Liver function tests should be performed prior to initiating therapy with APTIVUS and 200 mg of ritonavir, and frequently throughout the duration of treatment. Patients with chronic hepatitis B or C co-infection or elevations in liver enzymes prior to treatment are at increased risk (approximately 2-fold) for developing further liver enzyme elevations or severe liver disease. Caution should be exercised when administering APTIVUS/ritonavir to patients with liver enzyme abnormalities or history of chronic liver disease. Increased liver function testing is warranted in these patients. APTIVUS should not be given to patients with moderate to severe hepatic impairment.

17.2  Intracranial Hemorrhage

Patients should be informed that APTIVUS co-administered with 200 mg of ritonavir has been associated with reports of both fatal and non-fatal intracranial hemorrhage. Patients should report any unusual or unexplained bleeding to their physician.

17.3  Drug Interactions

APTIVUS may interact with some drugs; therefore, patients should be advised to report to their healthcare provider the use of any other prescription or non-prescription medications or herbal products, particularly St. John’s wort.

17.4  Use of Vitamin E

Patients taking APTIVUS oral solution should be advised not to take supplemental vitamin E greater than a standard multivitamin as APTIVUS oral solution contains 116 IU/mL of vitamin E and when taken at the recommended maximum dose of 500 mg/200 mg tipranavir/ritonavir BID, results in a daily dose of 1160 IU. This intake is higher than the Reference Daily Intake (adults 30 IU, pediatrics approximately 10 IU).

17.5  Rash

Rash, including flat or raised rashes or sensitivity to the sun, have been reported in approximately 10% of subjects receiving APTIVUS. Some patients who developed rash also had one or more of the following symptoms: joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or peeling of the skin. Women taking birth control pills may get a skin rash. Patients should be told to discontinue use of APTIVUS and call their physician right away if any of these symptoms develop.

17.6  Sulfa Allergy

Patients should be told to report any history of sulfonamide allergy to the physician.

17.7  Contraceptives

Women receiving estrogen-based hormonal contraceptives should be instructed that additional or alternative contraceptive measures should be used during therapy with APTIVUS/ritonavir. There may be an increased risk of rash when APTIVUS is given with hormonal contraceptives.

17.8  Fat Redistribution

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

17.9  Administration

Patients should be informed that APTIVUS must be co-administered with ritonavir to ensure its therapeutic effect. Failure to correctly co-admini