Aptivus - Indications for Usage

The FDA has approved tipranavir in combination with the protease inhibitor ritonavir (Norvir) for use in adult HIV patients who have active HIV replication, have used other anti-HIV medications or who show evidence of HIV strains that are resistant to multiple protease inhibitors. tipranavir/ritonavir in combination should be used in combination with other active anti-HIV agents to produce a greater likelihood of a robust treatment response.

When considering use of tipranavir, genotypic and phenotypic resistance testing should be performed to help determine which additional agents may yield the best outcome in combination with tipranavir.

Due to FDA concerns about the safety of the tipranavir/ritonavir combination, the agency recommends to clinicians that tipranavir should be prescribed only to HIV patients for whom other effective drug regimens are not available. In addition, tipranavir is contraindicated in individuals with known hypersensitivity to any of the ingredients in this product. It is also contraindicated in individuals with moderate and severe hepatic insufficiency.

Aptivus - Dosing Information

Tipranavir is available in 250 mg soft gel capsules and is taken with ritonavir. The recommended dosing regimen is 500 mg tipranavir taken with 200 mg ritonavir twice daily.


Aptivus - Drug and Food Interactions

Absorption of tipranavir increases when taken with a high-fat meal. Antacids reduce absorption of tipranavir, requiring timing adjustments of antacid use.

Tipranavir/ritonavir at the recommended dosage is an inhibitor of CYP 3A and may thus increase plasma concentrations of agents that are primarily metabolized by this enzyme. Coadministration of tipranavir/ritonavir with drugs that are highly dependent on CYP 3A for clearance are contraindicated. These drugs include amiodarone, bepridil, flecainide, propafenone, quinidine, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonamine, cisapride, St. John's wort, lovastatin, simvastatin, pimozide, midazolam, and triazolam. 

When used with other antiretrovirals in vitro, tipranavir was shown to be additive to antagonistic with other PIs, generally additive with non nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs), and synergistic with the fusion inhibitor enfuvirtide (Fuzeon).

Patients should tell their doctor about any other medications they are taking, including prescription, nonprescription (over-the-counter), or herbal medications. It is particularly important for doctor s to know if a patient is allergic to sulfa drugs, because people with sulfa allergies may be at a higher risk of having an allergic reaction to tipranavir.

Aptivus - Potential Adverse Events and Side Effects

Like all anti-HIV drugs, tipranavir may cause some unwanted side effects. The most common side effects are diarrhea, nausea, fatigue, headache, and vomiting.

Adverse effects leading to discontinuation of treatment were reported in 7.8 percent of individuals receiving tipranavir. Other adverse effects include rash, elevated lipid levels, fat redistribution, and immune reconstitution syndrome.  Women using estrogens may have an increased risk of non serious rash. Individuals with hemophilia may have increased risk of bleeding.

Tipranavir in combination with ritonavir has been associated clinical hepatitis (liver inflammation) and hepatic decompensation, including some fatalities. Extra vigilance is warranted in individuals with advanced HIV disease or those with chronic hepatitis B or hepatitis C co-infection [with HIV] as these individuals have an increased risk of hepatotoxicity. Symptoms of hepatitis include fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, acholic stools, liver tenderness, or hepatomegaly.

Aptivus - Pharmacology

The most common amino acid substitutions that occurred in more than 20 percent of virologic failure isolates were L33/I/F, V82t, and I84V. Tipranavir resistance was detected at virologic rebound after an average of 38 weeks of tipranavir/ritonavir treatment with a median 14-fold decrease in tipranavir susceptibility. Cross-resistance to PIs has been observed. Tipranavir-resistant viruses that emerged in vitro had decrease susceptibility to the PIs amprenavir (Agenerase), atazanavir (Reyataz), indinavir (Crixivan), lopinavir (Kaletra), nelfinavir (Viracept), and ritonavir (Norvir) but remained sensitive to saquinavir (Invirase).

Genotypic or phenotypic analysis of baseline virus may help determine tipranavir susceptibility before initiating treatment.

Tipranavir is in FDA Pregnancy Category C. No adequate or well-controlled studies of tipranavir have been done in pregnant women. In laboratory animal studies, no teratogenecitiy was detected in pregnant rats and rabbits at exposure levels approximately 1.1-fold those of human exposure. Fetal toxicity was observed in rats at exposure levels approximately 0.2-fold those of human exposure. Tipranavir should be used during pregnancy only when clearly needed.

An Antiretroviral Pregnancy Registry has been established to monitor the outcomes of pregnant women exposed to antiretroviral agents, including amprenavir. Physicians may register patients by calling 800-258-4263.

Alternative methods of non-hormonal contraception should be used when estrogen-based oral contraceptives are coadministered with tipranavir/ritonavir. Women using estrogens as hormone replacement therapy should be clinically monitored for signs of estrogen deficiency.

Aptivus - Storge

Store tipranavir capsules at 20 C to 800 C (360 to 460 F) prior to opening the bottle. After opening, store at 250 C (770 F); excursions permitted to 15 to 300 C (59 to 860 F). Use within 60 days after opening.