[Undesired drug effects after taking chlormezanone (Muscle Trancopal) with lethal results]. / Unerwünschte Arzneimittelwirkung nach Einnahme von Chlormezanon (Muskel Trancopal) mit letalem Ausgang.

HISTORY AND CLINICAL FINDINGS: A 34-year-old woman was admitted for treatment of toxic epidermolysis of the skin and mucosa. 16 days previously she had started to take chlormezanone (Muskel Trancopal) and some other medications for pain in the shoulder and neck. On admission she had a fever of 39 degrees C and, in addition to the epidermolysis, diffuse abdominal pain on pressure and blood-streaked stool. INVESTIGATIONS: Liver enzyme activities (GOT 979 U/I, GPT 1496 U/I, gamma GT 201 U/I) alkaline phosphatase 515 U/I), bilirubin (3.9 mg/dl) and pancreatic enzyme activities were raised. Sonography was nondiagnostic, computed tomography demonstrated only a small amount of ascites. TREATMENT AND COURSE: The epidermolytic lesions, cholestatic hepatitis and pancreatitis markedly regressed under aseptic wound treatment, antibiotics and parenteral nutrition. Persistent blood-streaked stools and bilateral pneumonia with progressive respiratory failure developed. Despite intensive medical care the patient died after 14 days from protracted sepsis with multi-organ failure. Autopsy additionally revealed adult respiratory distress syndrome and complete loss of colonic mucosa. CONCLUSION: The severe course of a toxic epidermal necrosis with fatal outcome is the first such case reported in Germany that very probably was caused by chlormezanone. 4 weeks after this case was reported to the German Doctors' Drug Commission, the manufacturers of the drug withdrew it from the market.

Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case-control study to quantify the risks associated with the use of specific drugs. METHODS: Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. RESULTS: Among drugs usually used for short periods, the risks were increased for trimethoprim-sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to infinity); valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124). For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk. CONCLUSIONS: The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. But for none of the drugs does the excess risk exceed five cases per million users per week.

Chlormezanone in primary fibromyalgia syndrome: a double blind placebo controlled study.

Primary fibromyalgia syndrome (PFS) is a common condition that often proves resistant to health interventions. Chlormezanone combines corrective effects on disturbed sleep with muscle-relaxant properties, and therefore could be of potential benefit in PFS. Forty-two female patients with PFS (mean age 49, range 24-72 years) were randomly and blindly allocated either chlormezanone 400 mg nocte or placebo. Patients were assessed by single observer at 0, 3 and 6 weeks of treatment; assessments included sleep quality, inactivity and morning stiffness, morning alertness, tender point score, mood change and global opinion (patient and observer). No beneficial therapeutic effect could be attributed to chlormezanone. Although there are problems in assessing severity of a predominantly subjective condition, this essentially negative finding is of interest in respect to the pathogenesis of PFS.

Chlormezanone-induced fulminant hepatitis in a pregnant woman: successful delivery and liver transplantation.

The case of a 29 year old woman affected by fulminant hepatitis during the third trimester of pregnancy, after a 3 week administration of chlormezanone is reported. Following induced Caesarean delivery, the patient underwent an orthotopic liver transplantation. The mother and her baby were in good condition 26 months after liver transplantation. In this case, chlormezanone was probably responsible for the fulminant hepatitis.

Drug-induced toxic epidermal necrolysis (Lyell syndrome) in patients infected with the human immunodeficiency virus.

BACKGROUND: Although patients infected with the human immunodeficiency virus (HIV) are predisposed to cutaneous adverse drug reactions, only a few cases of toxic epidermal necrolysis (TEN) have been reported in this setting. OBJECTIVE: Our purpose was to examine the features of TEN in HIV-infected patients. METHODS: We performed a retrospective analysis of all HIV-infected patients in a series of 80 consecutive cases of TEN during a 6-year period. RESULTS: Fourteen patients were HIV infected. They had typical TEN, with epidermal detachment involving 20.6% +/- 8.0% of the skin surface. Suspected drugs were sulfadiazine, trimethoprim-sulfamethoxazole, sulfadoxine, clindamycin, phenobarbital, and chlormezanone. Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a dramatically increased risk of TEN. During our study period 15 cases of AIDS-associated TEN occurred in the greater Paris area, whereas 0.04 case would have been expected if the incidence of TEN were the same in these patients as in the general population. CONCLUSION: HIV-infected patients, especially those with AIDS, may develop TEN that shares many similarities with the disease in immunocompetent patients.

Provocation tests in a chlormezanone-induced fixed drug eruption.

Although as few as seven cases of fixed drug eruption (FDE) due to chlormezanone have been reported, it should not be overlooked as a cause of FDE. To identify the causative agent in FDEs, topical provocation tests are much safer and more convenient than systemic provocation tests. If results of topical provocation tests are reliable, they could become useful diagnostic as well as screening tests. Patch tests were performed in a suspected case of FDE due to chlormezanone on the patient's normal and prelesional skin with all ingested drugs whose concentrations were one and ten percent. The base was petrolatum. A positive reaction occurred only at the previously lesional site tested with chlormezanone, and was confirmed with oral provocation tests.

[Drug-induced hepatitis with cholestasis following therapy with chlormezanone]. / Arzneimittelbedingte Hepatitis mit Cholestase nach Therapie mit Chlormezanon.

The history of a 46 years old female patient is reported who suffered from rheumatoid arthritis. During therapy with chlormezanon and paracetamol symptoms of cholestatic liver disease developed. We believe that this was a side-effect of chlormezanon.

Fixed drug eruption due to a drug combination but not to its constituents.

A fixed drug eruption due to a paracetamol-chlormezanone combination but not to either drug separately is described.