ti-PRAN-a-veer

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

• Advanced HIV disease resistant to >1 protease inhibitor (in combination with ritonavir).

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

• Decreased viral load and sequelae of HIV infection.

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99.9%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; requires coadministration with ritonavir as a metabolic inhibitor to achieve therapeutic blood levels; eliminated mostly in feces, minimal renal excretion.

Half-life: 5.5–6 hr.

(plasma concentrations*)

* With ritonavir.

Contraindicated in:

• Hypersensitivity
• Moderate to severe hepatic impairment
• Concurrent use of amiodarone, flecainide, propafenone, quinidine, ergot derivatives, sildenafil (Revatio), alfuzosin, pimozide, lurasidone, rifampin, St. John's wort, or triazolam
• Concurrent use of colchicine in patients with renal or hepatic impairment
• Lactation: Breastfeeding not recommended in women with HIV.

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
• OB: Not a recommended antiretroviral agent during pregnancy
• Pedi: Children <2 yr (safety and effectiveness not established).

Derm: rash (↑ in women and children).

Endo: hyperglycemia.

GI: abdominal pain, diarrhea, nausea, vomiting, HEPATOTOXICITY.

Hemat: bleeding.

Metab: fat redistribution, hypercholesterolemia, hypertriglyceridemia.

Neuro: fatigue, headache, INTRACRANIAL HEMORRHAGE.
Misc: fever, immune reconstitution syndrome.

Drug-Drug:

• ↑levels and risk of toxicity from amiodarone, flecainide, propafenone, quinidine, ergot derivatives(dihydroergotamine, ergotamine, methylergonovine), sildenafil (Revatio), alfuzosin, pimozide, lurasidone, rifampin, and triazolam; concurrent use contraindicated.
• May ↑ colchicine levels; ↓ dose of colchicine; concurrent use in patients with renal or hepatic impairment contraindicated.
• May ↑ levels of atorvastatin and rosuvastatin; avoid concurrent use with atorvastatin.
• May ↑ levels of salmeterol and fluticasone; avoid concurrent use.
• May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day once patient receiving tipranavir for 10 days; if patient already receiving bosentan, discontinue bosentan 36 hr before initiation of tipranavir and then restart bosentan 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 once patient receiving tipranavir for 1 wk; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) 24 hr before initiation of tipranavir and then restart tadalafil (Adcirca) 7 days later at 20 mg once daily.
• May ↑ sildenafil, tadalafil, and vardenafil levels in patients being treated for erectile dysfunction; do not exceed the following starting doses (sildenafil 25 mg within 48 hr; tadalafil 10 mg every 72 hr; vardenafil 2.5 mg every 72 hr).
• May ↓ levels of abacavir, atazanavir, dolutegravir, fosamprenavir, lopinavir, raltegravir, and zidovudine; separate tipranavir doses by 2 hr.
• May ↓ levels of etravirine; avoid concurrent use.
• May ↑ levels of rilpivirine.
• Antacids↓ absorption (separate dosing).
• May ↓ effectiveness of hormonal contraceptives.
• Enfuvirtide and atazanavir may ↑ levels.
• Fluconazole may ↑ levels; fluconazole doses >200 mg/day not recommended.
• May ↑ levels of ketoconazole and itraconazole; ketoconazole and itraconazole doses >200 mg/day not recommended.
• May ↑ clarithromycin levels; clarithromycin may also ↑ tipranavir levels.
• May ↑ rifabutin levels; ↓ rifabutin dose by 75%.
• Carbamazepine, phenytoin, phenobarbital, and buprenorphine/naloxone may ↓ levels
• May ↓ valproic acid levels.
• May ↑trazodone, desipramine, fluoxetine, paroxetine, and sertraline levels; ↓ dose of trazodone and desipramine.
• May ↑ quetiapine levels; ↓ quetiapine dose to 1/6 of current dose.
• May ↓ meperidine and methadone levels.
• May ↓ omeprazole levels.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; concurrent use contraindicated.

• PO (Adults): 500 mg twice daily with ritonavir 200 mg twice daily.
• PO (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;

• 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.

• 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 (ULN) or symptomatic ↑ of AST and ALT of 5–10 times the ULN and bilirubin ↑ 2.5 time the ULN 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.

• PO: 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 prior to opening the bottle. Once bottle is opened, store at room temperature. Use within 60 days of opening bottle.

• 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 Rx refill in case of changes. 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.
• 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, especially St. John's wort.
• Inform patient that tipranavir does not cure HIV or prevent associated or opportunistic infections. Tipranavir may 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 HIV 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 females of reproductive potential taking oral contraceptives to use a nonhormonal method of birth control during tipranavir therapy. If pregnancy is suspected, notify health care professional promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise females to avoid breastfeeding during therapy.
• Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

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

Aptivus