| The nimesulide
adverse effects.
Efectos adversos del nimesulide..
Data-Medicos
Dermagic/Express No. 3-(103)
12 August 2.001.12 August 2.001.
COUNTRIES THAT DERMAGIC/EXPRESS RECEIVES:
Venezuela, Brazil, Chile, Colombia, Argentina, Paraguay, Peru, Panama,
United States of America,
Spain, Italy, Portugal,Turkey, Holland, Morocco, Egypt, Israel, The India,
Belgium, Danmark, New
Zealand, Baharian, England, Kuwait, Mexico, Greece. and Germany.
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EFECTOS ADVERSOS/ ADVERSE EFFECTS
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1.) Hepatitis.
2.) Increased hepatic enzyme levels.
3.) Hepatocellular necrosis.
4.) Cholestasis
5.) Fatal liver damage./ Fulminant hepatic failure.
6.) Gastrointestinal tract ulcers. /Bleeding gastric ulcers.
7.) Hepatic insufficiency.
8.) Renal failure./ Renal impairment.
9.) Urticaria.
10.) Jaundice.
11.) Neonatal chronic kidney failure./Neonatal end-stage renal failure./
Perinatal vasoconstrictive renal insufficiency.
12.) Purpura.
13.) synergistic effect with use of cetirizine with nimesulide.
14.)Fixed drug eruptions.
15.) Toxic hepatitis in pregnancy.
16.) Hypothermia.
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REFERENCIAS BIBLIOGRAFICAS /BIBLIOGRAPHICAL REFERENCES
=============================================================
1.) Nimesulide
2.)COX 2 inhibitor and fulminant hepatic failure.
3.) CASE REPORT
Fatal hepatitis and renal failure during treatment with nimesulide
4.) Nimesulide and renal impairment.
5.) Aspirin and paracetamol tolerance in patients with nimesulide-induced
urticaria.
6.) Risk factors for acetaminophen and nimesulide intolerance in patients
with NSAID-induced skin disorders.
7.) Neonatal chronic kidney failure associated to cyclo-oxygenase
inhibitors administered during pregnancy.
8.) Nimesulide aggravates kainic acid-induced seizures in the rat.
9.) Nimesulide-induced hepatitis and acute liver failure.
10.) Nimeulide and neonatal renal failure.
11.) Fatal hepatitis associated with nimesulide.
12.) Neonatal end-stage renal failure associated with maternal ingestion of
cyclo-oxygenase-type-1 selective inhibitor nimesulide as tocolytic.
13.) [Nimesulide acute hepatitis: description of 3 cases].
14.) Analgesics for pediatric use.
15.) Nimesulide, clavulanic acid and hepatitis.
16.) Nimesulide-induced hepatitis and acute liver failure.
17.) [Toxic hepatitis caused by nimesulide, presentation of a new case and
review of the literature].
18.) [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse
reactions due to nimesulide in a case].
19.) Nimesulide-induced acute hepatitis: evidence from six cases.
20.) Nimesulide-induced purpura.
21.) Modification of antihistaminic activity of cetirizine by nimesulide.
22.) Perinatal vasoconstrictive renal insufficiency associated with
maternal nimesulide use.
23.) Acute renal failure induced by nimesulide in a patient suffering from
temporal arteritis.
24.) Drug-induced cholestasis.
25.) Adverse drug reactions postal survey-bronchial asthma and angioedema
with nimesulide.
26.) Hypothermia with nimesulide.
27.) [Nimesulide-induced acute hepatitis].
28.) [Nimesulide toxic hepatitis in pregnancy].
29.) Positive lesional patch tests in fixed drug eruptions from nimesulide.
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1.) Nimesulide
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SOURCE: THE WHO. /Organizacion Mundial de la SALUD
WHO PHARMACEUTICALS NEWSLETTER
Nimesulide
A total of 17 of the reports on adverse effects on the liver were linked
with the use of nimesulide. Eight of these cases involved hepatitis and 9
increased hepatic enzyme levels. The majority of patients (14) were women.
The average age was 61 years (ranging between 23 and 88 years), and 9 of
the patients were over 60 years of age. The symptoms or findings of liver
effects usually appeared after 1-6 weeks of treatment. In 11 patients the
laboratory values had returned to normal at the follow-up after nimesulide
was stopped. Six patients had still not recovered 2-8 weeks after
withdrawal of medication, when the report on the adverse effect was made.
Five patients were using concomitant drugs which have been reported to have
hepatic reactions. According to published case reports, nimesulide can
cause both hepatocellular necrosis and pure cholestasis. Individual cases
of fatal liver damage have also been reported.
Nimesulide is a relatively new drug, introduced on the Finnish market in
January 1998. However, it is widely used and the number of daily doses (0.2
g) by September 2000 totalled over 14 million. One reason for the
popularity of nimesulide is probably its selectivity – which, as a COX-2
inhibitor, is claimed to be higher than that of older anti-inflammatory
analgesics – and the fewer cases of gastrointestinal tract ulcers it causes.
Due to its adverse effects on the liver, the product information on
nimesulide was updated at the beginning of 2000. Hepatic insufficiency was
added to the contraindications and additional text was included in the
section on warnings according to which patients with abnormal values in
their liver function tests and/or patients with symptoms indicative of
liver damage (anorexia, nausea, vomiting, jaundice) during nimesulide
therapy must be closely monitored and medication stopped. These patients
should not be re-exposed to nimesulide. Increased hepatic enzyme values
were included in the section on rare adverse effects in the SPC, and
cholestasis and rapidly developing hepatitis were included in the list of
very rare adverse effects.
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2.)COX 2 inhibitor and fulminant hepatic failure.
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McCormick PA, Kennedy F, Curry M, Traynor O.
Lancet. 1999 Jan 2;353(9146):40-1.
This article reports on the case of a patient who developed fulminant
hepatic failure from treatment with the selective COX2 inhibitor Nimesulide.
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3.) CASE REPORT
Fatal hepatitis and renal failure during treatment with nimesulide
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A. Schattner1, 3, N. Sokolovskaya2 & J. Cohen2, 3
Schattner A, Sokolovskaya N, Cohen J (Kaplan Medical Center, Rehovot, and
the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel).
Fatal hepatitis and renal failure during treatment with nimesulide (Case
Report). J Intern Med 2000; 247: 153–155.
A healthy 70-year-old woman who took nimesulide for 5 days, presented 2
weeks later with jaundice for which no other cause was found. Laboratory
evidence of coagulopathy, hypoalbuminaemia and hypoglycaemia were present
on admission, and liver biopsy showed massive necrosis of hepatocytes and
severe inflammatory infiltrate. Despite supportive and corticosteroid
treatment, her jaundice deepened and progressive acute renal failure
developed, characterized by a ‘prerenal’ profile changing into irreversible
acute tubular necrosis pattern, coma, occult Gram-negative sepsis and
death. Although rare, nimesulide-associated hepatotoxicity and
nephrotoxicity may occur and should be recognized as early as possible, to
ensure immediate drug withdrawal and treatment.
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4.) Nimesulide and renal impairment.
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Eur J Clin Pharmacol 1999 Apr;55(2):151-4 Related Articles, Books, LinkOut
Leone R, Conforti A, Ghiotto E, Moretti U, Valvo E, Velo GP.
Clinical Pharmacology Unit, Institute of Pharmacology, Policlinico B.go
Roma, University of Verona, Italy. [email protected]
OBJECTIVES: To analyse from spontaneous reporting data the renal adverse
reactions associated with the use of nimesulide. METHODS: Case reports were
obtained from a Northern Italian Regional database (Veneto
Pharmacovigilance System), containing all the spontaneous reports filed
between 1988 and 1997. The Veneto Region is the principal contributor to
the Italian spontaneous reporting system, with an annual report rate of
approximately 17 per 100,000 inhabitants. The clinical records of
hospitalized patients were also analysed. RESULTS: Of the 120 reports
associated with oral nimesulide, 11 referred to suspected renal adverse
reactions. The drug was taken by ten patients for a short period. All the
patients discontinued the therapy and hospitalization was required in six
cases. Other risk factors were identified in six cases. DISCUSSION:
Together with the new insights into the possible consequences of renal
cyclooxygenase-2 (COX-2) inhibition, the reported cases should draw the
attention of doctors and patients to the importance of recognizing any
possible signs of renal impairment during nimesulide therapy, although only
extensive epidemiological data can define the real impact of its renal
toxicity.
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5.) Aspirin and paracetamol tolerance in patients with nimesulide-induced
urticaria.
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Ann Allergy Asthma Immunol 1998 Sep;81(3):237-8 Related Articles, Books,
LinkOut
Asero R.
Ambulatorio di Allergologia, Ospedale Caduti Bollatesi, Bollate (MI), Italy.
BACKGROUND: The administration of aspirin and other nonsteroidal
anti-inflammatory drugs in patients sensitive to nimesulide might be
hazardous. OBJECTIVE: To assess the tolerance to both acetaminophen
(paracetamol) and aspirin in patients with a history of urticaria induced
by nimesulide. METHODS: Nine patients with a history of nimesulide
intolerance were submitted to single-blind, placebo-controlled peroral
challenges with increasing doses of acetaminophen and aspirin. RESULTS:
Acetaminophen was tolerated by all patients, whereas two experienced
immediate systemic urticaria after the administration of 125 mg of aspirin.
CONCLUSION: Acetaminophen and aspirin are well tolerated by most
nimesulide-sensitive patients. Since a minority of patients show aspirin
sensitivity, tolerance of this agent should always be ascertained by
properly performed peroral challenges.
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6.) Risk factors for acetaminophen and nimesulide intolerance in patients
with NSAID-induced skin disorders.
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Ann Allergy Asthma Immunol 1999 Jun;82(6):554-8 Related Articles, Books,
LinkOut
Asero R.
Allergy Clinic, Caduti Bollatesi Hospital, Bollate, Italy.
BACKGROUND: Previous studies show skin reactions after exposure to
acetaminophen and/or nimesulide to occur in about 10% of patients with a
history of urticaria induced by aspirin or other nonsteroidal
anti-inflammatory drugs (NSAIDs). This fact is surprising since
cross-reactivity among different NSAIDs should not occur among subjects
without a history of chronic urticaria. OBJECTIVE: To detect risk factors
for intolerance to alternative drugs such as acetaminophen and nimesulide
in different groups of patients with a history of adverse skin reactions
(urticaria/angioedema, or anaphylaxis) after the ingestion of aspirin and
other NSAIDs. METHODS: Two hundred fifty-six patients with a history of
recent pseudoallergic skin reactions caused by NSAIDs underwent elective
oral challenges with increasing doses of both acetaminophen and nimesulide.
Patients were divided into three groups: A = 69 subjects with chronic
urticaria, B = 163 otherwise normal subjects with a history of urticaria
after the ingestion of aspirin, and C = 24 otherwise normal subjects with a
history of urticaria after the ingestion of pyrazolones but
aspirin-tolerant. RESULTS: Forty-eight (19%) patients reacted to
acetaminophen and/or nimesulide. Similar numbers of patients with chronic
urticaria (23%) and of normal subjects with a history of aspirin-induced
urticaria (19%) did not tolerate one of the alternative drugs challenged.
Pyrazolones-intolerant patients showed the lowest number of reactors (4%).
Aspirin intolerance represented a risk factor for acetaminophen- and/or
nimesulide-induced urticaria (RR = 5.4). A history of anaphylactoid
reactions induced by NSAID represented a risk factor for urticaria after
the ingestion of the alternative study drugs (RR = 5.7). Atopic status was
associated with a higher risk of reactivity to nimesulide: this drug
induced urticaria in 11/47 (23%) atopics versus 18/209 (9%) non-atopics (P
< .005; RR = 3.2). A history of intolerance to antibacterial drugs was not
associated with a higher prevalence of reactivity against acetaminophen
and/or nimesulide. CONCLUSIONS: In at least 20% of patients with a history
of urticaria/angioedema or anaphylaxis induced by aspirin or other NSAIDs,
but without a history of chronic urticaria, cross-reactivity with other
NSAIDs occurs. Atopy as well as a history of aspirin-induced anapylactoid
reactions seem to represent relevant risk factors for intolerance to
alternative NSAIDs. In view of these findings, aspirin-intolerant patients
with such clinical features should be submitted to peroral tolerance tests
with at least two alternative substances in order to avoid potentially
severe reactions.
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7.) Neonatal chronic kidney failure associated to cyclo-oxygenase
inhibitors administered during pregnancy.
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Minerva Urol Nefrol 2001 Jun;53(2):113-6
Peruzzi L, Gianoglio B, Porcellini G, Conti G, Amore A, Coppo R.
Nefrologia e Dialisi, Ospedale Infantile Regina Margherita, Turin, Italy.
Non-steroidal anti-inflammatory drugs (NSAID) are used since years as
tocolytic due to their capacity to inhibit cyclo-oxygenase (COX) expressed
in uterus and fetal membranes, fundamental for labour initiation and
maintenance. The use of nimesulide, a COX-2 selective NSAID, has been
recently proposed due to its capacity to selectively inhibit the enzyme
expressed in the myometrium and endometrium. A case of neonatal
irreversible end stage renal failure after maternal assumption of
nimesulide as tocolytic for 6 week is reported. Cesarean section at the
32nd week due to oligohydramnios gave birth to a baby girl of 2090 g, in
good general conditions, without signs of respiratory distress and of
visible abnormalities. From birth she displayed oligo-anuria which required
dialytic substitutive therapy from the second day of life. At US scan both
kidneys had normal diameters for gestational age slightly increased
echogenicity and a reduced cortico-medullary differentiation. On the 20th
day of life she had a surgical renal biopsy for the persistence of
oligo-anuria, showing fetal glomeruli, without lymphocytic interstitial
infiltrate, and normal tubuli without evidence of necrosis. She is now 16
months old and under automated peritoneal dialysis on a home dialysis
program. The occurrence of chronic renal failure in strict relationship
with maternal nimesulide assumption in this case is strongly suggestive for
a pharmacological damage, either direct or mediated by renin angiotensin
inhibition, and possibly modulated by genetic factors, likely to account
for the different outcome of similarly treated patients. A cautious use of
this drug as long term tocolytic should be recommended while waiting for ad
hoc experimental and clinical evidences of safeness.
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8.) Nimesulide aggravates kainic acid-induced seizures in the rat.
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Pharmacol Toxicol 2001 May;88(5):271-6
Kunz T, Oliw EH.
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala
Biomedical Centre, Sweden. [email protected]
Treatment of rats with kainic acid (10 mg/kg, intraperitoneally) triggers
limbic seizures. Cyclooxygenase-2 mRNA is expressed in the hippocampus and
cortex after 8 hr and marked cell loss occurs after 72 hr in the CA1-CA3
areas of the hippocampus. We examined the effect of the cyclooxygenase-2
inhibitor, nimesulide (N-(4-nitro-2-phenoxyphenyl)-methanesulfonamide), on
kainate-induced seizures and delayed neurotoxicity. Nimesulide (10 mg/kg,
intraperitoneally) was well tolerated given alone or 6-8 hr after kainate.
However, pretreatment with nimesulide augmented seizures and increased the
mortality rate from approximately 10% to 69%. We examined the effect of
nimesulide on delayed cell loss after 72 hr in the surviving animals with
histological staining. Cell loss did not seem to be reduced in animals
treated with nimesulide 6-8 hr after kainate, but in the surviving animals
pretreated with nimesulide less cell loss occurred. We conclude that
nimesulide should be used with caution as an antiinflammatory drug in
patients with convulsive disorders.
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9.) Nimesulide-induced hepatitis and acute liver failure.
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Isr Med Assoc J 1999 Oct;1(2):89-91
Comment in:
Isr Med Assoc J. 1999 Nov;1(3):221
Isr Med Assoc J. 1999 Oct;1(2):98-9
Weiss P, Mouallem M, Bruck R, Hassin D, Tanay A, Brickman CM, Farfel Z,
Bar-Meir S.
Department of Gastroenterology, Sheba Medical Center, Tel-Hashomer, Israel.
BACKGROUND: Nimesulide is a relatively new non-steroidal anti-inflammatory
drug that is gaining popularity in many countries because it is a selective
cyclooxygenase 2 inhibitor. Occasionally, treatment is associated with mild
elevation of liver enzymes, which return to normal upon discontinuation of
the drug. Several cases of nimesulide-induced symptomatic hepatitis were
also recently reported, but these patients all recovered. OBJECTIVES: To
report the characteristics of liver injury induced by nimesulide. PATIENTS
AND METHODS: We report retrospectively six patients, five of them females
with a median age of 59 years, whose aminotransferase levels rose after
they took nimesulide for joint pains. In all patients nimesulide was
discontinued, laboratory tests for viral and autoimmune causes of hepatitis
were performed, and sufficient follow-up was available. RESULTS: One
patient remained asymptomatic. Four patients presented with symptoms,
including fatigue, nausea and vomiting, which had developed several weeks
after they began taking nimesulide (median 10 weeks, range 2-13).
Hepatocellular injury was observed with median peak serum alanine
aminotransferase 15 times the upper limit of normal (range 4-35), reversing
to normal 2-4 months after discontinuation of the drug. The remaining
patient developed symptoms, but continued taking the drug for another 2
weeks. She subsequently developed acute hepatic failure with encephalopathy
and hepatorenal syndrome and died 6 weeks after hospitalization. In none of
the cases did serological tests for hepatitis A, B and C, Epstein-Barr
virus and cytomegalovirus, as well as autoimmune hepatitis reveal findings.
CONCLUSIONS: Nimesulide may cause liver damage. The clinical presentation
may vary from abnormal liver enzyme levels with no symptoms, to fatal
hepatic failure. Therefore, monitoring liver enzymes after initiating
therapy with nimesulide seems prudent.
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10.) Nimeulide and neonatal renal failure.
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Lancet 2000 Feb 12;355(9203):575
Comment on:
Lancet. 1999 Nov 6;354(9190):1615
Balasubramaniam J.
Publication Types:
Comment
Letter
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11.) Fatal hepatitis associated with nimesulide.
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J Hepatol 2000 Jan;32(1):174
Comment on:
J Hepatol. 1998 Jul;29(1):135-41
Andrade RJ, Lucena MI, Fernandez MC, Gonzalez M.
Publication Types:
Comment
Letter
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12.) Neonatal end-stage renal failure associated with maternal ingestion of
cyclo-oxygenase-type-1 selective inhibitor nimesulide as tocolytic.
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Lancet 1999 Nov 6;354(9190):1615
Comment in:
Lancet. 2000 Feb 12;355(9203):575
Lancet. 2000 Jan 15;355(9199):236-7
Comment on:
Lancet. 1997 Jul 26;350(9073):265-6
Peruzzi L, Gianoglio B, Porcellini MG, Coppo R.
Cyclo-oxygenase-type-2 (COX-2) enzyme is fundamental for nephrogenesis,
upregulated on fetal membranes and myometrium at parturition. Fetal COX-2
inhibition, due to maternal nimesulide assumption, can be responsible for
neonatal chronic renal failure.
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13.) [Nimesulide acute hepatitis: description of 3 cases].
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Med Clin (Barc) 1999 Sep 25;113(9):357-8
[Article in Spanish]
Romero Gomez M, Nevado Santos M, Fobelo MJ, Castro Fernandez M.
Publication Types:
Letter
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14.) Analgesics for pediatric use.
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Indian J Pediatr 2000 Aug;67(8):589-90
Malhotra S, Pandhi P.
Department of Clinical Pharmacology, PGIMER, Chandigarh.
The use of nimesulide is increasing and recently, concerns have been raised
regarding its hepatotoxicity, especially in children. At least two deaths
due to fulminant hepatic failure have been attributed to nimesulide. In
India, nimesulide has been approved and about twelve pediatric preparations
are available. Lack of effective postmarketing surveillance means that
adverse drug reactions may not be picked or reported. Therefore, quick
approval of those drugs for which substitutes are available may not be
desirable in India and in other developing countries.
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15.) Nimesulide, clavulanic acid and hepatitis.
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J Intern Med 2000 Aug;248(2):168-9
Comment on:
J Intern Med. 2000 Jan;247(1):153-5
Elmalem E.
Publication Types:
Comment
Letter
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16.) Nimesulide-induced hepatitis and acute liver failure.
=============================================================
Isr Med Assoc J 1999 Nov;1(3):221
Comment on:
Isr Med Assoc J. 1999 Oct;1(2):89-91
Weiss P.
Publication Types:
Comment
Letter
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17.) [Toxic hepatitis caused by nimesulide, presentation of a new case and
review of the literature].
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Gastroenterol Hepatol 2000 Nov;23(9):428-30
[Article in Spanish]
Ferreiro C, Vivas S, Jorquera F, Dominguez AB, Espinel J, Munoz F, Herrera
A, Fernandez MJ, Olcoz JL, Ortiz de Urbina J.
Seccion de Aparato Digestivo y Servicio de Farmacia, Hospital de Leon, Leon.
Nimesulide is a potent non-steroidal anti-inflammatory drug. It is a new,
selective cyclooxygenase-2 inhibitor with few adverse effects on the
gastrointestinal system. We present a case of hepatotoxicity in which other
possible causes of liver damage were excluded. A biochemical pattern of
cholestasis was predominant. Evolution was favorable after the drug was
stopped and enzymatic alterations progressively returned to normal. The
cases reported to date are reviewed. The precise mechanism by which
nimesulide produces liver damage is not known but it is probably caused by
an idiosyncratic reaction. Because of the severity of the hepatitis
described in some cases, treatment should be stopped when liver dysfunction
is detected and the patients should be closely monitored.
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18.) [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse
reactions due to nimesulide in a case].
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Rev Med Chil 2000 Dec;128(12):1349-53
[Article in Spanish]
Tejos S, Torrejon N, Reyes H, Meneses M.
Servicios de Medicina y de Anatomia Patologica, Hospital del Salvador,
Departamento de Medicina (Campus Oriente), Facultad de Medicina,
Universidad de Chile, Santiago, Chile. [email protected]
A 66 year-old obese woman with arthrosis, self-medicated with oral
nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and
dark urine. Two weeks later she had recurrent hematemesis and was
hospitalized. Besides obesity and anemia her physical examination was
unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a
4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly
enlarged liver with diffuse reduction in ecogenicity; the gallbladder and
biliary tract were normal. Blood tests demonstrated a conjugated
hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT
850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49%
and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were
negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A
liver biopsy showed bridging necrosis and other signs of acute toxic liver
damage. Gastric ulcers healed after conventional treatment and hepatitis
subsided after 2 months leaving no signs of chronic liver damage. The
diagnosis of toxic hepatitis due to nimesulide was supported by the
time-course of drug usage, sex, age, absence of other causes of liver
disease, a compatible liver biopsy and the improvement after drug
withdrawal. Peptic ulcers or toxic hepatitis have been previously described
as independent adverse reactions in patients taking nimesulide or other
NSAIDs but their simultaneous occurrence in a single patient is a unique
event that deserves to be reported.
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19.) Nimesulide-induced acute hepatitis: evidence from six cases.
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J Hepatol 1998 Jul;29(1):135-41
Comment in:
J Hepatol. 2000 Jan;32(1):174
Van Steenbergen W, Peeters P, De Bondt J, Staessen D, Buscher H, Laporta T,
Roskams T, Desmet V.
Department of Internal Medicine, University Hospital Gasthuisberg-St
Rafael, Catholic University of Leuven, Belgium.
BACKGROUND/AIMS: A number of nonsteroidal anti-inflammatory drugs have been
reported to provoke hepatic injury. Nimesulide is a new agent of the
sulfonanilide class, and is a more selective inhibitor of cyclooxygenase
type 2 than of type 1. Well-documented cases of acute hepatitis have not
yet been reported with this drug. We report on six patients who developed
acute liver damage after initiation of nimesulide. METHODS: Between April
1996 and January 1997, six patients with apparent nimesulide-induced liver
injury were admitted. Clinical, laboratory, serologic, radiological, and
histologic data of all six cases were extensively analyzed. The causal
relationship between nimesulide and liver injury was assessed, using a
scoring system elaborated by the French and International consensus meeting
group. RESULTS: Four women developed a centrilobular (three) or panlobular
(one) bridging necrosis, whereas two men showed a bland intrahepatic
cholestasis. Jaundice was the presenting symptom in five of the six cases.
One patient with hepatocellular necrosis and one with cholestasis had
hallmarks of hypersensitivity with an increased blood and tissue
eosinophilia. The causal relationship could be designated as "highly
probable" in one, "probable" in four, and "possible" in one patient. One
patient died from a pancreatic tumor 5 months after the diagnosis of toxic
liver injury. In all other patients, liver tests returned to completely
normal values within a late follow-up period of 6 to 17 months.
CONCLUSIONS: Nimesulide-induced liver injury can present with
hepatocellular necrosis or with pure cholestasis. From clinical and
histologic data, it appears that both immunologic and metabolic
idiosyncratic reactions can be invoked as the pathogenic mechanisms of
nimesulide-induced liver disease.
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20.) Nimesulide-induced purpura.
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Dermatology 2000;201(4):376
Kanwar AJ, Kaur S, Thami GP.
Publication Types:
Letter
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21.) Modification of antihistaminic activity of cetirizine by nimesulide.
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J Assoc Physicians India 1999 Apr;47(4):389-92
Rewari S, Gupta U.
Dept of Pharmacology, Maulana Azad Medical College and Associated
Hospitals, New Delhi.
OBJECTIVE: To study the effect of nimesulide (4-nitro-2-phenoxymethane
sulfonanilide) a non-steroidal anti-inflammatory drug, on antihistaminic
activity of cetirizine. METHOD: A randomized, double blind, cross over
study was conducted in ten healthy male volunteers. Wheal and flare
responses to histamine were measured by performing intradermal injection of
histamine (2 micrograms base) diluted in 100 microliters volume of saline
on the volar surface of forearm, on four occasions (0, 2, 4, and 6 hrs.
post-dosing). Each volunteer was randomized to receive either treatment A
(cetirizine 10 mg + placebo) or treatment B (cetirizine 100 mg + nimesulide
100 mg), with one week wash out period in between each administration.
Wheal and flare responses were measured ten minutes after each histamine
injection. RESULTS: Both cetirizine 10 mg alone and cetirizine 10 mg +
nimesulide 100 mg, decreased wheal and flare responses significantly at 2
hrs. and this continued till 6 hrs. post-dosing. This decrease was highly
significant when cetirizine was given along with nimesulide. CONCLUSION:
The results suggest a synergistic effect exhibited by the combined use of
cetirizine with nimesulide.
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22.) Perinatal vasoconstrictive renal insufficiency associated with
maternal nimesulide use.
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Am J Perinatol 1999;16(9):441-4
Landau D, Shelef I, Polacheck H, Marks K, Holcberg G.
Department of Pediatrics, Soroka Medical Center and Ben Gurion University
of the Negev, Beer Sheva, Israel.
A full-term newborn developed oliguric renal failure at 24 hr of life,
which persisted for several days. Her mother ingested therapeutic doses of
nimesulide, a non-steroidal anti-inflammatory (cyclo-oxygenase-2 inhibitor)
drug, during the last 2 weeks of pregnancy. She was found at delivery to
have developed oligohydramnion, esophagitis, and a bleeding peptic ulcer.
The infant's fractional excretion of sodium was very low (0.5%) pointing
for a severe vasoconstrictive mechanism involved. Renal sonogram showed
hyperechogenic medullary papillae, which resolved during convalescence.
This case emphasizes the importance of renal prostagandins in the control
of vascular tone and sodium homeostasis. This is the first report of an
adverse effect of fetal renal circulation by maternal ingestion of nimesulide.
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23.) Acute renal failure induced by nimesulide in a patient suffering from
temporal arteritis.
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Nephrol Dial Transplant 1997 Jul;12(7):1493-6 Related Articles, Books,
LinkOut
Apostolou T, Sotsiou F, Yfanti G, Andreadis E, Nikolopoulou N,
Diamantopoulos E, Billis A.
Department of Medicine, Evangelismos Hospital, Athens, Greece.
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24.) Drug-induced cholestasis.
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Semin Gastrointest Dis 2001 Apr;12(2):113-24
Chitturi S, Farrell GC.
Storr Liver Unit, Westmead Millennium Institute, University of Sydney,
Westmead Hospital, New South Wales, Australia.
The spectrum of drug-induced cholestasis ranges from 'bland' reversible
cholestasis to chronic forms due to the vanishing bile duct syndrome.
Agents known for many years to cause cholestasis include estrogens and
anabolic steroids, chlorpromazine, erythromycin, and the oxypenicillins;
structurally similar congeners of these drugs (tamoxifen, newer macrolides)
may also cause cholestasis. Contemporary drugs linked to cholestastic liver
injury include ticlopidine, terfenadine, terbinafine, nimesulide,
irbesartan, fluoroquinolones, cholesterol-lowering 'statins,' and some
herbal remedies (greater celandine, glycyrrhizin, chaparral).
Amoxillin-clavulanate, ibuprofen, and pediatric cases of the vanishing bile
duct syndrome are recent additions to a long list of drugs associated with
the vanishing bile duct syndrome. Particular human leukocyte antigen
profiles have recently been identified among those who have developed
cholestasis with specific drugs (tiopronin and amoxicillin-clavulanate),
and the mechanistic relevance of these genetic associations is being
explored. The treatment of drug-induced cholestasis is largely supportive.
The offending drug should be withdrawn immediately. Cholestyramine or
ursodeoxycholic acid are used to alleviate pruritus, with rifampicin and
opioid antagonists being reserved for those who fail first line therapy.
Nutritional support is essential for those with prolonged cholestasis, a
subgroup who are at risk of developing biliary cirrhosis and liver failure.
Timely referral for liver transplant assessment is crucial in these patients.
=============================================================
25.) Adverse drug reactions postal survey-bronchial asthma and angioedema
with nimesulide.
=============================================================
J Assoc Physicians India 2000 May;48(5):548
Mangalvedhekar SS, Gogtay NJ, Phadke AV, Gore S, Shah JM, Shah SM,
Kshirsagar NA.
Publication Types:
Letter
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26.) Hypothermia with nimesulide.
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Indian Pediatr 2001 Jul;38(7):799-800
Sharma S.
Professor, Department of Pediatrics, Medical College, Amritsar, Punjab, India.
=============================================================
27.) [Nimesulide-induced acute hepatitis].
=============================================================
Gastroenterol Hepatol 2001 Apr;24(4):219-20
[Article in Spanish]
Montesinos S, Hallal H, Rausell V, Conesa F, Lopez A.
Servicio de Farmacia y aSeccion de Aparato Digestivo. Hospital Santa Maria
del Rosell. Cartagena. Murcia.
Publication Types:
Letter
=============================================================
=============================================================
28.) [Nimesulide toxic hepatitis in pregnancy].
=============================================================
Gastroenterol Hepatol 2000 Dec;23(10):498-9
[Article in Spanish]
Perez-Moreno J, Llerena Guerrero RM, Puertas Montenegro M, Jimenez Arjona MJ.
Publication Types:
Letter
=============================================================
=============================================================
29.) Positive lesional patch tests in fixed drug eruptions from nimesulide.
=============================================================
Contact Dermatitis 2000 Nov;43(5):307
Cordeiro MR, Goncalo M, Fernandes B, Oliveira H, Figueiredo A.
Clinica de Dermatologia, Hospitais da Universidade, Coimbra, Portugal.
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DATA-MEDICOS/DERMAGIC-EXPRESS No 3-(103) 12/08/2.001 DR. JOSE
LAPENTA R.
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