Drug interactions between conivaptan and Lipitor

GENERALLY AVOID: Coadministration with conivaptan may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors and/or their pharmacologically active metabolites. The mechanism is conivaptan inhibition of CYP450 3A4 metabolism. Intravenous conivaptan 30 mg/day has been reported to cause a 3-fold increase in simvastatin systemic exposure (AUC). High levels of HMG-CoA reductase inhibitory activity in plasma (e.g., due to liver disease or interaction with other potent 3A4 inhibitors such as macrolide antibiotics and azole antifungal agents) is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. In clinical trials of oral conivaptan, two cases of rhabdomyolysis occurred in patients who were also receiving a CYP450 3A4-metabolized HMG-CoA reductase inhibitor.

MANAGEMENT: In general, lovastatin, red yeast rice (which contains lovastatin), and simvastatin should be avoided in patients treated with conivaptan due to the potential for severe interaction. Atorvastatin may possibly be used with caution, although clinical data are lacking. Patients currently receiving these agents should consider an interruption during administration of conivaptan, and allow an appropriate amount of time following completion of conivaptan therapy before resuming these medications. Conivaptan is not expected to interact with fluvastatin, pravastatin, and rosuvastatin, since these agents are not significantly metabolized by CYP450 3A4.