Vaprisol (Conivaptan Hydrochloride Conjunctival) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug Interactions

(see CLINICAL PHARMACOLOGY: Drug-Drug Interactions)

CYP3A4

Conivaptan is a substrate of CYP3A4. Coadministration of VAPRISOL with CYP3A4 inhibitors could lead to an increase in conivaptan concentrations. The consequences of increased conivaptan concentrations are unknown. Concomitant use of VAPRISOL with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir is contraindicated.

Conivaptan is a potent inhibitor of CYP3A4. VAPRISOL may increase plasma concentrations of coadministered drugs that are primarily metabolized by CYP3A4. In clinical trials of oral conivaptan hydrochloride, two cases of rhabdomyolysis occurred in patients who were also receiving a CYP3A4-metabolized HMG-CoA reductase inhibitor. Concomitant use of VAPRISOL with drugs that are primarily metabolized by CYP3A4 should be closely monitored or the combination should be avoided. If a clinical decision is made to discontinue concomitant medications at recommended doses, allow an appropriate amount of time following the end of VAPRISOL administration before resuming these medications.

Overdosage

Although no data on overdosage in humans are available, VAPRISOL has been administered as a 20 mg loading dose on Day 1 followed by continuous infusion of 80 mg/day for 4 days in hyponatremia patients and up to 120 mg/day for 2 days in CHF patients. No new toxicities were identified at these higher doses, but adverse events related to the pharmacologic activity of VAPRISOL, e.g. hypotension and thirst, occurred more frequently at these higher doses.

In case of overdose, based on expected exaggerated pharmacological activity, symptomatic treatment with frequent monitoring of vital signs and close observation of the patient is recommended.

Contraindications

VAPRISOL is contraindicated in patients with hypovolemic hyponatremia and in those who have hypersensitivity to any of its components.

The coadministration of VAPRISOL with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is contraindicated. (See PRECAUTIONS: Drug Interactions for details and other important considerations)