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Related to Aptivus: Invirase, Fuzeon, Lexiva, Agenerase



Pharmacologic class: Nonpeptidic protease inhibitor of human immunodeficiency virus type 1 (HIV-1)

Therapeutic class: Antiretroviral

Pregnancy risk category C

FDA Box Warning

When given concurrently with ritonavir 200 mg, drug has been linked to reports of fatal and nonfatal intracranial hemorrhage and clinical hepatitis and hepatic decompensation. Use extra vigilance in patients with chronic hepatitis B or hepatitis C co-infection.


Inhibits virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, preventing formation of mature virions


Capsules: 250 mg

Oral solution: 100 mg/ml

Indications and dosages

Combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor

Adults: 500 mg P.O. twice daily given with 200 mg ritonavir

Children ages 2 to 18: 14 mg/kg P.O. with ritonavir 6 mg/kg (or 375 mg/m2 with ritonavir 150 mg/m2) twice daily, not to exceed maximum dosage of tipranavir 500 mg with ritonavir 200 mg twice daily. For children who develop intolerance or toxicity and can't continue with tipranavir 14 mg/kg with ritonavir 6 mg/kg, consider decreasing dosage to tipranavir 12 mg/kg with ritonavir 5 mg/kg (or tipranavir 290 mg/m2 with ritonavir 115 mg/m2) twice daily provided virus isn't resistant to multiple protease inhibitors.


• Moderate to severe hepatic impairment
• Concurrent use of amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, methylergonovine, oral midazolam, pimozide, propafenone, quinidine, terfenadine, or triazolam
• Sildenafil (Revatio) when used for pulmonary hypertension


Use cautiously in:
• treatment-naïve patients (avoid use)
• sulfonamide allergy
• hepatic insufficiency, diabetes mellitus, hyperglycemia, hemophilia, increased risk of bleeding
• concurrent use of drugs known to increase risk of bleeding
• concurrent use of other protease inhibitors, fluticasone propionate, or salmeterol (use not recommended)
• concurrent use of calcium channel blockers, carbamazepine, itraconazole, ketoconazole, parenteral midazolam, PDE5 inhibitors (when used for erectile dysfunction), phenobarbital, phenytoin, trazodone, valproic acid
• pregnant or breastfeeding patients.


• Administer with or without food when given with ritonavir capsules or solution; must administer only with meals when given with ritonavir tablets.
• Give 2 hours before or 1 hour after antacids.

Adverse reactions

CNS: fatigue, headache, depression, insomnia, asthenia, intracranial hemorrhage

GI: diarrhea, nausea, vomiting, abdominal pain, dyspepsia, flatulence

Hematologic: leukopenia, anemia, neutropenia, thrombocytopenia

Hepatic: hepatotoxicity

Metabolic: hyperglycemia, new-onset or exacerbations of diabetes mellitus

Respiratory: bronchitis, cough

Skin: rash

Other: pyrexia, fat accumulation or redistribution, immune reconstitution syndrome


Drug-drug. Antacids: decreased tipranavir peak concentration

Atorvastatin, desipramine, fluticasone, itraconazole, ketoconazole, rifabutin, selective serotonin reuptake inhibitors, sildenafil, tadalafil, trazodone, vardenafil, voriconazole: increased levels of these drugs

Calcium channel blockers: possible unpredictable effects

Clarithromycin: increased levels of both drugs

Didanosine, ethinyl estradiol, methadone: decreased levels of these drugs

Disulfiram, other drugs that produce disulfiram-like reaction (such as metronidazole): increased risk of disulfiram-like reactions

Fluconazole: increased tipranavir level

Hormonal contraceptives: decreased hormonal concentration, increased risk of rash

Lovastatin, simvastatin: increased potential for serious reactions (such as myopathy and rhabdomyolysis)

Metronidazole: disulfiram-like interaction

PDE5 inhibitors: increased PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism

Rifampin: loss of virologic response, tipranavir resistance

Salmeterol: increased risk of cardiovascular adverse events including QT interval prolongation, palpitations, and sinus tachycardia

Trazodone: increased trazodone plasma concentrations

Valproic acid: decreased valproic acid effectiveness

Warfarin: altered warfarin blood level

Drug-diagnostic tests. Alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), cholesterol, triglycerides: increased

Platelets, WBCs: decreased

Drug-food. High-fat meal: increased drug bioavailability

Drug-herbs. St. John's wort: loss of virologic response, tipranavir resistance

Patient monitoring

• Monitor liver function tests and watch for signs and symptoms of hepatic impairment before and during therapy. Discontinue drug if signs and symptoms of clinical hepatitis, asymptomatic increases in ALT/AST of more than 10 times upper limit of normal (ULN), or asymptomatic increases in ALT/AST of 5 to 10 times ULN with concomitant increases in total bilirubin occur.
• Monitor triglyceride and cholesterol levels before therapy starts and at periodic intervals during therapy.
• Monitor CBC, platelets, and serum amylase levels.
• Monitor INR frequently when therapy starts in patients receiving warfarin.
• Closely monitor patients with hyperglycemia or chronic hepatitis B or C.
• Because this drug interacts with many other drugs, closely monitor patient's drug regimen for possible interactions and adjust dosage, as appropriate.
• Be aware that immune reconstitution syndrome has occurred in patients treated with combination antiretroviral therapy. During initial phase of combination antiretroviral treatment, patients whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia, tuberculosis, or reactivation of herpes simplex and herpes zoster), which may necessitate further evaluation and treatment.

Patient teaching

• Instruct patient to take capsules or solution with or without food when taking with ritonavir capsules or solution and to take with meals when taking with ritonavir tablets. Tell patient to swallow capsule whole, without chewing it.
• Tell patient to take drug 2 hours before or 1 hour after antacids.

Emphasize that patient must take prescribed ritonavir dosage with this drug to achieve desired therapeutic effect.
• Instruct patient not to alter dosage or discontinue tipranavir or ritonavir without consulting prescriber.
• Advise patient to take a missed dose as soon as possible and then return to normal schedule. Caution against taking double doses.

Instruct patient to immediately stop taking drug and contact prescriber if he develops unusual fatigue, general ill feeling, flulike symptoms, appetite loss, nausea, yellowing of skin or eyes, dark urine, pale stools, or right-sided abdominal pain.

Tell patient to discontinue drug and promptly report severe report rash to prescriber.
• Inform patient that because drug may cause many interactions, he shouldn't take other prescription or over-the-counter drugs without consulting prescriber.
• Tell patient drug may cause body fat redistribution or accumulation.
• Instruct patient to store capsules in refrigerator and to use contents within 60 days of opening bottle.
• Advise female taking estrogen-based hormonal contraceptives to use additional or alternative birth control method during therapy.
• Instruct female not to breastfeed because of risk of transmitting HIV infection and adverse drug effects to infant.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.


(ti-pran-a-veer) ,


(trade name)


Therapeutic: antiretrovirals
Pharmacologic: protease inhibitors
Pregnancy Category: C


Advanced HIV disease resistant to more than one protease inhibitor (must be used with ritonavir).


Inhibits processing of viral polyproteins, preventing formation of mature virions.

Therapeutic effects

Decreased viral load and sequelae of HIV infection.


Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: >99.9%.
Metabolism and Excretion: Rapidly and extensively metabolized (primarily by CYP3A4), requiring co-administration with ritonavir as a metabolic inhibitor to achieve therapeutic blood levels; eliminated mostly in feces, minimal renal excretion.
Half-life: 5.5–6 hr.

Time/action profile (blood levels*)

POrapid 2 hr12 hr
* With ritonavir


Contraindicated in: Hypersensitivity;Moderate to severe hepatic impairment (Child-Pugh Class B or C);Concurrent use of some antiarrhythmics (amiodarone, flecainide, propafenone, quinidine), ergot derivatives, sildenafil (Revatio), alfuzosin, midazolam (oral) or triazolam.
Use Cautiously in: Known sulfonamide allergy (contains sulfa moiety);Pre-existing liver disease (may ↑ risk of hepatotoxicity);History of or risk factors for diabetes (may cause hyperglycemia);Hemophilia (may ↑ risk of bleeding);Patients at ↑ risk for bleeding.

Adverse Reactions/Side Effects


  • intracranial hemorrhage (life-threatening)
  • fatigue (most frequent)
  • headache (most frequent)


  • hepatotoxicity (life-threatening)
  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)


  • rash (↑ in women and peds) (most frequent)


  • hyperglycemia


  • ↑ cholesterol
  • ↑ triglycerides


  • allergic reactions
  • bleeding
  • fat redistribution
  • fever (most frequent)
  • immune reconstitution syndrome


Drug-Drug interaction

↑ blood levels and risk of toxicity from some antiarrhythmics (amiodarone, flecainide, propafenone, quinidine ), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine ), sildenafil (Revatio), alfuzosin, midazolam (oral), and triazolam ; concurrent use contraindicated.↑ risk of myopathy with atorvastatin ; avoid concurrent use.May ↑ risk of adverse effects with salmeterol ; concurrent use not recommended.May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of tipranavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day.May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalfil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of tipranavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.May ↓ levels of raltegravir.Concurrent use with ritonavir may lead to intracranial hemorrhage.Antacids ↓ absorption (separate dosing).Hormonal contraceptives may ↑ risk of rash.May ↓ effectiveness of hormonal contraceptives.↑ risk of bleeding with antiplatelets, anticoagulants, or vitamin E.Enfuvirtide may ↑ levels.


Oral (Adults) 500 mg twice daily with ritonavir 200 mg twice daily.
Oral (Children ≥2 yr) 14 mg/kg (max: 500 mg/dose) twice daily with ritonavir 6 mg/kg (max: 200 mg/dose) twice daily; if intolerance develops, may ↓ dose to tipranavir 12 mg/kg twice daily with ritonavir 5 mg/kg twice daily.


Capsules: 250 mg
Oral solutionbuttermint-butter toffee: 100 mg/mL (contains vitamin E 116 IU/mL)

Nursing implications

Nursing assessment

  • Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
  • Monitor for hepatitis (fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, hepatomegaly).
  • Assess for sulfa allergy. May be cross sensitive.
  • Lab Test Considerations: Monitor viral load and CD4 counts regularly during therapy.
    • May cause ↑ AST and ↑ ALT; monitor prior to and frequently during therapy. Discontinue tipranavir if symptomatic ↑ of AST and ALT of 10 times the upper limit of normal or symptomatic ↑ of AST and ALT of 5–10 times the upper limit of normal and bilirubin ↑ 2.5 time the upper limit of normal occur.
    • Monitor triglyceride and cholesterol levels prior to and periodically during therapy; may cause ↑.
    • May cause hyperglycemia. Monitor blood glucose carefully, especially in patients with diabetes.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)


  • Oral: Administer tipranavir with ritonavir tablets twice daily with meals. Administer tipranavir with ritonavir capsules with or without meals. Swallow capsules whole, do not open or chew. Bioavailability is increased with high fat meal.
    • Store capsules in refrigerator. Use within 60 days of opening bottle. Write opening date on label; do not use after expiration date written. If used away from home, bottle may be kept at room temperature in a cool place.

Patient/Family Teaching

  • Emphasize the importance of taking tipranavir as directed, at evenly spaced times throughout day. Patients should read the Patient Package Insert before initiating therapy and with each prescription refill. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; do not double doses.
  • Advise patients taking oral solution not to take supplemental vitamin E greater than a standard multivitamin; oral solution contains 116 IU/mL of vitamin E which is higher than the RDA (adults 30 IU, pediatrics approximately 10 IU).
  • Instruct patient that tipranavir should not be shared with others.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Inform patient that tipranavir does not cure AIDS or prevent associated or opportunistic infections. Tipranavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others.
  • Advise patients to stop taking tipranavir and ritonavir and notify health care professional immediately if signs of hepatitis (fatigue, malaise, anorexia, nausea, jaundice) or unusual bleeding occur. May require discontinuation of therapy.
  • Inform patient that tipranavir may cause hyperglycemia. Advise patient to notify health care professional if increased thirst or hunger; unexplained weight loss; increased urination; fatigue; or dry, itchy skin occurs.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • Advise women taking hormonal contraceptives to use a nonhormonal form of contraception during tipranavir therapy, and of increased risk of rash.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and improvement in CD4 cell counts.


a trademark for tipranavir.
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References in periodicals archive ?
has identified 14 reports of intracranial hemorrhage, including 8 fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).
Patients will be randomised to receive 500 mg of APTIVUS boosted with 200 mg of ritonavir twice daily or 600mg of darunavir boosted with 100 mg of ritonavir twice daily.
AHF believes there is simply no justification for the high prices of drugs such as Kaletra, Aptivus, Reyataz, Invirase and Fuzeon.
Patients will also be included in a randomized evaluation to assess the impact of TDM on the efficacy and safety of APTIVUS boosted with ritonavir.
For someone with an income less than that, paying $1,187 a month for Aptivus is not an option; they will skip a month when they cannot afford to pay or stop taking treatment altogether.
Patients received either 20 mg, 50 mg, or 125 mg of elvitegravir with 100 mg of Norvir or Norvir boosted by a protease inhibitor (either Aptivus [tiptranavir] or Prezista).
The launches of Aptivus and Cymbalta may prove vital for the Virology and CNS therapeutic areas, both of which are currently threatened by falling sales of their major products in the short-to-medium term.
Data show that APTIVUS provides a durable treatment option through nearly two years of therapy.
BI's response letter states: "Boehringer Ingelheim is committed to ensuring that patients who need Aptivus (tipranavir) and Viramune (nevirapine) tablets and oral suspension have access to the medications.
Boehringer Ingelheim Receives FDA Approval for Aptivus Oral
APTIVUS is a registered trademark of Boehringer Ingelheim Pharmaceuticals.
Efficacy and safety results of 48 weeks of treatment with APTIVUS oral solution co-administered with low dose ritonavir (APTIVUS/r) in children and teenagers (Phase I/IIa study); 16th International AIDS Conference; August 13 - 18, 2006, Toronto, Canada.