Patients receiving PDE5 inhibitors for erectile dysfunction (eg, sildenafil, tadalafil, or vardenafil) should be advised that they may be at an increased risk of associated adverse events including hypotension, visual changes, and sustained erection, and should promptly report any symptoms to their doctor. Concomitant use of sildenafil with NORVIR is contraindicated in patients with pulmonary arterial hypertension (PAH).

Patients receiving estrogen-based hormonal contraceptives should be instructed that additional or alternate contraceptive measures should be used during therapy with NORVIR.

Patients should be informed that NORVIR may produce changes in the electrocardiogram (e.g., PR prolongation). Patients should consult their physician if they experience symptoms such as dizziness, lightheadedness, abnormal heart rhythm, or loss of consciousness.

Laboratory Tests
Ritonavir has been shown to increase triglycerides, cholesterol, SGOT (AST), SGPT (ALT), GGT, CPK, and uric acid. Appropriate laboratory testing should be performed prior to initiating NORVIR therapy and at periodic intervals or if any clinical signs or symptoms occur during therapy. For comprehensive information concerning laboratory test alterations associated with reverse transcriptase inhibitors, physicians should refer to the complete product information for each of these drugs.

Drug Interactions
Ritonavir has been found to be an inhibitor of cytochrome P450 3A (CYP3A) both invitro and in vivo (Table 3). Agents that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in AUC (> 3-fold) when co-administered with ritonavir. Ritonavir also inhibits CYP2D6 to a lesser extent. Co-administration of substrates of CYP2D6 with ritonavir could result in increases (up to 2-fold) in the AUC of the other agent, possibly requiring a proportional dosage reduction. Ritonavir also appears to induce CYP3A as well as other enzymes, including glucuronosyl transferase, CYP1A2, and possibly CYP2C9.

Drugs that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed both in CONTRAINDICATIONS - Table 4 and under Drugs That Should Not Be Co-administered with NORVIR in Table 5.

Those drug interactions that have been established based on drug interaction studies are listed with the pharmacokinetic results in CLINICAL PHARMACOLOGY - Table 2 and Table 3. The clinical recommendations based on the results of these studies are listed in Table 6. Established and Other Potentially Significant Drug Interactions. A systematic review of over 200 medications prescribed to HIV-infected patients was performed to identify potential drug interactions with ritonavir.2 There are a number of agents in which CYP3A or CYP2D6 partially contribute to the metabolism of the agent. In these cases, the magnitude of the interaction and therapeutic consequences cannot be predicted with any certainty.

When co-administering ritonavir with calcium channel blockers, immunosuppressants, some HMG-CoA reductase inhibitors, some steroids, or other substrates of CYP3A; or most antidepressants, certain antiarrhythmics, and some narcotic analg