What is Aptivus?

• Aptivus is an HIV medication. It is in a category of HIV medicines called protease inhibitors (PIs). Aptivus prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.
   
• Aptivus must be used in combination with Norvir (ritonavir) and other HIV drugs.
   
• Aptivus, manufactured by Boehringer Ingelheim, was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) in June 2005. Aptivus/ritonavir is only approved for HIV-infected people who have tried and failed HIV drug regimens (including those containing protease inhibitors) in the past. It is not approved for HIV-infected people starting HIV treatment, or a protease inhibitor, for the first time (unless they were infected with a strain of HIV resistant to multiple protease inhibitors).
   
• Boehringer Ingelheim has established a patient assistance program (PAP) for people living with HIV who do not have private or public health insurance and are unable to afford Aptivus. To learn more about the PAP for Aptivus, call 800-556-8317.

• Aptivus has a different structure than other protease inhibitors and is active against strains of the virus that are resistant to the other protease inhibitors that are currently available.
   
• The correct dose of Aptivus is 500mg twice a day (two 250mg capsules twice daily) . To help keep levels of Aptivus high in the blood, which is very important for the drug to be effective, it is necessary to combine Aptivus with low doses (200mg twice daily) of the protease inhibitor Norvir (ritonavir).
   
• Aptivus/ritonavir can be taken with or without food.
   
• Aptivus is recommended by the U.S. Department of Health and Human Services (DHHS) for HIV-positive people who have tried and failed other protease inhibitors in the past. It is not recommended by the DHHS for patients who are new to HIV treatment or starting a protease inhibitor for the first time.
   
• Clinical trials have demonstrated that Aptivus is an effective option for patients who are not likely to respond to older protease inhibitors, especially when it is combined with other HIV medications that a patient's virus is still at least partially sensitive to.
   
• Aptivus/ritonavir works best when it is combined with HIV drugs that the virus is still sensitive to. However, this can be challenging for HIV-positive people who have tried and failed several HIV drug regimens in the past. Drug resistance tests, such as genotypic assays and phenotypic assays, can be very useful in figuring out which HIV drugs the virus is still likely to respond to. Drug-resistance tests are recommended when putting together a regimen that contains Aptivus/ritonavir. In clinical trials, Aptivus/ritonavir worked best when it was combined with Fuzeon (enfuvirtide; T-20), particularly in people who had not been on Fuzeon in the past.
   
• A clinical trial of Aptivus has been discontinued due to limited effectiveness, along with earlier concerns of liver toxicities, in patients starting treatment for the first time. These study results suggest that Aptivus will not likely be a recommended protease inhibitor option for HIV-positive people starting therapy for the first time.
   
• Aptivus is approved for children between 2 and 18 years of age. The dose will depend on the child's body weight (or size). The recommended Aptivus dose in 14 mg per kilogram (mg/kg) of body weight, combined with 6 mg/kg of Norvir, taken twice a day (not exceeding a maximum dose of 500 mg Aptivus plus 200 mg Norvir). For children unable to swallow capsules, a liquid formulation of Aptivus is available. To learn about treatment options for children, click here.

• Because of the ways Aptivus and ritonavir are metabolized (broken down) in the body, they can interact with many other medications used to treat HIV, AIDS-related complications, and other diseases. Aptivus/ritonavir may cause blood levels of other medications to be become too low (which can decrease their effectiveness) or high (which can increase the risk of side effects). Similarly, other medications may cause blood levels of Aptivus and/or ritonavir to become too low or high.
   
• Tell your doctors and pharmacists about all medicines you take. This includes those you buy over-the-counter and herbal or natural remedies, such as St. John's wort. Bring all your medicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.
   
• The following medications should not be taken while you are being treated with Aptivus/ritonavir:
  Antifungals: Vfend (voriconazole)
  Acid reflux/heartburn medications: Propulsid (cisapride)
  Antibiotics: Rifadin (rifampin)
  Antimigraine medications: Methergine, Methylergometrine (methylergonovine); Ergostat, Cafergot, Ercaf, Wigraine (ergotamine); Ergotrate, Methergine (ergonovine); or D.H.E. 45, Migranal (dihydroergotamine)
  Heart medications: Cordarone (amiodarone), Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), or Quinaglute/Quinidex (quinidine)
  Cholesterol-lowering drugs (statins): Zocor (simvastatin) and Mevacor (lovastatin)
  Antipsychotics: Orap (pimozide)
  Sedatives: Versed (midazolam) and Halcion (triazolam)
  Herbal products: St. John's wort
   
• Aptivus/ritonavir can greatly decrease the levels of other protease inhibitors—including Lexiva (fosamprenavir), Kaletra (lopinavir), and Invirase (saquinavir)—in the blood. It is currently recommended that Aptivus/ritonavir not be taken with other protease inhibitors, until adequate drug-interaction and dosing studies have been completed.
   
• Aptivus/ritonavir can interact with HIV nucleoside reverse transcriptase inhibitors (NRTIs). Aptivus/ritonavir decreases Ziagen (abacavir) levels in the blood by 40% and Retrovir (zidovudine) levels by 35%. It might be necessary to increase the doses of Ziagen or Retrovir, if they are combined with Aptivus/ritonavir. However, no dosing recommendations have been made. Aptivus/ritonavir can also decrease levels of Videx EC (didanosine) in the blood. In turn, Aptivus/ritonavir should be taken at least two hours before or two hours after taking Videx/Videx EC.
• Aptivus/ritonavir may interact with HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). Aptivus/ritonavir blood levels may be decreased by efavirenz (found in Sustiva and Atripla). No change in the dose of either drug is recommended if combined. Aptivus/ritonavir can significantly lower blood levels of Intelence (etravirine), and combining these drugs is not recommended.  
   
• Aptivus/ritonavir can interact with some medications used to treat thrush (candidiasis) and other fungal infections. Diflucan (fluconazole) can increase Aptivus levels in the blood (total daily dose of Diflucan should not exceed 200mg). Aptivus/ritonavir may increase Sporanox (itraconazole) or Nizoral (ketoconazole) levels in the bloodstream (total daily doses of Sporanox and Nizoral should not exceed 200mg). It is also possible that Aptivus/ritonavir either increases or decreases Vfend (voriconazole) levels in the blood.
   
• Aptivus/ritonavir can interact with some medications used to treat TB, MAC, and other bacterial infections. Aptivus/ritonavir raises Biaxin (clarithromycin) levels in the bloodstream. Similarly, Biaxin raises Aptivus levels in the bloodstream. The dose of Biaxin does not need to be decreased, although this may be necessary in people with altered kidney function. Aptivus/ritonavir can also increase Mycobutin (rifabutin) levels in the bloodstream. If Mycobutin is taken at the same time as Aptivus/ritonavir, it is recommended that the Mycobutin dose be reduced to 150mg every other day.
   
• Aptivus/ritonavir may interact with calcium channel blockers, medications used to treat heart disease. Studies of Aptivus/ritonavir combined with calcium channel blockers have not yet been conducted. Healthcare providers should be cautious when prescribing Aptivus/ritonavir with either Cardizem (diltiazem), Plendil/Lexxel (felodipine), Cardene (nicardipine), Sular (nisoldipine), or Calan/Verelan (verapamil). Aptivus/ritonavir should not be combined with Vascor (bepridil).
   
• Aptivus/ritonavir may also effect the blood levels of Coumadin (warfarin), and anti-coagulating drug used to treat people at risk of blood clots. Providers should frequently check blood levels of Coumadin, known as the international normalization ratio (INR).
   
• Aptivus/ritonavir may alter the blood levels of drugs used to treat diabetes, including: Amaryl (glimepiride), Glucotrol (glipizide), Micronase (glyburide), Actos (pioglitazone), Prandin (repaglinide) and Tol-Tab (tolbutamide). The effect on blood levels of these drugs varies. People should monitor their blood sugar carefully.
   
• Aptivus/ritonavir can interact with drugs used to treat depression. Aptivus/ritonavir may increase blood levels of Norpramin (desipramine). The dose of Norpramin may need to be decreased. Similarly, Aptivus/ritonavir can increase blood levels of Desyrel (trazadone), making Desyrel side effects more likely. Prozac (fluoxetine), Paxil (paroxetine) and Zoloft (sertraline) blood levels may also be increased by Aptivus/ritonavir, though no changes in dosing are recommended.
   
• Antabuse (disulfiram) is a medication taken by people with an alcohol-dependency problem. This medication can make people very sick if they consume even small amounts of alcohol. Because Aptivus/ritonavir contains small amounts of alcohol, it should not be combined with Antabuse.
   
• Flagyl (metronidazole) is used to treat some types of parasitic infections. People should not drink alcohol—or take medications that contain alcohol (such as Aptivus/ritonavir)—while taking this drug. The combination of alcohol and Flagyl can cause someone to become very ill. In turn, HIV-positive people taking Aptivus/ritonavir should not take Flagyl.
   
• Cholesterol-lowering drugs, also known as "statins," can interact with Aptivus/ritonavir. There are two statins that should not be used with Aptivus/ritonavir: Zocor (simvastatin) and Mevacor (lovastatin). Levels of these two drugs can become significantly increased in the bloodstream if they are combined with Aptivus/ritonavir, which increases the risk of side effects. The two statins that are believed to be the safest in combination with Aptivus/ritonavir are Pravachol (pravastatin) and Lescol (fluvastatin). It is also possible to take Aptivus/ritonavir with Lipitor (atorvastatin) or Crestor (rosuvastatin) although Aptivus/ritonavir can increase the levels of these drugs in the bloodstream. If Lipitor or Crestor is prescribed, it's best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary.
• Aptivus/ritonavir may have an unpredictable effect on the blood levels of drugs used to suppress the immune system, including Sandimmune (cyclosporine), Rapamune (sirolimus, rapamycin) and Prograf (tacrolimus). It is recommended that blood levels of the immune suppressants be checked regularly.
   
• Aptivus/ritonavir can significantly increase blood levels of the inhaled steroid, Flonase (fluticasone), used to treat allergies. This may increase the risk of side effects from Flonase, including Cushing's syndrome. Combining these drugs is not recommended unless the possible benefits from Flonase outweigh the risks.
   
• Aptivus/ritonavir may decrease blood levels of the stomach-acid reducer Prilosec (omeprazole). The dose of Prilosec may need to be increased.
   
• People taking anti-seizure medication may need to use caution when combining these medications with Aptivus/ritonavir. Tegretol (carbamazepine), Luminal (phenobarbital) and Dilantin (phenytoin) can all decrease blood levels of Aptivus, making the Aptivus less effective. Aptivus/ritonavir may decrease blood levels of Depakote (valproic acid), making the Depakote less effective.  
   
• Demerol (meperidine) is a powerful analgesic (painkiller). Aptivus/ritonavir can decrease meperidine, but can increase the amount of normeperidine (an active byproduct of Demerol), in the bloodstream. In turn, Demerol should be used cautiously if it must be combined with Aptivus/ritonavir.
   
• Another painkiller, methadone, commonly used to treat drug heroin addiction, can interact with Aptivus/ritonavir. Methadone levels in the bloodstream can decrease when combined with Aptivus/ritonavir. Because of this, it might be necessary to increase the dose of methadone.
   
• Aptivus/ritonavir decreases the amount of oral contraceptives (taken by women to help avoid pregnancy) in the bloodstream. This means that there may be a higher risk of becoming pregnant if Aptivus/ritonavir and oral contraceptives are taken at the same time. To reduce the risk of pregnancy, barrier protection (e.g., condoms) should be used.
• Children (or adults) using the liquid version of Aptivus should not take vitamin E supplements in excess of the amount found in a single multivitamin. This is because liquid Aptivus already contains vitamin E.  
   
• Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) levels in the bloodstream may increase when combined with Aptivus/ritonavir. In turn, it is best to use a lower dose of these drugs in order to reduce the risk of side effects.

• The most common short-term side effects noticed in clinical trials involving HIV-positive people taking Aptivus/ritonavir were: nausea, vomiting, diarrhea, stomach pain, tiredness, and headache.
   
• Aptivus/ritonavir may increase the risk of intracranial hemorrhage (ICH)—bleeding in the brain due to ruptured blood vessels in the head—that can lead to stroke or death. Aptivus/ritonavir should be used with caution in patients who may have other risk factors for excessive bleeding from trauma, surgery or other medical conditions, or who are receiving medications known to increase the risk of bleeding (e.g., anticoagulants or antiplatelets used to prevent or treat heart attacks).
   
• Aptivus/ritonavir has been associated with reports of hepatitis and significant liver damage (hepatic decompensation), including some fatal cases. Extra caution is recommended for HIV-positive patients with chronic hepatitis B or hepatitis C, who are at the highest risk of liver-related side effects. Aptivus/ritonavir is not recommended for people with moderate to severe liver impairment (Child-Pugh Class B or C).
  
  All HIV-positive people receiving Aptivus/ritonavir should be carefully monitored. Liver function tests should be performed prior to starting treatment with Aptivus/ritonavir and rechecked frequently throughout the duration of treatment. HIV-positive people who develop symptoms of liver problems, such as fatigue, loss of appetite, yellowing of the eyes or skin, or liver tenderness, should consult their healthcare providers to discuss stopping Aptivus/ritonavir treatment. HIV-positive people with moderate to severe liver problems should not take Aptivus/ritonavir.
   
• Aptivus, a sulfa-containing drug, should be used with caution in patients with a known sulfa allergy. Mild to moderate rashes and increased sensitivity to the sun (photosensitivity) have been reported in HIV-positive people taking Aptivus/ritonavir. In clinical trials, rash was seen in 10 percent of females and in 8 percent of males receiving Aptivus/ritonavir. Additionally, in one drug interaction trial involving HIV-study female study volunteers who were administered a single dose of an oral contraceptive (ethinyl estradiol) followed by Aptivus/ritonavir, 33% developed a rash. Rash accompanied by joint pain or stiffness, throat tightness, or itching has been reported in both men and women receiving Aptivus/ritonavir. Women taking Aptivus/ritonavir with medications that contain estrogen have an increased risk of developing a rash.
   
• Some people may have large increases in their lipid levels (triglycerides and cholesterol). The long-term chance of getting complications such as heart attacks or stroke due to increases in blood lipids caused by protease inhibitors is not known at this time. Click here for our lesson called "Risks To Your Heart (Hyperlipidemia)".
   
• Diabetes and high blood sugar may occur in people who take Aptivus/ritonavir or other protease inhibitors.
   
• HIV drug regimens containing protease inhibitors, including Aptivus/ritonavir, can cause abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs). These side effects of HIV drug therapy are reviewed in our lesson on lipodystrophy.

• Aptivus/ritonavir is classified by the FDA as a pregnancy category C drug. Pregnancy category C means that animal studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. HIV-positive women who become pregnant should discuss the benefits and possible side effects of HIV treatment to help protect their babies from HIV (see our lesson called Family Planning, Pregnancy & HIV).
   
• It is not known whether Aptivus/ritonavir passes into breast milk and what effect it may have on a nursing baby. To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.

• If you would like to find out if you are eligible for any clinical trials that include Aptivus, there is an interactive web site run by ACRIA, the AIDS Community Research Initiative of America.
   
• Another useful service for finding clinical trials is AIDSinfo.nih.gov, a site run by the U.S. National Institutes of Health. They have "health information specialists" you can talk to at their toll-free number at 1-800-HIV-0440 (1-800-448-0440).