tipranavir

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, pimozide, lurasidone, rifampin, St. John's wort or triazolam;
Lactation: Breastfeeding is not recommended in females 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).

Adv. Reactions/Side Effects ⬆ ⬇

CV: INTRACRANIAL HEMORRHAGE, fatigue, headache

Derm: rash (↑ in women and children)

Endo: hyperglycemia

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

Hemat: bleeding

Metab: hypercholesterolemia, hypertriglyceridemia

Misc: fever, fat redistribution, immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

↑levels and risk of toxicity from some antiarrhythmics (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 raltegravir, abacavir, didanosine, zidovudine, atazanavir, fosamprenavir, lopinavir, and saquinavir levels; separate tipranavir and didanosine 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

Availability ⬆ ⬇

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

Route/Dosage ⬆ ⬇

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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

Decreased viral load and sequelae of HIV infection.

Classifications ⬆ ⬇

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99.9%.

Metabolism/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*)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2 hr	12 hr

* With ritonavir.

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 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.
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, especially St. John's Wort.
Inform patient that tipranavir does not cure AIDS 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 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.
Rep: Advise patient 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 female patient to avoid breastfeeding during therapy.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇