Clozapine

Question 1

Metabolism

Answer 1

Clozapine is mainly metabolised by CYP1A2. Therefore inducers and inhibitors of CYP1A2 can have a profound effect on plasma clozapine levels.

Others mechanisms appear to be important including CYP2D6.

Question 2

SSRIs

Answer 2

Effect on plasma clozapine levelsIncreased

Question 3

Erythromycin

Answer 3

Effect on plasma clozapine levelsIncreased

Question 4

Caffeine

Answer 4

Effect on plasma clozapine levelsIncreased

Question 5

Carbamezapine

Answer 5

Effect on plasma clozapine levelsDecreased

Question 6

Phenytoin

Answer 6

Effect on plasma clozapine levelsDecreased

Question 7

Tobacco

Answer 7

Effect on plasma clozapine levelsDecreased

Question 8

The main ‘active’ metabolites (note: some sources regard the metabolites as inactive) are:

Answer 8

N-desmethylclozapine (norclozapine)

clozapine N-oxide

Question 9

Anticholinergic effect

Answer 9

Clozapine has marked anticholinergic activity, and concurrent use with other anticholinergic drugs can increase side-effects, such as dry mouth, constipation, loss of accommodation and urinary retention.