FactSHEET

FOSAMPRENAVIR (Telzir)

Summary Fosamprenavir is a type of anti-HIV drug called a protease inhibitor. The most common side effects of fosamprenavir can include gastrointestinal problems, headache, and rash. For treatment-naïve patients, it is usually taken at a dose of 1400 mg (two tablets) with 200 mg (two capsules) ritonavir once daily. For treatment-experienced patients, it is usually taken at a dose of 700 mg (one tablet) twice daily with 100 mg (one capsule) ritonavir also twice daily. Both medications may be taken with or without food.

What is fosamprenavir? active, anti-HIV form called amprenavir. Since amprenavir inhibits, or reduces the activity of Fosamprenavir, sold under the brand name this enzyme, this drug causes HIV-infected Telzir (Lexiva in the US), is a type of anti-HIV cells to produce fewer viruses. (antiretroviral) drug called a protease inhibitor (PI). Fosamprenavir is used in combination with other anti-HIV drugs to treat (but not cure) How do people with HIV/AIDS HIV/AIDS. use fosamprenavir? Fosamprenavir is used in combination with How does fosamprenavir work? several other anti-HIV drugs, usually nukes To explain how fosamprenavir works, we need (nucleoside analogues), and sometimes to first tell you some information about HIV. including drugs from other classes such as When HIV infects a cell, it takes control of non-nukes (non-nucleoside reverse that cell. HIV then forces the cell to make transcriptase inhibitors). Combinations such many more copies of the virus. In order to as this are called highly active antiretroviral make these copies, the cell uses proteins therapy, or HAART. For more information on called enzymes. When the activity of these HAART, see CATIE’s Practical Guide to HAART enzymes is reduced or blocked, production of for People Living with HIV/AIDS at HIV slows or stops. www.catie.ca/PG_HAART_e.nsf. Fosamprenavir belongs to a group or class of For many people with HIV/AIDS (PHAs), the drugs called protease inhibitors. Fos- use of HAART has increased their CD4+ cell amprenavir interferes with an enzyme called counts and decreased the amount of HIV in protease, which is used by HIV-infected cells their blood (viral load). These beneficial effects to make new viruses. Once fosamprenavir is help to reduce the risk of developing a life- absorbed in the body, it is converted to its threatening infection. Neither fosamprenavir nor any other anti-HIV medication is a cure

CATIE FactSHEET FOSAMPRENAVIR, page 1 of 6 for HIV/AIDS. It is therefore important that you 3. Rash do the following: Rash can be a side effect of fosamprenavir. • see your doctor regularly so that he/she However, this is usually mild and can clear monitors your health within two or three weeks. However, in cases • continue to practice safer sex and take other of severe rash, or rash of moderate intensity precautions so as not to pass HIV on to that is accompanied by other symptoms, it is other people important to contact your doctor right away because fosamprenavir must be discontinued. Side effects In clinical trials, less than 1% of fosamprenavir users developed a severe or life-threatening 1. General rash (Stevens-Johnson syndrome). Common side effects that have been reported 4. Lipodystrophy syndrome by some fosamprenavir users include the following: The HIV lipodystrophy syndrome is the name given to a range of symptoms that can develop • nausea over time when people use HAART regimens. • abdominal pain Some features of the lipodystrophy syndrome • vomiting include: • diarrhea • loss of fat just under the skin (subcutaneous • headache fat) in the face, arms, and legs • lack of energy • bulging veins in the arms and/or legs due to the loss of fat under the skin Most of these side effects were either mild or • increased waist and belly size moderate in severity. Also, if they did occur, these side effects happened early in the course • fat pads at the back of the neck (“buffalo of fosamprenavir therapy. hump”) or at the base of the neck (“horse collar”) 2. Abnormal laboratory results • small lumps of fat in the abdomen Between 4% and 8% of fosamprenavir users • increased breast size (in women) have developed severely or dangerously elevated levels of the following in their blood: Together with these physical changes, lab tests of your blood may detect the following: • ALT (alanine aminotransferase or SGPT) – a liver enzyme • increased levels of fatty substances called triglycerides • AST (aspartate aminotransferase or SGOT) – a liver enzyme • increased levels of LDL-cholesterol (low- density lipoprotein) or “bad” cholesterol • lipase – an enzyme produced by the pancreas gland • increased levels of sugar (glucose) • triglycerides – a fatty substance • increased levels of the hormone insulin • decreased sensitivity to insulin (insulin The reasons for increased levels of these resistance) substances are not clear. In some cases they may suggest liver damage (in the case of liver • decreased levels of HDL-cholesterol (high- enzymes), an inflamed pancreas gland density lipoprotein) or “good” cholesterol (elevated lipase) or an increased risk for The precise causes of the HIV lipodystrophy cardiovascular disease (high triglycerides). It syndrome are not clear and are difficult to is important to discuss your lab test results understand because in some PHAs there may with your doctor(s) and nurse. CATIE FactSHEET FOSAMPRENAVIR, page 2 of 6 be one or more aspects of the syndrome taking • adjust your dose of either your anti-HIV drugs place. For instance, some people may or other medication experience fat wasting, others fat gain, and • prescribe different anti-HIV drugs for you others may experience both fat gain and wasting. What is becoming increasingly clear is that unfavourable changes in the lab Drug interactions with readings of glucose, cholesterol, and fosamprenavir triglycerides over a period of several years increase the risk of diabetes and cardio- Below are lists of actual and potential drug vascular disease. So far, however, the many interactions. These lists are not exhaustive. benefits of HAART are much greater than the The manufacturer recommends that the increased risk of cardiovascular disease or following drugs should not be taken by other side effects. fosamprenavir users, because this could lead to serious (or life-threatening) reactions: Maintaining a normal weight, eating a healthy diet, exercising regularly and quitting smoking • anesthetics – lidocaine are all important in helping you to reduce your • antidepressants – tricyclic antidepressants risk of diabetes, heart disease, and other such as imipramine, amitriptyline complications. Regular visits to your doctor • antihistamines – astemizole (Hismanal), for checkups and blood tests are a vital part terfenadine (Seldane) of staying healthy. If necessary, your doctor can prescribe lipid-lowering therapy. • anti-malaria drugs – halofantrine (Halfan) • anti-psychotic drugs – pimozide (Orap) Researchers are studying the lipodystrophy syndrome to try to discover ways of helping • blood thinning agents – warfarin (Coumadin) PHAs avoid or reduce this problem. To find • gastrointestinal motility agents – cisapride out more about options for managing aspects (Prepulsid) of the lipodystrophy syndrome, see CATIE’s • drugs for abnormal heart rhythms – Practical Guide to HIV Drug Side Effects at amiodarone (Codarone) , bepridil (Vascor) www.catie.ca/sideeffects_e.nsf. flecanaide (Tambocor), propafenone (Rhthmol), quinidine Drug interactions • migraine medications (ergot derivatives) – Always consult your doctor and pharmacist dihydroergotamine (Migranal), ergotamine about taking any other prescription or non- (Ergomar), ergonovine prescription medication, including herbs, • anti-anxiety agents – midazolam (Versed), supplements, and recreational drugs. triazolam (Halcion), diazepam (Valium), flurazepam (Dalmane) Some drugs can interact with fosamprenavir, increasing or decreasing its levels in your body. The following drugs can increase levels of Increased drug levels can cause you to fosamprenavir in the blood: experience side effects or make pre-existing side effects worse. On the other hand, if drug • HIV protease inhibitors – indinavir (Crixivan) levels become too low, HIV can develop • HIV nukes – abacavir (Ziagen), AZT resistance and your future treatment options (zidovudine) may be reduced. • HIV non-nukes – efavirenz (Sustiva) If you must take a drug that has the potential • antibiotics – clarithromycin (Biaxin) to interact with your existing medications, your • anti-fungal agents – ketoconazole (Nizoral), doctor can do the following: itraconazole (Sporanox)

CATIE FactSHEET FOSAMPRENAVIR, page 3 of 6 The following drugs can decrease levels of Fosamprenavir can decrease the levels of the fosamprenavir in the blood: following drugs: • antibiotics / anti-tuberculosis medications • antidepressants – paroxetine (Paxil), trazodone – rifampin, rifampicin. These drugs should • narcotics – methadone; monitoring for signs not be used with fosamprenavir of methadone withdrawal and adjusting the • herbs – St. John’s wort (hypericin, hyperforin) dose may become necessary in some people also using fosamprenavir • anti-ulcer medications – (histamine H2 receptor antagonists) such as cimetidine • hormones – estrogens, proestrogens and (Tagamet), ranitidine (Zantac) some glucocorticoids may interact with • anti-seizure medications – phenytoin fosamprenavir. Use of the steroid fluticasone (Dilantin), carbamazepine (Tegretol), (Advair, Flonase, Flovent) should be avoided phenobarbital by fosamprenavir users. Fosamprenavir can increase levels of the following drugs in the blood: Resistance and cross-resistance • antibiotics – clarithromycin, dapsone, erythromycin, rifabutin (Mycobutin). If Over time, as new copies of HIV are made in rifabutin must be used, then the dose of the body, the virus changes its structure. These this drug should be reduced by at least 75%. changes are called mutations and can cause Regular blood tests are necessary to ensure HIV to resist the effects of anti-HIV drugs, that bone marrow damage does not occur. which means those drugs will no longer work for you. Combining fosamprenavir with at least • anti-fungal agents – itraconazole (Sporanox), two other anti-HIV drugs delays the ketoconazole (Nizoral) development of drug resistance. • erectile dysfunction (ED) medications – sildenalfil (Viagra), vardenafil (Levitra) and To reduce the risk of developing drug tadalafil (Cialis). When taken by users of resistance, all anti-HIV drugs should be taken fosamprenavir, these medications can reach every day exactly as prescribed and directed. very high levels in the blood, causing If doses are delayed, missed, or not taken as dangerous side effects. If you have difficulty prescribed, levels of fosamprenavir in the blood getting or maintaining an erection speak to may fall too low. If this happens, resistant virus your doctor about how you might safely use can develop. If you find you are having these ED medications. problems taking your medications as directed, speak to your doctor and nurse about this. • lipid-lowering medications commonly called They can find ways to help you. statins – lovastatin (Mevacor) and simvastatin (Zocor) are not recommended When HIV becomes resistant to one drug in a for use by people taking fosamprenavir. class, it sometimes becomes resistant to other When using other statins such as drugs in that class. This is called cross-resistance. atorvastatin (Lipitor), the lowest possible Feel free to talk with your doctor about your dose should be used and should not exceed current and future treatment options. To help 20 mg. Other statins such as fluvastatin you decide what these future therapies might (Lescol) and pravastatin (Pravachol) may be be, at some point your doctor can have a small considered. sample of your blood analysed using resistance • transplant medications – levels of the testing. Should HIV in your body become following may be increased in users of resistant to fosamprenavir, your doctor, with fosamprenavir: cyclosporine (Neoral), the help of resistance testing, can help put rapamycin (Sirolimus, Rapamune), together a new treatment regimen for you. tacrolimus (Prograf).

CATIE FactSHEET FOSAMPRENAVIR, page 4 of 6 Dosage and formulations References Fosamprenavir is available as 700 mg tablets Raquin G, Poizat G, Morand-Joubert L, et al. Salvage therapy and in a liquid formulation. with amprenavir, lopinavir and ritonavir is durably potent in HIV-infected patients in virological failure: 1-year results. AIDS Fosamprenavir is not well absorbed on its own 2007;21(2):241-243. and it is almost always taken in combination Ruane P, Luber AD, Wire MB, et al. Plasma amprenavir with another drug, called ritonavir (Norvir), pharmacokinetics and tolerability following administration of 1,400 milligrams of fosamprenavir once daily in combination which ‘boosts’ the absorption of fosamprenavir. with either 100 or 200 milligrams of ritonavir in healthy This combination of drugs is written as volunteers. Antimicrobial Agents and Chemotherapy fosamprenavir/r. 2007;51(2):560-565. Eron J, Yeni P, Gathe J, et al. The KLEAN study of For adults, there are several doses and fosamprenavir-ritonavir versus lopinavir-ritonavir, each in schedules that may be used when taking combination with abacavir-lamivudine, for initial treatment of fosamprenavir/r. For instance, in people who HIV infection over 48 weeks: a randomised non-inferiority trial. have never used protease inhibitors and who Lancet 2006;368(9534):476-482. are new to therapy, fosamprenavir/r may be GlaxoSmithKline Inc. Telzir Product monograph July 19, 2006. taken once daily at a dose of 1400 mg Wire MB, Baker KL, Jones LS, et al. Ritonavir increases plasma fosamprenavir (two tablets) with 200 mg amprenavir (APV) exposure to a similar extent when coadministered with either fosamprenavir or APV. Antimicrobial ritonavir (two capsules). Agents and Chemotherapy 2006;50(4):1578-1580. For treatment-experienced PHAs, the recom- Wire MB, Shelton MJ, Studenberg S. Fosamprenavir: clinical mended dose of fosamprenavir/r is 700 mg pharmacokinetics and drug interactions of the amprenavir prodrug. Clinical Pharmacokinetics 2006;45(2):137-168. fosamprenavir (one tablet) twice daily, along with 100 mg ritonavir (one capsule) also twice Zhou H, Gurley EC, Jarujaron S, et al. HIV protease inhibitors activate the unfolded protein response and disrupt lipid daily. Both medications can be taken with or metabolism in primary hepatocytes. American Journal of without food. Physiology - Gastrointestinal and Liver Physiology 2006;291(6):G1071-1080. Formulations can change, and dosages may Chapman TM, Plosker GL, Perry CM. Fosamprenavir: a review need to be customized. All medications should of its use in the management of antiretroviral therapy-naive always be taken as prescribed and directed. patients with HIV infection. Drugs 2004;64(18):2101-2124. Availability Fosamprenavir is licensed in Canada for the treatment of HIV infection in adults, in combination with other anti-HIV drugs. Your doctor can tell you more about the availability and coverage of fosamprenavir in your region. CATIE’s online module, Federal, Provincial and Territorial Drug Access Programs (on CATIE’s website at www.catie.ca/eng/Publications/ drugaccess/drugaccessIndex.shtml) also contains information about Canadian drug coverage. Credits Author: SR Hosein, D Thaczuk Design: Renata Lipovitch 2007

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