[Posted 3/1/2012]ISSUE:FDA notified healthcare professionals of updates to the prescribing information concerning interactions between protease inhibitors and certain statin drugs. Protease inhibitors and statins taken together may raise the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.
BACKGROUND:Statins are a class of prescription drugs used together with diet and exercise to reduce blood levels of low-density lipoprotein (LDL) cholesterol (''bad cholesterol''). HIV protease inhibitors are a class of prescription anti-viral drugs used to treat HIV. HCV protease inhibitors are a class of prescription anti-viral drugs used to treat hepatitis C infection.
RECOMMENDATION:Healthcare professionals should follow the recommendations in the prescribing information (drug labels) when prescribing HIV or HCV protease inhibitors with statins. See the FDA Drug Safety Communication for additional information, including a data summary. For more information visit the FDA website at: Web Siteand Web Site.
Tipranavir (taken with ritonavir [Norvir]) may cause bleeding in the brain. This condition may be life-threatening. Tell your doctor if you have recently had surgery or if you have recently been injured in any way. Also tell your doctor if you have a bleeding disorder such as hemophilia (condition in which the blood does not clot normally). Tell your doctor and pharmacist if you are taking any of the following medications: anticoagulants ('blood thinners') such as warfarin (Coumadin), aspirin or products containing aspirin, cilostazol (Pletal), clopidogrel (Plavix), or ticlopidine (Ticlid). You should also tell your doctor and pharmacist if you are taking vitamin E, other than the amount contained in a regular daily multivitamin. If you need to get emergency medical treatment for any reason, be sure to tell all of the doctors who treat you that you are taking tipranavir. Call your doctor immediately if you experience unusual bruising or bleeding during your treatment with tipranavir.
Tipranavir (taken with ritonavir [Norvir]) may cause liver damage that may be life-threatening. Tell your doctor if you have or have ever had hepatitis (swelling of the liver caused by a virus) or any other liver disease or if you drink or have drunk alcohol. If you experience any of the following symptoms, stop taking tipranavir and call your doctor immediately: tiredness; weakness; flu-like symptoms; loss of appetite; nausea; vomiting; pain, ache, swelling, or sensitivity on your right side below your ribs; yellowing of the skin or eyes; dark (tea-colored) urine; or pale bowel movements.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to tipranavir.
Talk to your doctor about the risks of taking tipranavir.
Tipranavir is used with ritonavir (Norvir) and at least 2 other medications to treat human immunodeficiency virus (HIV). Tipranavir is in a class of medications called protease inhibitors. It works by slowing the spread of HIV in the body. Tipranavir does not cure HIV infection and may not prevent you from developing HIV-related illnesses. Tipranavir does not prevent you from spreading HIV to other people.
Tipranavir comes as a capsule and an oral solution (liquid) to take by mouth. It is taken with ritonavir, usually twice a day, with or without food. Take tipranavir and ritonavir at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tipranavir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Do not take tipranavir without ritonavir.
Swallow the capsules whole; do not chew them. If you are unable to swallow the capsules, tell your doctor or pharmacist.
Tipranavir helps to control HIV infection but does not cure it. Continue to take tipranavir even if you feel well. Do not stop taking tipranavir without talking to your doctor. If you stop taking tipranavir or skip doses, your condition may become more difficult to treat. When your supply of tipranavir starts to run low, get more from your doctor or pharmacist.
Ask your doctor or pharmacist for a copy of the manufacturer's information for the patient. Read this information carefully and ask your doctor or pharmacist if you have any questions.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before taking tipranavir,
- tell your doctor and pharmacist if you are allergic to tipranavir, ritonavir (Norvir), sulfa medications, any other medications, or any of the ingredients in tipranavir. Ask your pharmacist if you are unsure if a medication you are allergic to is a sulfa medication.
- do not take tipranavir if you are taking cisapride (Propulsid); astemizole (Hismanal) (no longer available in the US); ergot medications for migraines such as dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylate (Hydergine), ergonovine (Ergotrate), ergotamine (Bellamine, Cafergot, Ergomar, others), or methylergonovine (Methergine); certain medications for irregular heartbeat including amiodarone (Pacerone), bepridil (Vascor) (no longer available in the US), flecainide (Tambocor), lovastatin (Altoprev, Mevacor, in Advicor), propafenone (Rythmol), or quinidine (Quinaglute); midazolam (Versed) by mouth; pimozide (Orap); rifampin (Rifadin, Rimactane, in Rifater); simvastatin (Zocor, in Vytorin); St. John's wort; terfenadine (Seldane) (no longer available in the US); and triazolam (Halcion).
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antifungal medications such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend); calcium-channel blockers such as diltiazem (Cardizem, Dilacor, Tiazac, others), felodipine (Lexxel, Plendil), nicardipine (Cardene), nisoldipine (Sular), or verapamil (Calan, Covera, Isoptin, Verelan, others); certain cholesterol-lowering medications ('statins') such as atorvastatin (Lipitor, in Caduet) and rosuvastatin (Crestor); clarithromycin (Biaxin, in Prevpac); desipramine (Norpramin); disulfiram (Antabuse); estrogen hormone replacement therapy; fluticasone (Flonase, Flovent, in Advair); immunosuppressants such as cyclosporine (Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Prograf); medications for diabetes such as glimepiride (Amaryl), glipizide (Glucotrol, in Metaglip), glyburide (Diabeta, Glycron, Glynase, Micronase, others), pioglitazone (Actos, in Actoplus), repaglinide (Prandin), or tolbutamide; certain medications for erectile dysfunction including sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra); certain medications for seizures including carbamazepine (Carbatrol, Epitol, Tegretol), phenobarbital (Luminal), phenytoin (Dilantin, Phenytek), and valproic acid (Depakene, Depakote); other medications for HIV including abacavir (Ziagen, in Epzicom, in Trizivir), atazanavir (Reyataz), fosamprenavir (Lexiva), lopinavir (in Kaletra), saquinavir (Invirase), and zidovudine (AZT, retrovir, in Combivir, in Trizivir); meperidine (Demerol, in Mepergan); methadone (Dolophine, Methadose); metronidazole (Flagyl); omeprazole (Prilosec, Zegerid); rifabutin (Mycobutin); oral contraceptives; rifapentine (Priftin); selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac, Sarafem, in Symbyax), paroxetine (Paxil), or sertraline (Zoloft); and trazodone. Many other medications may also interact with tipranavir, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Be sure to talk to your doctor or pharmacist before you begin taking any new medications during your treatment with tipranavir. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- if you are taking didanosine, take it 2 hours before or 2 hours after you take tipranavir.
- if you are taking antacids, take them 1 hour before or 2 hours after you take tipranavir.
- tell your doctor if you have or have ever had diabetes or high blood sugar; high blood cholesterol or triglycerides (blood fats); or an infection that comes and goes such as tuberculosis (TB), cytomegalovirus (CMV), herpes, Mycobacterium avium, shingles, or pneumonia.
- you should know that some people with diabetes develop worsening of their diabetes while taking tipanavir. If you have diabetes, it is important to carefully monitor your blood sugar while taking tipranavir and call your doctor if your blood sugar becomes difficult to control. Your doctor may need to change your diabetes medication or prescribe new medication to control your blood sugar.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking tipranavir, call your doctor. Do not breast-feed if you are infected with HIV or are taking tipranavir.
- you should know that tipranavir may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, and injections). You will need to use another method of contraception to prevent pregnancy while taking tipranavir. Talk to your doctor about other ways to prevent pregnancy while you are taking this medication.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tipranavir.
- plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Tipranavir may make your skin sensitive to sunlight.
- you should know that your body fat may increase or move to different areas of your body such as the back of your neck and upper shoulders ('buffalo hump'), stomach, and breasts. Your body may lose fat from your arms, legs, face, and buttocks. Talk to your doctor if you notice any of these changes in your body fat.
Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine.
Take the missed dose together with ritonavir as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
Call your doctor immediately if you have any of the following symptoms of hyperglycemia (high blood sugar):
- extreme thirst
- frequent urination
- extreme hunger
- blurred vision
If high blood sugar is not treated, a serious, life-threatening condition called diabetic ketoacidosis could develop. Get medical care immediately if you have any of these symptoms:
- dry mouth
- nausea and vomiting
- shortness of breath
- breath that smells fruity
- decreased consciousness
Tipranavir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- weight loss
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:
- fever, chills, cough, or other signs of infection
- redness, blistering, or peeling of skin
- throat tightness
- difficulty breathing or swallowing
- muscle or joint pain or stiffness
Tipranavir may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store unopened bottles of tipranavir capsules in the refrigerator. Store opened bottles of tipranavir capsules at room temperature, and away from excess heat and moisture (not in the bathroom). Store tipranavir solution at room temperature. Do not refrigerate or freeze tipranavir solution. Mark the date you open the bottle of tipranavir on the label; if the medication is not used within 60 days, throw the remaining medication away. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
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.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: March 15, 2012.