Aptivus

tipranavir

Aptivus

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.

Action

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

Availability

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.

Contraindications

• 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

Precautions

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.

Administration

• 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

Interactions

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.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved