• A greater proportion of patients receiving APTIVUS/ritonavir 375 mg/m2/150 mg/m2 compared to 290 mg/m2/115 mg/m2 achieved HIV-1 RNA <400 and <50 copies/mL.
• A greater proportion of patients 6 to 18 years of age with multiple baseline protease inhibitor resistance-associated substitutions receiving APTIVUS/ritonavir 375 mg/m2/150 mg/m2 achieved HIV-1 RNA <400 copies/mL at 48 weeks compared to patients receiving APTIVUS/ritonavir 290 mg/m2/115 mg/m2.
• No clinically significant increase in adverse event rates observed with 375 mg/m2/150 mg/m2 compared to 290 mg/m2/115 mg/m2.
• Overall, 6 (5%) patients ages 6 to 18 had AIDS defining illness during the treatment period and all received the 290 mg/m2/115 mg/m2 dose.

The guidance for possible dose reduction for patients who develop intolerance or toxicity and cannot continue with APTIVUS/ritonavir 14 mg/kg/6 mg/kg (or 375 mg/m2/150 mg/m2) is based on the following:

• The 290 mg/m2/115 mg/m2 twice daily regimen provided tipranavir plasma concentrations similar to those obtained in adults receiving 500/200 mg twice daily. The 375 mg/m2/150 mg/m2 twice daily regimen provided tipranavir plasma concentrations 37% higher than those obtained in adults receiving 500/200 mg twice daily.
• The observed response rates for APTIVUS/ritonavir dose of 290 mg/m2/115 mg/m2 as shown in Table 13.

Dose reduction is not appropriate for patients whose virus is resistant to more than one protease inhibitor.

When body surface area (BSA) dosing is converted to mg/kg dosing, the APTIVUS/ritonavir 375 mg/m2/150 mg/m2 twice daily regimen is similar to 14 mg/kg/6 mg/kg and APTIVUS/ritonavir 290 mg/m2/115 mg/m2 twice daily regimen is similar to 12 mg/kg/5 mg/kg twice daily [see Dosage and Administration (2.2)].

16  HOW SUPPLIED/STORAGE AND HANDLING

APTIVUS capsules 250 mg are pink, oblong soft gelatin capsules imprinted in black with "TPV 250". They are packaged in HDPE unit-of-use bottles with a child resistant closure and 120 capsules. (NDC 0597-0003-02)

APTIVUS oral solution is a clear yellow viscous buttermint-butter toffee flavored liquid containing 100 mg tipranavir in each mL. The solution is supplied in a unit-of-use amber glass bottle providing 95 mL of solution with a child resistant closure. A 5 mL plastic oral dispensing syringe is also provided. (NDC 0597-0002-01).

Storage

APTIVUS capsules should be stored in a refrigerator 2°-8°C (36°-46°F) prior to opening the bottle. After opening the bottle, the capsules may be stored at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) and must be used within 60 days after first opening the bottle.

APTIVUS oral solution should be stored at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). Do not refrigerate or freeze. The solution must be used within 60 days after first opening the bottle.

Store in a safe place out of the reach of children.

17  PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling

17.1  Hepatic Impairment and Toxicity

Patients should be informed that APTIVUS co-administered with 200 mg of ritonavir, has been associated with severe liver disease, including some deaths. Patients with signs or symptoms of clinical hepatitis should discontinue APTIVUS/ritonavir treatment and seek medica