Abacavir & Lamivudine & Zidovudine

Abacavir/lamivudine/zidovudine is a prescription medication used to treat human immunodeficiency virus (HIV). It is a single tablet containing 3 medications, abacavir, lamivudine, and zidovudine. All 3 of these medicines are called nucleoside analogue reverse transcriptase inhibitors (NRTIs). When used together, they help lower the amount of HIV in your blood.

This medication comes in tablet form and is taken twice daily, with or without food.

Common side effects of this medication include nausea, headaches, tiredness, and diarrhea.

Abacavir/lamivudine/zidovudine is a prescription medicine used to treat HIV infection. It may be used alone or in combination with other medications.

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

Each tablet contains 300 mg of abacavir as abacavir sulfate, 150 mg of lamivudine, and 300 mg of zidovudine.

The recommended oral dose of abacavir/lamivudine/zidovudine for adults and adolescents is 1 tablet twice daily. Use is not recommended in adolescents who weigh less than 40 kg because it is a fixed-dose tablet.

WARNINGS

This medication contains 3 nucleoside analogues (abacavir sulfate, lamivudine, and zidovudine) and is intended only for patients whose regimen would otherwise include these 3 components.

Hypersensitivity Reactions:

Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir sulfate, a component of this medication. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: (1) fever, (2) rash, (3) gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain), (4) constitutional (including generalized malaise, fatigue, or achiness), and (5) respiratory (including dyspnea, cough, or pharyngitis). Discontinue this medication as soon as a hypersensitivity reaction is suspected.

Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended; this approach has been found to decrease the risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. HLA-B*5701-negative patients may develop a suspected hypersensitivity reaction to abacavir; however, this occurs significantly less frequently than in HLA-B*5701-positive patients.

Regardless of HLA-B*5701 status, permanently discontinue this medication if hypersensitivity cannot be ruled out, even when other diagnoses are possible.

Following a hypersensitivity reaction to abacavir, NEVER restart this medication or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death.

Reintroduction of this medication or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours.

Hematologic Toxicity:

Zidovudine has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced Human Immunodeficiency Virus (HIV-1) disease. Prolonged use of zidovudine has been associated with symptomatic myopathy.

Lactic Acidosis and Severe Hepatomegaly:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, zidovudine, and other antiretrovirals.

Exacerbations of Hepatitis B:

Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, which is one component of this medication. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue this medication and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Abacavir/lamivudine/zidovudine can cause serious side effects:

• Serious Allergic Reaction to abacavir. Patients taking abacavir/lamivudine/zidovudine may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not. Your doctor can determine with a blood test if you have this gene variation.

If you get a symptom from 2 or more of the following groups while taking abacavir/lamivudine/zidovudine, call your doctor right away to determine if you should stop taking this medicine:

• Group 1 Fever
• Group 2 Rash
• Group 3 Nausea, vomiting, diarrhea, abdominal (stomach area) pain
• Group 4 Generally ill feeling, extreme tiredness, or achiness
• Group 5 Shortness of breath, cough, sore throat

If you stop abacavir/lamivudine/zidovudine because of an allergic reaction, NEVER take this medication or any other abacavir-containing medicine, such as Ziagen and Epzicom, again. If you take this medication or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

If you stop abacavir/lamivudine/zidovudine, for any other reason, even for a few days, and you are not allergic to this medication, talk with your doctor before taking it again. Taking abacavir/lamivudine/zidovudine again can cause a serious or life-threatening reaction, even if you never had an allergic reaction to it before. If your doctor tells you that you can take this medication again, start taking it when you are around medical help or people who can call a doctor if you need one.

• Blood problems. Retrovir, one of the medicines in abacavir/lamivudine/zidovudine, can cause serious blood cell problems. These include reduced numbers of white blood cells (neutropenia) and extremely reduced numbers of red blood cells (anemia). These blood cell problems are especially likely to happen in patients with advanced human immunodeficiency virus (HIV) disease or AIDS. Your doctor should be checking your blood cell counts regularly while you are taking this medication. This is especially important if you have advanced HIV or AIDS. This is to make sure that any blood cell problems are found quickly.
• Lactic Acidosis. Some HIV medicines, including this medication, can cause a rare but serious condition called lactic acidosis with liver enlargement (hepatomegaly). Nausea and tiredness that don't get better may be symptoms of lactic acidosis. In some cases this condition can cause death. Women, overweight people, and people who have taken HIV medicines like abacavir/lamivudine/zidovudine for a long time have a higher chance of getting lactic acidosis and liver enlargement. Lactic acidosis is a medical emergency and must be treated in the hospital.
• Worsening of hepatitis B virus (HBV) infection. Patients with HBV infection who take abacavir/lamivudine/zidovudine and then stop it, may get flare-ups of their hepatitis. Flare-up is when the disease suddenly returns in a worse way than before. If you have HBV infection, your doctor should closely monitor your liver function for several months after stopping this medication. You may need to take anti-HBV medicines.
• Muscle weakness (myopathy). Retrovir, one of the medicines in abacavir/lamivudine/zidovudine, can cause muscle weakness. This can be a serious problem.
• Use with interferon- and ribavirin-based regimens. Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking abacavir/lamivudine/zidovudine as well as interferon with or without ribavirin and you experience side effects, be sure to tell your doctor.

This medication can have other serious side effects. Be sure to read the section below entitled "Side Effects" section.

Do not take abacavir/lamivudine/zidovudine if you:

• have ever had a serious allergic reaction (a hypersensitivity reaction) to abacavir/lamivudine/zidovudine or any other medicine that has abacavir as an ingredient such as Ziagen and Epzicom
• have a liver that does not function properly
• are an adolescent who weighs less than 90 pounds

Abacavir/lamivudine/zidovudine can cause the following serious side effects. See "Drug Precautions" section.

• Serious allergic reaction that can cause death.
• Lactic acidosis with liver enlargement (hepatomegaly) that can cause death.
• Worsening of hepatitis B viral infection. (See "Drug Precautions" section.)
• Blood problems.
• Muscle weakness.
• Changes in immune system. When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your doctor.
• Changes in body fat. These changes have happened in patients taking antiretroviral medicines like abacavir/lamivudine/zidovudine. The changes may include an increased amount of fat in the upper back and neck (buffalo hump), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known.

Some HIV medicines including abacavir/lamivudine/zidovudine may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes, tell your doctor.

The most common adverse events (5%) of at least moderate intensity associated with the use of abacavir/lamivudine/zidovudine include nausea, headache, weakness or tiredness, vomiting, hypersensitivity reaction, diarrhea, fever and/or chills, depression, muscle and joint pain, skin rashes, ear/nose/throat infections, cold symptoms, and nervousness.

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

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take any of the following medicines:

• methadone
• trimethoprim (TMP/sulfamethoxazole [SMX] [Bactrim, Septra])
• ganciclovir (Cytovene, DHPG)
• interferon-alfa
• doxorubicin (Adriamycin)
• ribavirin (Copegus, Rebetol, Virazole)
• any bone marrow suppressive medicines or cytotoxic medicines. Ask your doctor if you are not sure.
• any of the following anti-HIV medicines: Combivir (lamivudine and zidovudine), Emtriva (emtricitabine), Epivir or Epivir-HBV (lamivudine, 3TC), Epzicom (abacavir sulfate and lamivudine), Hivid (zalcitabine, ddC), Retrovir (zidovudine, AZT, or ZDV), Truvada (emtricitabine and tenofovir), Zerit (stavudine, d4T), or Ziagen (abacavir sulfate).

This is not a complete list of abacavir/lamivudine/zidovudine drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

If you take this medication while you are pregnant, talk to your healthcare provider about how you can take part in the Pregnancy Registry. The purpose of the pregnancy registry is to collect information about the health of you and your baby.

Tell your doctor if you are breastfeeding. Some of the ingredients in abacavir/lamivudine/zidovudine can be passed to your baby in your breast milk. It is not known if they could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.