Label changes for indinavir warn of several interactions including atazanavir and PDE5 inhibitors

Graham McKerrow, HIV i-Base

Several changes have been made to the product label for indinavir (Crixivan) to warn of interactions with a number of drugs and to say that it should not be coadministered with atazanavir and that patients and doctors should be alert to interactions with the phosphodiesterase type 5 (PDE5) inhibitors sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra).

Indinavir (800 mg every 8 hours) coadministered with a single 10 mg dose of vardenafil resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax, and a 2-fold increase in vardenafil halflife.

Taking indinavir with atazanavir (Reyataz) is now not recommended because both sometimes cause increased levels of bilirubin in the blood.

Text was revised in Ritonavir section to clarify PK when 100mg or 200mg ritonavir boosting is used.

Patients are now advised to tell their doctor if they are taking calcium channel blockers (eg amlodipine, felodipine), antiarrhythmics (eg quinidine), anticonvulsants (eg phenobarbital, phenytoin, or carbamazepine) or steroids (eg dexamethasone).

Advice on methadone has been revised to say: “Administration of indinavir (800 mg every 8 hours) with methadone (20 mg to 60 mg daily) for one week in subjects on methadone maintenance resulted in no change in methadone AUC. Based on a comparison to historical data, there was little or no change in indinavir AUC.”

Terfenadine (Seldane) was deleted and amiodarone (Cordarone) and D.H.E. 45, Migranal, Ergotrate, and Methergine were added under the “Medicines you should not take with indinavir” section of the patient package insert.

The revised product label says delavirdine (Rescriptor) inhibits the metabolism of indinavir such that coadministration of 400 mg or 600 mg indinavir three times daily with 400 mg delavirdine three times daily alters indinavir area AUC, Cmax and Cmin, but that indinavir had no effect on delavirdine pharmacokinetics.

The complete revised label is at the US Food and Drug Administration site:,047_crixivan_lbl.pdf

Links to other websites are current at date of posting but not maintained.