Tipranavir

Tipranavir is a prescription medication used for 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; must be used with ritonavir in addition to other antiretrovirals.

• Tipranavir is available under the following different brand names: Aptivus

Common side effects of Tipranavir include:

• diarrhea
• nausea
• stomach pain
• drowsiness
• dizziness
• headache
• vomiting
• changes in the shape or location of body fat (especially in the arms, legs, face, neck, breasts, and waist)

Serious side effects of Tipranavir include:

• fever, chills, cough, or other signs of infection
• rash
• redness, blistering, or peeling of skin
• itching
• throat tightness
• shortness of breath
• weakness, numbness, and pain, in hands and feet
• difficulty breathing or swallowing
• muscle or joint pain or stiffness

Rare side effects of Tipranavir include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsule

• 250 mg

Oral solution

• 100 mg/mL

HIV Infection

Adult dosage

• 500 mg orally every 12 hours; coadministration with ritonavir 200 mg orally every 12 hours is required (boosted therapy)
• Administration with ritonavir is essential to achieve correct dosing and adequate blood levels

Pediatric dosage

• Children younger than 2 years: Safety and efficacy not established
• Children aged 2 years and older: 14 mg/kg plus ritonavir 6 mg/kg orally every 12 hours, or
• 375 mg/m² plus ritonavir 150 mg/m² orally every 12 hours
• Not to exceed the adult dose of 500 mg plus ritonavir 200 mg orally every 12 hours
• Administration with ritonavir is essential to achieve correct dosing and adequate blood levels
• Dose reduction
  • If not tolerated, may reduce dose if a patient does not have resistance to multiple protease inhibitors
  • 12 mg/kg plus ritonavir 5 mg/kg orally every 12 hours, or
  • 290 mg/m² plus ritonavir 115 mg/m² orally every 12 hours

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Tipranavir has severe interactions with at least 49 other drugs
• Tipranavir has serious interactions with at least 167 other drugs
• Tipranavir has moderate interactions with at least 277 other drugs
• Tipranavir has minor interactions with at least 28 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity
• Moderate-severe hepatic impairment (Child-Pugh Class B & C)
• Drugs that are contraindicated with tipranavir (when coadministered 'boosted' with ritonavir) include alpha1-adrenoreceptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for PAH), midazolam, and triazolam

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Tipranavir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Tipranavir?”

Cautions

• Caution in mild hepatic impairment
• Risk of severe, potentially fatal hepatotoxicity
• Not recommended in treatment-naive patients
• May have antiplatelet/anticoagulant action
• Risk of potentially fatal intracranial hemorrhage
• Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs
• Fat redistribution with "cushingoid appearance" and "buffalo hump" may occur
• Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment
• Must be coadministered with ritonavir
• Sulfonamide allergy
  • Coadministration with other CYP3A4 substrates (ritonavir inhibits CYP3A4 and increases toxicity risk for drugs metabolized by CYP3A4)
• Increased risk of rash, especially with hormonal contraceptives
• Use of drug may reduce the efficacy of estrogen-based oral contraceptives; advise patients to use alternative methods of nonhormonal contraception
• Risk of large increase in total cholesterol and triglycerides
• Contains 116 IU/mL vitamin E (above RDA); limit supplemented vitamin E

Pregnancy and Lactation

• The pregnancy exposure registry monitors pregnancy outcomes in women exposed to drugs during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
• Prospective pregnancy data from the APR and an Expanded Access program are not sufficient to adequately assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; tipranavir use during pregnancy has been evaluated in a limited number of women as reported by the APR and an Expanded Access program, and available data show no birth defects in 13 first trimester exposures compared with the background rate for major birth defects of 2.7% in the US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); rate of miscarriage not reported in the APR; methodological limitations of APR include the use of MACDP as the external comparator group; MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation
• In animal reproduction studies, fetal toxicities were observed with Tipranavir at maternally toxic doses with systemic exposures (AUC) less than those in humans at the recommended human dose
• Based on prospective reports to APR and an Expanded Access program for approximately 17 live births following exposure to Tipranavir-containing regimens (including 13 live births exposed in the first trimester and 4 live births exposed in the second/third trimester), there were no birth defects reported in live-born infants; Tipranavir has been shown to cross the placenta
• Lactation
  • The CDC recommend that HIV-1 infected mothers in the US not breast-feed their infants to avoid risking postnatal transmission of HIV-1 infection; there is no information regarding the presence of tipranavir in human milk, its effects on breastfed infants, or milk production; tipranavir is present in rat milk; because of potential for (1) HIV-1 transmission (in HIV-negative infants), developing viral resistance (in HIV-positive patients), and any possible adverse effects of drug, mothers should not breastfeed if they are receiving drug