Version July 2025
Clinical hepatitis and hepatic decompensation, including some fatalities, have been reported. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C coinfection, as these patients have an increased risk of hepatotoxicity.
Both fatal and nonfatal intracranial hemorrhage have been reported.
HIV-1 infection, treatment: Note: Although FDA approved, tipranavir is no longer recommended for use in the treatment of HIV (Ref). Use in combination with other antiretroviral (ARV) agents; evaluate gene mutation and ARV resistance patterns (refer to https://www.iasusa.org and https://hivdb.stanford.edu/ for more information). Not recommended for treatment-naive patients. Coadministration with ritonavir is required; the ritonavir boosting dose with tipranavir is higher than doses used with other protease inhibitors.
Children and Adolescents, weighing ≥36 kg: Note: When previously available as an oral solution, tipranavir was FDA-approved in patients 2 years of age and older (Ref).
Oral: 500 mg twice daily. Note: Coadministration with ritonavir (200 mg twice daily) is required.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal elimination of tipranavir is negligible.
Baseline (at therapy initiation):
Mild impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Moderate to severe impairment: Use is contraindicated.
During therapy:
Asymptomatic patients:
AST or ALT 5 to 10 times ULN and total bilirubin >2.5 times ULN: Discontinue therapy.
AST or ALT >10 times ULN: Discontinue therapy.
Symptomatic patients: For any signs or symptoms of clinical hepatitis: Discontinue therapy.
(For additional information see "Tipranavir: Drug information")
HIV-1 infection, treatment: Oral: 500 mg twice daily; Note: Coadministration with ritonavir (200 mg twice daily) is required. Tipranavir is not recommended for use in the initial treatment of HIV (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, renal elimination of tipranavir is negligible.
Child-Pugh class A (mild impairment): There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Child-Pugh class B or C (moderate-to-severe impairment): Use is contraindicated
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with combination therapy in adults unless otherwise indicated.
>10%:
Gastrointestinal: Diarrhea (15%)
Hepatic: Increased serum transaminases (including increased serum alanine aminotransferase [2%], aspartate aminotransferase [grades 2 to 4: 2% to 11%])
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (children, adolescents: grades 3/4: 11%)
1% to 10%:
Dermatologic: Pruritus (<2%), skin rash (children, adolescents, adults: 3% to 6%)
Endocrine & metabolic: Dehydration (2%), diabetes mellitus (<2%), hyperglycemia (<2%), hyperlipidemia (3%; including hypercholesterolemia [<2%]), hypertriglyceridemia (4%), weight loss (3%)
Gastrointestinal: Abdominal distension (<2%), abdominal pain (4%; upper abdominal pain: 2%), anorexia (<2%), decreased appetite (<2%), dyspepsia (<2%), flatulence (<2%), gastroesophageal reflux disease (<2%), increased serum amylase (children, adolescents: 8%; adults: <2%), increased serum lipase (<2%), nausea (9%), pancreatitis (<2%), vomiting (6%)
Hematologic & oncologic: Anemia (3%), decreased white blood cell count (grades 3/4: ≤5%), neutropenia (2%), thrombocytopenia (<2%)
Hepatic: Hepatic failure (<2%), hepatitis (<2%; including hepatic cytolysis, toxic hepatitis), hyperbilirubinemia (<2%), increased gamma-glutamyl transferase (2%), liver steatosis (<2%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Nervous system: Dizziness (<2%), drowsiness (<2%), fatigue (6%), headache (5%), insomnia (2%), intracranial hemorrhage (<2%), malaise (<2%), peripheral neuropathy (2%), sleep disturbance (<2%)
Neuromuscular & skeletal: Amyotrophy (facial) (<2%), lipoatrophy (<2%), lipodystrophy (acquired; <2%), lipohypertrophy (<2%), muscle cramps (<2%), myalgia (2%)
Renal: Kidney impairment (<2%)
Respiratory: Dyspnea (2%), flu-like symptoms (<2%)
Miscellaneous: Fever (8%)
Postmarketing:
Hepatic: Decompensated liver disease
Immunologic: Immune reconstitution syndrome
Coadministration of tipranavir/ritonavir with drugs highly dependent upon CYP3A for clearance or potent CYP3A inducers, including alfuzosin, amiodarone, bepridil, cisapride, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), flecainide, lovastatin, lurasidone, midazolam (oral), pimozide, propafenone, quinidine, rifampin, sildenafil (for pulmonary arterial hypertension [eg, Revatio]), simvastatin, St John’s wort, and triazolam; moderate to severe hepatic impairment (Child-Pugh class B or C).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to tipranavir, Cremophor EL, or any component of the formulation; rare hereditary conditions that may be incompatible with an excipient of the product; concurrent therapy with colchicine or quetiapine.
Concerns related to adverse effects:
• Fat redistribution: May cause redistribution/accumulation of fat (eg, central obesity, buffalo hump, peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).
• Hepatotoxicity: [US Boxed Warning]: Clinical hepatitis and hepatic decompensation, including some fatalities, have been reported. Patients with chronic hepatitis B or C coinfection have an increased risk; use with caution. Reactions generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications. Assess liver function tests at baseline and frequently throughout treatment. Monitor patients closely, especially those with chronic hepatitis B or C coinfection; discontinue use if signs or symptoms of hepatotoxicity occur (eg, fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly) or if asymptomatic AST/ALT elevations >10 times ULN or AST/ALT elevations >5 to 10 times ULN concurrently with total bilirubin >2.5 times ULN occur.
• Hyperlipidemia: With coadministered ritonavir, increases in total cholesterol and triglycerides have been reported; screening should be done prior to therapy and periodically throughout treatment.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Intracranial hemorrhage: [US Boxed Warning]: Use has been associated with fatal and nonfatal intracranial hemorrhage. Events often occurred in patients with medical conditions (eg, CNS lesions, head trauma, recent neurosurgery, coagulopathy, alcohol abuse) or concurrent medications which may have influenced these events. No abnormal pattern of coagulation parameters has been observed in patients in general, or preceding intracranial hemorrhage development.
• Skin reactions: Has been associated with a variety of skin reactions including rash (urticarial or maculopapular) and possible photosensitivity. In some cases rash was accompanied by joint pain or stiffness, throat tightness or generalized pruritus. Rash (mild to moderate) may be more frequent in pediatric patients. Discontinue treatment if severe skin rash develops.
• Sulfonamide allergy: Use with caution in patients with sulfonamide allergy; contains a sulfonamide moiety. The potential for cross-sensitivity between drugs in the sulfonamide class and tipranavir is unknown.
Disease-related concerns:
• Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of diabetes, DKA, and new-onset diabetes mellitus have been reported in HIV-1 infected patients receiving protease inhibitors.
• Hemophilia A or B: Use with caution in patients with hemophilia A or B; increased bleeding (including spontaneous skin hematomas and hemarthrosis) during protease inhibitor therapy has been reported.
• Hepatic impairment: Use with caution in patients with Child-Pugh class A (mild) hepatic impairment; contraindicated in Child-Pugh class B or C (moderate-to-severe) impairment.
• Platelet aggregation: May impair platelet aggregation, resulting in bleeding; use with caution in patients who may be at risk for increased bleeding (trauma, surgery, other medical conditions, or taking antiplatelet agents, anticoagulants, or supplemental high doses of vitamin E).
Dosage forms specific issues:
• Ethanol: Capsules contain dehydrated alcohol 7% w/w (0.1 g per capsule).
Skin rash may occur with tipranavir plus ritonavir use, including urticarial rash, maculopapular rash, or photosensitivity; may be accompanied by joint pain or stiffness, throat tightness, or generalized pruritus; reported incidence (all grades): Pediatric patients: 21%, adults: 8% to 10%; median onset: 53 days; treatment may be continued if rash is mild to moderate (rash may resolve; median duration: 22 days); discontinue therapy in cases of severe rash.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Aptivus: 250 mg
Solution, Oral:
Aptivus: 100 mg/mL (95 mL [DSC]) [contains polyethylene glycol (macrogol), propylene glycol, tocophersolan (vit e peg 1000 succinate)]
No
Capsules (Aptivus Oral)
250 mg (per each): $20.96
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Aptivus: 250 mg [contains alcohol, usp]
Oral: Swallow capsules whole; do not chew or open. Coadministration with ritonavir is required. Administer tipranavir plus ritonavir tablets at the same time with food.
Oral: Swallow tipranavir capsules whole; do not open or chew. Tipranavir must be coadministered with ritonavir. When using with ritonavir tablets, administer with food. When using with ritonavir solution, administer without regard to meals.
Prior to opening bottle, store at 2°C to 8°C (36°F to 46°F). After bottle is opened, may be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) for up to 60 days.
Treatment of HIV-1 infections in combination with ritonavir and other antiretroviral agents in patients who are highly treatment-experienced and multiprotease inhibitor-resistant (FDA approved in pediatric patients weighing ≥36 kg and adults). Note: Although FDA approved, tipranavir is no longer recommended for use in the treatment of HIV in pediatric patients (HHS [pediatric] 2024). HIV regimens consisting of three antiretroviral agents from at least two classes are strongly recommended.
Substrate of CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BSEP, CYP2D6 (Strong); Induces UGT1A1;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acoramidis: UGT1A1 Inducers may decrease serum concentration of Acoramidis. Risk X: Avoid
Agents with Antiplatelet Effects: Tipranavir may increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ajmaline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Ajmaline. Risk C: Monitor
Amiodarone: Tipranavir may increase serum concentration of Amiodarone. Risk X: Avoid
Amitriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amitriptyline. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Amitriptyline. Risk C: Monitor
Amoxapine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amoxapine. Risk C: Monitor
Amphetamines: CYP2D6 Inhibitors (Strong) may increase serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a strong CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs. Risk C: Monitor
Anticoagulants: Tipranavir may increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification
Artemether and Lumefantrine: Protease Inhibitors may increase serum concentration of Artemether and Lumefantrine. Specifically, the concentrations of lumefantrine may be increased. Protease Inhibitors may decrease serum concentration of Artemether and Lumefantrine. Specifically, concentrations of artemether and dihydroartemisinin (DHA), the active metabolite of artemether, may be decreased. Risk C: Monitor
Atazanavir: May increase serum concentration of Protease Inhibitors. Risk X: Avoid
Atidarsagene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Atidarsagene Autotemcel. Risk X: Avoid
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider Therapy Modification
Atorvastatin: Tipranavir may increase serum concentration of Atorvastatin. Risk X: Avoid
Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Benzhydrocodone. Risk C: Monitor
Bictegravir: UGT1A1 Inducers may decrease serum concentration of Bictegravir. Risk C: Monitor
Bosentan: Protease Inhibitors may increase serum concentration of Bosentan. Management: Dose adjustment of bosentan and increased monitoring for bosentan toxicities is necessary when these agents are combined. See full drug interaction monograph for details. Risk D: Consider Therapy Modification
Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with strong CYP2D6 inhibitors, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder Risk D: Consider Therapy Modification
Broom: CYP2D6 Inhibitors (Strong) may increase serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor
Cabotegravir: UGT1A1 Inducers may decrease serum concentration of Cabotegravir. Risk X: Avoid
Carvedilol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Carvedilol. Risk C: Monitor
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Chlorpheniramine. Risk C: Monitor
Cholic Acid: BSEP/ABCB11 Inhibitors may decrease excretion of Cholic Acid. Management: Avoid the use of bile salt efflux pump inhibitors with cholic acid. If such a combination cannot be avoided, monitor serum transaminases (eg, AST, ALT) and bilirubin closely. Risk D: Consider Therapy Modification
Cisapride: Tipranavir may increase serum concentration of Cisapride. Risk X: Avoid
Clarithromycin: May increase serum concentration of Tipranavir. Tipranavir may increase serum concentration of Clarithromycin. Management: Limit adult clarithromycin doses to 1,000 mg/day if combined with tipranavir. Consider reducing the clarithromycin dose by 50% for patients with CrCl 30 to 60 mL/min, and for patients with CrCl <30 mL/min consider reducing the clarithromycin dose by 75%. Risk D: Consider Therapy Modification
ClomiPRAMINE: CYP2D6 Inhibitors (Strong) may increase serum concentration of ClomiPRAMINE. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ClomiPRAMINE. Risk C: Monitor
CloZAPine: CYP2D6 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobicistat: May increase serum concentration of Tipranavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Risk X: Avoid
Codeine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor
Colchicine: Tipranavir may increase serum concentration of Colchicine. Management: Colchicine should not be used with tipranavir in patients with impaired renal or hepatic function. In those with normal renal and hepatic function, reduced colchicine doses (as directed) are required if used with tipranavir. Risk D: Consider Therapy Modification
CycloPHOSphamide: Protease Inhibitors may increase adverse/toxic effects of CycloPHOSphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased. Protease Inhibitors may increase serum concentration of CycloPHOSphamide. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Tipranavir. Risk C: Monitor
Dapoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk C: Monitor
Darunavir: Protease Inhibitors may decrease serum concentration of Darunavir. Protease Inhibitors may increase serum concentration of Darunavir. Risk X: Avoid
Deferasirox: UGT1A1 Inducers may decrease serum concentration of Deferasirox. Management: Avoid concomitant use of deferasirox and UGT1A1 inducers when possible. If combined, consider a 50% increase in the initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical response to guide further dosing. Risk D: Consider Therapy Modification
Desipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Desipramine. Risk C: Monitor
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Dextromethorphan: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dextromethorphan. Risk C: Monitor
Didanosine: Tipranavir may decrease serum concentration of Didanosine. Management: Separate didanosine and tipranavir administration by at least 2 hours to minimize any potential dosage form-related interaction. Monitor antiviral response closely in patients receiving didanosine in combination with tipranavir/ritonavir. Risk D: Consider Therapy Modification
Disulfiram: Tipranavir may increase adverse/toxic effects of Disulfiram. Risk X: Avoid
Dolutegravir: Tipranavir may decrease serum concentration of Dolutegravir. Specifically, Tipranavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Tipranavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. Risk D: Consider Therapy Modification
Doxepin (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Doxepin (Systemic). Risk C: Monitor
Doxepin (Topical): CYP2D6 Inhibitors (Strong) may increase serum concentration of Doxepin (Topical). Risk C: Monitor
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DULoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of DULoxetine. Risk C: Monitor
Elbasvir and Grazoprevir: Tipranavir may increase serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Eliglustat: CYP2D6 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification
Eluxadoline: Tipranavir may increase serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with tipranavir and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider Therapy Modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Tipranavir may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid
Estrogen Derivatives: Protease Inhibitors may decrease serum concentration of Estrogen Derivatives. Protease Inhibitors may increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Etravirine: Tipranavir may decrease serum concentration of Etravirine. Risk X: Avoid
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Fesoterodine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Risk C: Monitor
Flecainide: Tipranavir may increase serum concentration of Flecainide. Risk X: Avoid
Fluconazole: May increase serum concentration of Tipranavir. Management: Limit fluconazole adult maximum dose to 200 mg/day in patients treated with tipranavir. Risk D: Consider Therapy Modification
FLUoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FLUoxetine. Risk C: Monitor
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluPHENAZine. Risk C: Monitor
FluvoxaMINE: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluvoxaMINE. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of Protease Inhibitors. Protease Inhibitors may increase serum concentration of Fusidic Acid (Systemic). Management: Avoid this combination if possible, due to the risk of increased concentrations of both agents which increases the risk of hepatotoxicity. If combined, monitor patients closely for adverse effects of both agents. Risk D: Consider Therapy Modification
Garlic: May decrease serum concentration of Protease Inhibitors. Risk X: Avoid
Gefitinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Haloperidol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Haloperidol. Risk C: Monitor
Hormonal Contraceptives: Protease Inhibitors may decrease serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may increase concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with protease inhibitors. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider Therapy Modification
HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor
Iboga: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iboga. Risk C: Monitor
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iloperidone. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor and monitor for increased iloperidone toxicities, including QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification
Imipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Imipramine. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Imipramine. The concentrations of desipramine may be increased. Risk C: Monitor
Indoramin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Indoramin. Risk C: Monitor
Inhibitors of the Proton Pump (PPIs and PCABs): Tipranavir may decrease serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor
Itraconazole: Tipranavir may increase serum concentration of Itraconazole. Management: Adult itraconazole doses greater than 200 mg/day are not recommended in patients treated with tipranavir. Risk D: Consider Therapy Modification
Ketoconazole (Systemic): Tipranavir may increase serum concentration of Ketoconazole (Systemic). Management: Adult ketoconazole doses greater than 200 mg/day are not recommended in patients treated with tipranavir. Risk D: Consider Therapy Modification
Ledipasvir: Tipranavir may decrease serum concentration of Ledipasvir. Risk X: Avoid
Lenacapavir: Tipranavir may decrease serum concentration of Lenacapavir. Risk X: Avoid
Letermovir: UGT1A1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid
Levomethadone: Tipranavir may decrease serum concentration of Levomethadone. Risk C: Monitor
Lofepramine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor
Lofexidine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Lofexidine. Risk C: Monitor
Lomitapide: Tipranavir may increase serum concentration of Lomitapide. Risk X: Avoid
Lovastatin: Tipranavir may increase serum concentration of Lovastatin. Risk X: Avoid
Maprotiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Maprotiline. Risk C: Monitor
Mequitazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mequitazine. Risk X: Avoid
Methadone: Tipranavir may decrease serum concentration of Methadone. More specifically, the combination of Tipranavir and Ritonavir may decrease Methadone serum concentrations. Risk C: Monitor
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider Therapy Modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoprolol. Risk C: Monitor
MetroNIDAZOLE (Systemic): May increase adverse/toxic effects of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor
Mexiletine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mexiletine. Risk C: Monitor
Midazolam: Protease Inhibitors may increase serum concentration of Midazolam. Management: Oral midazolam is contraindicated with protease inhibitors. Avoid use with nasal midazolam. Consider alternatives to use with other routes of midazolam (IV, IM) when possible. Consider use of lower midazolam doses if combined. Risk X: Avoid
Nebivolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nebivolol. Risk C: Monitor
Nicergoline: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor
Nortriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nortriptyline. Risk C: Monitor
Obeticholic Acid: BSEP/ABCB11 Inhibitors may increase active metabolite exposure of Obeticholic Acid. Management: Avoid concomitant use of obeticholic acid and bile salt efflux pump (BSEP) inhibitors if possible. If concomitant therapy is necessary, monitor patients for elevated liver transaminases and elevated bilirubin. Risk D: Consider Therapy Modification
Oliceridine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Opipramol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Opipramol. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiretroviral Agents. Risk C: Monitor
OxyCODONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of OxyCODONE. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor
PARoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of PARoxetine. Risk C: Monitor
Perhexiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perhexiline. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perphenazine. Risk C: Monitor
PHENobarbital: May decrease serum concentration of Tipranavir. Tipranavir may decrease serum concentration of PHENobarbital. Risk C: Monitor
Pimozide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid
Pitolisant: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification
Primaquine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Primaquine. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Primaquine. Management: Consider alternatives to the combination of primaquine and strong CYP2D6 inhibitors. If concomitant use is necessary, monitor for signs and symptoms of possible primaquine treatment failure. Risk D: Consider Therapy Modification
Primidone: May decrease serum concentration of Tipranavir. Tipranavir may decrease serum concentration of Primidone. Risk C: Monitor
Propafenone: Tipranavir may increase serum concentration of Propafenone. Risk X: Avoid
Propranolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propranolol. Risk C: Monitor
Protease Inhibitors: Tipranavir may decrease serum concentration of Protease Inhibitors. Protease Inhibitors may increase serum concentration of Tipranavir. Risk X: Avoid
Protriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Protriptyline. Risk C: Monitor
QuiNIDine: Tipranavir may increase serum concentration of QuiNIDine. Risk X: Avoid
Raltegravir: Tipranavir may decrease serum concentration of Raltegravir. Management: Concurrent use of tipranavir/ritonavir with once-daily raltegravir (Isentress HD) is not recommended. Risk C: Monitor
Red Yeast Rice: Tipranavir may increase serum concentration of Red Yeast Rice. Risk X: Avoid
Rifabutin: Tipranavir may increase active metabolite exposure of Rifabutin. Tipranavir may increase serum concentration of Rifabutin. Management: Reduce rifabutin doses. Tipranavir prescribing information recommends a decrease of at least 75%, to 150 mg every other day or 3 times per week for adults. Clinical guidelines recommend 150 mg daily when used with tipranavir/ritonavir. Risk D: Consider Therapy Modification
RifAMPin: May decrease serum concentration of Tipranavir. Risk X: Avoid
RisperiDONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Rosuvastatin: Protease Inhibitors may increase serum concentration of Rosuvastatin. Risk C: Monitor
Sacituzumab Govitecan: UGT1A1 Inducers may decrease active metabolite exposure of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid
Salmeterol: Tipranavir may increase serum concentration of Salmeterol. Risk X: Avoid
Saquinavir: Tipranavir may decrease serum concentration of Saquinavir. Risk X: Avoid
Sertindole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider Therapy Modification
Sildenafil: Protease Inhibitors may increase serum concentration of Sildenafil. Management: Use of protease inhibitors and sildenafil for the treatment of PAH is contraindicated. If using sildenafil for the treatment of erectile dysfunction, limit the sildenafil dose to 25 mg and do not use more frequently than every 48 hours. Risk D: Consider Therapy Modification
Simvastatin: Tipranavir may increase serum concentration of Simvastatin. Risk X: Avoid
Sofosbuvir: Tipranavir may decrease serum concentration of Sofosbuvir. Risk X: Avoid
Sofpironium: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sofpironium. Risk X: Avoid
St John's Wort: May decrease serum concentration of Tipranavir. Risk X: Avoid
Tacrolimus (Systemic): Protease Inhibitors may increase nephrotoxic effects of Tacrolimus (Systemic). Protease Inhibitors may decrease metabolism of Tacrolimus (Systemic). Management: Consider reducing the tacrolimus dose to 1 mg once or twice per week if coadministered with protease inhibitors that are strong inhibitors of CYP3A4. Monitor response, plasma concentrations (as appropriate), and for signs of toxicity. Risk D: Consider Therapy Modification
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk C: Monitor
Taurursodiol: BSEP/ABCB11 Inhibitors may increase adverse/toxic effects of Taurursodiol. Specifically, the risk for liver dysfunction may be increased. Management: Avoid coadministration of sodium phenylbutyrate and taurursodiol with BSEP inhibitors when possible. If concomitant use is necessary, monitoring of serum transaminases and bilirubin is recommended. Risk D: Consider Therapy Modification
Tenofovir Alafenamide: Tipranavir may decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid
Tenofovir Disoproxil Fumarate: May decrease serum concentration of Tipranavir. Tipranavir may decrease serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Therapeutic Antiplatelets: Tipranavir may increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Thioridazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Thioridazine. Risk X: Avoid
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tolterodine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tolterodine. Risk C: Monitor
TraMADol: CYP2D6 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of TraMADol. Risk C: Monitor
Triazolam: Tipranavir may increase serum concentration of Triazolam. Risk X: Avoid
Trimipramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Trimipramine. Risk C: Monitor
Valbenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider Therapy Modification
Valproic Acid and Derivatives: Protease Inhibitors may decrease serum concentration of Valproic Acid and Derivatives. Risk C: Monitor
Vitamin E (Systemic): Tipranavir may increase adverse/toxic effects of Vitamin E (Systemic). Management: Patients taking tipranavir oral solution are advised to avoid taking additional vitamin E, beyond the amounts contained in a multivitamin product. This interaction does not apply to tipranavir capsules. Risk D: Consider Therapy Modification
Vortioxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level. Risk D: Consider Therapy Modification
Xanomeline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Xanomeline. Risk C: Monitor
Zidovudine: Tipranavir may decrease serum concentration of Zidovudine. Risk C: Monitor
Zuclopenthixol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Zuclopenthixol. Risk C: Monitor
Capsule contains dehydrated ethanol.
Contraception is not required to initiate or continue antiretroviral therapy (ART). Patients with HIV not planning to become pregnant may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. Consult drug interactions database for more detailed information specific to use of tipranavir and specific contraceptives.
Tipranavir (unboosted or boosted with ritonavir) is not one of the recommended antiretroviral agents for use in patients who are trying to conceive.
Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Prior to pregnancy, select or make changes to a specific antiretroviral regimen as part of a shared decision-making process. In most cases, recommendations based on data obtained from cisgender women can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2024).
Tipranavir crosses the placenta.
Outcome data specific to tipranavir use in pregnancy are no longer being reviewed and updated in the Health and Human Services perinatal guidelines. Tipranavir (unboosted or boosted with ritonavir) is not recommended for use during pregnancy; patients who are pregnant should be changed to a preferred or alternative therapy.
Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm birth, low birth weight, and small for GA infants. High viral loads are also associated with adverse outcomes, including preterm birth and pregnancy loss. Treatment improves the health of the pregnant patient and reduces the risk of perinatal transmission. Do not withhold appropriate maternal ART due to concerns for adverse neonatal outcomes. Closely monitor for pregnancy complications. Document in utero ART exposure in the long-term medical record of a child born without HIV; evaluate for potential metabolic dysfunction if significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) develop. The risk of hepatic dysfunction and gestational diabetes may be increased in pregnant patients taking protease inhibitors. Consider performing the standard glucose screening test earlier in pregnancy in patients who initiated protease inhibitor therapy prior to conception.
ART is recommended for all pregnant people with HIV to maximize their health, maintain the viral load below the limit of an ultrasensitive assay detection, and reduce the risk of perinatal transmission. Start ART prior to conception or as soon as possible during pregnancy. During pregnancy, select or make changes to a specific antiretroviral regimen as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitor pregnant patients more frequently than nonpregnant patients. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations based on data obtained from cisgender women can be applied to transgender and gender diverse people assigned female sex at birth.
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Enroll all patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263).
Health care providers caring for pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2024).
HIV: General recommendations: Management of HIV infection requires extensive monitoring; refer to current guidelines (https://clinicalinfo.hiv.gov/en/guidelines) for additional guidance. Antiretroviral drug-resistance testing is recommended before initiation of therapy in treatment-naive patients and before changing regimens in patients for whom treatment has failed. After initiation of or change in antiretroviral therapy regimen, pediatric patients should be evaluated for clinical adverse effects and treatment adherence at 1 to 2 weeks, and laboratory testing for drug toxicity should occur at 2 to 4 weeks; monitor for therapy adherence, effectiveness, and toxicities every 3 to 4 months.
Drug-specific monitoring: Frequency may vary based on several factors including age, concomitant therapy, and clinical response; refer to current guidelines for additional information.
Lipid profiles, liver function tests, serum glucose, creatine phosphokinase (baseline and periodically with therapy or if clinical presentation indicates need), body composition, CBC (if clinical presentation indicates need).
Plasma trough concentration ≥20.5 mg/L (Punyawudho 2016)
Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.
Absorption: Incomplete (percentage not established)
Distribution: Vd:
Children: 2 to <6 years: 4 L
Children: 6 to <12 years: 4.7 L
Children and Adolescents 12 to 18 years: 5.3 L
Adults: 7.7 to 10.2 L
Protein binding: >99.9% (albumin, alpha-1 acid glycoprotein)
Metabolism: Hepatic, via CYP3A4 (minimal when coadministered with ritonavir)
Bioavailability: Not established
Half-life elimination: Children 2 to <6 years of age: ~8 hours, 6 to <12 years of age: ~7 hours, 12 to 18 years: ~5 hours; Adults: Males: 6 hours; Females: 5.5 hours
Time to peak, plasma:
Children and Adolescents 2 to 18 years: 2.5 to 2.7 hours
Adults: 3 hours
Excretion: Feces (82.3%); urine (4.4%); primarily as unchanged drug (when coadministered with ritonavir)
Hepatic function impairment: Tipranavir and ritonavir plasma concentrations are increased in patients with mild hepatic impairment (Child-Pugh class A).
