Tipranavir

Class:

Protease Inhibitor

Antiviral Activity:

Tipranavir has activity against HIV-1 and is indicated for combination treatment of HIV infected adults who are treatment experienced and have strains resistant to more than one protease inhibitor.

Mechanism of Action:

Binds to HIV protease and inhibits the formation of individual functional proteins required for formation of mature virions.

Mechanism of Resistance:

Six mutations, I13V, V321I, L33F, K45I, V82L, and I84V, are needed to confer a >10-fold decrease in tipranavir susceptibility. In vitro studies have shown that resistance to tipranavir developed slowly, and required up to 9 months of passage in culture

Pharmacokinetics:

Tipranavir has limited oral absorption. Coadministration with ritonavir increases tipranavir concentrations almost 30 fold and bioavailability is enhanced with high fat meals. For this reason, tipranavir should be taken with food. Tipranavir is extensively bound (>99.9%) to alpha-1-acid-glycoprotein and albumin. It has a volume of distribution of 8-10 L when boosted with 200mg of ritonavir. Tipranavir reaches an average Cmax of 77.6 ▒ 16.6 ÁM (males) and 94.8 ▒ 22.8 ÁM (females) ~ 3 hours after dosing. The terminal half life of tipranavir is 5.5-6 hours. Tipranavir is predominantly metabolized by CYP3A4 and is mainly eliminated in the feces and minimally in urine as unchanged drug (with ritonavir coadministration)

Adverse Effects:

The most common adverse events associated with tipranavir are headache, nausea, diarrhea, abdominal discomfort, vomiting, and fever.

Dosage:

Tipranavir should be taken with a high fat meal to increase absorption and should be coadministered with ritonavir.

Adult dose: 500 mg twice daily with 200mg of ritonavir

Children dose: ≥2 years: 14 mg/kg or 375 mg/m2 (maximum: 500 mg/dose) twice daily with ritonavir (6 mg/kg or 150 mg/m2 [maximum: 200 mg/dose] twice daily)

Renal impairment: No dose adjustment

Mild hepatic impairment (Child-Pugh class A): No adjustment required.

Moderate-to-severe hepatic impairment (Child-Pugh class B-C): Concurrent use is contraindicated

Drug Interactions:

Tipranavir co-administered with ritonavir and concomitant use of drugs that are potent CYP 3A4 inducers or are dependent on CYP 3A4 for clearance is contraindicated.

Pregnancy:

Category: C

Brand Names:  

Aptivus «/Boehringer-Ingelheim