AHFS Class:

• HIV Protease Inhibitors 8:18.08.08

Generic Name(s):

• Tipranavir

Tipranavir, an antiretroviral agent, is a human immunodeficiency virus (HIV) protease inhibitor (PI).1

Treatment of HIV Infection

Tipranavir, co-administered with low-dose ritonavir ( ritonavir-boosted tipranavir), is used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in treatment-experienced adult and pediatric patients weighing ≥36 kg infected with strains of HIV-1 resistant to more than one protease inhibitor.1 Ritonavir-boosted tipranavir should not be used in antiretroviral-naïve patients.1

Tipranavir, a protease inhibitor (PI), was previously used in combination with ritonavir ( ritonavir-boosted ) as part of a fully suppressive antiretroviral regimen; however, guidelines no longer recommend its use due to inferior virological efficacy and toxicities.200,201,202 Consult guidelines for the most current information on recommended regimens.200,201,202 Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.200,201,202

Clinical Experience

Antiretroviral-experienced Adults

Ritonavir-boosted tipranavir has been evaluated in 2 randomized, open-label, multicenter studies (Study 1182.12 [RESIST-1] and Study 1182.48 [RESIST-2]).1 All patients received prior treatment with at least 2 PI-based antiretroviral regimens and were experiencing virologic failure to a PI-based regimen at the time of study entry (HIV-1 RNA levels ≥1000 copies/mL).1 At least one mutation in the HIV protease gene had to be present at 30N, 46I, 46L, 48V, 50V, 82A, 82F, 82L, 82T, 84V, or 90M at baseline, with no more than 2 mutations at codon 33, 82, 84, or 90.1

Patients were randomized to receive ritonavir-boosted tipranavir in conjunction with an optimized background antiretroviral regimen (OBR; consisting of antiretroviral agents selected on the basis of the individual's prior antiretroviral treatment and results of baseline genotypic viral resistance testing) or a comparator ritonavir-boosted PI (approximately 50% received lopinavir, 26% amprenavir, 20% saquinavir, and 4% indinavir) in conjunction with an OBR.1 The primary outcome assessed was treatment response, defined as the proportion of patients achieving an HIV-1 RNA load reduction of ≥1 log₁₀ copies /mL after 24 weeks.500,501

RESIST-1 enrolled 620 adult patients and RESIST-2 enrolled 863 adult patients, for a total of 1483 patients.1,500,501 The median patient age was 43 years, with a median HIV-1 RNA level of 4.8 log₁₀ copies/mL (range, 2-6.8 log₁₀ copies/mL) and a median CD4⁺ T-cell count of 162 cells/mm³ (range, 1-1894 cells/mm³); 38.4% of patients had a baseline HIV-1 RNA level >100,000 copies/mL and 58.6% had a baseline CD4⁺ T-cell count ≤200 cells/mm³.1

In RESIST-1, through 24 weeks of therapy, 41.5% of those receiving ritonavir-boosted tipranavir and an OBR and 22.3% of those receiving a comparator ritonavir-boosted PI and an OBR were virologic responders (achieved and maintained a reduction in plasma HIV-1 RNA levels of ≥1 log₁₀ copies/mL below baseline without evidence of treatment failure).500 In RESIST-2, virologic response rates were 41% or 14.9% for ritonavir-boosted tipranavir or comparator PI, respectively.501 Through 24 weeks, 34.7% or 25.1% of those receiving the tipranavir-containing regimen and 16.5% or 10% of those receiving the comparator PI-containing regimen had plasma HIV-1 RNA levels <400 or <50 copies/mL, respectively, in RESIST-1.500 Corresponding values in RESIST-2 were 33.6% or 22.5% for ritonavir-boosted tipranavir and 13.1% or 8.6% for the comparator PI, respectively.501

At 48 weeks, virologic response rates for RESIST-1 and RESIST-2 were 33.8% or 14.9% for ritonavir-boosted tipranavir plus OBR or comparator ritonavir-boosted PI plus OBR, respectively.1 The proportions of patients with an HIV-1 RNA level <400 or <50 copies/mL were 30.3% or 22.7% for ritonavir-boosted tipranavir and 13.6% or 10.2% for the ritonavir-boosted PI comparator, respectively.1 The median change from baseline in CD4⁺ T-cell count was +23 cells/mm³ for ritonavir-boosted tipranavir and +4 cells/mm³ for the ritonavir-boosted comparator PI.1 Patients receiving the tipranavir-containing regimen achieved better virologic outcomes when enfuvirtide was included in the regimen.1

Antiretroviral-experienced Pediatric Patients

Safety and efficacy of ritonavir-boosted tipranavir in pediatric patients 12-18 years of age were evaluated in an open-label study.1,502 In this study, 52 children with HIV infection (baseline HIV-1 RNA levels ≥1500 copies/mL) received 1 of 2 ritonavir-boosted tipranavir dosages (tipranavir 375 mg/m² twice daily boosted with ritonavir 150 mg/m² twice daily or tipranavir 290 mg/m² twice daily boosted with ritonavir 115 mg/m² twice daily) in conjunction with an OBR.1,502 At baseline, the median patient age was 15 (range 12-18) years; the median HIV-1 RNA level was 4.7 (range 2.98-6.78) log₁₀ copies/mL, median CD4⁺ T-cell count was 318 (range 2-650) cells/mm³, and 63.5% had a CD4⁺ T-cell count ≤200 cells/mm³.1 At 48 weeks, 33% of patients had an HIV-1 RNA level <400 copies/mL and 25% of patients had an HIV-1 RNA level <50 copies/mL.1

Clinical Perspective

Therapeutic options for the treatment and prevention of HIV infection and recommendations concerning the use of antiretrovirals are continuously evolving.200,201,202 Antiretroviral therapy is recommended for all individuals with HIV regardless of CD4+ counts, and should be initiated as soon as possible after diagnosis of HIV and continued indefinitely.200,201,202 The primary goals of antiretroviral therapy are to achieve and maintain durable suppression of HIV viral load (as measured by plasma HIV-1 RNA levels) to a level below which drug-resistance mutations cannot emerge (i.e., below detectable limits), restore and preserve immunologic function, reduce HIV-related morbidity and mortality, improve quality of life, and prevent transmission of HIV.200,202 While the most appropriate antiretroviral regimen cannot be defined for each clinical scenario, the US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents, HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV, and HHS Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission, have developed comprehensive guidelines that provide information on selection and use of antiretrovirals for the treatment or prevention of HIV infection.200,201,202 Because of the complexity of managing patients with HIV, it is recommended that clinicians with HIV expertise be consulted when needed.200,201,202

The use of combination antiretroviral regimens that generally include 3 drugs from 2 or more drug classes is currently recommended to achieve viral suppression.200,201 In both treatment-naïve adults and children, an initial antiretroviral regimen generally consists of 2 nucleoside reverse transcriptase inhibitors (NRTIs) administered in combination with a third active antiretroviral drug from 1 of 3 drug classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a PI with a pharmacokinetic enhancer (also known as a booster; the 2 drugs used for this purpose are cobicistat and ritonavir).200,201,202 Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance-test results, comorbid conditions, access, and cost.200,201,202 In patients with comorbid infections (e.g., hepatitis B, tuberculosis), regimen selection should also consider the potential for activity against other present infections and timing of initiation relative to other anti-infective regimens.200

Tipranavir, a PI, was previously used in combination with ritonavir ( ritonavir-boosted ) as part of a fully suppressive antiretroviral regimen.200 In the 2024 HHS adult and adolescent HIV treatment guideline, tipranavir is no longer recommended for treatment of HIV infection due to inferior virological efficacy and toxicities.200

In the 2024 HHS pediatric HIV treatment guideline, tipranavir is no longer recommended for use in the treatment of HIV infection due to inferior virological efficacy and toxicities.201

In the 2024 HHS perinatal HIV treatment guideline, tipranavir is not recommended for use during pregnancy; if pregnancy occurs during tipranavir therapy, tipranavir should be discontinued and another recommended antiretroviral regimen should be initiated.202

General

Pretreatment Screening

• Perform liver function testing (e.g., serum AST, ALT, bilirubin).1
• Use genotype or phenotype testing and consider treatment history to guide the use of ritonavir-boosted tipranavir.1 Ritonavir-boosted tipranavir should not be used in antiretroviral-naïve patients.1
• Evaluate serum triglyceride and cholesterol concentrations; manage lipid disorders as clinically appropriate.1

Patient Monitoring

• Monitor liver function (e.g., serum AST, ALT, bilirubin) frequently during treatment and monitor for signs or symptoms of hepatitis (e.g., fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, hepatomegaly).1
• Monitor for bleeding in patients with hemophilia.1
• Monitor for persistent hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus.1 It may be necessary to initiate or adjust dosage of antidiabetic therapy (e.g., insulin, oral hypoglycemic agents).1
• Monitor serum triglyceride and cholesterol concentrations periodically during therapy with ritonavir-boosted tipranavir ; manage lipid disorders as clinically appropriate.1

Other General Considerations

• Use of other antiretroviral agents active against HIV-1 with ritonavir-boosted tipranavir is associated with a greater likelihood of treatment response.1
• Use ritonavir-boosted tipranavir with caution in patients with elevated AST or ALT, in the presence of hepatitis B or C co-infection, and in patients with mild hepatic impairment (Child-Pugh Class A).1
• Use ritonavir-boosted tipranavir with caution in patients with known hypersensitivity to sulfonamide-containing drugs.1
• Use ritonavir-boosted tipranavir with caution in patients at an increased risk for bleeding, or in those receiving concomitant medications that increase bleeding risk.1

Administration

Tipranavir is administered orally as capsules; capsules must be swallowed whole and not opened or chewed.1

Tipranavir must be used in conjunction with low-dose ritonavir ( ritonavir-boosted tipranavir);1 tipranavir should not be administered without low-dose ritonavir.1

Tipranavir and low-dose ritonavir should be taken at the same time with a meal.1

Children should be assessed for the ability to swallow capsules before prescribing.1

Tipranavir capsules should be stored at 2-8°C prior to opening the bottle; after the bottle is opened, it should be stored at 20-25°C (excursions permitted to 15-30°C).1 The capsules should be used within 60 days after the bottle is first opened.1

Dosage

Adult Dosage

Treatment of HIV Infection

For treatment of HIV-1 infection in antiretroviral-experienced adults, the recommended dosage of ritonavir-boosted tipranavir is 500 mg (two 250 mg capsules) of tipranavir twice daily with ritonavir 200 mg twice daily.1

Pediatric Dosage

Treatment of HIV Infection

For treatment of HIV-1 infection in antiretroviral-experienced pediatric patients who weigh ≥36 kg, the recommended dosage of ritonavir-boosted tipranavir is 500 mg (two 250 mg capsules) of tipranavir twice daily with ritonavir 200 mg twice daily.1

Special Populations

Hepatic Impairment

Dosage adjustments are not necessary in patients with mild hepatic impairment (Child-Pugh class A).1 Tipranavir is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1

Renal Impairment

The manufacturer makes no specific dosage recommendations in renal impairment.1 Renal clearance of tipranavir is negligible, and a decrease in total body clearance is not expected in patients with renal impairment.1

Geriatric Patients

The manufacturer makes no specific dosage recommendations for geriatric patients.1 However, the manufacturer states that in general, caution should be exercised with administration and monitoring when tipranavir is used in geriatric patients because of the increased frequency of reduced hepatic, renal, and cardiac function, as well as the presence of concomitant diseases and other medications in this population.1

Contraindications

• Moderate or severe hepatic impairment (Child-Pugh class B or C).1
• Concomitant use with drugs highly dependent on cytochrome P-450 (CYP) isoenzyme 3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, certain antiarrhythmics, cisapride, ergot alkaloids, lurasidone, pimozide, sildenafil used for treatment of pulmonary arterial hypertension [PAH], oral midazolam, triazolam, lovastatin, simvastatin) is contraindicated.1
• Concomitant use with drugs that are potent inducers of CYP3A (e.g., rifampin, St. John's wort [ Hypericum perforatum ]) is contraindicated since such use may result in decreased plasma concentrations of tipranavir and possible loss of virologic response.1

Warnings/Precautions

Warnings

Hepatotoxicity

A boxed warning regarding the risk of hepatic decompensation and hepatitis is included in the prescribing information for tipranavir.1 Hepatitis and hepatic decompensation, including some fatalities, have been reported in patients receiving ritonavir-boosted tipranavir; causal relationship not established.1 Hepatotoxicity generally has occurred in patients with advanced HIV infection receiving multiple concomitant drugs.1 Increases in hepatic transaminase concentrations (grade 3 and 4) have been reported in approximately 10% of antiretroviral-experienced patients receiving ritonavir-boosted tipranavir in clinical studies.1 Perform appropriate laboratory tests to evaluate hepatic function prior to initiating ritonavir-boosted tipranavir and frequently during treatment.1 Patients with coexisting hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or elevated transaminase concentrations prior to ritonavir-boosted tipranavir therapy may be at increased risk for hepatotoxicity, including further increases in transaminase concentrations or hepatic decompensation.1 Discontinue ritonavir-boosted tipranavir therapy if signs or symptoms of hepatitis develop, if asymptomatic increases in serum AST or ALT concentrations greater than 10 times the upper limit of normal (ULN) occur, or if asymptomatic increases in AST or ALT concentrations 5-10 times the ULN and increases in total bilirubin greater than 2.5 times the ULN develop.1 Clinicians and patients should be vigilant for the appearance of signs or symptoms of hepatitis (e.g., fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, hepatomegaly).1

Intracranial Hemorrhage

A boxed warning regarding the risk of intracranial hemorrhage is included in the prescribing information for tipranavir.1 Intracranial hemorrhage (including some fatalities) has been reported in patients receiving ritonavir-boosted tipranavir in conjunction with other antiretrovirals.1 Many of these patients had other medical conditions or were receiving concomitant therapy that may have caused or contributed to these events.1 Ritonavir-boosted tipranavir therapy generally has not been associated with abnormal coagulation parameters; abnormal coagulation parameters have not preceded intracranial hemorrhage.1 Based on data available to date, the manufacturer states that routine monitoring of coagulation parameters generally is not necessary in patients receiving ritonavir-boosted tipranavir.1

Other Warnings/Precautions

Rash

Rash, including maculopapular rash, urticarial rash, and possible photosensitivity reaction, has been reported in patients receiving ritonavir-boosted tipranavir.1 Rash occurred in 10% of women, 8% of men, and 21% of children receiving ritonavir-boosted tipranavir in clinical studies.1 The median time to onset of rash was 53 days and the median duration of rash was 22 days in adults.1 Rash accompanied by joint pain or stiffness, throat tightness, or generalized pruritus also has been reported.1 Discontinue tipranavir if severe rash develops and provide appropriate treatment.1

Women receiving concomitant estrogen-containing oral contraceptives or estrogens for hormone replacement therapy may be at an increased risk for developing a non-serious rash when receiving ritonavir-boosted tipranavir.1

Sulfonamide Allergy

Tipranavir contains a sulfonamide moiety, which may cause allergic-type reactions in certain susceptible individuals.1 The potential for cross-sensitivity between drugs with sulfonamide moieties and tipranavir is unknown.1

Tipranavir should be used with caution in patients with known hypersensitivity to sulfonamide-containing drugs.1

Importance of Co-administration with Ritonavir

Tipranavir must be used in conjunction with low-dose ritonavir ( ritonavir-boosted tipranavir) and administered with a meal to achieve an adequate antiviral response.1 Failure to administer tipranavir with the recommended dosage of ritonavir with meals will result in subtherapeutic tipranavir concentrations and inadequate antiviral response.1 The usual cautions, precautions, and contraindications associated with ritonavir should be considered.1

Risk of Serious Adverse Reactions Due to Drug Interactions

Concomitant use of ritonavir-boosted tipranavir and certain drugs is not recommended or requires particular caution or dosage adjustments.1 The potential for drug interactions should be considered prior to and during ritonavir-boosted tipranavir therapy.1 Clinicians should review all drugs the patient is receiving and should monitor for adverse effects during ritonavir-boosted tipranavir therapy.1

Effects on Platelet Aggregation and Coagulation

Ritonavir-boosted tipranavir should be used with caution in patients who may be at risk for increased bleeding from trauma, surgical procedures, coagulation disorders, or other medical conditions, in those receiving concomitant therapy known to increase the risk of bleeding (e.g., anticoagulants, antiplatelet agents) and in those receiving high-dose vitamin E.1

Change in coagulation parameters (e.g., vitamin K dependent factors, factor V, prothrombin time [PT], or activated partial thromboplastin time [aPTT]) did not occur in patients receiving tipranavir capsules with low-dose ritonavir.1 Change in coagulation parameters (e.g., increased PT, increased aPTT, decreased vitamin K dependent factors) occurred in rats given tipranavir; effects on these parameters were increased in rats given tipranavir with vitamin E (i.e., d-alpha-tocopherol polyethylene glycol 1000 succinate).1 Change in coagulation parameters was not observed in dogs.1

Tipranavir inhibits platelet aggregation in vitro at concentrations that correspond to concentrations observed in patients receiving ritonavir-boosted tipranavir.1

Diabetes Mellitus/Hyperglycemia

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus has been reported in patients receiving HIV protease inhibitors (PIs); diabetic ketoacidosis has occurred.1 It may be necessary to initiate or adjust dosage of antidiabetic therapy (e.g., insulin, oral hypoglycemic agents).1

Immune Reconstitution Syndrome

Patients receiving antiretroviral therapy may experience an immune reconstitution syndrome during the initial phase of therapy.1 Patients whose immune system responds to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis , cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii ], herpes simplex, herpes zoster); this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Fat Redistribution

Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance have been reported in patients receiving antiretroviral therapy.1 The mechanism and long-term consequences of fat redistribution are unknown; a causal relationship has not been established.1

Elevated Lipids

Increases in total serum cholesterol and triglyceride concentrations have occurred.1 Serum triglyceride and cholesterol concentrations should be determined before initiating therapy with ritonavir-boosted tipranavir and monitored periodically; lipid disorders should be managed as clinically appropriate.1

Patients with Hemophilia

Spontaneous bleeding has been reported in patients with hemophilia A or B receiving HIV PIs; use caution in such patients.1 Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.1

Resistance/Cross-resistance

Potential for cross-resistance with other HIV PIs has not been evaluated in patients receiving ritonavir-boosted tipranavir.1 The possible effect of ritonavir-boosted tipranavir therapy on subsequent therapy with other HIV PIs is unknown.1

Specific Populations

Pregnancy

The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in patients exposed to tipranavir during pregnancy.1 Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting [Web].1

Prospective pregnancy data from the APR and an Expanded Access program are not sufficient to adequately assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 Data from the APR indicate no birth defects in 13 first trimester exposures.1

Lactation

It is not known whether tipranavir is distributed into human milk or whether the drug has an effect on the breastfed infant or on mild production; tipranavir has been detected in rat milk.1 Patients should be advised of the potential risks of breastfeeding including HIV transmission, development of viral resistance (in HIV positive infants), and other adverse effects.1

Females and Males of Reproductive Potential

Concomitant use of tipranavir with estrogen-containing oral contraceptives may result in reduced efficacy of the contraceptive agent.1 Advise patients receiving tipranavir with an estrogen-based oral contraceptive to use additional or alternative nonhormonal contraceptives.1

Pediatric Use

Safety and efficacy of ritonavir-boosted tipranavir have been established in children weighing ≥36 kg who are antiretroviral-experienced with HIV-1 strains resistant to >1 protease inhibitor.1

Adverse effects reported in children ≥36 kg were similar to those reported in adults; rash was reported more frequently in children than in adults.1

Safety and efficacy of ritonavir-boosted tipranavir have been established in children >2 years of age weighing <36 kg; however, the drug is not recommended in this population due to the lack of a pediatric formulation suitable for administration.1

Geriatric Use

Experience in those 65 years of age and older is insufficient to determine whether they respond differently from younger adults.1 Exercise appropriate caution in administration and monitoring because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Hepatic Impairment

Plasma concentrations of tipranavir and ritonavir are increased in mild hepatic impairment (Child-Pugh Class A), but dosage adjustment is not required.1

The pharmacokinetics of ritonavir-boosted tipranavir have not been evaluated in moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment; use of ritonavir-boosted tipranavir is contraindicated in patients with moderate or severe hepatic impairment.1

HIV-infected patients with chronic HBV or HCV coinfection and those with increased AST or ALT concentrations prior to therapy with ritonavir-boosted tipranavir may be at increased risk for further elevations in hepatic enzyme concentrations or severe liver disease.1

Renal Impairment

Pharmacokinetics of tipranavir have not been evaluated in renal impairment; however, since renal clearance of tipranavir is negligible, a decrease in clearance of the drug is not expected in patients with renal impairment.1

Common Adverse Effects

Adverse effects reported in >4% of adults receiving ritonavir-boosted tipranavir in conjunction with other antiretroviral agents are diarrhea, nausea, pyrexia, fatigue, vomiting, headache, and abdominal pain.1

Adverse effects reported in pediatric patients were generally similar to those observed in adults, except for the incidence of rash, which occurred more frequently in pediatric patients.1

Drug interaction studies were conducted using tipranavir in conjunction with low-dose ritonavir ( ritonavir-boosted tipranavir).1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Tipranavir is metabolized principally by CYP3A4.1 Caution is advised if ritonavir-boosted tipranavir is used concomitantly with substrates or inducers of CYP3A4.1

Tipranavir with low-dose ritonavir inhibits cytochrome P-450 (CYP) isoenzyme 3A and 2D6.1

Drugs Affecting or Affected by P-glycoprotein Transport

Tipranavir is a substrate of the P-glycoprotein (P-gp) transport system; in addition, the drug is both a weak inhibitor and potent inducer of P-gp transport.1 Potential pharmacokinetic interactions with P-gp inhibitors or inducers (altered metabolism of tipranavir or the other drug).1

Alfuzosin

Concomitant use of alfuzosin and ritonavir-boosted tipranavir is contraindicated because increased alfuzosin concentrations are expected and may result in hypotension.1

Antiarrhythmic Agents

Possible pharmacokinetic interactions with amiodarone, flecainide, propafenone, or quinidine (increased plasma concentrations of the antiarrhythmic agent).1 Potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias).1 Concomitant use of these antiarrhythmic agents and ritonavir-boosted tipranavir is contraindicated.1

Anticoagulants

Caution is advised if ritonavir-boosted tipranavir is used concomitantly with an anticoagulant.1

Warfarin

Possible pharmacokinetic interaction with warfarin (altered warfarin concentrations).1

If warfarin is used concomitantly with ritonavir-boosted tipranavir, the international normalized ratio (INR) should be monitored, especially when initiating or discontinuing the antiretroviral agent.1

Anticonvulsants

Carbamazepine

Possible pharmacokinetic interaction with carbamazepine (decreased tipranavir concentrations and possible decreased antiretroviral efficacy).1

Concomitant use of carbamazepine (100 mg 2 times daily for 43 doses) with ritonavir-boosted tipranavir resulted in no effects on carbamazepine peak plasma concentrations and AUC.1

When a higher dosage of carbamazepine (200 mg 2 times daily for 29 doses) was used concomitantly with a single dose of ritonavir-boosted tipranavir, there were no effects on the peak plasma concentration and AUC of carbamazepine; however, when the same carbamazepine dose was given for 43 doses concomitantly with 15 doses of ritonavir-boosted tipranavir, peak plasma concentrations and AUC of carbamazepine were increased.1

Caution is advised if ritonavir-boosted tipranavir is used concomitantly with carbamazepine.1

Phenobarbital and Phenytoin

Possible pharmacokinetic interaction with phenobarbital or phenytoin (decreased tipranavir concentrations and possible decreased antiretroviral efficacy).1

Caution is advised if ritonavir-boosted tipranavir is used concomitantly with phenobarbital or phenytoin.1

Valproic Acid

Possible pharmacokinetic interaction if valproic acid is used concomitantly with ritonavir-boosted tipranavir (decreased valproate concentrations).1

Caution is advised if valproic acid and ritonavir-boosted tipranavir are used concomitantly.1

Antidiabetic Agents

Possible pharmacokinetic interactions with glimepiride, glipizide, glyburide, pioglitazone, or repaglinide (altered plasma concentrations of the hypoglycemic agent).1 Careful glucose monitoring is warranted.1

Antifungal Agents

Fluconazole

Pharmacokinetic interaction with fluconazole (increased tipranavir concentrations; no change in fluconazole concentrations and AUC).1

If ritonavir-boosted tipranavir and fluconazole are used concomitantly, fluconazole dosage does not need to be adjusted but fluconazole dosage exceeding 200 mg daily is not recommended.1

Itraconazole

Possible pharmacokinetic interaction with itraconazole (increased itraconazole concentrations).1

Itraconazole should be used concomitantly with ritonavir-boosted tipranavir with caution; high itraconazole dosage (exceeding 200 mg daily) is not recommended.1

Ketoconazole

Possible pharmacokinetic interaction with ketoconazole (increased ketoconazole concentrations).1

Ketoconazole should be used concomitantly with ritonavir-boosted tipranavir with caution;1 high ketoconazole dosage (exceeding 200 mg daily) is not recommended.1

Voriconazole

Possible pharmacokinetic interaction with voriconazole (altered voriconazole concentrations); however, due to multiple enzymes involved with voriconazole metabolism, it is difficult to predict the interaction.1

Antimycobacterial Agents

Rifabutin

Pharmacokinetic interaction with rifabutin (increased rifabutin and 25-O desacetyl metabolite concentrations; no change in tipranavir concentrations).1

Concomitant use of a single dose of rifabutin (150 mg) and ritonavir-boosted tipranavir resulted in an 86% and 433% increase in the peak plasma concentrations and AUC of rifabutin plus its active metabolite (25-0 desacetyl-rifabutin), respectively.1

If rifabutin is used concomitantly with ritonavir-boosted tipranavir, dosage of rifabutin should be reduced to 150 mg every other day; increased monitoring for adverse effects is warranted.1

Rifampin

Potential pharmacokinetic interaction with rifampin (decreased tipranavir concentrations); possible decreased antiretroviral efficacy and increased risk of resistance to tipranavir or other HIV PIs.1

Concomitant use of ritonavir-boosted tipranavir and rifampin is contraindicated.1

Antiplatelet Agents

Caution is advised if ritonavir-boosted tipranavir is used concomitantly with an antiplatelet agent.1

Antipsychotic Agents

Lurasidone

Potential for serious and/or life-threatening adverse effects associated with lurasidone.1

Concomitant use of ritonavir-boosted tipranavir and lurasidone is contraindicated.1

Pimozide

Potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias) with pimozide.1

Concomitant use of ritonavir-boosted tipranavir and pimozide is contraindicated.1

Quetiapine

Pharmacokinetic interactions expected if quetiapine is used concomitantly with ritonavir-boosted tipranavir (increased quetiapine concentrations).1

Alternative antiretroviral therapy should be considered to avoid increased quetiapine exposures.1 If ritonavir-boosted tipranavir is necessary in a patient receiving a stable dosage of quetiapine, the quetiapine dosage should be reduced to one-sixth of the original dosage and the patient should be monitored for quetiapine efficacy and adverse effects.1 If quetiapine is necessary in a patient receiving ritonavir-boosted tipranavir, refer to the prescribing information for quetiapine for initial dosing and titration of quetiapine.1

Antiretroviral Agents

HIV Entry and Fusion Inhibitors

Enfuvirtide

Concomitant use of enfuvirtide and ritonavir-boosted tipranavir increases trough tipranavir concentrations by approximately 45%.1 The manufacturer of tipranavir states that dosage adjustments are not recommended if the drugs are used concomitantly.1

There are no antagonistic antiretroviral effects based on in vitro evidence between tipranavir and enfuvirtide.1

HIV Integrase Inhibitors (INSTIs)

Dolutegravir

Concomitant use of dolutegravir (50 mg daily) and ritonavir-boosted tipranavir decreased dolutegravir peak plasma concentrations and AUC by 46% and 59%, respectively.1 When dolutegravir and ritonavir-boosted tipranavir are used concomitantly, refer to the dolutegravir prescribing information for recommendations.1

Raltegravir

Concomitant use of raltegravir and ritonavir-boosted tipranavir results in decreased raltegravir plasma concentrations and AUC.1

Dosage adjustments are not needed if raltegravir 400 mg two times daily and ritonavir-boosted tipranavir are used concomitantly.1 When other dosage regimens of raltegravir (Isentress^®) are used concomitantly with ritonavir-boosted tipranavir, refer to the prescribing information for raltegravir (Isentress^®) for recommendations.1

HIV Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

No antagonistic antiretroviral effects in vitro between tipranavir and delavirdine, efavirenz, and nevirapine.1

Efavirenz

Concomitant use of efavirenz (600 mg once daily) and ritonavir-boosted tipranavir (tipranavir 500 mg twice daily with ritonavir 100 mg twice daily) results in decreased plasma concentrations and AUC of tipranavir, but does not affect the pharmacokinetics of efavirenz.1 Efavirenz pharmacokinetics are not affected if efavirenz (600 mg once daily) is used concomitantly with a higher dosage of ritonavir-boosted tipranavir (tipranavir 750 mg twice daily with ritonavir 200 mg twice daily).1

Etravirine

Possible pharmacokinetic interaction with etravirine (decreased etravirine concentrations and loss of therapeutic efficacy).1 Etravirine and ritonavir-boosted tipranavir should not be used concomitantly.1

Nevirapine

Concomitant use of nevirapine and ritonavir-boosted tipranavir does not result in clinically important effects on nevirapine concentrations.1

Rilpivirine

Possible pharmacokinetic interaction with rilpivirine (increased rilpivirine concentrations; not expected to affect tipranavir concentrations).1

HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

In vitro evidence of additive to antagonistic antiretroviral effects between tipranavir and lamivudine.1 No in vitro evidence of antagonistic antiretroviral effects between tipranavir and abacavir, didanosine, emtricitabine, tenofovir, and zidovudine.1

Abacavir

Pharmacokinetic interaction with abacavir (35-44% decrease in abacavir AUC).1 Clinical importance unknown; appropriate dosages for concomitant use have not been established.1

Didanosine

Pharmacokinetic interaction with didanosine delayed-release capsules (decreased didanosine concentrations).1 The clinical importance of this interaction is unknown.1

For optimal absoprtion, didanosine doses should be administered at least 2 hours before or after doses of ritonavir-boosted tipranavir.1

Lamivudine

In multiple-dose pharmacokinetic studies in HIV-infected individuals, concomitant use of ritonavir-boosted tipranavir and lamivudine did not have any clinically important effects on lamivudine pharmacokinetics.1

Tenofovir

Pharmacokinetic interaction with tenofovir DF (decreased tenofovir concentrations; no change in tenofovir AUC; slightly decreased tipranavir concentrations).1

Zidovudine

Although the clinical importance is unknown, concomitant use of ritonavir-boosted tipranavir decreases the AUC of zidovudine by approximately 35% and may also decrease peak plasma concentrations and AUC of tipranavir.1

HIV Protease Inhibitors

In vitro evidence of additive to antagonistic antiretroviral effects between tipranavir and atazanavir, lopinavir, and saquinavir.1 No antagonistic antiretroviral effects in vitro between tipranavir and nelfinavir or ritonavir.1

Atazanavir

Pharmacokinetic interaction between ritonavir-boosted atazanavir and ritonavir-boosted tipranavir (decreased atazanavir plasma concentrations and AUC; increased tipranavir plasma concentrations and AUC).1

Concomitant use of atazanavir (with or without low-dose ritonavir) and ritonavir-boosted tipranavir is not recommended.1

Fosamprenavir

Potential pharmacokinetic interaction between fosamprenavir and ritonavir-boosted tipranavir (decreased concentrations of amprenavir [active metabolite of fosamprenavir]).1 Concomitant use is not recommended.1

Lopinavir

Concomitant use of ritonavir-boosted tipranavir with the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) results in decreased lopinavir plasma concentrations and AUC.1

Concomitant use of lopinavir/ritonavir and ritonavir-boosted tipranavir is not recommended.1

Ritonavir

Pharmacokinetic interaction with ritonavir (increased plasma concentration and AUC of tipranavir).1 Low-dose ritonavir is used with tipranavir for therapeutic advantage ( ritonavir-boosted tipranavir).1

Saquinavir

Pharmacokinetic interaction with saquinavir (decreased saquinavir plasma concentrations and AUC).1 Concomitant use is not recommended.1

Benzodiazepines

Midazolam or Triazolam

Increased concentrations of midazolam or triazolam expected if used concomitantly with tipranavir; potential for serious and/or life-threatening adverse effects (e.g., prolonged or increased sedation or respiratory depression).1 Concomitant use with oral midazolam expected to result in higher plasma concentrations of midazolam than concomitant use with parenteral midazolam.1

Concomitant use of ritonavir-boosted tipranavir and oral midazolam or triazolam is contraindicated.1

The manufacturer of tipranavir states that concomitant use of parenteral midazolam and ritonavir-boosted tipranavir should be undertaken in a monitored setting where respiratory depression and/or prolonged sedation can be managed and that use of a reduced dose of midazolam should be considered.1

Calcium-channel Blocking Agents

Potential pharmacokinetic interactions with calcium-channel blocking agents (e.g., diltiazem, felodipine, nicardipine, nisoldipine, verapamil); the effect of ritonavir-boosted tipranavir on calcium channel blockers that are dual substrates of CYP3A and P-gp cannot be predicted.1 Use concomitantly with caution; clinical monitoring of the patient recommended.1

Clarithromycin

Pharmacokinetic interactions (increased clarithromycin concentrations; decreased hydroxyclarithromycin concentrations; increased tipranavir concentrations).1 Modification of the usual dosage of clarithromycin or tipranavir is not necessary in patients with normal renal function; however, the clarithromycin dosage should be reduced by 50% in those with creatinine clearances of 30-60 mL/minute and reduced by 75% in those with a creatinine clearances less than 30 mL/minute.1

Colchicine

Potential pharmacokinetic interaction with colchicine (increased colchicine concentrations).1

Concomitant use of colchicine and ritonavir-boosted tipranavir is contraindicated in patients with renal or hepatic impairment.1 When colchicine and ritonavir-boosted tipranavir are used concomitantly in patients with normal renal and hepatic function, dosage adjustments are recommended in the following individuals:1

When colchicine is used for treatment of gout flares in patients receiving ritonavir-boosted tipranavir, a colchicine dose of 0.6 mg should be given followed by 0.3 mg 1 hour later, and the colchicine dose should be repeated no earlier than 3 days later.1

When colchicine is used for prophylaxis of gout flares in patients receiving ritonavir-boosted tipranavir, colchicine dosage should be reduced to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decreased to 0.3 mg once every other day in those originally receiving 0.6 mg once daily.1

When colchicine is used for treatment of familial Mediterranean fever (FMF) in patients receiving ritonavir-boosted tipranavir, a maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily) should be used.1

Disulfiram

Potential pharmacokinetic interaction with the alcohol contained in tipranavir capsules; possible disulfiram-like reaction.1

Ergot Alkaloids

Potential for serious and/or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of the extremities and other tissues) with ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine).1 Concomitant use of ritonavir-boosted tipranavir and ergot alkaloids is contraindicated.1

Estrogens and Progestins

Potential for increased risk of non-serious rash in women receiving estrogens.1

Conjugated Estrogen

If conjugated estrogens are used concomitantly with ritonavir-boosted tipranavir, patients should be monitored for signs of estrogen deficiency and estrogen dosage should be adjusted based on clinical effects.1

Estradiol

If estradiol is used concomitantly with ritonavir-boosted tipranavir, patients should be monitored for signs of estrogen deficiency and estrogen dosage should be adjusted based on clinical effects and/or endogenous hormone concentrations.1

Ethinyl Estradiol and Norethindrone

Pharmacokinetic interaction with oral contraceptives containing ethinyl estradiol and norethindrone (50% decrease in ethinyl estradiol concentrations; no effect on norethindrone concentrations).1 Alternative nonhormonal or additional methods of contraception should be considered.1

GI Drugs

Antacids

Pharmacokinetic interaction with antacids (decreased tipranavir peak concentrations and AUC).1

Cisapride

Potential for serious and/or life-threatening adverse effects such as cardiac arrhythmias.1

Concomitant use of ritonavir-boosted tipranavir and cisapride is contraindicated.1

Proton-pump Inhibitors

Pharmacokinetic interaction with omeprazole (decreased plasma concentrations of omeprazole; no change in plasma concentrations of tipranavir).1

If concomitant use is necessary, increased omeprazole dosage may be considered based on clinical response.1

HMG-CoA Reductase Inhibitors

Pharmacokinetic interactions with HMG-CoA reductase inhibitors (statins) metabolized by CYP3A isoenzyme.1 Concomitant use of ritonavir-boosted tipranavir and certain statins (e.g., atorvastatin, lovastatin, rosuvastatin, simvastatin) may increase plasma concentrations and AUC of the antilipemic agent and increase the risk of statin-associated adverse effects, including myopathy and rhabdomyolysis.1

Atorvastatin

Concomitant use of atorvastatin and ritonavir-boosted tipranavir should be avoided.1

Lovastatin

Concomitant use of lovastatin and ritonavir-boosted tipranavir is contraindicated.1

Rosuvastatin

Pharmacokinetic interaction with rosuvastatin (increased rosuvastatin peak concentrations and AUC; no effect on tipranavir concentrations).1

Simvastatin

Concomitant use of simvastatin and ritonavir-boosted tipranavir is contraindicated.1

Loperamide

Pharmacokinetic interaction (decreased loperamide concentrations; no clinically important change in tipranavir concentrations).1

Opiates and Opiate Partial Agonists

Buprenorphine

Pharmacokinetic interaction with buprenorphine or fixed combination of buprenorphine and naloxone (buprenorphine/naloxone) (decreased tipranavir concentrations).1 Concomitant use of ritonavir-boosted tipranavir did not result in changes in therapeutic efficacy of buprenorphine/naloxone.1

Dosage adjustments cannot be recommended if buprenorphine or buprenorphine/naloxone is used concomitantly with ritonavir-boosted tipranavir.1

Methadone

Pharmacokinetic interaction if methadone is used concomitantly with ritonavir-boosted tipranavir (decreased methadone concentrations).1 Methadone dosage adjustment may be required.1

Phosphodiesterase Type 5 Inhibitors

Concomitant use of ritonavir-boosted tipranavir and selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) expected to result in substantially increased plasma concentrations of the PDE5 inhibitor and increase the risk of adverse effects (e.g., hypotension, visual disturbances, priapism, syncope) associated with these agents.1

Sildenafil

Concomitant use of sildenafil for treatment of pulmonary arterial hypertension (PAH) is contraindicated in patients receiving ritonavir-boosted tipranavir.1 Safe and effective dosages for concomitant use of the drugs have not been established.1

Sildenafil should be used with caution for treatment of erectile dysfunction in patients receiving ritonavir-boosted tipranavir; sildenafil dosage should not exceed 25 mg once every 48 hours and the patient should be closely monitored for sildenafil-related adverse effects.1

Tadalafil

If tadalafil is indicated for treatment of PAH in patients who have been receiving ritonavir-boosted tipranavir for at least 1 week, tadalafil should be initiated at a dosage of 20 mg once daily and, if tolerated, dosage may be increased to 40 mg once daily.1 Ritonavir-boosted tipranavir should not be initiated in patients receiving tadalafil for treatment of PAH; tadalafil therapy should be discontinued at least 24 hours prior to initiating ritonavir-boosted tipranavir.1 After at least 1 week, tadalafil may be resumed at a dosage of 20 mg once daily and, if tolerated, dosage may be increased to 40 mg once daily.1

Tadalafil should be used with caution for treatment of erectile dysfunction in patients receiving ritonavir-boosted tipranavir; tadalafil dosage should not exceed 10 mg once every 72 hours and the patient should be closely monitored for tadalafil-related adverse effects.1

Vardenafil

Vardenafil should be used with caution for treatment of erectile dysfunction in patients receiving ritonavir-boosted tipranavir, and vardenafil dosage should not exceed 2.5 mg once every 72 hours.1

St. John's Wort

Potential pharmacokinetic interaction with St. John's wort ( Hypericum perforatum ) (decreased tipranavir concentrations); potential for loss of virologic response and possible resistance to tipranavir or other HIV PIs.1 Concomitant use is contraindicated.1

Selective Serotonin-reuptake Inhibitors

Possible pharmacokinetic interaction if selective serotonin-reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, or sertraline, are used concomitantly with ritonavir-boosted tipranavir (increased SSRI concentrations).1

Dosage of the SSRI may need to be adjusted when ritonavir-boosted tipranavir is initiated.1

Trazodone

Possible pharmacokinetic interaction if trazodone is used concomitantly with ritonavir-boosted tipranavir (increased trazodone concentrations and AUC); nausea, dizziness, hypotension, and syncope have been reported when trazodone is used with ritonavir.1 Caution is advised and a lower trazodone dosage should be considered.1

Tricyclic Antidepressants

Potential pharmacokinetic interaction with desipramine (increased plasma concentrations of desipramine).1

If desipramine is used concomitantly with ritonavir-boosted tipranavir, desipramine dosage should be reduced and plasma concentrations of the antidepressant monitored.1

Valacyclovir

Concomitant use of valacyclovir and ritonavir-boosted tipranavir does not have a clinically important effect on tipranavir or acyclovir plasma concentrations or AUCs.1

Vitamin E

Possible increased risk of bleeding if high doses of vitamin E are used.1 Caution is advised if ritonavir-boosted tipranavir is used concomitantly with supplemental high doses of vitamin E.1

Description

Tipranavir, a pyrone derivative, inhibits replication of human immunodeficiency virus type 1 (HIV-1) by interfering with HIV protease.1 During HIV replication, HIV protease cleaves viral polypeptide products of the gag and gag-pol genes to form structural proteins of the virion core and essential viral enzymes.1 By interfering with the formation of these essential proteins and enzymes, tipranavir blocks maturation of the virus and causes formation of nonfunctional, immature, noninfectious virions.1 Tipranavir-resistant HIV-1, including strains with decreased susceptibility to other HIV PIs (e.g., atazanavir, lopinavir, nelfinavir, ritonavir), has been reported.1

Tipranavir is a P-glycoprotein (P-gp) substrate, a weak P-gp inhibitor, and a potent P-gp inducer.1 Tipranavir is metabolized by cytochrome P 450 3A (CYP3A).1 Because ritonavir inhibits hepatic CYP3A, the intestinal P-gp efflux pump, and possibly intestinal CYP3A, concomitant administration of low-dose ritonavir and tipranavir ( ritonavir-boosted tipranavir) results in increased plasma concentrations of tipranavir.1 The antiretroviral activity of ritonavir-boosted tipranavir is due to tipranavir.1

Following twice-daily oral dosing, steady state of tipranavir is attained in most individuals after 7-10 days.1 Steady-state trough concentrations are 70% lower than day 1, presumably due to intestinal P-glycoprotein (P-gp) induction.1 It is not known what impact food has on tipranavir exposure when tipranavir capsules are administered with ritonavir tablets.1 Tipranavir is >99% bound to human plasma proteins.1 It is not known if tipranavir distributes in human cerebrospinal fluid or semen.1 After the addition of ritonavir, oral clearance of tipranavir is decreased, which may be due to the reduced first-pass clearance of tipranavir in the GI tract and in the liver.1 With the coadministration of 200 mg of ritonavir, tipranavir undergoes minimal metabolism.1 Tipranavir is principally excreted in feces (about 82% of a dose) and small amounts (about 4% of a dose) are eliminated in urine.1 The mean elimination half-life of ritonavir-boosted tipranavir in healthy patients and in HIV-1 infected patients is 4.8 and 6 hours, respectively, when doses are administered with a light meal.1 Administration of ritonavir-boosted tipranavir generally results in higher tipranavir plasma concentrations in females compared to males; however, the manufacturer states that a dosage adjustment based on gender is not necessary.1 Although white male patients have more variability in tipranavir concentrations compared to black males, the majority of tipranavir plasma concentrations are comparable between races.1

Advice to Patients

• Advise patients of the ciritical nature of compliance with human immunodeficiency virus (HIV) therapy and importance of remaining under the care of a clinician.1 Stress importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1
• Use tipranavir with low-dose ritonavir ( ritonavir-boosted tipranavir); stress importance of using these 2 drugs in conjunction with other antiretrovirals.1
• Advise patients to take tipranavir at the same time as ritonavir with a meal.1
• If a dose is missed, the dose should be taken as soon as it is remembered and the next dose taken at the regularly scheduled time.1 If a dose is skipped, a double dose should not be taken to make up for the missed dose.1
• Stress importance of patients informing their clinician if they are allergic to sulfonamides.1
• Possibility of fatal or nonfatal intracranial hemorrhage.1 Stress importance of informing clinician if unusual or unexplained bleeding develops.1
• Advise patients that severe liver disease (including fatalities) has been reported.1 Stress importance of discontinuing ritonavir-boosted tipranavir and seeking medical attention if signs or symptoms of liver disease (e.g., fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, hepatomegaly) occur.1
• Need for periodic clinical and laboratory monitoring, including liver function tests, prior to and during treatment.1 Stress importance of extra vigilance in patients with chronic HBV or HCV coinfection because of increased risk of hepatotoxicity.1
• Possibility of rash.1 Stress importance of discontinuing ritonavir-boosted tipranavir and seeking medical attention if a rash, with or without joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or skin peeling occurs.1
• Inform patients that redistribution/accumulation of body fat may occur with antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.1
• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., PDE5 inhibitors) and over-the-counter (OTC) drugs (e.g., vitamin E supplements) and herbal products (e.g., St. John's wort), and any concomitant illnesses.1
• Advise women to use a reliable nonhormonal (e.g., barrier) method of contraception due to the potential interaction with estrogen-based hormonal contraceptives.1
• Stress importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Inform patients that an antiretroviral pregnancy registry is available that monitors fetal outcomes of infants exposed to tipranavir.1 Providers can register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263.1 Advise HIV-infected women not to breast-feed.1
• Inform patients of other important precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Boehringer Ingelheim. Aptivus^® (tipranavir) capsules prescribing information. Ridgefield, CT; 2024 Apr. [Web]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV (February 27, 2024). Updates may be available at HIV.gov website. [Web]

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (January 31, 2024). Updates may be available at HIV.gov website. [Web]

202. Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States (January 31, 2024). Updates may be available at HIV.gov website. [Web]

500. Gathe J, Cooper D, Farthing C, et al. Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-week analysis from the RESIST-1 trial. Clin Infect Dis. 2006;43:1337-1346.

501. Cahn P, Villancian J, Lazzarin A, et al. Ritonavir-boosted tipranavir demonstrates superior efficacy to ritonavir-boosted protease inhibitors in treatment-experienced HIV-infected patients: 24-week results of the RESIST-2 trial. Clin Infect Dis. 2006;43:1347-1356.

502. Salazar JC, Cahn P, Yogev R, et al. Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents. AIDS. 2008;22(14):1789-1798.