Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of
plasma levels). The risks of using ziprasidone in combination with other drugs have been evaluated as described
below. Based upon the pharmacodynamic and pharmacokinetic profile of ziprasidone, possible interactions could be
- GEO should not be used with any drug that prolongs the QT interval .
- Given the primary CNS effects of ziprasidone, caution should be used when it is taken in combination with other
centrally acting drugs.
- Because of its potential for inducing hypotension, ziprasidone may enhance the effects of certain
- GEO may antagonize the effects of levodopa and dopamine agonists.
The Effect of Other Drugs on GEO
Carbamazepine Carbamazepine is an inducer of CYP3A4; administration of 200 mg BID for 21 days resulted in a
decrease of approximately 35% in the AUC of ziprasidone. This effect may be greater when higher doses of
carbamazepine are administered.
Ketoconazole Ketoconazole, a potent inhibitor of CYP3A4, at a dose of 400 mg QD for 5 days, increased the
AUC and C max of ziprasidone by about 35-40%. Other inhibitors of CYP3A4 would be expected to have similar
Cimetidine Cimetidine at a dose of 800 mg QD for 2 days did not affect ziprasidone pharmacokinetics.
Antacid The coadministration of 30 mL of MAALOX with ziprasidone did not affect the pharmacokinetics of
In addition, population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials
has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol,
Effect of GEO on Other Drugs
In vitro studies revealed little potential for ziprasidone to interfere with the metabolism of drugs
cleared primarily by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, and little potential for drug interactions with
ziprasidone due to displacement.
Lithium GEO at a dose of 40 mg BID administered concomitantly with lithium at a dose of 450 mg BID
for 7 days did not affect the steady-state level or renal clearance of lithium.
Oral Contraceptives GEO at a dose of 20 mg BID did not affect the pharmacokinetics of concomitantly
administered oral contraceptives, ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg).
Dextromethorphan Consistent with in vitro results, a study in normal healthy volunteers showed that
ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its major metabolite,
dextrorphan. There was no statistically significant change in the urinary dextromethorphan/dextrorphan ratio.