A 40-year-old man has been treated with paracetamol and chlormezanone (Lobac), the dose unknown. Th

Fråga: A 40-year-old man has been treated with paracetamol and chlormezanone (Lobac), the dose unknown. The day after having started treatment, the patient reacted with a mucocutaneous syndrome and was brought to an emergency unit. Two days later he was improved and discharged from the hospital.

Has mucocutaneous syndrome been reported after intake of paracetamol/chlormezanone? Is there any risk for a cross-reaction with chlorzoxazone (Paraflex)?

Sammanfattning: Skin reactions have been the most frequently reported adverse effects of Lobac, constituting 55 per cent of the total number of side-effects. In 37 cases reported in SADRAC the most serious were epidermal necrolysis (8 cases), mucocutaneous syndrome (23 cases) and erythema multiforme (6 cases). Thirty one developed fixed drug eruptions. No reports of cross-reaction have been found between chlormezanone/paracetamol and chlorzoxazone. However, such a reaction cannot be excluded.

Svar: Mucocutaneous syndrome is also called Stevens-Johnson syndrome and erythema multiforme is a mild form. Toxic epidermal necrolysis (also called Lyell´s syndrome or scaled skin syndrome, a severe type of erythema multiforme) is a rare but very serious drug reaction which can also be caused by, for example, a Staphylococcus/viral infection, radiation therapy, vaccination or even develop for no recognisable internal or external reason (1). However, it is believed to be caused by drugs in most cases (2). Lobac contains 450 mg paracetamol and 100 mg chlormezanone. The drug was withdrawn by the manufacturer from the Swedish market in September 1992 because of economic reasons.

Skin reactions are the most frequently reported adverse reactions to chlormezanone. Since 1966 141 cases of skin reactions associated with chlormezanone treatment have been reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) (3). Twenty three cases of mucocutaneous syndrome have been reported with a judged probable relation to chlormezanone treatment. Many of these patients had serious reactions and were treated in hospital. The reactions have occurred one to 32 days after beginning treatment with Lobac and do not seem to be related to the dose.

Also, eight cases of epidermal necrolysis and six cases of erythema multiforme associated with chlormezanone treatment have been reported.

Two of the eight patients who developed epidermal necrolysis died. One was a 73-year-old man who took six tablets of Lobac and one to three tablets of Alvedon (paracetamol) per day. He developed hepatic failure, progressing skin exfoliation, uraemia and hepatic insufficiencyand later died. The other patient was a 53-year-old woman who had taken two tablets of Lobac per day for about four weeks in addition to a long-term medication with sulindac and penicillamine. She developed epidermal necrolysis and later died from this disease. Four of the patients who developed epidermal necrolysis had taken Lobac for more than two weeks whereas one patient had taken an overdose of Lobac and other drugs within 24 hours (2).

Thirty one cases of fixed drug eruptions have been reported in relation to treatment with Lobac. The eruptions are often located on the mouth, hands, feet and sexual organs. On the skin the eruptions are mostly circular, red or blue-red, and are seen at precisely the same locations if the drug is given again. On the mucous membranes the eruptions are usually more in the form of an erosion or vesicle (2).

No case report of mucocutaneous syndrome associated treatment with paracetamol (acetaminophen) has been found in the literature, nor in the databases Medline or Drugline (4), though a few single cases have been reported to SADRAC. In one case a woman with a history of drug allergy, renal impairment and carcinoma of the breast with pulmonary micrometastases developed Stevens-Johnson syndrome following the use of mefenamic acid, paracetamol and furosemide. However, mefenamic acid was judged as the most likely culprit (5).

In the database Medline we found no report of Stevens-Johnson syndrome in connection with chlorzoxazone treatment. Rarely, allergic-type skin rashes, petchiae, or ecchymoses may develop during treatment with chlorzoxazone (6).

SADRAC has only received one report since 1966 in which it was judged that a probable relation existed between chlorzoxazone and mucocutaneous syndrome. This patient had however also been treated with chlormezazone/paracetamol (Lobac) and clomipramine (Anafranil) at the same time. There is also one case of erythema multiforme reported in treatment with chlorzoxazone but no case of epidermal necrolysis (3).

No cases of cross-reaction between chlormezanone and other drugs (including chlorzoxanone) are documented in the literature, nor has paracetamol been reported to cross-react with chlorzoxazone.

The case should be reported to SADRAC. 1 Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H, Walker AM: The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990; 126: 43-47

2 Adverse effects of Lobac (chlormezanone - paracetamol). Bulletin from SADRAC 1984; No 43
3 SADRAC
4 Paracetamol + chlormezanone (Lobac). A survey of adverse reactions. Bulletin from SADRAC 1991; No 60
5 Drugline nr 06143 (year 1988)

6 Bork, Cutaneous side effects of drugs. 1988; page 122-132