Reduction of clozapine-induced hypersalivation by pirenzepine is safe.

Abstract

INTRODUCTION:

Hypersalivation is known as a frequent, disturbing, and socially stigmatizing side effect of therapy with the atypical antipsychotic clozapine. It has been shown that the addition of the anticholinergic pirenzepine is able to reduce clozapine-induced hypersalivation, probably by blocking M4-receptors. Nevertheless, a pharmacokinetic interaction between both compounds cannot be excluded.

METHODS:

In this pilot study, 29 schizophrenic patients (ICD-10; 51.7 % female; age: 36.7 +/- 8.7 years [mean +/- SD]) were included. Serum concentrations of clozapine and its pharmacologically active metabolite N-desmethylclozapine were determined under steady-state conditions by automated HPLC with UV detection before and after addition of pirenzepine for 3 days.

RESULTS:

Significantly fewer patients reported hypersalivation after addition of pirenzepine (69 % vs. 34.5 %, P = 0.002). No significant differences of clozapine and N-desmethylclozapine serum levels before (329 +/- 181 ng/ml and 218.0 +/- 123.4 ng/ml, respectively) and 3 days after (336 +/- 215 ng/ml and 235.9 +/- 164.4 ng/ml, respectively) addition of pirenzepine were found. In three patients, however, clozapine serum levels increased; this was probably unrelated to pirenzepine.

CONCLUSION:

In conclusion, treatment of clozapine-induced hypersalivation with pirenzepine is a recommendable combination with low risk of additional side effects.

• Authors: B Schneider, H Weigmann, C Hiemke, B Weber, J Fritze
• Journal: Pharmacopsychiatry (Pharmacopsychiatry) Vol. 37 Issue 2 Pg. 43-5 (Mar 2004) ISSN: 0176-3679 [Print] Germany
• PMID: 15048609 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Antipsychotic Agents
• Muscarinic Antagonists
• norclozapine
• Pirenzepine
• Clozapine

Topics

• Adult
• Antipsychotic Agents (adverse effects)
• Chromatography, High Pressure Liquid (methods)
• Clozapine (adverse effects, analogs & derivatives, blood)
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Drug Interactions
• Female
• Humans
• Male
• Middle Aged
• Muscarinic Antagonists (therapeutic use)
• Pilot Projects
• Pirenzepine (therapeutic use)
• Schizophrenia (blood, drug therapy)
• Sialorrhea (chemically induced, drug therapy)
• Spectrophotometry, Ultraviolet (methods)