Trizivir

Trizivir is a combination oral medication that is used for treating infections with the human immunodeficiency virus (HIV). Trizivir contains abacavir (Ziagen), lamivudine (Epivir) and zidovudine (Retrovir), which are three different anti-HIV drugs with different mechanisms of action. Anti-HIV drugs are often used in combination to increase HIV suppression and to reduce the chance of the HIV developing resistance to any single drug. Combining these three drugs into one pill reduces the number of individual medications that a patient has to take, which makes it easier for patients to comply with therapy. Administration of one tablet of Trizivir is equal to giving 300 mg of abacavir, 150 mg of lamivudine and 300 mg of zidovudine together. Trizivir does not reduce the transmission of HIV among individuals, and it does not cure HIV or AIDS. Trizivir was approved by the FDA in November 2000.

• Keep your regular appointments with your doctor so that your progress can be monitored. You will need to have regular blood tests to check how well your medicines are working.
• It is important that you continue to take zidovudine and your other antiretroviral treatment regularly. This will help to prevent the HIV from becoming resistant to the medicines you are taking. Even if you miss only a small number of doses, the virus can become resistant to treatment.
• If you develop an infection soon after you start the treatment, let your doctor know. As a result of taking zidovudine, your immune system may start fighting an infection which was present before you started the treatment, but which you may not have been aware of.
• Follow carefully any advice your doctor gives to you about making lifestyle changes to reduce any risk of damage to your heart and blood vessels. These can include stopping smoking, eating healthily and taking regular exercise.
• Some people taking antiretroviral medicines develop changes to the way body fat is distributed in the body. This can result in changes to body image. Your doctor will discuss the possibility of this with you.
• Although treatment with antiretroviral medicines may reduce the risk of you passing HIV to others through sexual contact, it does not stop it. It is important that you use condoms.
• It is not uncommon for people with HIV to feel low or even depressed, especially soon after the diagnosis has been made and treatment has been started. If you have any feelings of depression, or any distressing thoughts about harming yourself then you should speak with your doctor straightaway.
• Zidovudine has been associated with a serious side-effect in some people who have taken it. This is known as lactic acidosis. It is a problem where there is too much lactic acid in the blood. The symptoms associated with it are listed in the next section 'Can zidovudine cause problems?'. If you develop any of the symptoms listed below, you must let your doctor know straightaway, as they can worsen, and may even become life-threatening.
• Some people who have taken antiretroviral medicines (particularly over a long time) have developed a condition called osteonecrosis. This is a bone disease where bone tissue dies because there is a reduced blood supply to it. It leads to joint pains and stiffness, and can cause difficulties in movement. If you notice any of these symptoms, speak with your doctor.
• If you buy any medicines, supplements or herbal remedies 'over the counter', check with a pharmacist that they are suitable to take with zidovudine and your other medicines. This is because some medicines interfere with antiretrovirals and can stop them from working properly.
• If you are having an operation or dental treatment, tell the person carrying out the treatment which medicines you are taking.
• Treatment for HIV is usually lifelong. Continue to take zidovudine regularly for as long as your doctor tells you to, even if you feel well. This is to keep your immune system healthy.

Trizivir can cause serious side effects:

• Serious Allergic Reaction to abacavir. This medication contains abacavir which is also found in Ziagen and Epzicom. Patients taking Trizivir 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 Trizivir, 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 Trizivir because of an allergic reaction, NEVER take this medication or any other abacavir-containing medicine (Ziagen, 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 Trizivir, 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 Trizivir 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 Trizivir, 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 Trizivir 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 Trizivir 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 Trizivir, 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 Trizivir 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 Trizivir if you:

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

Before starting this medication, tell your doctor about all your medical problems, including if you:

• have been tested and know whether or not you have a particular gene variation called HLA-B*5701.
• are pregnant or planning to become pregnant. It is not known if this medication will harm your unborn child. You and your doctor will need to decide if Trizivir is right for you. If you use Trizivir while you are pregnant, talk to your doctor about how you can be on the Antiviral Pregnancy Registry for this medication.
• are breastfeeding. Some of the ingredients in Trizivir 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.
• have liver problems including hepatitis B virus infection.
• have kidney problems.
• have low blood cell counts (bone marrow problem). Ask your doctor if you are not sure.
• 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 about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

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.

If you take too much this medication, call your doctor or poison control center right away.

If Trizivir is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Tell all of your health care providers that you take Trizivir. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may raise the chance of heart attack. Talk with the doctor.
• Use care if you have risks for heart disease (high blood pressure, high cholesterol, overweight, high blood sugar or diabetes, cigarette smoking, man older than 40 years of age, other family members with early heart disease, woman after change of life). Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If this medicine is stopped because you have an allergy to it, do not restart it. It may not be safe to restart Trizivir. Throw away any of this medicine that you have not taken. If you are not sure how to throw away unused drugs, check with your pharmacist.
• If Trizivir (abacavir, lamivudine, and zidovudine) is stopped for any other reason, do not restart it without talking to the doctor. It could be very risky to restart on your own.
• Do not run out of this medicine.
• Talk with your doctor before you drink alcohol.
• This medicine is not a cure for HIV. Stay under the care of your doctor.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Trizivir while you are pregnant.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Trizivir is indicated in combination with other antiretrovirals or alone for the treatment of human immunodeficiency virus type 1 (HIV‑1) infection.

Limitations of Use:

Screening for HLA-B*5701 Allele prior to Starting Trizivir

Screen for the HLA-B*5701 allele prior to initiating therapy with Trizivir [see Boxed Warning, Warnings and Precautions (5.1)].

Recommended Dosage for Adults and Pediatric Patients Weighing at Least 40 kg

The recommended dosage of Trizivir is one tablet taken orally twice daily with or without food.

Not Recommended Due to Lack of Dosage Adjustment

Because Trizivir is a fixed-dose tablet and cannot be dose adjusted, Trizivir is not recommended for:

Trizivir tablets contain the following 3 synthetic nucleoside analogues: abacavir (ZIAGEN), lamivudine (also known as EPIVIR or 3TC), and zidovudine (also known as RETROVIR, azidothymidine, or ZDV) with inhibitory activity against HIV-1.

Trizivir tablets are for oral administration. Each film-coated tablet contains the active ingredients 300 mg of abacavir as abacavir sulfate, 150 mg of lamivudine, and 300 mg of zidovudine, and the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (OPADRY® green 03B11434) that is made of FD&C Blue No. 2, hypromellose, polyethylene glycol, titanium dioxide, and yellow iron oxide.

Abacavir Sulfate: The chemical name of abacavir sulfate is (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. It has a molecular formula of (C14H18N6O)2•H2SO4 and a molecular weight of 670.76 g per mol. It has the following structural formula:

Abacavir sulfate is a white to off-white solid and soluble in water. Dosages are expressed in terms of abacavir.

Lamivudine: The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (-)2′,3′-dideoxy, 3′-thiacytidine. It has a molecular formula of C8H11N3O3S and a molecular weight of 229.3 g per mol. It has the following structural formula:

Lamivudine is a white to off-white crystalline solid and is soluble in water.

Zidovudine: The chemical name of zidovudine is 3′-azido-3′-deoxythymidine. It has a molecular formula of C10H13N5O4 and a molecular weight of 267.24 g per mol. It has the following structural formula:

Zidovudine is a white to beige, odorless, crystalline solid with a solubility of 20.1 mg per mL in water at 25°C.

Applies to abacavir / lamivudine / zidovudine: oral tablet

Along with its needed effects, abacavir / lamivudine / zidovudine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking abacavir / lamivudine / zidovudine:

• Chills

• Abdominal or stomach pain
• cough
• diarrhea
• fever
• headache
• muscle weakness
• nausea
• numbness or tingling of the face, feet, or hands
• pain in the joints
• pain in the muscles
• pale skin
• skin rash
• sore throat
• swelling of the feet or lower legs
• unusual feeling of discomfort or illness
• unusual tiredness or weakness
• vomiting
• yellow eyes or skin

• Black, tarry stools
• blood in the urine or stools
• pinpoint red spots on the skin
• unusual bleeding or bruising

Some side effects of abacavir / lamivudine / zidovudine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bone pain
• loss of appetite
• trouble sleeping