Tipranavir

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Some people taking tipranavir with ritonavir have developed fatal medical problems including liver damage and bleeding in the brain. Stop taking this medicine and get emergency medical attention if you have:

• unusual bleeding, sudden severe headache, numbness, problems with speech or vision; or
• nausea, upper stomach pain, tired feeling, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Call your doctor at once if you have:

• severe skin rash, blistering, peeling, redness or sunburn;
• skin rash and also joint or muscle pain, fever, or tightness in your throat; or
• increased thirst, increased urination, hunger, dry mouth.

Tipranavir may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with tipranavir. Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;
• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;
• cold sores, sores on your genital or anal area;
• rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;
• severe lower back pain, loss of bladder or bowel control; or
• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common side effects may include:

• nausea, vomiting, diarrhea, stomach pain;
• skin rash (especially in children);
• headache, fever, tired feeling; or
• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Once HIV has infected a cell and made copies of itself, it uses an enzyme called protease to process itself correctly so it can be released from the cell to infect other cells. Protease inhibitors work by blocking that enzyme.

Mechanism of Action

Protease Inhibitor; inhibits cleavage of Gag-Pol polyprotein precursors, which in turn causes the formation of immature, noninfectious viral particles.

Pharmacokinetics

Bioavailability: Increased by food

Protein Bound: 99.9%

Vd: 7.7-10 L

Half-Life: 5.5-6 hr

Metabolism: primarily by liver CYP3A4

Excretion: Feces (82.3% ); urine (4%)

Peak plasma time: 3 hr

• HIV and AIDS: Antiretroviral Drugs, Treatments and Medications

Tipranavir is a prescription medicine used to treat adults with Human Immunodeficiency Virus (HIV). Tipranavir is always taken with Norvir (ritonavir).

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your healthcare professional about all of your medical conditions, including if you:

• have hemophilia or another medical condition that increases your chance of bleeding, or are taking medicines which increase your chance of bleeding. These patients may have an increased chance of bleeding.
• have liver problems or are infected with hepatitis B or hepatitis C. These patients may have worsening of their liver disease.
• are allergic to sulfa medicines.
• have diabetes. Tipranavir may worsen diabetes or high blood sugar levels.
• are pregnant or planning to become pregnant. It is not known if tipranavir can harm your unborn baby. You and your healthcare professional will need to decide if tipranavir is right for you. If you take tipranavir while you are pregnant, talk to your healthcare professional about how you can be in the Antiretroviral Pregnancy Registry.
• are breastfeeding. Do not breastfeed. It is not known if tipranavir can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.
• are using estrogens for birth control or hormone replacement. Women who use estrogens for birth control or hormone replacement have an increased chance of developing a skin rash while taking tipranavir. If a rash occurs, it is usually mild to moderate, but you should talk to your healthcare professional as you may need to temporarily stop taking either tipranavir or the other medicine that contains estrogen or female hormones.

Tell your healthcare professional about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements.

In the U.S.

• Aptivus

Available Dosage Forms:

• Solution
• Capsule, Liquid Filled

Therapeutic Class: Antiviral

Pharmacologic Class: Protease Inhibitor

• PNU-140690E
• TPV

• Aptivus

Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.

Absorption

Incomplete (percentage not established)

Distribution

Vd:

Children 2 to <6 years: 4 L

Children 6 to <12 years: 4.7 L

Children and Adolescents 12 to 18 years: 5.3 L

Adults: 7.7 to 10 L

Metabolism

Hepatic, via CYP3A4 (minimal when coadministered with ritonavir)

Excretion

Feces (82%); urine (4%); primarily as unchanged drug (when coadministered with ritonavir)

Time to Peak

Children and Adolescents 2 to 18 years: 2.5 to 2.7 hours; Adults: 3 hours

Half-Life Elimination

Children 2 to <6 years of age: ~8 hours, 6 to <12 years of age: ~7 hours, 12 to 18 years: ~5 hours; Adults: Males: 6 hours; Females: 5.5 hours

Protein Binding

>99% (albumin, alpha-1 acid glycoprotein)

HIV-1 infection, treatment: Oral: 500 mg twice daily; Note: Coadministration with ritonavir (200 mg twice daily) is required.

Capsule: Prior to opening bottle, store at 2°C to 8°C (36°F to 46°F). After bottle is opened, may be stored at 25°C (77°F) for up to 60 days.

Oral solution: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). After bottle is open, use within 60 days. Do not refrigerate or freeze oral solution.