Version May 2024
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: 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
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.
Refer to adult dosing.
(For additional information see "Tipranavir: Pediatric drug information")
Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.
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 ARV agents. 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 ≥2 years and Adolescents:
Weight-directed dosing: Oral: Tipranavir 14 mg/kg (maximum: 500 mg) plus ritonavir 6 mg/kg (maximum: 200 mg) twice daily.
If intolerance or toxicity develops and virus is not resistant to multiple protease inhibitors: May decrease dose to: Tipranavir 12 mg/kg plus ritonavir 5 mg/kg twice daily; do not exceed adult doses.
BSA-directed dosing: Oral: Tipranavir 375 mg/m2 (maximum: 500 mg) plus ritonavir 150 mg/m2 (maximum: 200 mg) twice daily.
If intolerance or toxicity develops and virus is not resistant to multiple protease inhibitors: May decrease dose to: Tipranavir 290 mg/m2 plus ritonavir 115 mg/m2 twice daily; do not exceed adult doses.
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin rash (children: 21%; adults: 3% to 10%)
Endocrine & metabolic: Hypertriglyceridemia (>400 mg/dL: 61%), hypercholesterolemia (>300 mg/dL: 22%)
Gastrointestinal: Diarrhea (15%; children: 4%)
Hepatic: Increased serum transaminases (>2.5 x ULN: 26% to 32%; grades 3/4: 10% to 20%)
Neuromuscular & skeletal: Increased creatine phosphokinase (children, grades 3/4: 11%)
1% to 10%:
Central nervous system: Fatigue (6%), headache (5%), dizziness, drowsiness, insomnia, intracranial hemorrhage, malaise, peripheral neuropathy, sleep disorder
Dermatologic: Pruritus
Endocrine & metabolic: Increased amylase (grade 3: 6% to 8%), weight loss (3%), dehydration (2%), increased gamma-glutamyl transferase (2%), diabetes mellitus, hyperglycemia, lipodystrophy (acquired), lipohypertrophy
Gastrointestinal: Nausea (5% to 9%), vomiting (6%), abdominal pain (4%), abdominal distension, anorexia, decreased appetite, dyspepsia, flatulence, gastroesophageal reflux disease, increased serum lipase, pancreatitis
Hematologic & oncologic: Hemorrhage (children: 8%), decreased white blood cell count (grade 3: 5%), anemia (3%), neutropenia (2%), thrombocytopenia
Hepatic: Increased serum ALT (2%, grades 3/4: 10%), increased serum AST (grades 3/4: 6%), hepatic failure, hepatitis, hyperbilirubinemia, liver steatosis
Hypersensitivity: Hypersensitivity reaction
Immunologic: Immune reconstitution syndrome
Neuromuscular & skeletal: Myalgia (2%), amyotrophy (facial), lipoatrophy, muscle cramps
Renal: Renal insufficiency
Respiratory: Cough (children: 6%), dyspnea (2%), epistaxis (children: 4%), flu-like symptoms
Miscellaneous: Fever (6% to 8%), drug toxicity (mitochondrial damage)
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).
• Vitamin E: Oral solution contains vitamin E 116 units/mL.
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.
Tipranavir oral solution contains vitamin E (116 units/mL), which is significantly higher than the RDA; avoid taking additional vitamin E (other than a daily multivitamin). The recommended pediatric dose of tipranavir (14 mg/kg body weight) results in a vitamin E dose of 16 units/kg body weight per day, significantly higher than the reference daily intake for vitamin E (approximately 6 to 22 units) and close to the upper limit of tolerability for children. Epistaxis is more common with the oral solution than the capsule formulation.
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); buttermint-butter toffee flavor]
No
Capsules (Aptivus Oral)
250 mg (per each): $20.55
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 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 capsules or solution, administer without regard to meals.
Coadministration with ritonavir is required. In pediatric patients, may administer tipranavir plus ritonavir capsules or solution together with food (Ref). Administer tipranavir plus ritonavir tablets at the same time with food. Swallow capsules whole; do not chew or open.
HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with ritonavir and other antiretroviral agents; limited to treatment-experienced, multiprotease inhibitor-resistant patients. Note: Tipranavir is not recommended for use in the initial treatment of HIV (HHS [adult] 2023).
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BSEP/ABCB11, 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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Tipranavir may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ajmaline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy
Amiodarone: Tipranavir may increase the serum concentration of Amiodarone. Risk X: Avoid combination
Amitriptyline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy
Amoxapine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amoxapine. Risk C: Monitor therapy
Amphetamines: CYP2D6 Inhibitors (Strong) may increase the 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 therapy
Anticoagulants: Tipranavir may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the 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
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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
Artemether and Lumefantrine: Protease Inhibitors may increase the serum concentration of Artemether and Lumefantrine. Specifically, the concentrations of lumefantrine may be increased. Protease Inhibitors may decrease the serum concentration of Artemether and Lumefantrine. Specifically, concentrations of artemether and dihydroartemisinin (DHA), the active metabolite of artemether, may be decreased. Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of Protease Inhibitors. Risk X: Avoid combination
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the 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 the serum concentration of Atorvastatin. Risk X: Avoid combination
Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Risk C: Monitor therapy
Bictegravir: UGT1A1 Inducers may decrease the serum concentration of Bictegravir. Risk C: Monitor therapy
Bosentan: Protease Inhibitors may increase the 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 the 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 the serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor therapy
Cabotegravir: UGT1A1 Inducers may decrease the serum concentration of Cabotegravir. Risk X: Avoid combination
Carvedilol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Chlorpheniramine. Risk C: Monitor therapy
Cholic Acid: BSEP/ABCB11 Inhibitors may decrease the 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 the serum concentration of Cisapride. Risk X: Avoid combination
Clarithromycin: May increase the serum concentration of Tipranavir. Tipranavir may increase the 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 concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Strong) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
CloZAPine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: May increase the serum concentration of Tipranavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Risk X: Avoid combination
Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
Colchicine: Tipranavir may increase the 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 enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased. Protease Inhibitors may increase the serum concentration of CycloPHOSphamide. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Tipranavir. Risk C: Monitor therapy
Dapoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Risk C: Monitor therapy
Darunavir: Protease Inhibitors may decrease the serum concentration of Darunavir. Protease Inhibitors may increase the serum concentration of Darunavir. Risk X: Avoid combination
Deferasirox: UGT1A1 Inducers may decrease the 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 the serum concentration of Desipramine. Risk C: Monitor therapy
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the serum concentration of Dextromethorphan. Risk C: Monitor therapy
Didanosine: Tipranavir may decrease the 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: May enhance the adverse/toxic effect of Tipranavir. Risk X: Avoid combination
Dolutegravir: Tipranavir may decrease the 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 the serum concentration of Doxepin (Systemic). Risk C: Monitor therapy
Doxepin (Topical): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DULoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy
Elbasvir and Grazoprevir: Tipranavir may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eliglustat: CYP2D6 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Estrogen Derivatives: Protease Inhibitors may decrease the serum concentration of Estrogen Derivatives. Protease Inhibitors may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Etravirine: Tipranavir may decrease the serum concentration of Etravirine. Risk X: Avoid combination
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase the 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 serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Flecainide: Tipranavir may increase the serum concentration of Flecainide. Risk X: Avoid combination
Fluconazole: May increase the 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 the serum concentration of FLUoxetine. Risk C: Monitor therapy
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of FluPHENAZine. Risk C: Monitor therapy
FluvoxaMINE: CYP2D6 Inhibitors (Strong) may increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy
Galantamine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy
Garlic: May decrease the serum concentration of Protease Inhibitors. Risk X: Avoid combination
Gefitinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy
Haloperidol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: Protease Inhibitors may decrease the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase the 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 serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor therapy
Iboga: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iboga. Risk C: Monitor therapy
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. 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 concentrations of the active metabolite(s) of Imipramine. The concentrations of desipramine may be increased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Imipramine. Risk C: Monitor therapy
Indoramin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): Tipranavir may decrease the serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy
Itraconazole: Tipranavir may increase the 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 the 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 the serum concentration of Ledipasvir. Risk X: Avoid combination
Lenacapavir: Tipranavir may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination
Letermovir: UGT1A1 Inducers may decrease the serum concentration of Letermovir. Risk X: Avoid combination
Levomethadone: Tipranavir may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Lofepramine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy
Lofexidine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine. Risk C: Monitor therapy
Lomitapide: Tipranavir may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lovastatin: Tipranavir may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Maprotiline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Maprotiline. Risk C: Monitor therapy
Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Risk X: Avoid combination
Methadone: Tipranavir may decrease the serum concentration of Methadone. More specifically, the combination of Tipranavir and Ritonavir may decrease Methadone serum concentrations. Risk C: Monitor therapy
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the 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 the serum concentration of Metoprolol. Risk C: Monitor therapy
MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor therapy
MetroNIDAZOLE (Topical): May enhance the adverse/toxic effect of Tipranavir. Risk C: Monitor therapy
Mexiletine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mexiletine. Risk C: Monitor therapy
Midazolam: Protease Inhibitors may increase the 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 combination
Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor therapy
Nortriptyline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nortriptyline. Risk C: Monitor therapy
Obeticholic Acid: BSEP/ABCB11 Inhibitors may increase serum concentrations of the active metabolite(s) 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 the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
PARoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Perhexiline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy
Perphenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy
PHENobarbital: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pitolisant: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. Risk D: Consider therapy modification
Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Primaquine. Risk C: Monitor therapy
Primidone: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Primidone. Risk C: Monitor therapy
Propafenone: Tipranavir may increase the serum concentration of Propafenone. Risk X: Avoid combination
Propranolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propranolol. Risk C: Monitor therapy
Protease Inhibitors: Tipranavir may decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Tipranavir. Risk X: Avoid combination
Protriptyline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Protriptyline. Risk C: Monitor therapy
QuiNIDine: Tipranavir may increase the serum concentration of QuiNIDine. Risk X: Avoid combination
Raltegravir: Tipranavir may decrease the serum concentration of Raltegravir. Management: Concurrent use of tipranavir/ritonavir with once-daily raltegravir (Isentress HD) is not recommended. Risk C: Monitor therapy
Red Yeast Rice: Tipranavir may increase the serum concentration of Red Yeast Rice. Risk X: Avoid combination
Rifabutin: Tipranavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Tipranavir may increase the 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 the serum concentration of Tipranavir. Risk X: Avoid combination
RisperiDONE: CYP2D6 Inhibitors (Strong) may increase the 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 the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Sacituzumab Govitecan: UGT1A1 Inducers may decrease serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid combination
Salmeterol: Tipranavir may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saquinavir: Tipranavir may decrease the serum concentration of Saquinavir. Risk X: Avoid combination
Sertindole: CYP2D6 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Simvastatin. Risk X: Avoid combination
Sofosbuvir: Tipranavir may decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Tipranavir. Risk X: Avoid combination
Tacrolimus (Systemic): Protease Inhibitors may enhance the nephrotoxic effect of Tacrolimus (Systemic). Protease Inhibitors may decrease the 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 serum concentrations of the active metabolite(s) 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 the serum concentration of Tamsulosin. Risk C: Monitor therapy
Taurursodiol: BSEP/ABCB11 Inhibitors may enhance the adverse/toxic effect 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 the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Tenofovir Disoproxil Fumarate: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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
Thioridazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Thioridazine. Risk X: Avoid combination
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy
Tolterodine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy
TraMADol: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
Triazolam: Tipranavir may increase the serum concentration of Triazolam. Risk X: Avoid combination
Trimipramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Trimipramine. Risk C: Monitor therapy
Valbenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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
Valproate Products: Protease Inhibitors may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy
Vitamin E (Systemic): Tipranavir may enhance the adverse/toxic effect 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 the 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
Zidovudine: Tipranavir may decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Zuclopenthixol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
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.
Based on the Health and Humans Services perinatal HIV guidelines, 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. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (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] 2023).
Tipranavir crosses the placenta.
Outcome information specific to tipranavir use in pregnancy is no longer being reviewed and updated in the Health and Human Services (HHS) perinatal guidelines. The HHS perinatal HIV guidelines do not recommend tipranavir (unboosted or boosted with ritonavir) as one of the recommended antiretroviral agents 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-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, GA at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction. 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 detection, and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done 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. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (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. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.
Health care providers caring for pregnant patients with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2023).
It is not known if tipranavir is present in breast milk.
Maintaining maximum viral suppression during pregnancy and postpartum decreases but does not eliminate the risk of HIV transmission via breast milk. In addition, multiclass-resistant virus has been detected in breastfeeding infants who acquire HIV despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients with HIV when safer infant feeding options are available. Persons with HIV who maintain an undetectable viral load while taking antiretroviral therapy (ART) should evaluate infant feeding options (formula, banked donor milk, or breastfeeding) as part of a shared decision-making process (if breastfeeding is being considered, see guidelines for measures to reduce the risk of HIV transmission). When the HIV status at delivery is not known, breast milk may be expressed and stored until a negative test is available. If HIV infection is diagnosed after breastfeeding has been initiated, breastfeeding should be discontinued immediately. Breastfeeding is not recommended for persons with HIV who are not taking ART and/or who do not have sustained viral suppression.
Information is available for counseling and managing patients with HIV who are considering breastfeeding (888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2023).
Capsule contains dehydrated ethanol. Oral solution formulation contains vitamin E; additional vitamin E supplements should be avoided.
Triglycerides and total cholesterol at baseline and during therapy. Liver function tests (including bilirubin) at baseline and frequently throughout therapy; patients with chronic hepatitis B or C coinfection should be monitored closely. Monitor for symptoms of hepatotoxicity (eg, fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, acholic stools, liver tenderness or hepatomegaly). Monitor viral load, CD4, and serum glucose as clinically indicated.
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).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
