Active ingredient: Tipranavir - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anti-HIV Agents
• HIV Protease Inhibitors

Dosage Forms

• Capsules (250 mg)

Brands / Synonyms

Aptivus; TPV

Indications

For combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors.

Pharmacology

Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Mechanism of Action

Tipranavir (TPV) is a non-peptidic HIV-1 protease inhibitor that inhibits the virus-specific processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions.

Absorption

Absorption is limited, although no absolute quantification of absorption is available.

Toxicity

Oral LD₅₀ in rat is over 5,000 mg/kg. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.

Biotrnasformation / Drug Metabolism

Hepatic. In vitro metabolism studies with human liver microsomes indicated that CYP 3A4 is the predominant CYP enzyme involved in tipranavir metabolism.

Contraindications

APTIVUS (tipranavir) is contraindicated in patients with known hypersensitivity to any of the ingredients of the product.

APTIVUS is contraindicated in patients with moderate and severe (Child-Pugh Class B and C, respectively) hepatic insufficiency.

Co-administration of APTIVUS with 200 mg of ritonavir with drugs that are highly dependent on CYP 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life- threatening events is contraindicated. These drugs are listed below.

Drugs that are Contraindicated with Tipranavir, Co-Administered with 200 mg of Ritonavir

• Antiarrhythmics - Amiodarone, bepridil, flecainide, propafenone, quinidine
• Antihistamines - Astemizole, terfenadine
• Ergot derivatives - Dihydroergotamine, ergonovine, ergotamine, methylergonovine
• GI motility agent - Cisapride
• Neuroleptic - Pimozide
• Sedatives/hypnotics - Midazolam, triazolam

Due to the need for co-administration of APTIVUS with 200 mg of ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.

Drug Interactions

Tipranavir administered with ritonavir can alter plasma exposure of other drugs and other drugs can alter plasma exposure of tipranavir and ritonavir.

Tipranavir co-administered with 200 mg of ritonavir at the recommended dosage is a net inhibitor of CYP 3A and may increase plasma concentrations of agents that are primarily metabolized by CYP 3A. Thus, co-administration of tipranavir/ritonavir with drugs highly dependent on CYP 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events should be contraindicated. Co-administration with other CYP 3A substrates may require a dose adjustment or additional monitoring.

• Nucleoside reverse transcriptase inhibitors: Abacavir, Didanosine (EC), Zidovudine
• Protease inhibitors: Amprenavir, Lopinavir, Saquinavir
• Antifungals: Fluconazole, Itraconazole, Ketoconazole, Voriconazole