Can elevated liver test values be caused by moclobemide?/nAn 84-year-old female patient with depres

Fråga: Can elevated liver test values be caused by moclobemide?

An 84-year-old female patient with depression has been treated with moclobemide (Aurorix) since April 28, 1992, 100 mg x1 or 100 mg x2 daily. The dose was increased to 100 mg x3 daily on May 5, 1992. Liver functions were not then tested. On June 1, 1992 the doctor in charge of the patient at the Geriatric Department of Huddinge Hospital wrote a letter stating that the patient´s liver test values had been elevated but at the present time had begun to normalize: ASAT and ALAT were normal, GT was marginally elevated, and ALP was maximally 9.2, now slowly but steadily decreasing.

The patient has been taking other drugs including Distalgesic (dextropropoxyphen 32.5 mg and paracetamol 0.325 gram) 6 tablets per day and even more when necessary and Heminevrin (clomethiazol) 2 tablets daily.

Is it necessary to decrease the dose of moclobemide considering the changed liver values? How is this drug eliminated (metabolized or excreted)?

Sammanfattning: Moclobemide is almost exclusively eliminated by hepatic metabolism. There are no data available which indicate an increase in liver enzymes and/or liver damage in connection with moclobemide therapy. In the present case there is no clear time-effect relationship for the hepatic abnormality and treatment with moclobemide, particularly with decreasing liver values while still on the drug. Considering the advanced age of the patient and the long-term use of paracetamol, an additive effect of the drugs on the liver function can not be excluded.

Svar: Recently a comprehensive review of the pharmacological properties and therapeutic use of moclobemide has been published, upon which the present answer is mainly based (1).

Following oral administration moclobemide is almost completely (>95 per cent) absorbed from the gastrointestinal tract. Moclobemide undergoes extensive first-pass hepatic metabolism. The major metabolic reactions include morpholin-N- and C-oxidation, aromatic hydroxylation and deamination. More than 19 metabolites have been identified and isolated, of which only two retain modest MAO-A inhibitory activity in humans. Clearance of moclobemide is almost exclusively due to hepatic metabolism with less than 0.5 per cent of the parent compound being excreted unchanged in the urine. Moclobemide displays first-order elimination kinetics with a short plasma elimination half-life of 1-2 hours. Renal impairment and advanced age do not significantly modify the absorption and elimination kinetics, while hepatic dysfunction or co-administration with cimetidine can lead to decreased systemic clearance of moclobemide (1). An analytical method of determining plasma levels of moclobemide is available from the Institution of Clinical Pharmacology, Lund.

According to this review (1) no abnormalities in ALAT or ASAT activities have been observed in man and there is even a lack of hepatotoxicity in animals. There have been two suspected cases reported to SWEDIS concerning moclobemide and hepatic side-effects, but none of them was felt to have been caused by moclobemide treatment. In the present case, the time course and effect relationship for the liver damage is not clear. Considering the fact that the liver values were decreasing while the patient was still taking the drug, it seems unlikely that the liver abnormality was caused by moclobemide.

It should be mentioned, however, that the patient has been taking paracetamol at least 2 grams daily for a long time, which can be a risk factor for liver function (2). 1 Fitton A, Faulds D, Goa KL: Moclobemide, A Review of its Pharmacological Properties and Therapeutic Use in Depressive Illness. Drugs 1992; 43: 561-596 2 Drugline nr 04883 (year 1985)