Monograph: |
Tipranavir
Adverse Effects
As for HIV-protease inhibitors in general, see Indinavir Sulfate. The most common adverse effects are gastrointestinal. Lipid abnormalities, rashes (particularly in women), and severe hepatotoxicity and intracranial haemorrhage including some fatalities have been associated with tipranavir. Rash accompanied by joint pain, stiffness, throat tightness, or generalised pruritus has also been reported.
Precautions
Tipranavir should not be used in patients with moderate to severe hepatic impairment (Child-Pugh class B or C), and should be used with caution in those with mild impairment (Child-Pugh A) and those with chronic hepatitis B or C co-infection. Treatment should not be started in patients with pre-treatment liver enzymes levels greater than 5 times the upper limit of normal. Monitoring of liver enzymes is recommended before treatment with tipranavir and after 2, 4, and 8 weeks, and then every 8 to 12 weeks during therapy. In patients with mild hepatic impairment, chronic hepatitis, or other underlying liver disease more frequent monitoring is recommended. Treatment should be interrupted or stopped if liver function deteriorates and should be permanently stopped in those patients with liver enzymes greater than 10 times the upper limit of normal or in those who develop signs or symptoms of clinical hepatitis.
Tipranavir should be used with caution in patients who may be at risk for increased bleeding or who are taking antiplatelet drugs or anticoagulants. Cholesterol and triglyceride testing should be carried out before starting treatment and at regular intervals throughout therapy.
Tipranavir contains a sulfonamide moiety and should be used with caution in patients with a known sulfonamide allergy.
Interactions
Interactions involving HIV-protease inhibitors are discussed under Indinavir Sulfate. Tipranavir is both an inducer and an inhibitor of the cytochrome P450 isoenzyme CYP3A although when given with low-dose ritonavir there is a net inhibition of the P450 isoenzyme CYP3A; there is therefore the potential for complex interactions with other drugs metabolised by this enzyme. The combination of tipranavir and ritonavir is also a net inducer of P-glycoprotein.
Antiviral Action
As for HIV-protease inhibitors in general, see Indinavir Sulphate. Tipranavir is a non-peptide HIV-protease inhibitor and is active against many strains of HIV that are resistant to other HIV-protease inhibitors.
Pharmacokinetics
Tipranavir is absorbed to a limited extent after oral doses. Food improves the tolerability and bioavailability is increased with a high fat meal. Peak plasma concentrations are reached within 1 to 5 hours and steady state is usually reached after 7 to 10 days of treatment. Tipranavir is about 99.9% bound to plasma proteins. It is metabolised by the cytochrome P450 system (predominantly the isoenzyme CYP3A4), although when given with ritonavir metabolism is minimal with the majority of ritonavir being excreted unchanged in the faeces. The mean elimination half-life of tipranavir is 4.8 to 6 hours.
Uses and Administration
Tipranavir is a non-peptide HIV-protease inhibitor with antiviral activity against HIV (see Antiviral Action, under Indinavir. It is used with other antiretrovirals for treatment-experienced patients or those with multi-drug-resistant HIV infection. It is given with low-dose ritonavir, which acts as a pharmacokinetic enhancer. The dose in adults is tipranavir 500 mg (with ritonavir 200 mg) twice daily with food.
No dose adjustment is required for patients with renal impairment or mild liver disease. Tipranavir should not be given to patients with moderate to severe liver disease.
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