Information About Viagra®
5.) Viagra May Cause Heart Attack Deaths In Younger Men With No Heart Problems, Study Finds
6.) Viagra linked to heart attacks and 522 deaths
7.) Viagra faces 2 potent competitors
8.) Sildenafil adverse effects in PRN flexible-dosing studies
9.) Sildenafil adverse effects: combined studies and doses
10.) Last performance with VIAGRA: post-mortem identification of sildenafil and its metabolites in biological specimens
11.) [Side effects of sildenafil: findings from two years practical experience]
12.) Uprima vs. Viagra
13.) THE VIAGRA in the FDA
===============================================================
THE REGITINA SECRET X FILES
===============================================================
14.) The Regitina 40 mg 4 caps Novartis
15.) The phentolamine definition and adverse effects
16.) Adverse effects of the phentolamine mesylate
17.) PHENTOLAMINE MESYLATE for Injection, USP
18.) REGITINA Laboratorio: Novartis
19.) Phentolamine mesylate in postmenopausal women with female sexual arousal disorder: a psychophysiological study.
20.) Oral phentolamine and female sexual arousal disorder: a pilot study
21.) Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction.
22.) Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind, placebo-controlled, crossover study.
23.) Challenging Viagra: The Erection Connection
===============================================================
THE UPRIMA SECRET X FILES
===============================================================
24.) Apomorphine-induced penile erections in Parkinson's disease
25.) Sequential administration enhances the effect of apomorphine SL in men with erectile dysfunction.
26.) Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug.
27.) Oral treatment of erectile dysfunction with apomorphine SL.
28.) The management of erectile dysfunction in the community.
29.) Safety and tolerability of apomorphine SL (Uprima).
30.) Characterising the benefit of apomorphine SL (Uprima) as an optimised treatment for representative populations with erectile dysfunction.
31.) Apomorphine to Uprima: the development of a practical erectogenic drug: a personal perspective.
32.) FDA WARNINGS LETTERS (UPRIMA)
33.) Apomorphine – another medication for erectile dysfunction
34.) TAP PHARMACEUTICAL PRODUCTS INC. WITHDRAWS NDA FOR
UPRIMA (APOMORPHINE HCL TABLETS) SUBLINGUAL
35.) The UPRIMA Background and adverse effects:
36.) Serious adverse events: with THE UPRIMA TRIALS
37.) THE VIACREME FOR WOMEN
38.) THE VIACREME IN THE NEWS
39.) VIACREME, lacreme d'Amour
40.) Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel.
===============================================================
===============================================================
THE VIAGRA SECRET X FILES
===============================================================
1.) FDA Issues New Viagra Warnings
===============================================================
Source: Associated Press, November 25, 1998)
The Food and Drug Administration is cautioning doctors to carefully consider who they are handing
out prescriptions to of the immensely popular impotence pill, Viagra. An estimated 6 million
prescriptions have been filled since the release of Viagra, 3 million by American men. There have
been 130 confirmed heart attack deaths among Americans who were taking the drug. Though it is
impossible to prove that Viagra is responsible for these deaths, the FDA has required manufacturer
Pfizer Inc. to add more explicit warnings to Viagra labels. The label already contained warnings that
anyone taking nitrate-containing medicines should never take Viagra because the drug interaction can
cause a deadly drop in blood pressure. Associated Press Medical Writer Lauran Neergaard reports
that the following warnings are also being added:
"The FDA has received reports of heart attacks, sudden cardiac deaths and hypertension among
Viagra users."
"Doctors should be cautious about prescribing Viagra to men who had a heart attack, stroke or
life-threatening arrhythmia in the last six months, or who have significantly low blood pressure,
significantly high blood pressure, a history of cardiac failure or unstable angina or the eye disease
retinitis pigmentosa."
"Sexual activity itself is risky for certain men with cardiovascular disease; and for those men, Viagra
obviously 'is inadvisable'."
"Doctors should consider whether temporary drops in blood pressure caused by Viagra, especially
during sexual activity, would harm a heart patient before prescribing him the drug."
"The FDA has received reports of men suffering painful, prolonged erections after taking Viagra. An
erection that lasts longer than four hours requires prompt medical attention."
There are some critics of Viagra who feel that these FDA warnings are not adequate in safe guarding
the health of American men , siting the banning of Viagra use in Britian by men how have had heart
attacks. Viagra can also impair vision, which has lead federal authorities to investigate whether
Viagra may have caused the plane crash in Maryland that killed actor William Gardner Knight.
===============================================================
2.) Postmarketing Safety of Sildenafil Citrate (Viagra)
===============================================================
Source: The FDA
In response to Freedom of Information requests, the FDA is posting a summary of reports of death
in sildenafil citrate (Viagra) users. This posting does not suggest a change in FDA's perspective
concerning the safety of Viagra. The intent is simply to provide easier access for those who have
requested this information.
The limitations of spontaneous postmarketing adverse drug event data should be considered when
interpreting these data:
Reports are submitted voluntarily, and the magnitude of underreporting is unknown. Some of the
factors that may influence whether an event is reported include: awareness by health professionals
and consumers of adverse drug event reporting, seriousness of the reaction, market share of the
drug, length of time since marketing, publicity about a drug or an adverse event, litigation, and
regulatory actions.
Because of underreporting and uncertainty concerning the number of persons exposed to a drug, it is
not possible to calculate a true incidence rate of a particular event for a specified drug.
In some reports, clinical information (such as medical history, validation of diagnosis, time from drug
use to onset of illness, dose, and use of concomitant drugs) is missing or incomplete. Follow-up
information may not be available.
An accumulation of adverse event reports does not necessarily indicate that the adverse event was
caused by the drug; rather, the event may be due to an underlying disease or some other factor(s).
The reports summarized below have been reviewed to eliminate duplicates. Numbers of reports
from a computerized listing of the Adverse Event Reporting System (AERS) should therefore not be
expected to match the numbers below, as those listings also contain duplicate reports and reports
that are little more than hearsay.
===============================================================
3.) Summary of Reports of Death in Viagra Users Received from Marketing (late March) through
mid-November 1998
===============================================================
Source: The FDA
From the marketing of sildenafil citrate (Viagra) in late March through mid-November 1998, during
which more than 6 million outpatient prescriptions (representing about 50 million tablets) were
dispensed, the FDA received reports of 130 U.S. patients who died after having been prescribed
this drug. Excluded were reports of 55 foreign patients, 35 with unverifiable information (from
hearsay, rumor, the media, or unidentifiable reporters), and 22 with unconfirmed Viagra use.
Of the 130 U.S. patients, two men died from homicide and drowning; three had strokes; and 77 had
cardiovascular events (41 with definite or suspected myocardial infarction, 27 with cardiac arrest, 6
with cardiac symptoms, and 3 with coronary artery disease). Cause of death was unmentioned or
unknown for 48. All with gender specified were men. Age was provided for 104 individuals whose
average age was 64 years (median = 64, range = 29-87). Of 62 with Viagra dose reported, 3 had
taken 25 mg; 46, 50 mg; 9, 100 mg; 2, 50-100 mg.; 1, more than 100 mg (exact dose unknown);
and 1, an overdose. Sixteen men took or were administered nitroglycerin or a nitrate medication that
is contraindicated with the use of Viagra. In addition, three men were found with nitroglycerin in their
possession, but it is not known if it was taken.
Time from use of Viagra to death or onset of symptoms leading to death was examined since the
drug is taken periodically and since a direct effect of the drug would be limited to a finite period after
drug ingestion. Excluding the two men who died from homicide and drowning, 44 (34%) of the 128
patients died or had onset of symptoms leading to death within 4 to 5 hours of Viagra use (including
27 during or immediately after sexual intercourse). Six died or developed symptoms later the same
day; 8, the next day; 5, two days later; and 4, three to seven days after Viagra use. The time from
drug ingestion to death or onset of symptoms leading to death was not stated or was unknown for
61 men (48%).
Ninety (70%) of the 128 patients had one or more risk factors reported for cardiovascular or
cerebrovascular disease (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus,
obesity, previous cardiac history). Three additional persons without identified heart disease or risk
factors had severe coronary artery disease detected at autopsy. Twelve were reported to have no
previous history of cardiac disease or risk factors, but for 10 of these, the time from last Viagra use
to death or onset of symptoms leading to death was unknown or was at least two days later. Two
men, 60 and 70 years old, had no mentioned risk factors, no sexual activity, and died shortly after
Viagra ingestion.
Consideration has been given to the following factors in assessing the relevance of these reports: the
high background rate of sudden cardiac death in men in the United States; the large prevalence of
risk factors for sudden cardiac death in Viagra users who have died; the additional risk associated
with sexual activity; the number of deaths in relation to the amount of drug use; underreporting of
adverse events; the quality of reports received; temporal relationship between the drug and the
adverse event; the possible biological plausibility between the drug and the adverse event; and
others.
Based on these reports and other information, the manufacturer, in consultation with the FDA, has
revised the product label (see http://www.fda.gov/cder/foi/nda/98/viagra/viagralabel.pdf).
As with all approved medications, the FDA will continue to monitor the postmarketing safety of
Viagra by carefully reviewing reports of death and other serious adverse events and will continue to
evaluate the need for regulatory action
===============================================================
4.) Information About Viagra®
===============================================================
Source: www.a1-drugstore
In a recent AP National article, writer David Crary reported that an estimated 7 million American
men are taking Viagra®. There have been other reports about the fact that some men have
experienced a heart attack while on the drug. What percentage of men have actually died while
taking Viagra?
A number of the men who have died of heart attacks had been mixing nitrate drugs with Viagra.
Pfizer warns on its Viagra Web site that if you mix the two drugs your blood pressure could
suddenly drop to an unsafe or life threatening level. A common nitrate drug is nitroglycerine, which is
usually taken for the treatment of chest pains.
In a recent article in Associated Press, Daniel Q. Haney reported the finding of Dr. Sanjay Kaul of
Cedars-Sinai Medical Center in Los Angeles who had reviewed Viagra reports sent to the U.S.
Food and Drug Administration between April 1998 and May 1999. There were 522 deaths
reported. Of that number 200 were heart attacks and 94 were cardiac arrests. There were 79 of the
heart attack victims who had been taking nitroglycerin for chest pains.
In his article Haney also reported the finding of a study done by Doctors from Beth Israel Deaconess
Medical Center in Boston. In the study 4,497 men were taking Viagra and 3,136 were taking a
placebo. There were 21 heart attacks or deaths among the Viagra users and 12 in the group not
taking Viagra.
Haney reported that other factors were included in a follow up to the Viagra users and the end result
was that risk of heart attack was the same for the two groups. In other words men with erectile
dysfunction also have other medical problems and the chances are they will die of heart attack
whether they are taking Viagra or not.
Reporting on the 49th annual meeting of the American College of Cardiology in Anaheim, Reuters
wrote that a Swedish team had come up with the same results . The team concluded that "Viagra is
safe and well tolerated in men with cardiovascular disease as long as they are not on nitrate therapy.
"
Dr. Arne M. Olsson of University Hospital in Lund reported on the study, which included 224 men
with erectile dysfunction and heart disease. `None of these men were on nitrate therapy. Some of the
patients were prescribed Viagra, while others were given a placebo or "dummy" pill for comparison
purposes. Olsson said that Viagra "significantly improved erectile dysfunction," although 17% of
users experienced flushing and 15% experienced headaches that were "mild to moderate." Olsson
said that four patients in the Viagra group and three patients in the placebo group developed cardiac
complications, but Olsson said that he does not believe that these were treatment related. "
Reuters further reported that more research was needed in order to confirm the findings.
In his article Crary talked about the fact that some people have unrealistic expectations in respect to
Viagra. He quoted Pfizer spokeswoman Mariann Caprino who said that ,`"It fixes a mechanical
problem...It does not fix the broader, more complex emotional problems within a couple."'
He also quoted psychologist Dr. Eli Coleman, director of the Program in Human Sexuality at the
University of Minnesota Medical School. Coleman said, "Many men feel the problems in their
relationship stem from an inability to have an erection, and they are oblivious to the intimacy
problems ...Viagra doesn't replace communication. It doesn't replace caring," he said. "If there are
lots of problems _ it isn't going to solve them. It could make things worse." '
Crary further reported that Viagra fails to help about 30 per cent of the men who try it. Some men
apparently respond well in the beginning but later require increasingly higher doses.
Gina Kolata wrote in the New York Times in March 1998 when Viagra first got FDA approval that
it helped 70 to 80 percent of the impotent men who tried it. Two years later on the Viagra Website it
reports that it helps 82 per cent or four out of five couples who try it.
There have also been studies done to see if Viagra can help postmenopausal women with sexual
dysfunction. The first peer-reviewed study was published in the March 99 issue of Urology. The
results of that study indicated that Viagra did not improve sexual function in most women but there
was some improvement in a few cases.
In May Reuters reported that researcher Dr. Jennifer Berman of the University of Boston had
conducted further studies. Her results showed that the drug did in fact help women in the same way
that it has been helping men. There will no doubt more studies done on this in the future.
In her article Kolata had interviewed Dr. Ian Osterloch, who had directed development of the drug.
It had initially been created to alleviate angina, the chest pains caused by the blocking of blood
vessels leading to the heart. The company had begun small pilot studies in 1991, and by the end of
1992 was ready to abandon the drug because the results had proved disappointing. Osterloch said
the unusual side effect was that some men were having erections.
Pfizer scientists did further research and soon suspected that there was a reason the men were
reporting erections: They came to the conclusion that Viagra just might alleviate impotence.
In 1999 Viagra sales totaled over a billion dollars. Today it is available in more than 90 countries
worldwide and is the most popular selling drug on the market. It is so popular in fact that Pfizer is
also trying to develop an inhalable version of the drug. It was recently reported in New Scientist
magazine that current research indicates that the nasal spray would be more convenient working
faster than the pill version. The pill is taken about an hour before intercourse. The development of
such a nasal spray is still in the early stages
===============================================================
5.) Viagra May Cause Heart Attack Deaths In Younger Men With No Heart Problems, Study Finds
===============================================================
Medical Pike
Source: www.psa-rising.com
March 14, 2000. Viagra, commonly prescribed by doctors to treat male erectile dysfunction, is
turning up too often at the scene of heart attack death in relatively young men. Some men may be
vulnerable to heart attack after taking this drug, made by Pfizer. That is not known, but the drug itself
is beginning to look like more than a bystander in the deaths.
Some men who have died after taking Viagra were elderly and on heart medication. But a study
reported March 14 finds that more men who have died were under age sixty-five. Most of the
deaths have occured within a few hours of taking the drug. Most of the men took the standard dose.
Most of the men had no reported heart problems. Although some men who died were taking nitrates
as well as Viagra, men who were not taking nitrates died at a higher rate.
This new evidence comes from post-marketing adverse event reports about Viagra made to the
FDA. Researchers at Cedars-Sinai Medical Center in Los Angeles analyzed these reports and found
that there "appears to be a high number of deaths and serious cardiovascular events associated with
the use of Viagra." They presented the study March 14 at the meeting of the American College of
Cardiologists in Anaheim, CA.
In an analysis of 1,473 major adverse events recorded in these reports about Viagra to the FDA,
522 people died, most of them from cardiovascular causes. According to the study's senior author,
Dr. Kaul, the majority of deaths were associated with standard Viagra dosages (70 percent of the
deaths were associated with the 50 mg dose). The deaths were due to cardiovascular causes and
appeared to be clustered around the time of dosing (two thirds of deaths in which the time from
ingestion to death was reported, occurred within 4-5 hours of taking Viagra). The majority of deaths
occurred in patients who were less than 65 years of age, and who had no reported cardiac risk
factors.
The study confirmed the well-documented increased risk with combined use of nitrates and Viagra.
Of 90 patients who suffered major heart events while taking Viagra on top of nitrates, death
occurred in about 68 percent, and when myocardial infarction was counted, the number of major
cardiovascular events in that group rose to 88 percent. However, the study found that most deaths
(88 percent) actually occurred in patients who were not taking nitrates, leading investigators to
speculate whether there are some susceptible individuals who don't need nitrates to unmask the
harmful effects of Viagra.
===============================================================
6.) Viagra linked to heart attacks and 522 deaths
===============================================================
SOURCE: "Viagra May Have Adverse Cardiovascular Effects," Cedars-Sinai Medical Center,
Mar. 15, 2000.
A study conducted at Cedars-Sinai Medical Center in Los Angeles has shown a high number of
deaths and serious cardiovascular events may be associated with the use of Viagra, the most
commonly prescribed therapy for erectile dysfunction in men.
These findings were presented March 14 at the meeting of the American College of Cardiologists in
Anaheim, Calif.
Researchers Sanjay Kaul, M.D., and Babak Azarbal, M.D. analyzed 1,473 major adverse events
reported to the Food & Drug Administration. These included 522 deaths, primarily due to
cardiovascular causes.
According to Dr. Kaul, the study's senior author, the majority of deaths were associated with
standard Viagra dosages (70% of the deaths were associated with the 50mg dose), were due to
cardiovascular causes and appeared to be clustered around the time of dosing (two thirds of deaths
in which the time from ingestion to death was reported, occurred within four-five hours of taking
Viagra).
The majority of deaths occurred in patients younger than 65 years of age, who had no reported
cardiac risk factors.
Although the study also confirmed the already well-documented increased risk of Viagra when taken
with nitrates, most of the deaths (88%) actually occurred in patients who were not taking nitrates.
===============================================================
7.) Viagra faces 2 potent competitors
===============================================================
By Rita Rubin, USA TODAY
March 16, 2000
If Ragab El-Rashidy had only had more money, Jay Leno might be wisecracking about Uprima, not
Viagra.
El-Rashidy founded Pentech - for "penis technology" - Pharmaceuticals several years before Viagra
became the first impotence pill in March 1998.
His goal was to develop a molecule called apomorphine into a treatment for erectile dysfunction.
Eventually, apomorphine was christened Uprima, sounding like a cross between "urological" and
"supreme."
Pentech's pockets weren't as deep as Pfizer's, Viagra's manufacturer, El-Rashidy says, so Uprima
missed out on becoming the first impotence pill to market. Although second place wouldn't be too
shabby, he says.
Next month, Uprima could move a step closer to joining Viagra. On April 10, TAP Pharmaceuticals,
licensed by Pentech to develop and market Uprima, will present clinical trial data to a Food and
Drug Administration committee.
A third drug, phentolamine, or Vasomax, was further along in the FDA pipeline, but clinical trials
were put on hold last year after a small number of rats given the drug were found to have unusual
benign tumors called brown fat proliferations.
"We don't think the finding of these brown fat proliferations in rats poses a significant human health
risk," says Scott Reding, chief financial officer of Zonagen, the Texas company that developed
Vasomax for impotence. The medical literature contains few reports of humans with such tumors,
Reding notes.
Already, many urologists are using an injectable form of phentolamine, on the market to treat
hypertension, as part of a drug cocktail for impotence.
Battling for No. 2
At the earliest, Reding says, Vasomax could go before the FDA committee in the first three months
of 2001. Still, he's hoping that Vasomax, not Uprima, will be the first impotence pill to join Viagra on
the U.S. market. "They don't have approval yet," Reding says. "If they get approval, obviously, we'll
be the third to market, and that's going to be a problem."
Even No. 2 will have to try hard to beat Viagra's popularity. Last year, sales of the drug, available in
100 countries, topped $1 billion, says Pfizer spokeswoman Mariann Caprino. Doctors in the USA
write about 200,000 Viagra prescriptions a week, Caprino says, and about 6 million of their patients
have tried it.
Last month Pfizer began enrolling women with sexual dysfunction in a multicenter U.S. trial of
Viagra.
In the USA alone, figures Boston University urologist Irwin Goldstein, someone pops a blue,
diamond-shaped Viagra tablet every four seconds.
Yet, Goldstein notes, Viagra doesn't work for everyone, so there's room for Uprima and the other
impotence pills under development. "The exciting part of Uprima is it works differently" than Viagra
does, says Goldstein, who has studied both drugs.
While Viagra is swallowed, Uprima is placed under the tongue and absorbed directly into the
bloodstream. Users are able to get an erection within minutes, compared with about an hour with
Viagra. That might seem like a major selling point, but, Goldstein says, "it's not a big deal from the
patient perspective."
Once absorbed, the drugs work on different ends of the pathway between brain and penis. Viagra
blocks an enzyme produced in the penis that causes men to lose an erection. Uprima stimulates
production of dopamine, a chemical in the brain that helps transmit messages - including those
directing the penis to become erect - between nerve cells.
Uprima is the key needed to turn on a car engine, says El- Rashidy, while Viagra is the gas in the
tank.
"Down the road two or three years, we're going to see combination therapy," says Ronald Lewis of
the Medical College of Georgia, president of the International Society of Impotence Research.
"There's an ad- vantage to intensifying messages at each end."
Individually, Lewis says, "Uprima's going to work for a certain group of patients, Viagra's going to
work for another." But because Uprima has been tested in only about 2,000 men, he says, it's
impossible to predict which patients will do better on that drug.
The only men who would appear to be candidates for Uprima but not Viagra are those on nitrates.
Taken with nitrates, Viagra can lower blood pressure to dangerous levels.
In clinical trials, Uprima's main side effect has been nausea. Viagra's side effects include headache,
upset stomach, diarrhea and blue/green-tinted vision.
Some scientists wonder whether a group of patients might suffer more serious problems after taking
Viagra. Despite its wild success, the drug has been dogged by safety concerns.
Heart of the matter
Just two days ago, researchers presented three reports on the subject at the annual meeting of the
American College of Cardiology in Anaheim, Calif.
One was a Swedish trial involving 224 impotent men randomly assigned to take Viagra or a dummy
pill. Nearly all had high blood pressure, and many also had heart disease. None used nitrates. No
serious car dio vascular side effects were reported during the 12-week study, and three-quarters of
the men on Viagra reported improved erections.
A second study, by Murray Mittleman of Harvard Medical School, a Pfizer consultant, pooled data
from 36 trials comparing Viagra with a placebo and 46 using just Viagra. Men on Viagra had heart
attack and death rates comparable to those on a placebo.
"These data are reassuring and suggest that treatment of ED (erectile dysfunction) and resumption of
sexual activity are not associated with even a moderate increase in cardiac risk," Mittleman
concludes.
Sanjay Kaul, senior author of the third study presented at the meeting, wouldn't go that far.
Viagra safety
"We know that in most patients at low risk, Viagra is a wonderful drug," says Kaul, a cardiologist at
Cedars-Sinai Medical Center in Los Angeles. But, he says, "we really don't have any definitive data
for patients at high risk" for Viagra-related problems.
Kaul notes that the trials in Mittleman's analysis, which specifically excluded men with serious heart
disease, don't reflect real-world use of Viagra.
Through the Freedom of Information Act, Kaul obtained information on 1,473 Viagra-related
adverse events voluntarily reported to the FDA from April 15, 1998, until May 21, 1999. The FDA
and manufacturers acknowledge that such reports represent a small fraction of problems linked to
drugs.
Among the Viagra reports were 522 deaths.
"The 522 deaths throw up a caution flag," says Kaul, who urges the FDA and Pfizer to take
Viagra-related adverse events more seriously.
Pfizer argues that many impotent men have serious underlying health problems, so it's not surprising
that some would die after taking Viagra.
But after analyzing adverse events reported to the FDA through July 8, researcher John Urquhart
found that the number of deaths per million prescriptions of Viagra was many times that of other
impotence treatments.
Only part of the discrepancy could be attributed to Viagra's greater fame, which would generate
more reports to the FDA, says Urquhart, who teaches at the University of California at San
Francisco and Maastricht University in the Netherlands.
"There may be identifiable subgroups of people who have really pretty ratty cardiovascular
conditions where you wouldn't want to use it," says Urquhart, 65, himself a satisfied Viagra user.
===============================================================
8.) Sildenafil adverse effects in PRN flexible-dosing studies
===============================================================
Source:www.jr2.ox.ac.uk/bandolier
Adverse effect Placebo (N=725) Sildenafil (N=734) Number needed to harm (95%CI) Percent
Headache 4 16 8.4 (6.7 to 11)
Flushing 1 10 11 (8.9 to 15)
Dyspepsia 2 7 20 (14 to 36)
Rhinitis 2 4 53 (28 to 753)
Visual disturbance 0 3 33 (23 to 56)
Diarrhoea 1 3 49 (29 to 165)
Adverse effects were mild or moderate in 92% of cases
===============================================================
9.) Sildenafil adverse effects: combined studies and doses
===============================================================
Source:www.jr2.ox.ac.uk/bandolier
Placebo (N=382) Sildenafil (N=479) Number needed to harm (95%CI)
Adverse effect
Flushing 4 93 5.4 (4.5 to 6.8)
Headache 20 99 6.5 (5.1 to 9.0)
Dyspepsia 7 41 15 (10 to 26)
Visual disturbance 2 22 24 (16 to 49)
Rhinitis 5 24 27 (17 to 69)
Discontinuations
-----------------
Inadequate response 14 6
Treatment-related 2 5
===============================================================
10.) Last performance with VIAGRA: post-mortem identification of sildenafil and its metabolites in
biological specimens
===============================================================
including hair sample.
Forensic Sci Int 2002 Mar 28;126(1):71-6
Dumestre-Toulet V, Cirimele V, Gromb S, Belooussoff T, Lavault D, Ludes B, Kintz P.
Laboratoire BIOffice, Avenue Gay Lussac, F-33370, Artigues Pres Bordeaux, France.
[email protected]
A 43-year-old man was found dead in a hotel room during a sexual relation with a colleague.He was
treated both for cardiovascular disease and for erectile dysfunction with VIAGRA. A pillbox was
found in the room with several tablets of verapamil (Isoptine), trimetazidine (Vastarel), yohimbine
and bromazepam (Lexomil).
A box of VIAGRA 25mg was found in his raincoat and two tablets
were missing. His wife declared during the investigation that he was also treated by trinitrine.
Autopsy revealed severe coronary artery sclerosis as well as signs of previous myocardial
infarctions. Blood, urine, bile, gastric content and hair and representative tissues for histology were
collected for toxicological analysis.
Sildenafil and yohimbine were screened with liquid
chromatography/mass spectrometry (LC/MS) and trinitrine with headspace injection (HS)/GC/MS.
Verapamil and trimetazidine were identified and quantified with LC/diode array detection
(DAD).Sildenafil was identified in blood, urine, bile and gastric content at 105, 246, 1206 and
754ng/ml, respectively. Hair concentration was 177pg/mg. The desmethyl metabolite was quantified
in urine at 143ng/ml.
Blood concentrations of verapamil and trimetazidine were measured at 659 and
2133ng/ml, respectively and were above therapeutic ranges. Trinitrine and yohimbine were not
identified.
These results confirm the absorption of sildenafil, verapamil and trimetazidine before the
death and hair analysis indicates the chronic use of sildenafil.To the author's knowledge, this is the
first report of a fatal sildenafil-verapamil association, probably by hypotension and cardiac
dysrhythmia.
===============================================================
11.) [Side effects of sildenafil: findings from two years practical experience]
===============================================================
Ned Tijdschr Geneeskd 2001 Mar 17;145(11):526-9
[Article in Dutch]
van Grootheest AC, Straus SM, Heeringa M.
Stichting Landelijke Registratie Evaluatie Bijwerkingen (LAREB), Goudsbloemvallei 7, 5237 MH
's-Hertogenbosch. [email protected]
Sildenafil has been registered for the treatment of erectile dysfunction since 1998. World wide a
large number of patients were reported, dying of acute heart disease after using sildenafil. Therefore
the patient instruction text was adapted. Simultaneous use of sildenafil and nitrates is contraindicated
because of serious decrease of the blood pressure. The use of sildenafil can lead to physical stress in
patients with a history of heart disease and a treadmill test assessment is advisable. In two years 38
adverse reactions were seen in 25 Dutch patients. The Dutch reports (three cardiovascular deaths
since the introduction) also show the dilemmas in the assessment of the safety of sildenafil: is it the
underlying disease or is it the drug that causes death? Further research into the adverse reactions has
to be done, therefore reporting suspected side effects of sildenafil is important.
===============================================================
12.) Uprima vs. Viagra
===============================================================
Source: www.uprima-and-viagra.com
Viagra used to treat male impotence vs Uprima for male impotence. Which one is more effective
when treating erectile dysfunction? Recent Viagra information would suggest that Viagra is the only
cure for impotence, if Uprima had its way, it would want to conquer and take a big piece of the
Viagra market share-both the Viagra online business and traditional Viagra markets.
Pfizer's Viagra, a pill that is swallowed, works by improving blood flow to the penis. Uprima tablets,
made by Tap Pharmaceuticals, are absorbed under the tongue, stimulating the brain chemical
dopamine, which starts the signal for an erection. Another explanation on how Viagra works is that it
increases nitric oxide, a natural body chemical that dilates blood vessels, to get more blood flowing
to the penis. Uprima also affects the level of nitric oxide, but the drug is absorbed and transported to
the brain.
In recent studies between Viagra and Uprima the two drugs for male impotence compared very
similar in overall success in combating erectile dysfunction. However, Viagra, because it is digested
and not sublingual like Uprima takes anywhere from 30 minutes to an hour in order to achieve an
erection. Uprima on the other hand, is a little more convenient simply because it is dissolved when
placed under the tongue and usually allows the patient to reach erection in 20 minutes or less.
Uprima also lasts longer then Viagra. You can buy Viagra and Uprima online.
The most common adverse event reported in these studies was nausea, mostly mild-to-moderate.
===============================================================
13.) THE VIAGRA in the FDA
===============================================================
Source: The FDA
In March 1998, oral sildenafil (Viagra), a PGE5 inhibitor was approved. In contrast to previous
products, this medication requires sexual stimulation in order to be pharmacodynamically active.
It is the first orally administered drug for ED. For most patients the recommended dose is 50 mg
taken, as needed, approximately 1 hour before sexual intercourse. The dose may be increased to
100 mg or decreased to 25 depending on effectiveness or tolerability.
Approval of Viagra was based on 21 randomized, double blind, placebo controlled trials of up to
6 months duration using a variety of study designs. Patients in these trials generally were included
if they had erectile dysfunction for 6 months or more. ED was broadly defined as the inability to
attain or maintain a penile erection sufficient for satisfactory sexual performance). Patients in
these trials had mild-to-moderate ED and included patients with organic (58%, including
diabetics), psychogenic (17%) or mixed (24%) etiologies.
Trials for Viagra included ED patients with a variety of etiologies, representative of the ED
population as a whole.
Efficacy in most of the trials supporting approval of this product was based on the (IIEF).
Information regarding the patient's ability to obtain and maintain erections can be obtained from
the results of Question 3 (When you attempted intercourse, how often were you able to penetrate
{enter} your partner?) and Question 4 (During sexual intercourse, how often were you able to
maintain your erection after you had penetrated {entered} your partner?). These questions are
scored form 0 to 5 [0= no sexual activity, 1=Almost never, 2= a few times (much less than half
the time), 3= sometimes (about half the time), 4 = Most times (much more than half), 5 = almost
always/always].
In the fixed dose trials, (n=1800), patients had a baseline score of about 2 on question 3 and 4 of
the IIEF. Sixty-three per cent, 74% and 82% on the 25mg, 50 mg and 100mg of Viagra reported
an improvement in these score compared to 24% on placebo. Titration studies (n=644) were
similar. In some study reports, the proportion of successful attempts was reported. In general, for
the placebo group, 20% of attempts were successful compared to 50 % in the Viagra group. The
proportion of patients that had at least one success during the study was 60% for placebo and 85%
for Viagra.
Viagra was administered to over 3700 patients during the clinical trials with data on 550 patients
for longer than a year. Some of the adverse events that occurred more than 2% of the time and
were more than placebo were: headache (16%), Flushing (10%), abnormal vision (3%) and
dizziness (2%). Syncope occurred in one patient who received an 800-mg dose of Viagra in early
trials. Viagra was otherwise uncommonly associated with symptoms of orthostatic hypotension or
syncope.
===============================================================
THE REGITINA SECRET X FILES
===============================================================
14.) The Regitina 40 mg 4 caps Novartis
==============================================================
Source: www.farmamondo.com
Description
----------
Phentolamine mesylate 40 mg.
Common uses
----------
It is indicated in the treatment of erectile dysfunction.
Contraindications
----------------
Use of Regitina is contraindicated in patients with a known hypersensitivity to any component of the
tablet. Coronary artery disease including angina, MI, or coronary insufficiency. Acute Hypotension.
Gastritis, ulcers and history thereof.
Dosage
-------
For most patients, the recommended dosis is 40 mg taken, as needed, approximately 20 to 30
minutes before sexual activity. Regitina may be taken anywhere from 1 hour before or 2 hours after
the meals. The maximum recommended dosis is once per day.
==============================================================
15.) The phentolamine definition and adverse effects
==============================================================
Source: www.phoenix5.org / and
Definition: (fen-TOLE-a-meen) Given by injection, it causes blood vessels to expand, thereby
increasing blood flow. When injected into the penis , it increases blood flow to the penis,which
results in an erection. When used in combination with papaverine it is called a ''bimix.'' When
prostaglandin E-1 is added it is called a ''trimix.''
papaverine
Definition: (pa-PAV-uh-reen) a drug which causes blood vessels to expand, thereby increasing
blood flow. When papaverine is injected into the penis, it produces an erection by increasing blood
flow to the penis. A US brand name is Pavarine. When used in conjunction with phentolamine, it is
usually called a ''bi-mix.''.
Prostaglandin E-1
Definition: A relaxant found in an injectable form of alprostadil that is used to produce erections.
Originally marketed under the name Caverject. May be combined into a bimix or trimix. (Another
form of alprostadil is MUSE which is inserted as a small pellet into the end of the penis.)
alprostadil
Definition: A prostaglandin derivative that relaxes the smooth muscles of the penis, enhancing blood
flow. When injected into the penis, it can produce an erection in most cases. First produced as
Caverject by Upjohn in 1995.
===============================================================
16.) Adverse effects of the phentolamine mesylate
===============================================================
Source: www.rxlist.com
Acute and prolonged hypotensive episodes, tachycardia, and cardiac arrhythmias have been
reported. In addition, weakness, dizziness, flushing, orthostatic hypotension, nasal stuffiness, nausea,
vomiting, and diarrhea may occur.
===============================================================
17.) PHENTOLAMINE MESYLATE for Injection, USP
===============================================================
Source: www.rklist.com
Phentolamine Mesylate for Injection USP, is an antihypertensive, available in vials for intravenous
and intramuscular administration. Each vial contains phentolamine mesylate USP, 5 mg and mannitol
USP, 25 mg in sterile, lyophilized form.
Phentolamine mesylate is m-[N-(2-lmidazolin-2-ylmethyl)-p-toluidino] phenol
monomethanesulfonate (salt).
Its molecular formula is C17H19N3O•CH4O3S and molecular weight is 377.47.
Phentolamine mesylate USP is a white or off-white, odorless crystalline powder. Its solutions are
acid to litmus. It is freely soluble in water and in alcohol, and slightly soluble in chloroform. It melts at
about 178° C.
===============================================================
18.) REGITINA Laboratorio: Novartis
===============================================================
Source: www.manes.com
Composición:
------------
Cada ampolla contiene:Metansulfonato de Fentolamina 10 mg. Excipientes c.s. Cada comprimido
contiene: Mesilato de Fentolamina 40 mg.
Acción terapéutica:
-------------------
Bloqueador de los receptores alfa-adrenérgicos. Comprimidos: Disfunción sexual eréctil masculina
leve a moderada.
Presentación:
Envase conteniendo 1 ampolla de 1 ml. Envases conteniendo 2, 3 y 4 comprimidos.
Dosificación:
-------------
Adultos: Para tratar la crisis hipertensiva que aparezca en la fase preoperatoria o durante el inicio de
la anestesia, se administrará 2 a 5 mg por vía I.V. y en el caso necesario se repetirá la inyección
controlando pa tensión arterial. Niños: se aplicará la mínima dosis eficaz, es decir, 1 mg para los
mayores de 8 años. 1 comprimido, 20 a 30 minutos antes del acto sexual, 1 vez por día. Los
comprimidos deben ser ingeridos alejados de las comidas (por lo menos 1 hora antes o 2 horas
después).
Contraindicaciones:
--------------------
Hipersensibilidad a la fentolamina y compuestos relacionados.Hipersensibilidad a sulfitos.
Hipotensión. Infarto de miocardio. Insuficiencia coronaria, angina u otras evidencias de enfermedad
coronaria.
Precauciones:
Es esencial monitorear la presión sanguínea, la frecuencia cardíaca y las condiciones clínicas del
paciente. Taquicardia y arritmia cardíaca. Usar con cuidado en pacientes con gastritis y úlcera
péptica.
Efectos colaterales:
--------------------
Hipotensión ortostática y taquicardia. Ocacionales: Episodios de hipotensión breves o prolongados,
somnolencia, debilidad, náuseas, vómitos, diarrea, mala ventilación nasal y rubor. Raras: angina de
pecho y arritmias cardíacas.
===============================================================
19.) Phentolamine mesylate in postmenopausal women with female sexual arousal disorder: a
psychophysiological study.
===============================================================
J Sex Marital Ther 2002;28 Suppl 1:205-15
Rubio-Aurioles E, Lopez M, Lipezker M, Lara C, Ramirez A, Rampazzo C, Hurtado de Mendoza
MT, Lowrey F, Loehr LA, Lammers P.
Asociacion Mexicana para la Salud Sexual, AC Tezoquipa 26, Colonia la Joya, Delegacion Tlalpan,
Mexico DF 1400. [email protected]
The objective of this study was to assess the potential of phentolamine as a treatment of
postmenopausal women with female arousal disorder (FSAD). Vaginal photoplethismography and a
subjective questionnaire were used. Forty one women were enrolled and four treatments were
tested: vaginal solutions 5 mg and 40 mg and an oral tablet each of 40 mg of phentolamine and
placebo.
Physiological readings were significantly different from placebo in the women using
hormone replacement therapy (HRT) with 40 mg of phentolamine in vaginal solution (p = 0.0186).
Subjective reports also were significantly different from placebo with the vaginal solution 40 mg and
the oral tablet of 40 mg of phentolamine among hormone replacement users.
No significant
differences were found among women not receiving HRT. Results indicate that phentolamine may
show promise as treatment for FSAD in estrogenized postmenopausal women.
===============================================================
20.) Oral phentolamine and female sexual arousal disorder: a pilot study
===============================================================
by Rosen RC, Phillips NA, Gendrano NC 3rd, Ferguson DM
Department of Psychiatry,
UMDNJ-Robert Wood Johnson Medical School,
Piscataway, New Jersey 08854, USA.
J Sex Marital Ther 1999 Apr-Jun; 25(2):137-44
ABSTRACT
Female sexual arousal disorder (FSAD) is a highly prevalent problem, although little is known about
pathophysiology or treatment of the disorder. Given the potential role of vascular mechanisms, a
small pilot study was conducted on the effects of oral phentolamine in menopausal women with
FSAD. Six postmenopausal women with a lack of lubrication and with sexual arousal difficulties of at
least 6 months duration participated in the study.
All subjects received a single dose of oral
phentolamine (40 mg) and placebo in a single-blind, dose-escalation design. Dependent variables for
the study included vaginal pulse amplitude (VPA), as measured by vaginal photoplethysmography,
self-report measures of sexual response, and patient- and physician-based assessments of adverse
events.
Results indicated a mild, positive effect of phentolamine across all measures of arousal, with
significant changes (p < .05) in self-reported lubrication and pleasurable sensations in the vagina. The
drug was well tolerated, overall, with few reports of adverse side effects. Further studies are needed
to assess the potential value of phentolamine and other vasoactive agents in the treatment of female
sexual dysfunction.
===============================================================
21.) Combination therapy for erectile dysfunction: a randomized, double blind, unblinded
active-controlled, cross-over study of the pharmacodynamics and safety of combined oral
formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in
men with moderate to severe erectile dysfunction.
===============================================================
Int J Impot Res 2002 Feb;14(1):54-9; discussion 60
Lammers PI, Rubio-Aurioles E, Castell R, Castaneda J, Ponce de Leon R, Hurley D, Lipezker M,
Loehr LA, Lowrey F.
Zonagen, Inc., The Woodlands, TX 77380, USA. [email protected]
Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction
(ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated
with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome
P450 enzymes.
The objective was to compare the efficacy and safety of three different oral
combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized,
double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico.
After a 4-week placebo run-in period, patients received all four of the following treatments using a
4-way cross-over design: 40 mg phentolamine (PM) +6 mg apomorphine (Apo); 40 mg PM +150
mg papaverine (Pap); 40 mg PM +6 mg Apo +150 mg Pap (Tricombo); 100 mg sildenafil (SC).
With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED
was defined as a less than 50% vaginal penetration success rate during the placebo run-in period.
A
total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments
produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to
baseline, however, no statistically significant differences were found between treatments.
A significant
period effect was observed. Also, the four treatments were found not to differ significantly in five out
of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE)
occurred in the 40 mg PM +6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other
two combinations (16.7 and 17.5%, respectively).
Nasocongestion and headache were the most
frequently reported AE. An oral combination of vasoactive agents may provide an alternative
approach to sildenafil. Based on these results a combination of phentolamine and apomorphine
warrants further clinical investigation.
===============================================================
22.) Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind,
placebo-controlled, crossover study.
===============================================================
Int J Impot Res 2001 Oct;13(5):303-8
Hatzichristou DG, Apostolidis A, Tzortzis V, Hatzimouratidis K, Kouvelas D.
Department of Urology and Center for Sexual Dysfunction, Aristotle University of Thessaloniki,
Greece. [email protected]
The objective of this study was to determine the effects of oral phentolamine, administered before
sleep, on nocturnal penile erectile activity of men with mild to moderate erectile dysfunction (ED).
We studied five patients with mild to moderate ED (mean age 34.8 +/- 8.13 and mean duration of
ED 31.8 +/- 23.5 months), in a double-blind, placebo-controlled, crossover study.
All patients
received oral phentolamine (Vasomax) at a dose of 40 mg and placebo for three consecutive nights
respectively and were submitted to nocturnal penile tumescence and rigidity monitoring (NPTR) with
the Rigiscan device.
NPTR parameters of the two 3-night recordings were evaluated and compared.
Administration of oral phentolamine before sleep was associated with a statistically significant
increase in the number of erectile events with rigidity > or = 60% lasting > or = 10 min (P = 0.02),
as well as the rigidity activity units (RAU) value per hour sleep, both at the base (P = 0.023) and the
tip of the penis (P = 0.019).
The number of events as measured by Rigiscan software (20% change
in circumference), as well as tumescence activity units (TAU)/h values did not show any statistical
difference. No adverse effects were recorded. It is concluded that oral phentolamine administered
before sleep enhanced NPTR parameters associated with the quality of the erectile events. Such
results provide a pathway for the development of a prevention strategy for ED.
Future studies will
elucidate whether vasoactive agents taken on a regular basis before sleep, can prevent ED in men at
risk, protecting also minimally and moderately impotent patients to become moderately and severely
impotent respectively.
===============================================================
23.) Challenging Viagra: The Erection Connection
===============================================================
Source: www.nextwavestocks.com
By Bernard B. Tulsi
Biowave revisits one of our favorites: drug delivery companies. But this time around, we are adding a
sexy twist. We will limit our peek to companies working on hot new impotence drugs. Relax, this has
less to do with keeping up with our media brethren's creed that sex sells than with giving you simply
the hard facts.
Well, news that an impotence pill like Pfizer's Viagra is allegedly implicated in the deaths of more
than a dozen (recently happy) men suggests a vulnerable product. Many eager drug developers are
praying it's the latter. Not so long ago, one biotech guru foretold that Sequus (Nasdaq: SEQU) was
readying a drug that could unseat Viagra as the leading progenitor of the erect penis--the list of
players keeps growing.
Just as the methods for delivering impotence drugs vary, the companies developing them come in all
sizes. They range from the king-sized Pfizer and Pharmacia & Upjohn, to small-caps like Sequus,
Zonagen (Nasdaq: ZONA), Vivus (Nasdaq: VVUS), and MacroChem (Nasdaq: MCHM), and
down to the pint-sized Harvard Scientific (OTC BB: HVSF). They are all vying to become
significant players in a market that is growing from $260 million in 1997 to an estimated $4.5 billion
in 2002.
Let's start with the tiny Florida-based Harvard Scientific, which has a market cap of $36.7 million,
5.2 million shares outstanding, no sales and a loss of $3.7 million last year. In a series of recent
announcements, which became very intense mid-June, the company signaled that it wanted to be
serious player in the treatment of impotence.
On June 10, Harvard Scientific revealed that it had developed a topically applied product to treat
male erectile and sexual dysfunction. The new treatment will use the company's patented delivery of
Prostaglandin E-1, and will compliment its aqueus solution, intrameatal delivery treatment for
impotence. The lotion will be administered locally to the penis, and is very similar to a treatment for
female sexual dysfunction, the company announced in May.
Harvard Scientific plans to file for FDA approval to begin combined PhaseI/II trials shortly for the
new topical lotion. They claim that their lotion would not need dermal agents to enhance the
penetration of Prostaglandin. In fact, they eschew such agents. They believe such enhancers increase
the likelihood that the patient would contract sexually communicable diseases--presenting another
health problem. Meanwhile, Harvard Scientific has submitted international patent applications for the
product.
By contrast, MacroChem, which also has a topical product, Topiglan, relies for its performance
advantage on its proprietary delivery enhancement system SEPA. Topiglan, which is an alprostadil
preparation, is a smooth muscle relaxer that produces vasodilation. The company has reported 75 to
80% efficacy from Topiglan studies, while the side effects amounted to minimal warmth. The studies
show that it lasts 30 to 60 minutes, and is applied, along with stimulation, 15 to 20 minutes before
sex.
In a June 9 announcement, MacroChem expressed optimism that it will have licensing revenue from
its erectile dysfunction gel by year end. The company expects to begin negotiations within the next
few months with as many as eight multi-nationals on a license for Topiglan, according to its chief
executive.
Meanwhile, Vivus announced mid-June that the results of an independent study with their MUSE
delivery system for alprostadil achieved a 60% rate in diabetic men with erectile dysfunction. In the
230-person study there were 65 diabetic and 165 non-diabetic men with erectile dysfunction who
received MUSE for up to six months.
The company contends that MUSE is a good treatment option for men with diabetes and/or vascular
diseases because it has few systemic side effects. MUSE is a transurethral application that works by
relaxing smooth muscles, which results in vasodilation. It has been affected, however, by persistent
reports on inadequate performance, reliability questions and comfort problems.
Concerns about systemic side effects do not prevent companies like Zonagen, also with an oral
treatment, to attempt to bring another treatment to market.
In fact, Schering Plough Corp. has agreed to pay Zonagen an accelerated milestone of $5 million for
Vasomax, Zonagen's oral treatment. The milestone marks the end of a clinical program that will be
used to support an New Drug Application (NDA). Zonagen plans a July 1998 FDA submission.
Vasomax (phentolamine) a vasodilator, works by blocking adrenaline and causing penile blood
vessels to dilate. Its reported side affects--stuffy noses--are believed to be far fewer than Viagra's.
Vasomax is reported to last until ejaculation and must be taken 20 to 30 minutes before sex along
with some stimulation.
Another company, Senetek, is developing Invicorp, an injectible neurotransmitter that uses
phentolamine to relax smooth muscles. Studies are showing 67 to 81% efficacy, and this approach is
believed to be better than the alprostadil injections, such as Pharmacia & Upjohn's Caverject, which
was approved by the FDA in July 1995. Caverject has an 86% efficacy rating but its side effects
include pain, prolonged erection and bleeding. By contrast, Senetec's proprietary injection system is
said to cause minimal or no pain.
Erectile dysfunction affects an estimated 48 million men between the ages of 40 and 70, according to
the 1994 Massachusetts Male Aging Study. So there is no shortage of interest in the developments
in this area. But if the truth be told, we were really drawn to this story by no less than Pfizer's
Viagra--though hardly for the same reason that brings back eager users.
Earlier, Pfizer's spokesman Andrew McCormick had said that they were running eight-page glossy
ads featuring three older couples dancing--well come on now, they could only go so far. But the
happy, or better still, satisfied looks on the faces of the oldies in the JAMA, New England Medical
Journal and Cardiology publications were very compelling. So much so that we could hardly resist
the chance to tell them, and others like them, that there is more where Viagra came from. A string of
companies claiming that they have better answers want to bring more good things to their lives.
===============================================================
THE UPRIMA SECRET X FILES
===============================================================
24.) Apomorphine-induced penile erections in Parkinson's disease
===============================================================
by O'Sullivan JD, Hughes AJ
Neurology Department,
Austin & Repatriation Medical Centre,
West Heidelberg, Victoria, Australia.
Mov Disord 1998 May; 13(3):536-9
ABSTRACT
Penile erections were regularly induced by intermittent subcutaneous injections of apomorphine in
five patients with Parkinson's disease (PD) complicated by motor fluctuations. Four of the patients
reported erectile dysfunction before beginning apomorphine and two of these report a significant
improvement in their sexual function resulting from apomorphine use.
Animal studies suggest central
D2-type dopamine receptor stimulation and oxytocin release from the paraventricular nucleus of the
hypothalamus mediate the effect. Erections reported with other dopamine agonists and levodopa are
probably mediated by the same mechanism. Apomorphine-induced erections in PD are probably
more common than previously thought. The benefit of apomorphine on sexual function in some
patients suggests a possible role in the treatment of impotence in PD.
===============================================================
25.) Sequential administration enhances the effect of apomorphine SL in men with erectile
dysfunction.
===============================================================
Int J Impot Res 2002 Feb;14(1):61-4
Heaton JP, Dean J, Sleep DJ.
Queens University, Kingston, Ontario, Canada. [email protected]
The response to Uprima (apomorphine sublingual, (apo SL)) has been well documented in
conventional clinical trials. Apo SL produces a predictable, consistent and durable response across a
wide variety of patients.
The positive reinforcement of a successful outcome should further support
clinical benefit. Apo SL with its rapid onset affords a greater opportunity for spontaneity, which can
be an important factor in influencing patient choice. It is recognised that patient counselling and the
setting of realistic expectations are vital to a successful outcome.
The impact of persisting with
sequential treatment on outcome has been calculated from the clinical data. While apo SL is effective
de novo in 50% of single doses, additional benefit is observed with repeat dosing. Full benefit may
not be achieved until four or more treatments have been taken in an optimal setting. The data also
confirm that 3 mg has superior activity. Patients should therefore be encouraged to try a minimum of
4 doses at 3 mg.
===============================================================
26.) Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central
nervous system-acting ED drug.
===============================================================
Int J Impot Res 2002 Feb;14 Suppl 1:S53-6
Giuliano F, Allard J.
Department of Urology, CHU de Bicetre, Assistance Publique Hopitaux de Paris, France.
[email protected]
An exclusive central site of action for the proerectile effect of apomorphine, including not only the
brain but also the spinal cord, is supported by extensive experimental data. Assuming that the
mechanisms of action of apomorphine are similar in humans and animal models, its use for the
treatment of erectile dysfunction (ED) validates the emerging idea that erectile response could be
enhanced by acting directly within the central nervous system (CNS).
It also emphasized the key role
of the dopaminergic system in the control of erection. As exemplified with the clinical development of
apomorphine, targeting the CNS does not rule out the occurrence of undesirable side effects.
Because the rare event of syncope induced by apomorphine is not well understood, further research
should be conducted to explore its possible mechanisms.
In clinical practice, however, approved
doses of apomorphine SL are well tolerated. It is noteworthy that no modification of sexual desire
was observed with apomorphine. Indeed, drugs acting within the CNS may more likely interact with
sexual desire than peripherally acting drugs, and care should be taken to assess this point in the
future.
Although our knowledge of the control of penile erection by the CNS is restricted, there are
many potential sites for CNS-acting ED drugs. New centrally acting therapy for ED should
concentrate on receptor targets more specific to erectile command. Clinical efficacy of new
centrally-acting compounds will assess the well-founded purpose of this rationalization.
===============================================================
27.) Oral treatment of erectile dysfunction with apomorphine SL.
===============================================================
Urol Int 2001;67(4):257-63
Altwein JE, Keuler FU.
Department of Urology, Krankenhaus der Barmherzigen Bruder, Munich, Germany.
[email protected]
Apomorphine SL (Ixense, Uprima) is a new oral medication shown to be effective in the treatment of
erectile dysfunction. This compound is a dopaminergic agonist with affinity for dopamine receptor
sites - mostly D(2) - within the brain known to be involved in sexual function. Apomorphine induces
selective activation in the nucleus paraventricularis leading to erectogenic signals. More than 5,000
men with erectile dysfunction participated in phase II/III clinical trials assessing the safety and
efficacy of doses ranging from 2 to 6 mg.
The most favorable risk/benefit ratio is seen with a
dose-optimization regimen of 2-3 mg: the 3-mg dose provides efficacy comparable to that of 4 mg
but with fewer side effects. Consequently, review of clinical studies focuses on data with the 2- to
3-mg dose, the registered dose for use in clinical practice. The primary efficacy endpoint in most
clinical trials with apomorphine SL was the percentage of attempts resulting in erections firm enough
for intercourse - one of the most rigorous endpoints used in ED trials to date.
These data were
collected from both patients and their partners by reviewing entries in patient diaries and partner
BSFI questionnaires. Secondary endpoints included percentage of attempts resulting in intercourse
and improvement in ED severity based on the International Index of Erectile Function (IIEF). The
proportion of attempts resulting in erections firm enough for intercourse was 49.4% with 3 mg
compared with the baseline value of 24.3%. Partner evaluations corresponded with those of the
patients.
Erections occurred between 18 and 19 min after taking apomorphine SL 2 or 3 mg. The
most common side effect was nausea which declined with continued use. Vasovagal syncope was
reported in <0.2% of men, and was preceded by clear prodromal symptoms. Thus, apomorphine
SL is an effective, well-tolerated drug for erectile dysfunction. Copyright 2001 S. Karger AG, Basel
===============================================================
28.) The management of erectile dysfunction in the community.
===============================================================
Int J Impot Res 2001 Aug;13 Suppl 3:S45-51
von Keitz A.
[email protected]
Erectile dysfunction (ED) is a widely occurring benign disorder that affects men of all ages. The
prevalence and severity of ED increases with age and results in considerable distress and impact on
quality of life for those who suffer from it. As ED is associated with a wide variety of underlying
conditions and co-morbidities there is a requirement for diversity of treatment options beyond those
currently available. In the management of the ED patient both primary care and specialist physicians
have an important role to play.
This article reports on a stepwise approach for the diagnosis and
treatment of ED, with an emphasis on a 'shared care' approach. The suitability of apomorphine SL
(Uprima) for the front line management of the ED patient is described.
===============================================================
29.) Safety and tolerability of apomorphine SL (Uprima).
===============================================================
Int J Impot Res 2001 Aug;13 Suppl 3:S40-4
Bukofzer S, Livesey N.
Abbott International, Abbott Laboratories, Abbott Park, IL 60064-3537, USA.
[email protected]
The side effect profile of apomorphine SL (2-6 mg) has been determined in clinical studies of over
5000 patients using over 120 000 doses. Apomorphine, 2 and 3 mg, has been shown to have an
excellent safety profile. The most commonly occurring side effects (<7%), nausea, headache and
dizziness, tend to be mild and not compliance limiting. Neither the incidence nor the nature of the side
effects is significantly affected by common co-morbidites or by the use of many concurrent
medications.
Over this dose range there is little evidence of vasoactivity; there is little change in
haemodynamic baseline and there is no synergistic effect with nitrates. Although syncope can occur
at higher doses, it is rarely observed at approved doses (<0.2%).
===============================================================
30.) Characterising the benefit of apomorphine SL (Uprima) as an optimised treatment for
representative populations with erectile dysfunction.
===============================================================
Int J Impot Res 2001 Aug;13 Suppl 3:S35-9
Heaton JP.
Queen's University, Kingston, Ontario, Canada. [email protected]
The clinical profile for apomorphine sublingual (SL), a new centrally active agent for the management
of the erectile dysfunction (ED) patient, is described in this article. Apomorphine SL is shown to be
rapid in onset (71% of patients within 20 min) with a consistent, predictable response that is
independent of severity (mild, moderate or severe), the underlying aetiology or the presence of
significant co-morbidities (coronary artery disease, hypertension, etc). Importantly, there is also
consistent long-term clinical benefit (>90% of attempts being successful over 18 months), for
patients who respond to therapy and a benign side effect profile (<13.4% patients with adverse
events). This formulation of apomorphine has a speed of onset and overall clinical profile that may
offer particular advantages to the patient in terms of spontaneity and predictability of response. ED is
a complex disease of varying aetiologies and severities often associated with a number of
co-morbidities that require diverse solutions. Given the need for customisation of therapy to
individual patient needs, the clinical profile of apomorphine SL would indicate that it will make a
most welcome addition to the physician's armamentarium against ED.
===============================================================
31.) Apomorphine to Uprima: the development of a practical erectogenic drug: a personal
perspective.
===============================================================
Int J Impot Res 2001 Aug;13 Suppl 3:S29-34
Morales A.
Department of Urology Queen's University, Kingston, Canada. [email protected]
The development process for apomorphine SL as an effective treatment for patients with erectile
dysfunction has been somewhat unusual. As often is the case, much of the impetus for the basic
research originated in academia. However, somewhat unusually, the impetus for early stage clinical
research also lay in the hands of the academics. This article represents a historical perspective from
one of those involved throughout.
===============================================================
32.) FDA WARNINGS LETTERS (UPRIMA)
===============================================================
Source:www.pharmcast.com
Released by FDA: 4/12/00. Posted by FDA: 5/22/00
Binita Kwankin
Senior Regulatory Products Manager
TAP Pharmaceutical Products, Inc.
2355 Waukegan Road
Deerfield, Illinois 60015
RE: NDA#21-118
Uprima (apomorphine HCl tablets) sublingual
MACMIS ID #8899
Dear Ms. Kwankin:
As part of its routine monitoring an surveillance activities, the Division of Drug Marketing,
Advertising, and Communications (DDMAC) has become aware of a press release for Uprima
(apomorphine HCl tablets), disseminated by TAP Pharmaceutical Products, Inc. (TAP), that is in
violation of the Federal Food, Drug, and Cosmetic Act (Act) and applicable regulations. DDMAC
specifically refers to your press release issued on April 10, 2000, entitledFDA ADVISORY
COMMflTEE RECOMMENDS APPROVAL OF UPRIMA (APOMORPHINE HCl TABLETS)
SUBLINGUAL FOR THE TREATMENT OF ERECTILE DYSFUNCTION. This press release
is considered promotional labeling for Uprima and is in violation of the Act for the following reasons.
Omission of Material Facts
The most commonly reported side effect was nausea. Of the nausea reported in the NDA clinical
studies, most incidences were mild to moderate in severity.
Promotional materials are in violation of the Act if they fail to reveal facts material in light of
representations made about the product. The two statements above are represent the full extent of
risk information about Uprima in your press release. You fail to disclose, however, material facts
relating to significant and potentially life-threatening risks associated with Uprinia that were presented
at the Advisory Committee meeting. Specifically, syncope and severe hypotension were seen in
some patients taking Uprima in clinical trials. These serious adverse events prompted the Committee
to voice serious concerns about Uprimas safety profile. For example one Committee member, a
cardiologist, stated. There will be some people who will probably lose their lives because they pass
out at the top of the stairs or operating a car.
The committee suggested some cautionary recommendations for labeling. In addition, the
committee advised that educational materials be provided to patient at the point of care.
The Committee recommended that the labeling for Uprima include contraindications for use with
concomitant ingestion of alcohol and in patients taking nitrate therapy. The Committee also
recommended a boxed warning describing vaso-vagal events and the potential for syncope and
cardiovascular compromise. These material facts are also omitted from your press release.
Pre-Appoval Promotion
New class of Erectile Dysfunction (ED) therapy may benefit millions of men with ED.
UPRIMA could offer several benefits for patients suffering from ED....data suggest that UPRIMA
is safe and effective in men with varying severities of ED.
...we feel that UPRIMA would greatly enhance the therapeutic options of millions of men with ED.
Section 21 CFR 312.7 states, among other things, that an investigational new drug may not be
promoted as being safe or effective for the uses under investigation. Your press release is violative
because it includes claims, representations, and conclusions concerning the safety and efficacy of
Uprima, an investigational new drug.
In order to address these objections, DDMAC recommends that TAP take the following actions:
1. Immediately discontinue the use of this, and all other promotional materials and activities for
Uprima that contain the same or similar violations.
2. Provide to DDMAC, in writing, your intent to comply with #1 above. Your response should be
received by April 26, 2000.
3. This response should include a list of all similarly violative promotional materials and your method
for discontinuing their use.
If you have any questions or comments, please contact the undersigned by facsimile at (301)
594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising and
Communications, HFD-42, Rm. l7B-20, 5600 Fishers Lane, Rockville, MD 20857. DDMAC
reminds you that only written communications are considered official.
In all future correspondence regarding this particular matter, please refer to MACMIS ID #8899 in
addition to the NDA number.
Sincerely,
Mark W. Askine, R.Ph.
Regulatory Review Officer
Division of Drug Marketing,
Advertising and Communications
===============================================================
33.) Apomorphine another medication for erectile dysfunction
===============================================================
Source: www.apomorphine.org
By Serge Kreutz
Version 3.0, May 2002
In 2001, a "new" treatment has been launched in Europe for erectile dysfunction. The medication is
known as Uprima. If you consider Viagra an expensive medication, you havent paid yet out of your
own pocket for Uprima. The 3 mg pill costs about 30 US dollars, and the one with 2 mg is only
marginally cheaper.
Strictly speaking, Uprima is not a new drug. The active ingredient of Uprima is apomorphine, which
has been around for decades, and is used in the treatment of Parkinsons disease and as an emetic in
dogs and other domestic animals. (An emetic is a drug that induces vomiting.)
While apomorphine has a definite potential as a pleasure drug, this is about all it has in common with
its more famous colleague in name, morphine. Sure, apomorphine is produced from morphine. But
its pharmacological effects are completely different. Morphine is a sedative agent, while
apomorphine is a stimulant.
Apomorphine primarily works as a dopamine agonist, which accounts for its usefulness in the
management of Parkinson's disease, a condition characterized by the loss of dopamine-producing
neurons, leading to severe motor function disturbance.
Apomorphine is a D1 receptor-specific dopamine agonist that makes it different from mostly
ergot-derived dopamine agonists, which usually target D2 dopamine receptors, e.g. pergolide and
bromocriptine. D3 and D4 dopamine receptors are less often targeted in the management of
Parkinson's disease.
It has long been documented that most Parkinson's medications have sexuality-enhancing side
effects. I myself have been using Parkinsons medications for sexual enhancement long before
Uprima was launched. The most experience, I gained with Parlodel (bromocriptine), but I have also
tested Dopergine (lisuride), Dostinex (cabergoline), Mirapex (pramipexole), L-dopa, and
non-Uprima apomorphine.
It has to be noted that the sexuality-enhancing side effects hold true for many but not all
dopamine-enhancing Parkinson's medications. Whether or not a dopamine agonist enhances sexual
functions seems to depend primarily on the dopamine receptor and sub-receptor sites it targets.
Unlike sildenafil (Viagra), dopamine agonists exert their pro-sexual effect not upon the erectile organ
but upon the brain. They provoke erections not by messing with the plumbing of male sexual function
(speak: blood supply to the penis), but by interfering with the wiring necessary for arousal, pleasure,
and climax.
That Viagra only affects the plumbing, puts limits to its potential as a lifestyle drug. Viagra will add
little for men whose plumbing doesn't leak. On the other hand, a good shot of additional desire
would be a welcome life enhancement for many people with whom there is nothing wrong physically
but who just feel bored with their everyday life. For them, dopamine agonists could be a real
enrichment, and even a medication that saves their marriages.
But does Uprima fulfill this promise?
Dosage for a pro-sexual effect is difficult to determine for all dopamine agonists. This is the case
because a dosage that is too high will inevitably result in nausea. This nausea can be so bad that the
last thing one fancies is sex.
The trick with apomorphine and other dopamine agonists is to take an amount which is below the
nausea boundary but still strong enough to have a pro-sexual effect. Often, this is difficult to achieve.
(The article on how to take bromocriptine for sexual enhancement deals with the issue.)
If a FDA endorsement is to be obtained for the marketing of a dopamine agonist as treatment for
erectile dysfunction, the primary concern has to be to keep the nausea side effect at bay.
With apomorphine, nausea can be minimized if it gets into the bloodstream quick enough.
Parkinsons patients use injection apomorphine. Parkinsons is a serious condition, a matter of life
and death, and in such a case, it can be expected from a patient to bear with injections.
But as treatment for a light, non-life-threatening condition like erectile dysfunction, injection
medications have always been a flop.
Tap Pharmaceuticals, the makers of Uprima, got around the problem in two ways: by packaging the
drug as sub-lingual, and by keeping the dosage per tablet extremely low.
I have had some 20 readers relating to me their personal experience with Uprima. No one
complained about the nausea side effect. They all lamented that they didnt feel any pro-sexual effect
from the Uprima sublinguals. Some of those who related their experience went up to three 2 mg
tablets a time (an investment of more than 70 US dollars), and still didnt get it going.
The point is: with strongly underdosed apomorphine, the likelihood of nausea will be negligible. And
a good number of those trying the drug may still have a pro-sexual effect, even if its largely a
placebo one.
I wonder whether the awareness of these circumstances played a role in Tap Pharmaceuticals
decision to market the drug at such a stiff price. 30 dollars for a low-dose, 3-mg tablet doesnt
appear to be a price aimed at attracting repeat buyers. Nevertheless, many men may want to give it
a try, at least once. The rationale in setting a high price seems to be to at least cash in on first-time
users. Many wont come back anyway, not because of the price, but because the Uprima leaves
much to be desired.
This doesnt mean that dopaminergic drugs dont work. Some actually work beautifully. Please see
subsequent articles for details.
===============================================================
34.) TAP PHARMACEUTICAL PRODUCTS INC. WITHDRAWS NDA FOR
UPRIMA (APOMORPHINE HCL TABLETS) SUBLINGUAL
===============================================================
Source: www.takeda.com
June 30, 2000, LAKE FOREST, Ill. -- TAP Pharmaceutical Products Inc. announced
today that it has withdrawn the New Drug Application (NDA) for UPRIMA (apomorphine
HCl tablets) for erectile dysfunction (ED), which was submitted to the U.S. Food
and Drug Administration (FDA) June 30, 1999. TAP is withdrawing the NDA because
it has additional data and ongoing studies that could further establish the drug's
safety and efficacy profile. TAP will continue to work closely with the FDA, and
will resubmit the NDA at a later date.
"TAP is very committed to patient care, and it is our hope that by taking the extra
time to submit additional data, TAP will be able to provide a treatment with an
even stronger product profile for men with ED," says Thomas Watkins, president, TAP.
TAP Pharmaceutical Products Inc., located in Lake Forest, Ill., is a joint venture
between Abbott Laboratories, headquartered in Abbott Park, Ill., and Takeda Chemical
Industries, Ltd. of Osaka, Japan.
For more information about TAP, visit www.tap.com.
===============================================================
35.) The UPRIMA Background and adverse effects:
===============================================================
Source: THE FDA.
Uprima is a sublingual formulation of the active drug apomorphine hydrocloride. Apomorphine
is a member of the pharmacological class known as dopamine receptor agonists. Apomorphine
has been previously used as an oral treatment for symptoms of Parkinson's disease, an emetic in
cases of poisoning, a sedative for behavioral disturbances, and as a behavior-altering agent for
alcoholics. The sponsor believes that apomorphine demonstrates activity in enhancing penile
erection in man. Uprima is intended for use in men with erectile dysfunction, on an as needed
basis, immediately prior to anticipated sexual activity.
Adverse effects:
-----------------
The following additional treatment-emergent events were reported in <2% of patients
receiving UPRIMA in these same studies. A causal relationship to UPRIMA is
uncertain.
Body as a Whole: Abdominal pain, accidental injury, allergic reaction, back pain, chest
pain, chills, cyst, fever, flu syndrome, hernia, hostility, hypothermia, infection, infection
fungal, malaise, neck pain, neoplasm, pain, pelvic pain
Cardiovascular System: Bradycardia, cardiovascular disorder, cerebrovascular accident,
coronary artery disorder, hypertension, pallor, palpitation, syncope, tachycardia
Digestive System: Constipation, diarrhea, dry mouth, dyspepsia, eructation, gastritis,
hepatitis, increased appetite, melena, mouth ulceration, oral moniliasis, periodontal
abscess, sialadenitis, stomatitis, tongue edema, tooth disorder, ulcerative stomatitis,
vomiting
Hemic and Lymphatic System: Ecchymosis
Metabolic and Nutritional Disorders: Edema, peripheral edema
Musculoskeletal System: Arthralgia, bursitis, leg cramps, myalgia
Nervous System: Agitation, amnesia, anxiety, ataxia, circumoral paresthesia, confusion,
depression, euphoria, hypertonia, insomnia, libido decreased, nervousness, neuropathy,
paresthesia, sleep disorder, thinking abnormality, tremor, vertigo
Respiratory System: Apnea, asthma, bronchitis, cough increased, dyspnea, epistaxis,
laryngismus, lung disorder, pneumonia, rhinitis, sinusitis,
Skin and Appendages: Acne, dry skin, hair disorder, herpes simplex, lichenoid
dermatitis, psoriasis, rash, skin carcinoma, skin disorder, skin hypertrophy, skin ulcer,
vesiculobullous rash
Special Senses: Abnormal vision, amblyopia, conjunctivitis, deafness, ear disorder, ear
pain, eye disorder, tinnitus
Urogenital System: Abnormal ejaculation, dysuria, epididymitis, penis disorder, prostatic
disorder, testis disorder, urinary frequency, urinary incontinence, urinary tract infection
The treatment related adverse events in the long-term studies were similar to those seenin the
controlled clinical studies.
One hundred forty-six patients (146) administered their first UPRIMA dose at home. The reported
adverse events were generally similar to those observed during both the long-and short-term studies.
===============================================================
36.) Serious adverse events: with THE UPRIMA TRIALS
===============================================================
Source: The FDA
Three serious adverse events were reported during this study (one report on placebo and two on
apomorphine):
* A 55 year old male received his first dose of study drug for Treatment Period 2. Two days later,
he experienced chest pain lasting five days. Work-up revealed stenosis of the right coronary artery.
When the blind was broken, he was found to be on placebo.
* A 59 year old male received his first dose of study drug in the office for Treatment Period 2 on
March 23, 1998 (apomorphine 2 mg). He was dispensed a box of 19 tablets at that time.
On April 25, 1998, he suffered a temporary loss of consciousness and was involved in a car
accident. He was hospitalized for a wrist fracture. He used one tablet of study drug during this
period. He could not remember the exact date that he took that tablet. He returned the remainder
of the unused tablets. The investigator considered the AE as unrelated to study
drug.
Comment: Because the patient was unable to remember when he used his last dose of
apomorphine, it cannot be concluded that this event was unrelated to study medication
* A 54 year old male experienced nausea, hypotension, diaphoresis, light-headedness and a 30-
second loss of consciousness (syncope) approximately 1 hour after his first in-office dose of
apomorphine 6 mg. He received 0.4 mg of atropine intravenously. The duration of the event was
reported as 1 hour 10 minutes. The investigator believed that the event was definitely
related to study medication. The investigator believed that this patient's condition "required
intervention to prevent impairment or damage".
Premature discontinuations due to adverse event:
Thirty-six patients discontinued the study due at least in part to an adverse event. Of these, 25
patients reported symptoms which may have been related to an acute drop in the blood pressure
following dosing with apomorphine. The sponsor believes that only five patients actually
experienced "syncope" during this trial. However, many of the adverse event reports leading to
discontinuation described such terms as "hypotension", "vasodilatation", "light-headedness", "pallor",
"fatigue", "sleepiness", "clamminess", "queeeziness", etc. These 25 patients are
described in detail below.
* The 54 year old patient who expereinced syncope , was already discussed in the Serious
Adverse Events section.
* A 61 year old male experienced an onset of nausea approximately 2 minutes after taking his fourth
dose of apomorphine 6 mg. He became light-headed, went into the bathroom, experienced profuse
sweating, lost consciousness ("syncope") and woke up on the bathroom floor. It was estimated that
he was unconscious for a few seconds. The investigator believed that the event was possibly related
to apomorphine. He was discontinued. The sponsor
believes that the patients use of Zovirax for intermittent genital herpes 2 days previously may have
contributed to the event.
Comments: This patient is noteworthy because he fainted after his fourth
dose of apomorphine, not after his first dose.
* A 66 year old male experienced "syncope" 40 minutes after his first in-office dose of apomorphine
4 mg. The syncopal episode was reported to last approximately "10 seconds". He also experienced
hypotension (90/58), moderate nausea, light-headedness, pallor and diaphoresis. He was
discontinued. The investigator believed the event was probably related
to apomorphine.
* A 57 year old patient experienced diaphoresis, light-headedness, nausea, pallor and yawning
"with" his first in-office dose of apomorphine 5 mg. The duration of this event was reported as
30-60 minutes. He was discontinued. The investigator believed the event was probably related to
apomorphine.
* A 53 year old patient experienced hypotension, bradycardia (heart rate = 52 bpm), light-
headedness, drowsiness, and yawning "with" his first in-office dose of apomorphine 4 mg. The
duration of these events was approximately 10 minutes for bradycardia, 14 minutes for hypotension
and 61 minutes for drowsiness. No additional drug was taken and the patient
was discontinued. The investigator believed the event was probably related to apomorphine.
* A 52 year old patient experienced hypotension for 9 minutes, bradycardia for 13 minutes,
light-headedness for 17 minutes, nausea for 12 minutes and sleepiness for 55 minutes "with" his first
in-office dose of apomorphine 4 mg. Upon re-challenge 3 days later, similar symptoms were
observed, including dizziness (7 minutes), light-headedness (7) minutes), sleepiness (74 minutes) and
yawning (72 minutes). No additional drug was taken
and the patient was discontinued. The investigator believed the event was definitely related to
apomorphine.
* A 50 year old patient experienced diaphoresis, hypotension, and pallor with the first in-office dose
of apomorphine 5 mg. The duration of the hypotension was 14 minutes. No additional drug was
taken and the patient was discontinued. The investigator believed the event was definitely related to
apomorphine.
* A 39 year old patient experienced "queeziness" fatigue, nausea and vomiting approximately 30
minutes after his first in-office dose of apomorphine 5 mg. The "queeziness" lasted for 1 hour and 18
minutes. Upon re-challenge six days later, similar symptoms were observed. No additional drug was
taken and the patient was discontinued. The investigator believed the event was definitely related to
apomorphine.
* A 51 year old patient experienced light-headedness, nausea and yawning 40 minutes after his first
in-office dose of apomorphine 5 mg. The duration of the events was 30 minutes. After a second
dose, similar symptoms were experienced. No additional drug was taken and the patient was
discontinued. The investigator believed the event was probably related to apomorphine.
* A 64 year old patient experienced hypotension, bradycardia, diaphoresis and nausea with his first
in-office dose of apomorphine 6 mg. The patient was given 0.4 mg of intravenous atropine. The
duration of the event (as listed on the CRF) was 1.5 hours. No additional drug was taken and the
patient was discontinued. The investigator believed the event was probably
related to apomorphine.
* A 64 year old patient experienced light-headedness, diaphoresis, nausea and pallor with his first
in-office dose of apomorphine 6 mg. Upon re-challenge seven days later, similar symptoms were
observed. The duration of the events was 70 minutes. No additional drug was taken and the patient
was discontinued. The investigator believed the event was definitely related to apomorphine.
* A 64 year old patient experienced light-headedness, fatigue, nausea, pallor and retching with his
first in-office dose of apomorphine 5 mg. The duration of fatigue, nausea and pallor was 70 minutes.
No additional drug was taken and the patient was discontinued. The investigator believed the event
was probably related to apomorphine.
* A 49 year old patient experienced fatigue and nausea after his ninth dose of apomorphine 6 mg in
the first treatment period. He had experienced similar symptoms following previous doses. The
duration of the event was 22 minutes. No additional drug was taken and the patient was
discontinued. The investigator believed the event was definitely related to apomorphine.
* A 59 year old patient experienced hypotension, sweating, yawning and sleepiness after his first
in-office dose of apomorphine 4 mg. The duration of the event was 55 minutes. No additional drug
was taken and the patient was discontinued. The investigator believed the event was definitely
related to apomorphine.
* A 50 year old patient experienced hypotension, diaphoresis, light-headedness, nausea and
vomiting after his first in-office dose of apomorphine 4 mg. The duration of the hypotension was 1
hour 20 minutes. No additional drug was taken and the patient was discontinued. The investigator
believed the event was definitely related to apomorphine.
* A 68 year old patient experienced pallor, sweating and nausea after his sixth dose of apomorphine
5 mg. Similar symptoms were experienced with the previous dose of apomorphine. The duration of
the event was 25 minutes. No additional drug was taken and the patient was discontinued. The
investigator believed the event was probably related to apomorphine.
* A 56 year old patient experienced drowsiness, diaphoresis, nausea and vomiting after his first
in-office dose of apomorphine 5 mg. The duration of the diaphoresis and nausea was 1 hour 25
minutes. No additional drug was taken and the patient was discontinued. The investigator believed
the event was definitely related to apomorphine.
* A 62 year old patient experienced dizziness, flushing and nausea with his third dose of
apomorphine 5 mg. The duration of the dizziness was 30 minutes and the nausea was 1 hour 20
minutes. No additional drug was taken and the patient was discontinued. The investigator believed
the event was probably related to apomorphine.
* A 69 year old patient experienced hypotension, light-headedness, diaphoresis, nausea, sleepiness,
vomiting and yawning with his first in-office dosing of apomorphine 6 mg. The duration of the
hypotension was 8 minutes, and yawning, 72 minutes. No additional drug was taken and the patient
was discontinued. The investigator believed the event was probably
related to apomorphine.
* A 49 year old patient experienced hypotension, weakness, diaphoresis, and nausea with his first
in-office dosing of apomorphine 6 mg. The duration of the hypotension was 10 minutes, nausea 65
minutes, and weakness, 75 minutes. Upon re-challenge, similar symptoms were observed. No
additional drug was taken and the patient was discontinued. The investigator believed the event was
definitely related to apomorphine.
* A 60 year old patient experienced hypotension, diaphoresis, and nausea with his first in- office
dosing of apomorphine 5 mg. The duration of the hypotension was 10 minutes. No additional drug
was taken and the patient was discontinued. The investigator believed the event was definitely
related to apomorphine.
* A 52 year old patient experienced hypotension, diaphoresis, sleepiness, and nausea with his first
in-office dosing of apomorphine 4 mg. The duration of the hypotension was 30 minutes. The
sleepiness lasted for 1 hour 38 minutes. No additional drug was taken and the patient was
discontinued. The investigator believed the event was probably related to apomorphine.
* A 68 year old patient experienced lightheadedness and sleepiness with his first in-office dosing of
apomorphine 6 mg. The duration of the events was 60-90 minutes. He again experienced
lightheadedness, weakness, diaphoresis and chills after his seventh dose of apomorphine 6 mg. No
additional drug was taken and the patient was discontinued. The investigator believed the event was
probably related to apomorphine.
* A 69 year old patient experienced vasodilation and nausea with his first in-office dosing of
apomorphine 6 mg. The duration of the vasodilation was 25 minutes, and nausea 60 minutes. No
additional drug was taken and the patient was discontinued. The investigator believed the event was
definitely related to apomorphine.
* A 52 year old patient experienced "clamminess", nausea and retching with his first in-office dosing
of apomorphine 4 mg. The duration of the retching was 2 minutes and nausea almost 24 hours. No
additional drug was taken and the patient was discontinued. The investigator believed the event was
definitely related to apomorphine.
Of the remaining 11 discontinuations due to AE, seven were clearly not related to study drug. One
patient had foot surgery. One patient had chronic intermittent claudication. One patient had
new-onset atrial fibrillation on the last day of Treatment Period 1 (on placebo). One hypertensive
patient had an increased BP (188/111) on the last day of Treatment Period 1 (on placebo). One
patient had increased headaches during Treatment Period 1 (on placebo). One patient was noted to
have sinus bradycardia on an EKG during Treatment Period 1 (on placebo). One patient had
chest pain two days after his first in-office dose of placebo (see SAEs).
Of the remaining four discontinuations, one patient had epididymal pain while on apomorphine 6 mg.
Two reported "sleepiness" while on apomorphine. One patient experienced loss of consciousness
and a car accident during one of the treatment periods (while on 2 mg apomorphine). It is unknown
if he actually took a tablet prior to that incident.
Overall adverse effects: In the text of the study report, the sponsor summarized the adverse events
that were considered by the investigator to be at least possibly related to apomorphine and
reported by at least 10% of all patients.
===============================================================
37.) THE VIACREME FOR WOMEN
===============================================================
Source: www.viacreme4.com
What is Viacrème?
Viacrème For Women is an all natural, topical crème applied to the genital area, which acts as a
stimulant to the soft tissue and creates acool tingling sensation. It is a specially compounded cream
to sensitize a woman's clitoris. It is individually packaged in a a medical grade facility.
Viacrème For Women is patented and has been clinically evaluated by nurses and other women,
including physicians. Wrapped in sanitary, individual pillow-packs, Viacrème For Women is
convenient to use, to store or to carry. Viacrème contains menthol, propylene glycol, and
L-Arginine, an amino acid available in health food stores and found in dietary products. This answer
is intended to reassure a woman that Viacrème is safe and acceptable.
At long last, women can enjoy enhanced physical sensation, safely and naturally with Viacrème For
Women!
Use of Viacrème For Women can result in greater orgasmic pleasure, as well as to induce orgasm
for those women who have had difficulty achieving orgasm in the past.
A byproduct of the 1998 Nobel Prize winning Medicine and Physiology award received for the
discovery and understanding of the Nitric Oxide Pathway, the basis for penile and clitoral arousal,
erection, and sensitivity. Viacrème is a Patented, safe, clear, viscous compound that contains the
essential active ingredients, which promote clitoral sensitivity and improves the opportunity for
women to achieve orgasm. Viacrème is a topical cream and does not require a prescription.
The actual concentrations of the active ingredients are quite dilute, but because a womans genital
tissues are extremely sensitive, application of Viacrème For Women will stimulate a vigorous tingle.
Every order comes with an informative brochure and cassette tape with an interview with Dr.
Thompson and testimonials of women who have used Viacreme.
Viacrème is sold without a prescription.
The US FDA regulates:
What you claim your product does
Where and how your product is produced
Viacrème Regulatory Position
The material marketed as Viacrème is not considered a drug - it is a personal use product intended
for sexual enhancement, similar to massage oils and related products.
According to Title 21 of the United States Code, a "drug" is defined as:
(A) articles recognized in the official United States Pharmacopoeia, official Homeopathic
Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of
them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of
disease in man or other animals; and (C) articles (other than food) intended to affect the structure or
any function of the body of man or other animals; and (D) articles intended for use as a component
of any article in clause (A), (B), or (C).
Although the active ingredients in Viacrème (menthol, propylene glycol, and L-Arginine) are included
in the USP, Viacrème is NOT intended in the diagnosis, cure, mitigation, treatment of disease, NOR
is it intended to affect the structure or any function of the body.
The labeling for Viacrème will expressly state that this product is "not intended for use in the
diagnosis, cure, mitigation treatment or prevention of disease" and will also advise the user to seek
the advice of a physician if she believes that she suffers from any disease or medical condition that
may affect her sexual responsiveness. The labeling will not make any claims relative to the
physiological effects of Viacrème.
Viacrème:
can enhance a woman's sexual responsiveness
can improve a woman's sexual responsiveness
can sensitize a woman's genital tissues
does not stimulate a woman
does not improve orgasms
does not increase orgasms
does not cause multiple orgasms
This disclaimer is on each Viacrème individual dose;
"Viacrème is not intended to diagnose, cure, treat or prevent any known medical conditions."
Is a woman's acceptance of Viacrème Physiological or Psychological? YES and YES! A younger
woman will be more adventurous and experimental. "Let's try this stuff right away, I cant wait!" A
more mature woman will be more cautious. "Are you sure this is ok?" A more mature woman might
feel uncomfortable talking about sexual things. Women who are 20 and 30 years old talk about their
vagina, clitoris, orgasms and libido." "40 year old women talk about "down there"!" More mature
women have a mistrust and discomfort about estrogen because of breast cancer. Women really do
not have a mistrust about androgens (testosterone), but they really don't understand that libido and a
woman's sexual responsiveness are directly related to their androgen levels.
The Psychological Viewpoint
More mature women will gravitate to the acceptance of Viacrème over multiple uses.
On the first use, women will say; "I really didn't notice anything different, but I'll try it"
On the second use, women will say; "That wasn't bad, maybe I did feel something."
On the third use, women will say; "That was really pretty good, I must have been aroused."
On the fourth use, women will say; "That was great, I had an orgasm like when I was twenty. I'm
sold."
The Physiological Viewpoint
A general term in medicine is "Use it or Lose it"
When a cast is removed after six weeks, the muscle of the arm is much thinner because of the lack of
use of that muscle. More intercourse, with arousal of the woman's clitoris each time, will actually
increase the blood flow and heal the clitoris and the vulvar/vaginal tissues.
Need
A younger woman might like the Viacrème experience, but she doesn't have the physiological need
for Viacrème that a more mature woman has because of age related decreased responsiveness.
Ronald James Thompson, M.D. is a Board Certified obstetrician / gynecologist who has cared for
women and their health care concerns for over twenty years.
Dr. Thompson has experience in drug development and clinical drug evaluation, all within the focus
of gynecology and infertility.
Besides teaching surgery and surgical procedures, Dr. Thompson has numerous patents in infertility,
women's urinary incontinence, uterine bleeding, and women's sexual responsiveness: Dr. Thompson
is and has been a surgical consultant to a number of medical companies
Dr. Thompson has been married for twenty-nine years to his wife, Dr. JoAnn Thompson, and
together they have raised their four children in the same community where he, his parents, and
grandparents have all raised their children.
Dr. Thompson's children are currently following him into medical research and biomedical
engineering.
40 J's LLC Member Background
40 J's LLC is an "invitation only" development corporation of twenty eight individuals with in excess
of 300 years experience in medical/personal care product development, clinical evaluation and
patent protection of those products. Ronald J. Thompson MD established the LLC in early 1999.
The president of 40 J's is Robert C. Hassman, who brings twenty years of medical sales and medical
device company management to define, direct and execute the business objectives of 40 J's LLC.
The LLC has six defined skill set groups;
Physicians
The LLC has six physician members with medical/personal care product experience. Two of the
physicians are, in addition to Dr. Thompson, board certified gynecologists, and are partners of Dr.
Thompson in the practice of OB/GYN.
Biomedical Engineers
Three biomedical engineers, each who owns her/his own consulting companies for the development
and regulation of medical personal care products bring extensive experience to the LLC.
Medical Marketing and Management
The team includes eight very skilled and experienced individuals, one senior Vice President of the
largest pharmaceutical company in the world, and four others who have been or are the
President/CEO of medical device/personal care products companies.
Medical/Legal
The group includes five lawyers all in independent practice, one patent lawyer, one corporate lawyer
and three lawyers who practice medical malpractice defense, including product liability.
Nurses
The group includes three advanced degree nurses in obstetrics, gynecology, women's healthcare,
patient care and product evaluation. This group provides unique insight to properly evaluate and
position 40 J's products in the marketplace. As a company whose mission is to develop and market
products for women, this input is an essential component to product acceptance by women.
===============================================================
38.) THE VIACREME IN THE NEWS
===============================================================
Source: wwww.viacreme4.com
Viacreme has been featured in the following media:
Oprah's O Magazine, EXTRA, Houston Eyewitness News, King 5 Seattle TV News, and New
York Daily News.
The Oprah Magazine (May 2001, First Anniversary Issue)
Doctors Laura and Jennifer Berman mention viacreme as one possible non-prescription method of
helping to increase sexual responsiveness in women.
ABC Eyewitness News (5-14-2001)
by: Minerva Perez
Millions of women suffer from female sexual dysfunction. But by its very nature they don't talk about
it -- until now. Now there's an answer to that unspeakable sexual problem. It's been something you
don't talk about even with your mother or your longtime mate -- female sexual dysfunction. Women
tend to 'fake it' to avoid hurt feelings.
Susan Hadnott/Had Problem:
"My husband would say c'mon. And I'd say, oh, ok. Go through the process, you know how it is."
Devon Bankett/Viacreme Spokesman:
"Women still like what they've done for years, always doing the faking thing. And (men) got egos
(from being told) 'You're the greatest.'" The problem runs in epidemic proportions among American
women. Experts say 50 million suffer from not being able to reach orgasm during sexual intercourse.
The result -- strained relationships.
Terri Norton/Viacreme User:
"Women just don't like to talk about these little things." Now there is Viacreme, a doctor-designed,
all-natural topical cream that is being touted as the 'Viagra for women' and the answer to an age-old
problem.
Twiler Portis/Viacreme User:
"We had an awesome experience. I really believe in this product. Not just that I had a maximum
level of intensity." Invented two years ago, Viacreme is made of natural ingredients -- menthol and
amino acids. Unlike Viagra, you don't need a doctor's prescription and you don't ingest it.
Curtis Broome/Viacreme Spokesman:
"It is topically applied to clitoral tissues which allows women to experience maximum arousal in
clitoral erection, which is necessary for sexual orgasm."
Although not for men, they too are enjoying Viacreme's side benefits.
Darryl Tidbury/Likes Viacreme:
"It's just taken it to a different level (and made sex) more intense level for her."
With Viacreme, women are saying, you can have it all.
Dena Brooks/Viacreme User:
"Be successful, be powerful, have your children, have careers and have a great orgasm."
But seriously, Viacreme is not for everyone. Consult your doctor first. Pregnant women are advised
not to use it. It is sold only through distributors for about $12 a tube.
EXTRA! (5-16-2001)
Viagra for Women
Wednesday May 16th Viacreme was featured on the popular TV show "Extra". An excerpt of some
of the dialogue is below with a couple of powerful testimonials.
Aphrodisiacs have a long and spicy history. Roman orgies included oysters and eels. The ancient
Chinese secret was ginseng. Now men have Viagra. But what about women?
They finally may have found the secret to sizzling sex....Viacreme....The topical gel is supposed to
increase a woman's sexual pleasure. But does it really work? We had two couples put it to the test.
At first "Temptation Island" temptress Vanessa Norris and boyfriend Micki Steef were a little
skeptical. But after four tingly nights? Vanessa says, "It's kinda tingly and warm, and then you feel
like I'm a little fireball."
Sheri Thomas and Joey Scoleri got a major kick too. Sheri says, "It's exciting. It's like the craziest
thing that's ever come along."
While Joey says, "I just like the fact that's she's more excited."
HEALTHLINK: KING-5 SEATTLE TV NEWS
Gloria Larson says the cream made all the difference.
Women's version of Viagra
SEATTLE, March 29, 2001, 11:15 PM - It's a problem that affects about 42 percent of women
after menopause - decreased sex drive. But now a new treatment is being tested...
It's called Viacreme and one can guess where it got its name. Gloria Larson's sexual awakening
came in a box - a cream, to be exact. Viacreme is being dubbed a woman's version of Viagra.
Dr. K. Yankapolus is marketing Viacreme in Florida. He says the cream works wonders for women
who've lost their sexual appetite. For Gloria, the results were immediate. The cream is not a drug
and therefore has not been approved by the Food and Drug Administration. In fact, there's no hard
evidence that Viacreme really works, but there is a long list of satisfied customers like Gloria.
New York Daily News
From: Arts and Lifestyle | Health |
Tuesday, August 14, 2001
Equal Opportunity
Women are eager to participate in the Viagra revolution
By LAN N. NGUYEN
When Viagra hit the market in 1998, it caused a seismic shift in sexual attitudes and expectations.
Some 50 million men — Bob Dole included — and 500 million little blue pills later, Viagra has
removed erectile dysfunction (ED) from the list of taboo subjects and restored confidence to many
men who spent years struggling with ED.
But what about women?
Viagra has changed relationships between couples. The advent of Viagra has certainly affected
women, though not always positively. Wives who had grown accustomed to marriages with
infrequent sex have had to deal with their spouses' renewed desire. "Viagra made their husbands
want to add intimacy to a relationship that had not been there for 10 to 15 years," says Dr. Mark
Dykowski, a physician at Generations OB/Gyn Center in Birmingham, Mich. "That has put a lot of
stress on the relationship."
But other women have responded by demanding their own version of the miracle pill. "Twenty years
ago, you didn't talk about this," recalls Dr. Judith Reichman, a gynecologist and author of "I'm Not in
the Mood" (Quill, $12). "When women got older and their libido diminished, or when they were in
menopause and had dryness, it was not discussed — it was felt that that was the way it was. But the
baby boomers don't accept anything. They want a cure."
As a result, the medical and pharmaceutical communities have been encouraged to study female
sexual problems. In 1998, a panel of experts arranged female sexual dysfunction (FSD) into the four
categories: desire disorders, arousal disorders, orgasmic disorders and pain disorders (including
vaginismus, in which penetration is painful, if not impossible).
Despite the new classifications, FSD remains difficult to diagnose and treat. To begin with,
physicians and therapists need to consider whether the problem is chiefly physiological or
psychological. For example, certain medications, such as anti-depressants, can diminish libido,
lubrication and arousal. Hormonal imbalances and illnesses can also have an effect.
"Women are a little more complex than men," says Dr. Virginia Sadock, clinical professor of
psychiatry at New York University Medical Center. "It may be the feminization of the brain, that we
don't have the same androgen receptors. Also, testosterone is the hormonal basis for libido in men
and also in women, and men have more of it."
All in Her Head?
But a woman's feelings about the quality of her relationship or reservations about a partner can also
affect her desire, arousal and ability to achieve orgasm. Doctors first need to determine when the
problem arose and whether it has been manifested with all partners or just a current one. A woman
may also suffer from more than one disorder. Pain during intercourse, for instance, would
understandably lead to diminished desire and arousal.
Sadock points out that a dysfunction may also have a cultural explanation: A woman brought up to
think sex is dirty is more likely to experience sexual difficulties. Transient sexual disinterest may also
be rooted in our deep evolutionary history; sexual dysfunction may have developed as a way to
prevent unwanted pregnancies.
A visit to a Web site like drugstore.com can unearth a variety of remedies for diminished arousal —
from herbal supplements like horny goat weed to emollients like Viacreme. Other treatments include
marital counseling and pelvic exercises. Some women on anti-depressants have switched to
Wellbutrin, which has been found not to suppress libido like Prozac or Zoloft do.
===============================================================
39.) VIACREME, lacreme d'Amour
===============================================================
Source: www.1-4-viacreme.com
LaCreme d'Amour was the first product introduced to enhance a woman's sexual responsiveness.
It was formerly known as Viacreme.
LaCreme d'Amour was developed by a gynecologist. Its formulation is based on the discovery
that was awarded the 1998 Nobel Prize in Medicine and Physiology. LaCreme d'Amour is a
patented product and has been clinically tested and approved.
LaCreme d'Amour is a topical cream for women and is to be applied to the genital area. Use of
LaCreme d'Amour can result in greater orgasmic pleasure and can induce orgasm for those
women who have had difficulty achieving orgasm in the past.
LaCreme d'Amour is patented and is produced in a FDA approved pharmaceutical facility. It
contains no herbs or hormones.
We have more than 30 million users worldwide.
Back No and Yes! Libido is documented to be related to the circulatory level of testosterone for all
women. Clinically libido can be improved by estrogen or estrogen/testosterone administration to
women on oral contraceptives, birth control injections, or implants.
If a woman has a positive experience (orgasm) with intercourse, she is more likely to welcome or
encourage another sexual experience. This type of libido is not hormone dependent, but experience
related.
LaCreme d'Amour can help a woman achieve orgasm, especially if her partner is intent upon her
achieving orgasm.
Back It's all about blood flow. LaCreme d'Amour produces increased blood flow in the clitoral
area. Orgasm can only occur with continuous stimulation of the maximally aroused clitoris!
The bio-chemical explanation is as follows: LaCreme d'Amour is a pH adjusted topical cream and
is to be applied to the woman's genital area, specifically to the mucus membrane beneath the clitoris
and the clitoral hood.
LaCreme d'Amour provides the best results when a small amount is applied to and rubbed onto
the clitoral area daily, after a shower or bath. In addition, a large amount of LaCreme d'Amour
should be applied to and rubbed onto the clitoral area during intimacy. Best results can be expected
after 6 - 8 intimate uses.
Though response time varies with each individual woman, the pleasurable warming effects develop
more rapidly with the sexual stimulation of touching and rubbing in the clitoral area, and with the
activities of foreplay.
Natural lubrication also takes place as a woman responds to the beautiful feeling of LaCreme
d'Amour.
Both La Crème d'Amour and Viagra® are based on the discovery that was awarded the 1998
Nobel Prize in Medicine and Physiology. La Crème d'Amour and Viagra® both utilize the
L-Arginine Nitric Oxide Synthase Pathway with L-Arginine as the substrate. La Crème d'Amour
contains L-Arginine, which is intended to encourage the Nitric Oxide Pathway. When applied, La
Crème d'Amour stimulates the tissue surfaces resulting in dilation of the blood vessels in the
clitoral area. REMEMBER: Orgasm can only occur with continuous stimulation of the maximally
aroused clitoris! Viagra® is an oral medication that blocks the breakdown of Nitric Oxide;
therefore, the Nitric Oxide builds up in the penis and allows an erection. Both Viagra® and La
Crème d'Amour need "sexual stimulation" such as odors, thoughts, rubbing, kissing, genital
touching, and foreplay to initiate the impulses down the spinal cord, pudendal nerves, and
clitoral/penile nerves to establish an erection. Neither is automatic. La Crème d'Amour does not
require a prescription. La Crème d'Amour is patented in the US and Internationally.
Back Any woman who wants to enhance her sexual pleasure should use La Crème d'Amour as it
restores a sense of sexuality and allows for a more complete physical sexual satisfaction. If sexual
satisfaction is a concern of yours, you are not alone! Oprah recently declared the problem of
womens sexual satisfaction as theSilent Epidemic. Silent, because until recently women were
reluctant to discuss their desire for sexual satisfaction. Epidemic, because of the reported 40 to 50
million US women who endure reduced or absent sexual satisfaction.
Back Knowledge! The knowledge that a woman must be maximally aroused before she can achieve
orgasm is essential to each woman and her partner. The knowledge that age related decreases in
hormones can be normal or abnormal, but both can prevent a woman from achieving maximum
sexual arousal.
Estrogen (produced from each womans ovaries) is essential for each womans
sexual sensitivity and responsiveness. More importantly, testosterone (produced by each womans
adrenal glands) is necessary for both desire (libido) and formeaningful orgasms. There are MANY
interpersonal and physiological reasons for a womans decreased sexual responsiveness, such as: ·
Conditions such as depression, stress, diabetes, peri-menopause, menopause, childbirth, low
estrogen/testosterone levels, premature hysterectomy, lack of sleep, and breastfeeding have an affect
on your hormone levels, as discussed above.
These hormone-related causes that PREVENT sexual
arousal, responsiveness and therefore sexual satisfaction are physical, not emotional. These very real
physical problems are notall in your head. You cannot be psychologically counseled to increase
your hormones. · Medications. Many drugs can prevent sexual satisfaction by also altering a
womans hormones. Birth control pills, implants, anti-depressants, or hormone therapy are widely
recognized to decrease or even completely prevent a womans desire, sexual sensitivity, and sexual
responsiveness. Newer antidepressants that alter serotonin, a hormone produced in a womans
brain, can prevent normal sexual arousal and responsiveness.
This problem is reported by up to 80%
of women on serotonin altering anti-depressants. · Interpersonal relationship problems can also be a
factor; problems such as poor communication, alcoholism, uncaring partner,social training and
even putting others needs before your own. The good news is that thisepidemic now has
increased awareness of these problems and offers each woman hope. The first step to a solution is
to reassure each woman that it is normal and natural to desire sexual satisfaction. The second step is
to become knowledgeable about how a womans body should normally function and what factors
can prevent these normal functions. The third and final step is to become proactive and pursue your
unique individual solutions. In so doing, youll be on your way to finding Sexual Satisfaction.
Back La Crème d'Amour provides the best results when a small amount is applied to and rubbed
into the clitoral area daily after a shower or bath. A large amount of La Crème d'Amour should be
applied to and rubbed into the clitoral area during or just before intimacy. Of course, it is best if this
is accomplished by the husband/partner as a part of foreplay. Best results can be expected after 6-8
intimate uses. Complete directions for use are included with every La Crème d'Amour product.
Back Perhaps, but not necessarily. Although there usually are some immediately increased
sensations, most women find that responses improve progressively through six or more successive
uses of La Crème dAmour. The more one uses La Crème dAmour, the mores satisfaction is
derived. It has a cumulative effect. Continued use is recommended to acclimate the body. It has also
been found that there is a residual effect in the body. In our recent Sexual Satisfaction Survey of
women using La Crème d'Amour: · 94% of the women reported improved sexual responsiveness.
· 86% of womens husbands/partners reported that La Crème d'Amour enhanced their sexual
responsivenss and their relationships.
Back No. La Crème d'Amour is a completely safe topical cream that works through direct
application to the skin. It is not a pharmaceutical drug, a pill, a patch, or a powder that must be
ingested.
Back Yes. You may review all those details here:Not available Yet!
Back No! A host of medical problems, medications, and interpersonal relationship problems can
affect both the libido and a woman's sexual responsiveness. This is quite a complex problem and
every woman is uniquely different. See the next question and answer for further information regarding
this.
Back It is important that you apply the product according to the directions, specifically WHERE to
apply the product - under the clitoral hood. An anatomical diagram is provided with the product.
Also, please remember that it may takes several uses before you experience the level of satisfaction
you need or desire. If La Crème d'Amour does not work, it could be because of a lack of
estrogen mediated "youthfulness" of the vulva tissue. This can be replaced with oral or transdurmal
estrogen, or vaginal estrogen creams or inserts.
It will probably take 2-3 months of therapy before
an adequate genital response can re-estrogenize the vulvar tissues. Estrotest is a good combined
estrogen/testosterone tablet. This used once or twice/day can also help with both re-extrogenizations
of vulvar tissues and help improve libido. Further, if La Crème d'Amour does not help you find the
sexual responsiveness you desire, there is a 90% chance that your testosterone level is too low. You
would benefit from testosterone. Please consult your gynecologist, nurse practitioner, or your family
physician.
Back Testosterone cream has two effects: 1) The immediate effect is as an irritant that can cause a
reflex vaginal lubrication. 2) The prolonged effect is to increase a woman's testosterone blood level
to help improve libido.
Back Astroglide use is intended as a vulvar lubricant. La Crème d'Amour use is not intended to
be on the vulvar tissues, other than the underside of the clitoris, and use is not intended to be in the
vagina as a lubricant. However, most women report a marked increase in lubrication when using La
Crème d'Amour properly.
Back Usually the 0.25% menthol will merely cause a tingle and warmth when applied. If a patient
reports burning, she has either of these two issues: 1) A decreased estrogen effect in the vulvar
tissues (common with birth control medications and menopause), or 2) A sub-clinical vulvar irritation
due to yeast or some other infection, detergents used to wash underwear, or fragrances used in toilet
tissue. The precaution for La Crème d'Amour is to discontinue use if irritation develops. La
Crème d'Amour can again be tried after the underlying problem is identified and corrected.
Back . Men, whose partner is using La Crème d'Amour, sometimes report a menthol effect on the
glands and corona of the penis. This has been reported as "cooling" and pleasant, not unpleasant. In
our most recent Sexual Satisfaction Survey, La Crème d'Amour was endorsed by men as well as
by the women they love. In fact, 86% of womens husbands/partners reported that La Crème
d'Amour enhanced their sexual responsiveness and their relationships. One important thing to
remember - about how orgasms work - is this: Men are simple. Women are complex.
Back Yes, La Crème d'Amour is totally safe. It has been tested and found to be safe, non-toxic,
effective, and non-habit forming. In fact, La Crème d'Amour has been safely and effectively used
for more than two years. During this time, La Crème d'Amour has had over 30 Million uses, both
in the United States and Internationally.
La Crème d'Amour is produced under strict GMP (good
manufacturing practices) in a FDA approved pharmaceutical facility. La Crème d'Amour contains
L-Arginine, an amino acid found in dietary products that are readily available in health food stores,
and menthol as a vehicle in a viscous water based substrate. The menthol that is absorbed with La
Crème DAmour is actually less than that of a cough drop. L-Argentine, as found in a single use of
La Crème d'Amour, is 40 micrograms. In a recent survey, 30 grams were given to pregnant
patients (29) to treat preclamsia (high blood pressure) with no adverse effects. La Crème
d'Amour does NOT contain hormones or herbs with scientific unknown actions.
Back No. La Crème d'Amour is a personal healthcare product for helping a woman with her
sexual responsiveness and improving her sexual satisfaction. Prescription drugs are generally for
treating disease. Sexual satisfaction is aQuality of Life issue, not a disease.
Back Yes, the two components menthol and L-Arginine are safe. It has a very neutral taste and it
may be ingested without harm.
Back LaCreme d'Amour is compounded in a water base not a petroleum base. condom breakage
is reported as a problem with petroleum but not with water based products.
===============================================================
40.) Management of sexual dysfunction in patients with cardiovascular disease: recommendations of
the Princeton Consensus Panel.
===============================================================
Am J Cardiol 2000 Jul 20;86(2A):62F-68F
DeBusk R, Drory Y, Goldstein I, Jackson G, Kaul S, Kimmel SE, Kostis JB, Kloner RA, Lakin M,
Meston CM, Mittleman M, Muller JE, Padma-Nathan H, Rosen RC, Stein RA, Zusman R.
Stanford University School of Medicine, Palo Alto, California, USA.
Sexual dysfunction is highly prevalent in both sexes and adversely affects patients' quality of life and
well being. Given the frequent association between sexual dysfunction and cardiovascular disease, in
addition to the potential cardiac risk of sexual activity itself, a consensus panel was convened to
develop recommendations for clinical management of sexual dysfunction in patients with
cardiovascular disease. Based upon a review of the research and presentations by invited experts, a
classification system was developed for stratification of patients into high, low, and intermediate
categories of cardiac risk. The large majority of patients are in the low-risk category, which includes
patients with
(1) controlled hypertension;
(2) mild, stable angina;
(3) successful coronary
revascularization;
(4) a history of uncomplicated myocardial infarction (MI);
(5) mild valvular
disease; and (6) no symptoms and <3 cardiovascular risk factors. These patients can be safely
encouraged to initiate or resume sexual activity or to receive treatment for sexual dysfunction. An
important exception is the use of sildenafil in patients taking nitrates in any form.
Patients in the
intermediate-risk category include those with
(1) moderate angina;
(2) a recent MI (<6 weeks);
(3)
left ventricular dysfunction and/or class II congestive heart failure;
(4) nonsustained low-risk
arrhythmias; and (5) >/=3 risk factors for coronary artery disease.
These patients should receive
further cardiologic evaluation before restratification into the low- or high-risk category. Finally,
patients in the high-risk category include those with
(1) unstable or refractory angina;
(2)
uncontrolled hypertension;
(3) congestive heart failure (class III or IV);
(4) very recent MI (<2
weeks);
(5) high-risk arrhythmias;
(6) obstructive cardiomyopathies; and
(7) moderate-to-severe
valvular disease. These patients should be stabilized by specific treatment for their cardiac condition
before resuming sexual activity or being treated for sexual dysfunction. A simple algorithm is
provided for guiding physicians in the management of sexual dysfunction in patients with varying
degrees of cardiac risk.
==================================================================
DATA-MEDICOS/DERMAGIC-EXPRESS No 4-(3) X file) 15/08/2.002 DR. JOSE
LAPENTA R.
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Produced by Dr. José Lapenta R.
Dermatologist
Maracay Estado Aragua Venezuela
2002-2026
Telf.:
04142976087 - 04127766810
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