Expedientes Secretos X del antimicótico TERBINAFINA  !!!

Data-Médicos 
Dermagic/Express No. 6-(9) X-File 
30 julio 2.004 /30 July 2.004 
                                                 

EDITORIAL ESPAÑOL                                                  
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Decir que la TERBINAFINA ES UNA MALA MEDICINA es una MENTIRA, pero decir TAMBIÉN QUE NO TIENE EFECTOS ADVERSOS SEVEROS también ES una gran mentira.

Droga introducida en el mercado desde 1.996 como un NUEVO antimicótico, en el año 2.001 recibió de la FDA, junto al otro gran conocido ITRACONAZOLE una advertencia de sus potenciales efectos TÓXICOS y que debía usarse con cuidado.

Ya para ese época el DERMAGIC había hecho una revisión sobre estos efectos adversos y casualmente el ultimo de ellos estaba relacionado con Lupus Eritematoso.

Hoy día les traigo 4 artículos que confirman esa relación entre terbinafina y Lupus Eritematoso como efecto adverso, y el enlace sobre esa caliente revisión del año 2.001

Saludos a todos

Dr. José Lapenta R


EDITORIAL ENGLISH:
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To say that the TERBINAFINE is A BAD MEDICINE is a LIE, but to ALSO say THAT she doesn't HAVE SEVERE ADVERSE EFFECTS it is also a great lie.

The drug, introduced in the market from 1.996 as a NEW ANTIFUNGAL, in the year 2.001 received from the FDA, with the other great well-known ITRACONAZOLE a warning of their potential TOXIC effects and that it should be used carefully.

Already for that time the DERMAGIC had made a review on these adverse effects and accidentally the I finish of them it was related with Lupus Erythematosus.

Nowadays I bring to you 4 articles that confirm that relationship among terbinafine and Lupus Erythematosus like adverse effect, and the link on that hot review of the year 2.001

Greetings to all

                                                         HOT LINK

Itraconazole, terbinafine and cisapride in the eye of the storm !!!  

1.) Drug-induced lupus erythematosus.

Clin Dermatol. 2004 Mar-Apr;22(2):157-66.

Antonov D, Kazandjieva J, Etugov D, Gospodinov D, Tsankov N.

Department of Dermatology and Venereology, Sofia Faculty of Medicine, Sofia, Bulgaria. [email protected]

Among the numerous idiopathic immune-mediated diseases that can be drug-induced, such as pemphigus, psoriasis, lichen, etc, drug-induced lupus is the most widely commented upon and investigated. The terms drug-induced lupus (DIL) and drug-induced lupus erythematosus (DILE) are preferred, but other ones are also used--drug-related lupus, lupus-like syndrome, and lupus erythematosus medicamentosus. This review discusses the general issues in DILE, such as pathogenic mechanisms, clinical forms, and diagnostic criteria, and provides more detailed information for some of the implicated drugs: minocycline, statins, terbinafine, etc.
 

2.) Subacute cutaneous lupus erythematosus induced or exacerbated by terbinafine: a report of 5 cases.

Arch Dermatol. 2001 Sep;137(9):1196-8.

Callen JP, Hughes AP, Kulp-Shorten C.

Division of Dermatology, Department of Medicine, University of Louisville, 310 E Broadway, Suite 200, Louisville, KY 40202, USA. [email protected]

BACKGROUND: Subacute cutaneous lupus erythematosus is a nonscarring, non-atrophy-producing photosensitive cutaneous disorder. Half of the patients have 4 or more of the criteria for classification as systemic lupus erythematosus. In some patients, drugs induce or exacerbate the cutaneous disease. OBSERVATION: We describe 5 patients who had either an exacerbation or a new onset of subacute cutaneous lupus erythematosus while taking terbinafine for presumed onychomycosis. CONCLUSION: In general, terbinafine is a safe drug, but perhaps patients with known lupus erythematosus or photosensitivity are predisposed to drug-induced or drug-exacerbated disease.

3.) [Terbinafine-induced subacute cutaneous lupus erythematosusCase report and review of the literature]

Hautarzt. 2004 Jul;55(7):653-7.

[Article in German]

Matthes T, Hagedorn M.

Hautklinik des Klinikum Darmstadt, Darmstadt, [email protected]

We report on a patient with terbinafine-induced SCLE covering clinical, histopathological and serological findings. Positive serological results included ANA, SS-A (Ro)-antibodies and anti-histone-antibodies with specificity for H1 and H3. The literature on terbinafine-induced SCLE is reviewed. We discuss H1- and H3-specific anti-histone antibodies as a possible diagnostic criterion of drug-induced SCLE.
 

4.) Terbinafine-induced subacute cutaneous lupus erythematosus.

J Am Acad Dermatol. 2001 Jun;44(6):925-31.

Bonsmann G, Schiller M, Luger TA, Stander S.

Department of Dermatology, University of Munster, Germany. [email protected]

BACKGROUND: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported. OBJECTIVE: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis. METHODS: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated. RESULTS: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 4(1/2) months in 3 patients concomitant with subsidence of the SCLE eruption in all patients. CONCLUSION: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons.



5.) ITRACONAZOLE AND TERBINAFINE FDA HEALTH ADVISORY

FDA Issues Health Advisory Regarding the Safety of Sporanox® 
Products and Lamisil® Tablets to Treat Fungal Nail Infections


The Food and Drug Administration (FDA) today issued a Public Health Advisory to announce significant safety-related updates to the labeling of Sporanox® (itraconazole) products and Lamisil® (terbinafine hydrochloride) tablets. Sporanox® and Lamisil® are used to treat nail (onychomycosis), skin and other systemic fungal infections. The following may be used to answer questions. 

The purpose of today's FDA Public Health Advisory is to alert healthcare professionals to serious risks associated with the use of Sporanox® and Lamisil®. 

FDA believes there is a small but real risk of developing congestive heart failure (CHF) associated with the use of Sporanox®. Both Sporanox® and Lamisil® have been associated with serious liver problems resulting in liver failure and death. However, there is insufficient data to allow FDA to make any kind of statement about the comparative safety of Sporanox® and Lamisil®. 

Results of recent studies of Sporanox® revealed a potential for the drug to weaken the force of the heart muscle's contractions. This so-called "negative inotropic effect" was observed when intravenous Sporanox® was injected into anesthetized dogs and healthy human volunteers. In these studies, the adverse effect on the heart muscle resolved once the drug was stopped. 

Since becoming aware of the study findings, FDA analyzed US and international post-marketing adverse event reports involving Sporanox that were received between its approval in September 1992 and April 2001. 

During this period, FDA received 94 cases in which patients receiving Sporanox® developed CHF. In 58 of the 94 cases, FDA believes Sporanox® contributed to or may have been the cause of CHF. In 26 of these 58 cases, Sporanox® was being administered to treat fungal nail infections. Of these 58 patients, 28 were hospitalized. Death was reported in 13 cases. However, the causal relationship between the 13 deaths and Sporanox® is very unclear because of confounding factors. For example, 10 of the 13 patients who died had serious underlying conditions. 

In response to the study findings and the analysis of the post-marketing adverse event reports, FDA has added additional information to the current "black box" warning in the Sporanox® labeling. The warning now states that Sporanox® should not be administered for the treatment of fungal nail infections in patients with evidence of cardiac dysfunction, such as CHF, or a history of CHF. The Sporanox® "black box" warning also includes important information about heart-related adverse events caused by drug interactions. 

If signs and symptoms of CHF occur during treatment of fungal nail infections, the revised labeling recommends that Sporanox® should be discontinued. If signs and symptoms of CHF occur during treatment for more serious fungal infections involving other parts of the body, the revised labeling recommends that continued use of Sporanox® should be reassessed by the physician.

The advisory also alerts healthcare professionals to rare cases of serious liver problems including liver failure and death associated with the use of Sporanox® products and Lamisil® tablets. While adverse liver effects were already included in the labeling for both products, FDA decided to include this information in the advisory because some cases involved patients who had neither pre-existing liver disease nor a serious underlying medical condition. 

FDA's concerns do not apply to the topically applied versions of Lamisil® such as cream and solution.

As of April 2001, FDA has received and reviewed 16 possible Lamisil®-associated cases of liver failure, including 11 deaths and two liver transplantations.

As of March 2001, FDA has received and reviewed 24 cases of liver failure possibly associated with Sporanox®, including 11 deaths. Approximately half of the liver failure cases received Sporanox® for fungal nail infections or other dermatological infections. 

Given the possible serious risks associated with Sporanox® products and Lamisil® tablets, the new labeling for both products now recommends that healthcare professionals should obtain nail specimens for laboratory testing prior to prescribing the medications for fungal nail infections, to confirm the diagnosis. 

In conjunction with FDA's advisory, the manufacturer of Sporanox® (Janssen Pharmaceutica Products, L.P. of Titusville, NJ and Ortho Biotech Products, L.P. of Raritan, NJ) and Lamisil® (Novartis Pharmaceuticals of East Hanover, NJ) are notifying healthcare professionals of the labeling changes by issuing "Dear Healthcare Professional" letters. 

FDA encourages healthcare professionals and patients to report adverse events associated with the use of Sporanox® and Lamisil® to FDA's MEDWATCH Program. Reports may be submitted to MEDWATCH by phone at 1-800-FDA-1088, by fax at 1-800-FDA-1078, by mail at MEDWATCH, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MEDWATCH web site at www.fda.gov/medwatch.

 

6.) FDA PUBLIC HEALTH ADVISORY ABOUT SPORANOX AND LAMISIL II

THE SAFETY OF SPORANOX® CAPSULES AND LAMISIL® TABLETS FOR THE TREATMENT OF ONYCHOMYCOSIS
The Food and Drug Administration (FDA) is issuing a public health advisory concerning Sporanox® (itraconazole) Capsules and Lamisil® (terbinafine hydrochloride) Tablets for the treatment of onychomycosis. It is important for physicians to be aware of the association of congestive heart failure and hepatic adverse events with the administration of these therapies. Prior to prescribing systemic antifungal drug therapy for the treatment of onychomycosis, healthcare professionals should consider this new safety information.

Sporanox® Capsules and Lamisil® Tablets, synthetic antifungal agents, are approved in the United States for the treatment of onychomycosis [Sporanox® Capsules, Oral Solution, and Injection are also approved for the treatment of serious systemic fungal infections (e.g., esophageal candidiasis, aspergillosis, blastomycosis, and histoplasmosis).]

CARDIAC RISKS

FDA believes that there is a small but real risk of developing congestive heart failure associated with Sporanox® therapy. Recent studies conducted in dogs and healthy human volunteers revealed negative inotropic effects with intravenous (IV) itraconazole. In these studies, once the drug was stopped the negative inotropic effects resolved. The mechanism for these cardiac effects has not been determined.

Since becoming aware of these findings, FDA reviewed spontaneous post-marketing reports received between September 1992 and April 2001 for congestive heart failure (CHF) in association with itraconazole use. During this period, FDA received 94 U.S. and international spontaneous reports of CHF in which itraconazole was listed as a suspect drug. In 58 of the 94 cases, FDA believes itraconazole contributed to or may have been the cause of CHF. In 26 of the 58 cases, itraconazole was being administered for the treatment of onychomycosis. Of these 58 cases, 28 were hospitalized. Death was reported in 13 cases. However, the causal relationship between the 13 deaths and itraconazole is unclear because of confounding factors, including 10 of the 13 patients who had serious underlying conditions.

Because of the low but possible risk of cardiac toxicity, Sporanox® should NOT be administered for the treatment of onychomycosis in patients with ventricular dysfunction such as CHF or a history of CHF. If signs or symptoms of CHF occur during treatment for onychomycosis, Sporanox® should be discontinued.

If signs or symptoms of CHF occur during treatment for more serious systemic fungal infections, continued Sporanox® use should be reassessed as to the appropriate risk benefit analysis in relationship to any other therapeutic options.

HEPATIC RISKS

Both Sporanox® and Lamisil® have been associated with serious hepatic toxicity, including liver failure and death, including some cases involving patients who had neither pre-existing liver disease nor a serious underlying medical condition.

As of April 2001, the FDA is aware of 16 cases of liver failure in association with Lamisil® Tablet use (including 11 deaths and two liver transplantations). These patients received Lamisil® Tablets for the treatment of various dermatologic conditions, including onychomycosis.

FDA's concerns about hepatic risks associated with the use of Lamisil® do not apply to topically applied formulations of terbinafine, such as Lamisil® Solution and Lamisil® AT Cream.

As of March 2001, the FDA is aware of 24 cases of liver failure associated with Sporanox® use (including 11 deaths). These patients received Sporanox® for the treatment of either onychomycosis or systemic fungal infections.

Given the possible risks associated with both drugs, FDA wants healthcare providers to be aware of this new safety information for the two most commonly prescribed systemic onychomycosis drug therapies. Because of these risks, the new labeling for both Sporanox® and Lamisil® recommends that healthcare providers obtain nail specimens for laboratory testing prior to prescribing the medications for onychomycosis to confirm the diagnosis. However, there is insufficient data to allow FDA to make any kind of statement about the comparative safety of Sporanox® and Lamisil®.


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DATA-MÉDICOS/DERMAGIC-EXPRESS No 6-(X-9) 30/07/2.004 DR. JOSÉ LAPENTA
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Produced by Dr. José Lapenta R. Dermatologist 
Maracay Estado Aragua Venezuela 2.004-2026  
     Telf.: 04142976087 - 04127766810