Can paroxetine or lansoprazole cause liver damage?/nA 71-year-old woman with depression and a pepti

Fråga: Can paroxetine or lansoprazole cause liver damage?

A 71-year-old woman with depression and a peptic ulcer has been treated with paroxetine 20 mg for three months, lansoprazole 60 mg for one month and clonazepam 1.0 mg and zopiclone 5 mg for several months. Two months ago a slight increase in liver enzyme values was noted (ALAT 1.0, GT 2.0, ASAT 0.53). Today she has a more marked increase (ALAT 3.2, GT 7.7, ASAT 1.5). She has previously been treated for an intestinal cancer, but there are no signs of metastases.

Sammanfattning: We have found no solid evidence in the literature that any of the drugs lansoprazole, paroxetine, clonazepam or zopiclone should cause liver damage. However, as there is a time-relation between the start of paroxetine and lansoprazole treatment and the increase in liver enzymes, either of these two drugs must be considered as a possible cause. Also, the contribution of a drug interaction cannot be ruled out.

Svar: Similar questions have previously been answered in Drugline (1-3). One earlier question concerns a 41-year-old man with diabetes and epilepsy who developed increased liver enzymes when treated with lansoprazole 30 mg. The enzyme levels became even higher after an increase of the lansoprazole dose to 60 mg (ALAT and ASAT around 5, GT 97 and ALP 98). Treatment with lansoprazole and phenytoin was changed to carbamazepine and sucralphate and the liver enzymes stabilised (1). However, no cases of hepatic side-effects to lansoprazole have been reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC). There are 27 cases of hepatic side-effects in connection with the very widely used drug omeprazole, which is chemically closely related to lansoprazole.

The information concerning paroxetine or zopiclone and possible hepatic side-effects is also scarce. A few cases have been reported in connection with paroxetine (2), 4 cases with clonazepam (3) and a single case for zopiclone.

A Medline search has not revealed any reports of interactions between the drugs in the present case. However, all four drugs are extensively metabolised by the liver. Paroxetine is a known inhibitor of the liver enzyme CYP2D6. The metabolic pathways for lansoprazol, zopiclone and clonazepam are not fully known. A pharmacokinetic drug interaction cannot be excluded.

We recommend this case be reported to SADRAC. 1 Drugline nr 10000 (year 1993) 2 Drugline nr 10407 (year 1994) 3 Drugline nr 07580 (year 1990)