Can moclobemide (Aurorix) cause a toxic epidermal necrolysis (TEN) in a patient who has well tolera

Fråga: Can moclobemide (Aurorix) cause a toxic epidermal necrolysis (TEN) in a patient who has well tolerated trimethoprim-sulphamethoxazole for half a year? Background: A 39-year-old woman had a bonemarrow transplantation, due to a malignant lymphoma, in April 29, 1994. After that, she experienced a severe skin graft versus host (GVH) reaction and was treated with a wide list of drugs. In late September 1994, she was given moclobemide (Aurorix) against depression. On October 23, the patient was admitted to the hospital with a TEN syndrome that had a fatal outcome. The drug list, when the patient was admitted included trimetoprim-sulphamethoxazole (Bactrim) 2x2; prednisolone 20 mg 1x1; acyclovir (Zovirax) 400 mg 1x3; magnesium (Emgesan) 1x2; cimetidine (Tagamet) 400 mg 1x2; cyclosporine (Sandimmun) 75 mg x2; and moclobemide (Aurorix) 300 mg 1x2.

Sammanfattning: The majority of TEN cases are drug induced. Among the drugs taken by the patient, trimetoprim-sulphametoxazole, prednisolone and cimetidine have been associated several times with TEN but at least the two first of them had been taken by the patient for half a year or longer. No reports of TEN during moclobemide therapy are known. However, considering the limited use of this compound and the fact that TEN usually occurs in rather close relation to onset of therapy a possible causal relation to moclobemid can still be suspected.

Svar: In 1922, Stevens and Johnson (1) described children with febrile erosive stomatitis, severe ocular involvement, and a disseminated cutaneous eruption of discrete dark-red macules, sometimes with a necrotic center. This became known as Stevens-Johnson syndrome. In 1956, Lyell (2) introduced the term "toxic epidermal necrolysis" (TEN) to describe patients with extensive loss of epidermis (> 20 per cent of body-surface area) due to necrosis that leaves the skin looking scalded. From large population-based studies carried out in different countries (3-5), both disorders occur with an incidence ranging from 1.2 to 6 and 0.4 to 1.2 per million person-years, respectively. Both syndromes are potentially life-threatening with mortality rates of below 5 per cent for Stevens-Johnson syndrome and about 30 percent for TEN (4,6,7). Most cases of TEN are drug-induced and, less than 5 percent of patients report no drug use. A strong association with specific medications has been observed in about 80 per cent of the cases (6,7). Other occasionally reported causes include chemicals, mycoplasma pneumoniae, viral infections and immunization (7). The typical interval from beginning of drug therapy to onset of the reaction is 1-3 weeks (7). About 50 per cent of cases with Stevens-Johnson syndrome are caused by drugs (7).

Among the drugs that the patient took on admission, the most frequently associated with Stevens-Johnson syndrome and TEN are co-trimoxazole (8).

A thorough literature search, including Medline as well as pharmacological handbooks has revealed an association between intake of many drugs and TEN. However, among the drugs taken by the patient only co-trimoxazole, cimetidine and glucocorticosteroids have been implicated several times.

In the literature, neither documentation nor ADR reports have been found in concerning moclobemide and TEN syndrome.