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Interaction of the week: Olanzapine (Zyprexa) + Carbamazepine (Tegretol)

Pharmacokinetic Interaction

Carbamazepine may decrease the serum concentration of olanzapine by about 50% (25%-71%) by inDuction of CYP1A2 (and possibly UGT) enzymes.

carbamazepine decreases levels of olanzapine
carbamazepine decreases levels of olanzapine by about 50%

Reversal of inDuction

Monitor for increased olanzapine effects/toxicities if carbamazepine is discontinued.

Case report: A patient on stable doses of carbamazepine (600 mg) and olanzapine (15 mg) experienced a 114% increase in serum olanzapine concentration several weeks after discontinuation of carbamazepine (Licht et al, 2000).

InDuction (and reversal of inDuction) is Delayed.

Pharmacodynamic interactions

Nothing noteworthy. No overlapping mechanisms. Both medications can cause neutropenia and, rarely, agranulocytosis but risk is not increased with the combination. As with many psychotropic combos, there may be additive sedative effects.

The Visual Mnemonics

The CYP1A4 mnemonic frame of trees and axes is described here. Similar interactions are expected between carbamazepine and any of the "tree" medications.

CYP1A2 interactions mnemonic
Axes (like carbamazepine) decrease levels of trees (like olanzapine)
carbamazepine (Tegretol)
mnemonic phrase and medication mascot for carbamazepine
carbamazepine interaction visual mnemonics by Jason Cafer MD
Carbamazepine is a "shredder" inDucer of multiple metabolic enzymes.
olanzapine zyprexa
mnemonic phrase and medication mascot for olanzapine
olanzapine interactions
olanzapine is a tree = CYP1A2 substrate

Bergemann, N., Frick, A., Parzer, P., & Kopitz, J. (2004). Olanzapine plasma concentration, average daily dose, and interaction with co-medication in schizophrenic patients. Pharmacopsychiatry, 37(02), 63-68.

Lucas, R. A., Gilfillan, D. J., & Bergstrom, R. F. (1998). A pharmacokinetic interaction between carbamazepine and olanzapine: observations on possible mechanism. European journal of clinical pharmacology, 54, 639-643.

Licht, R. W., Olesen, O. V., Friis, P., & Laustsen, T. (2000). Olanzapine serum concentrations lowered by concomitant treatment with carbamazepine. Journal of Clinical Psychopharmacology, 20(1), 110-112.

Olesen, O. V., & Linnet, K. (1999). Olanzapine serum concentrations in psychiatric patients given standard doses: the influence of comedication. Therapeutic drug monitoring, 21(1), 87-90.

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