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Re: ziprasidone- Chris

Posted by Sunnely on July 29, 2000, at 23:02:24

In reply to Re: ziprasidone- Chris, posted by SLS on July 29, 2000, at 14:04:01

> According to Pfizer, ziprasidone is metabolized primarily by the CYP 3A4 enzyme, but it is not expected to produce major interactions with other drugs.

Indeed, ziprasidone is predominantly metabolized by CYP3A4. It is therefore a "substrate" of this liver enzyme. You can therefore expect that the product information will include the following warning regarding drug-drug interactions with ziprasidone:

Drugs that either moderately or markedly inhibit the action of CYP3A4, slowing down the metabolism of ziprasidone consequently raising its blood levels (with potential for prolongation of QTc on ECG) are:

1. cimetidine (Tagamet); 2. Erythromycin; 3. troleandomycin (Tao); 4. the antifungals such as ketoconazole (Nizoral), itraconazole (Sporanox); 5. antidepressants such as Prozac and Luvox; 6. diltiazem (Cardizem), a calcium-channel blocker; 7. propoxyphene (Darvon); 8. amiodarone (Cordarone); 9. some of the drugs for HIV called protease inhibitors such as ritonavir (Norvir) and saquinavir (Fortovase, Invirase); and 10. grapefruit juice.

Drugs that are known to stimulate or induce the action of CYP3A4, hastening the metabolism of ziprasidone leading to decrease in its blood levels, and consequently losing its effectiveness are:

1. carbamazepine (Tegretol); 2. phenytoin (Dilantin); 3. phenobarbital; 4. primidone (Mysoline); 5. anti-TB drug, rifampin (Rifadin); 6. dexamethasone.

Ziprasidone itself has not been found, in in vitro studies, to either induce or inhibit the cytochrome enzymes.

A couple of advantages of ziprasidone over the other atypical antipsychotics are: 1. low propensity to cause weight gain, and 2. may have antidepressant and antianxiety effect due to its moderate inhibition of both norepinephrine and serotonin reuptake.


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