Based on available clinical and in vitro data, tipranavir is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors.
Currently, phase II and III studies in paediatric and other populations are fully enrolled and ongoing.
In studies to date, tipranavir/r has been well tolerated by most patients and has a safety profile similar to other PIs. The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST studies taking tipranavir/r are gastrointestinal, including diarrhoea, nausea, vomiting and abdominal pain. Fever, fatigue, headache, bronchitis, depression and rash also occurred. Gastrointestinal symptom disorders and elevated transaminase, cholesterol and triglycerides were more frequent in the tipranavir/r arm than in the comparator-ritonavir group but necessitated discontinuation of treatment in a minority of cases. Rates of leucopenia and increased lipase concentrations were more frequent in the comparator-ritonavir arm. Gastrointestinal symptom disorders and elevated transaminase, cholesterol and triglycerides were more frequent in the tipranavir/r arm than in the comparator-ritonavir group but necessitated discontinuation of treatment in the minority of cases. Rates of leucopenia and increased lipase concentrations were more frequent in the comparator-ritonavir arm.
Tipranavir boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity.
The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.
Tipranavir boosted with low-dose ritonavir has been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH). Caution should be used when prescribing tipranavir/r in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding.
Tipranavir does not cure HIV infection/AIDS or prevent the transmission of HIV to others. Patients may continue to develop opportunistic infections and other complications associated with HIV disease.
Apart from the EU, tipranavir has received U.S. marketing authorization by the FDA and was launched there in June 2005. Additional marketing authorizations from different countries have been received or are expected.
Boehringer Ingelheim
Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. Apart from Aptivus(R) (tipranavir), Viramune(R) (nevirapine) is a product of original research done at Boehringer Ingelheim. nevirapine was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs on the market. The company is involved in basic research in that area and is committed to improving HIV therapy by providing physicians and patients with innovative antiretroviral treatment options.
For more information on Boehringer Ingelheim HIV Franchise, please see http://www.boehringer-ingelheim.com/hiv.
References:
(1) Gazzard et al. Combined analysis of RESIST 96-week data: durability
and efficacy of tipranavir/r in treatment-experienced patients; 8th
International Congress on Drug Therapy in HIV Infection; 12-16
November 2006, Glasgow, UK. Poster P23.
(2) Wu et al. Health-related quality of life and tolerability of patients
treated in RESIST; 8th International Congress on Drug Therapy in HIV
Infection; 12-16 November 2006, Glasgow, UK. Poster P25.
(3) Wu A Mos-HIV Health Survey Users Manual 1999.
(4) Walmsley et al. Better Treatment Response To Tipranavir/r Compared to
Lopinavir/r in Patients with Higher Lopinavir Mutation Scores; 8th
International Congress on Drug Therapy in HIV Infection; 12-16
November 2006, Glasgow, UK. Poster P197.
(5) Sungkanuparph S, Groger RK, Overton ET, Fraser VJ, Powderly WG.
Persistent low-level viraemia and virological failure in HIV-1-
infected patients treated with highly active antiretroviral therapy.
HIV Medicine 2006; 7: 437-441.
Prescribing Information (UK)
APTIVUS
Capsules containing 250mg tipranavir. Action: non-peptidic protease inhibitor. Indication: co-administered with low dose ritonavir, for combination antiretroviral treatment of HIV-1 infection in highly pre-treated patients with virus resistant to multiple protease inhibitors. Dose & administration: Adults only. 500mg co-administered with 200mg ritonavir twice daily with food. Contra-indications: Hypersensitivity to any component. Moderate or severe hepatic impairment. Co-administration with rifampicin, St John's wort, active substances highly dependent on CYP3A or CYP2D6 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g. amiodarone, flecainide, propafenone, quinidine, astemizole, terfenidine, ergometrine, ergotamine, cisapride, pimozide, triazolam, simvastatin, lovastatin). Warnings & precautions: The elderly- limited data available. Monitor liver function before initiation, after 2, 4, and 8 weeks, and then every 8-12 weeks. For patients with elevated AST or ALT, mild hepatic impairment, chronic hepatitis B or C, or other underlying liver disease, monitor every 2 weeks during the first 3 months and then monthly. Do not initiate if AST or ALT > 5x ULN. Discontinue permanently if AST or ALT > 10 x ULN, or patient develops signs or symptoms of clinical hepatitis. Haemophiliac patients should be warned of the possibility of increased bleeding. Use with caution in patients at an increased risk of bleeding. Monitor triglyceride and cholesterol before and during therapy. Clinical examination should include evaluation for physical signs of fat redistribution. An inflammatory reaction to asymptomatic or residual opportunistic infections may arise on initiation of CART. Interactions: see SPC. The interaction profile of Aptivus with low-dose ritonavir is complex and includes interaction with other antiretroviral agents. Pregnancy and lactation: No relevant data available. Undesirable effects: Serious reactions include hepatitis (uncommon) and, rarely, hepatic failure (including fatal outcome). Increased risk of bleeding. Cases of ICH reported, some cases fatal. Common/ very common: hypertriglyceridaemia, hyperlipidaemia, anorexia; headache; diarrhoea, nausea, vomiting, flatulence, abdominal distension, abdominal pain, loose stools, dyspepsia; rash, pruritus; fatigue. Uncommon/rare reactions include anaemia, neutropenia, thrombocytopenia; hypersensitivity; metabolism & nutrition disorders (e.g. diabetes mellitus, hypercholesterolaemia, facial wasting); insomnia, sleep disorder; dizziness, peripheral neuropathy, somnolence; dyspnoea; gastrooesophageal reflux disease, pancreatitis; exanthema, lipoatrophy, acquired lipodystrophy, lipohypertrophy; muscle cramp, myalgia; renal insufficiency; influenza like illness, malaise, pyrexia. See SPCs for other undesirable effects. Pack sizes and NHS price: 120 capsules 490.00 pounds Sterling. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, 55216 Ingelheim am Rhein, Germany. MA number: EU/1/05/315/001. For full prescribing information please see Summary of Product Characteristics for Aptivus and for ritonavir. Prepared in October 2006.
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