APTIVUS CO-ADMINISTERED WITH 200 MG RITONAVIR HAS BEEN ASSOCIATED WITH REPORTS OF BOTH FATAL AND NON-FATAL INTRACRANIAL HEMORRHAGE. (SEE WARNINGS)
APTIVUS CO-ADMINISTERED WITH 200 MG RITONAVIR HAS BEEN ASSOCIATED WITH REPORTS OF CLINICAL HEPATITIS AND HEPATIC DECOMPENSATION INCLUDING SOME FATALITIES. EXTRA VIGILANCE IS WARRANTED IN PATIENTS WITH CHRONIC HEPATITIS B OR HEPATITIS C CO-INFECTION, AS THESE PATIENTS HAVE AN INCREASED RISK OF HEPATOTOXICITY. (SEE WARNINGS)
Capsules, 250 mg
APTIVUS« (tipranavir) is the brand name for tipranavir (TPV), a non-peptidic protease inhibitor (PI) of HIV belonging to the class of 4-hydroxy-5,6-dihydro-2-pyrone sulfonamides. APTIVUS soft gelatin capsules are for oral administration. Each capsule contains 250 mg tipranavir.
APTIVUS (tipranavir), co-administered with 200 mg of ritonavir, is indicated 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.
This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of APTIVUS/ritonavir of 24 weeks duration. Both studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
The following points should be considered when initiating therapy with APTIVUS/ritonavir:
- The use of other active agents with APTIVUS/ritonavir is associated with a greater likelihood of treatment response (see CLINICAL PHARMACOLOGY, Microbiology and INDICATIONS AND USAGE, Description of Clinical Studies).
- Genotypic or phenotypic testing and/or treatment history should guide the use of APTIVUS/ritonavir (see CLINICAL PHARMACOLOGY, Microbiology). The number of baseline primary protease inhibitor mutations affects the virologic response to APTIVUS/ritonavir (see CLINICAL PHARMACOLOGY, Microbiology).
- Use caution when prescribing APTIVUS/ritonavir in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding (see WARNINGS).
- Liver function tests should be performed at initiation of therapy with APTIVUS/ritonavir and monitored frequently throughout the duration of treatment (see WARNINGS).
- Use caution when prescribing APTIVUS/ritonavir to patients with elevated transaminases, hepatitis B or C co-infection or other underlying hepatic impairment (see WARNINGS).
- The extensive drug-drug interaction potential of APTIVUS/ritonavir when co-administered with multiple classes of drugs must be considered prior to and during APTIVUS/ritonavir use (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS).
- The risk-benefit of APTIVUS/ritonavir has not been established in treatment-na´ve adult patients or pediatric patients.
There are no study results demonstrating the effect of APTIVUS/ritonavir on clinical progression of HIV-1.
Published Studies Related to Aptivus (Tipranavir)
Effects of tipranavir, darunavir, and ritonavir on platelet function, coagulation, and fibrinolysis in healthy volunteers. [2011.06.01]
The use of HIV protease inhibitors (PIs) as part of antiretroviral therapy in the treatment of HIV-1 infection may be associated with an increased risk of bleeding... There was large inter-patient variability in antiplatelet effect for all PI treatments, ranging from no effect to complete inhibition of AA-induced platelet aggregation.
Lack of a pharmacokinetic interaction between steady-state tipranavir/ritonavir and single-dose valacyclovir in healthy volunteers. [2011.03]
OBJECTIVE: This study assessed the single-dose pharmacokinetics of the herpes antiviral acyclovir (administered as the pro-drug valacyclovir) alone and in combination with twice-daily 200 mg ritonavir-boosted tipranavir (500 mg) at steady state... CONCLUSIONS: When administered as a single dose of valacyclovir with steady-state tipranavir/ritonavir, there were no clinically important changes in acyclovir pharmacokinetics. This result indicates that valacyclovir can be co-administered safely with no dose adjustments.
A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir. [2010.06]
The effects of tipranavir/ritonavir (TPV/r) on hepatic and intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) enzyme activity were evaluated in 23 volunteers. The subjects received oral (p.o.) caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, and midazolam and digoxin (p.o...
Pharmacokinetic characterization of three doses of tipranavir boosted with ritonavir on highly active antiretroviral therapy in treatment-experienced HIV-1 patients. [2010.01]
PURPOSE: This study characterized the pharmacokinetic effects, safety, and antiretroviral activity of three different doses of the nonpeptidic protease inhibitor tipranavir, in combination with ritonavir administered twice daily for 28 days, on a number of triple-combination regimens containing a nonnucleoside reverse transcriptase inhibitor (efavirenz or nevirapine) plus two nucleoside reverse transcriptase inhibitors (abacavir, didanosine, lamivudine, stavudine, and zidovudine) or a three nucleoside reverse transcriptase inhibitor combination (zidovudine, lamivudine, and abacavir)... CONCLUSIONS: Tipranavir coadministered with ritonavir has been demonstrated to be safe, effective, and pose little potential for clinically meaningful drug interactions when added to the highly active antiretroviral therapy regimens containing nevirapine, efavirenz, lamivudine, stavudine, or didanosine.
Effects of boosted tipranavir and lopinavir on body composition, insulin sensitivity and adipocytokines in antiretroviral-naive adults. [2008.11.12]
OBJECTIVES: Thymidine-based nucleoside analogue reverse transcriptase inhibitors and some protease inhibitors of HIV are associated with lipoatrophy, relative central fat accumulation and insulin resistance. The latter associations have not been well evaluated prospectively in adults commencing antiretroviral therapy. We studied the effects of protease inhibitor-based antiretroviral regimens on body composition, insulin sensitivity and adipocytokine levels... CONCLUSION: Unlike many other antiretroviral regimens, TPV/r or LPV/r with tenofovir-lamivudine increased subcutaneous fat without evidence for increasing visceral fat or insulin resistance over 48 weeks.
Clinical Trials Related to Aptivus (Tipranavir)
Observational Non-Interventional Study (Anwendungsbeobachtung) With Aptivus (Tipranavir) in HIV-Infected Patients [Recruiting]
This observational study is supposed to assess (under conditions of clinical practice in daily routine) whether treatment with Aptivus (tipranavir) in combination with low-dose Norvir (ritonavir) will durable suppress viral load and may achieve suppression of viral load below the limit of detection.
Pharmaco-Epidemiological Description of the Population Treated With Aptivus Under Market Conditions, Safety & Efficacy [Recruiting]
APost Marketing Surveillance Study Assessing the Long-term Efficacy and Safety of Aptivus Co-administered With Low-dose Ritonavir in Treatment Experienced Patients With HIV-1 Infection in the Daily Clinical Practice. [Not yet recruiting]
The aim of this trial is to evaluate the safety and virological and immunological efficacy
of Aptivus in treatment-experienced patients with advanced HIV-1 infection who had developed
resistance to more than one protease inhibitor.
Pharmacokinetic Interactions Between Buprenorphine and Tipranavir/Ritonavir [Completed]
The main purpose of this study is to examine the effect of tipranavir combined with
ritonavir, medications for the treatment of HIV-infection, on buprenorphine/naloxone (BUP) in
people who have been receiving the same dose of buprenorphine/naloxone for at least 3 weeks
before study entry.
Pharmacokinetics of Apricitabine and Tipranavir When Dosed Alone or Together [Completed]
The aim of the study is to see if apricitabine or tipranavir affect the levels of each other in the blood (pharmacokinetic interaction) when they are dosed together.
Page last updated: 2011-12-09