tipranavir

tipranavir,

an antiretroviral.

indications This drug is used in combination with other antiretrovirals to treat HIV.

contraindications Hepatic disease (Child-Pugh B to C) and known hypersensitivity to this drug prohibit its use.

adverse effects Adverse effects of this drug include dizziness, somnolence, fatigue, anorexia, dry mouth, nephrolithiasis, rash, pain, asthenia, and hyperlipidemia. Life-threatening side effects include hepatitis B or C, fatalities when given with ritonavir, insulin-resistant hyperglycemia, and ketoacidosis. Common side effects include headache, insomnia, diarrhea, abdominal pain, nausea, and vomiting.

---

tipranavir

Aptivus

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

Therapeutic class: Antiretroviral

Pregnancy risk category C

FDA Boxed 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

⊘Indications and dosages

➣ Combination antiretroviral treatment of HIV-1 in patients with evidence of viral replication who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors

Adults: 500 mg P.O. twice daily with high-fat meal, given with 200 mg ritonavir

Contraindications

• Hypersensitivity to drug or its components
• Moderate to severe hepatic impairment
• Concurrent use of amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, methylergonovine, midazolam, pimozide, propafenone, quinidine, terfenadine, or triazolam

Precautions

Use cautiously in:
• sulfonamide allergy
• hepatic insufficiency, diabetes mellitus, hyperglycemia, hemophilia, increased risk of bleeding
• concurrent use of drugs known to increase risk of bleeding
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Administer with food.
• Give 2 hours before or 1 hour after antacids.

Route	Onset	Peak	Duration
P.O.	Unknown	2.9-3 hr	Unknown

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

Respiratory: bronchitis, cough

Skin: rash

Other: pyrexia, fat accumulation or redistribution

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

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

Rifampin: loss of virologic response, tipranavir resistance

Warfarin: altered warfarin blood level

Drug-diagnostic tests. Alanine aminotransferase, amylase, aspartate aminotransferase, 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.
• 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.

Patient teaching

• Instruct patient to take drug with food and to swallow capsule whole, without chewing.
• 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 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.