Levomepromazine Amitriptyline

A 41-year-old man developed acute abdominal pain with profuse diarrhea and fever (39°C) while receiving intramuscular fluphenazine decanoate 125 mg once every 3 weeks. During the previous 3 months he had also taken oral alimemazine 50 mg/day, levomeproma-zine 50 mg/day, and amitriptyline 100 mg/day. Colonoscopy showed necrotic ulcers in the mucosa of the sigmoid and descending colon. After three weeks of parenteral nutrition, there was a marked reduction in the colonic lesions and he recovered. Levomepromazine 50 mg/day and fluphenazine decanoate 100 mg/day were reintroduced. Two days later he complained again of abdominal pain, and tomodensi-tometry confirmed distension. 

Simultaneous metabolites, amitriptyline, carbamazepine, chlorprothixene, clomipramine, levomepromazine, nortriptyhne... 

Thomare, R Wang, K. Van Der Meersch-Mougeot, V. Diquet, B. Sensitive micromethod for column liquid chromatographic determination of fluoxetine and norfluoxetine in human plasma. J.Chromatogr., 1992, 583, 217-221 [plasma extracted metabolites LOD 2 ng/mL simultaneous amineptine, amitriptyline, chlordiazepoxide, chlorpromazine, clomipramine, clonazepam, clorazepate, desipramine, diazepam, doxepin, flunitrazepam, fluvoxamine, imipramine, levomepromazine, loraze-pam, loxapine, maprotiline, mefloquine, nortriptyline, oxazepam, thioridazine]... 

Most APDs, as well as TCAs, are inhibitors of the cytochrome P450 enzymes, thus potentially increasing each other s serum levels. For haioperidoi, an increase in serum levels of TCAs (by about 2-fold) is found in up to 10% of patients treated with ciomipramine or nortriptyiine (but is not found with desipramine). Levomepromazine can significantly increase ciomipramine serum levels. Perphenazine has been found to increase serum levels of amitriptyline, desipramine, and nortriptyiine, while thioridazine has been reported to increase desipramine serum levels. Thiothixene levels are usually increased by TCAs such as doxepin, nortriptyline, and clomipramine (the latter combination increases the risk for tardive dyskinesia). 

Most antipsychotic drugs as well as tricyclic antidepressants (TCAs) are inhibitors of the chytochrome P450 liver catabolic enzymes, thus potentially increasing each other s serum levels. Chlorpromazine increases imipramine serum levels. Levomepromazine can cause a significant increase in clomipramine serum levels. Perphenazine has been reported to increase the serum levels of amitriptyline, desipramine, imipramine, and nortriptyline. Thioridazine has also been shown to increase TCA serum levels (mainly desipramine). Marked extrapyramidal side-effects have been reported in a few cases with fluphenazine or perphenazine when fluoxetine was added to the regimen. The mechanism is not known. A mutual increase in serum levels of both thioridazine and paroxetine is evident when these agents are... 

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