Apo-Abacavir-Lamivudine-Zidovudine: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

The Human Immunodeficiency Virus (HIV) is a retrovirus (a type of virus). Infection with HIV damages the immune system and can lead to Acquired Immune Deficiency Syndrome (AIDS) and other related illnesses.

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE belongs to a group of antiretroviral medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs), and is used in combination with other antiretrovirals to treat Human Immunodeficiency Virus (HIV) infection.

What it does:

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE does not cure HIV, but helps to prevent further damage to the immune system by slowing down production of new viruses. You must be sure to be seen regularly by your health care provider.

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE also increases the CD4 cell count in your blood. CD4 cells are a type of white blood cells that are important in helping your body fight infection.

When it should not be used:

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE should not be taken if:

• you previously had an allergic reaction (hypersensitivity) to the active ingredient abacavir, which is also included in medicines called ZIAGEN, KIVEXA and TRIUMEQ (see What the important nonmedicinal

  • ingredients are).
  • you previously had an allergic reaction to the active ingredient lamivudine which is included in medicines called 3TC, COMBIVIR or KIVEXA or zidovudine which is included in a medicine called RETROVIR^® or any of the other ingredients found in APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE (see What the important nonmedicinal ingredients are).
  • you have liver disease.
  • you have a very low red blood cell count (anemia) or very low white blood cell count (neutropenia).

What the medicinal ingredient is:

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE is a treatment that contains a fixed dose combination of three active ingredients that are currently available as separate medicines: ZIAGEN (abacavir sulfate), 3TC (lamivudine) and RETROVIR (zidovudine). Each APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE contains 300 mg abacavir (as abacavir sulfate), 150 mg of lamivudine and 300 mg zidovudine.

What the important nonmedicinal ingredients are:

Each APO-ABACAVIR-LAMIVUDINE-

ZIDOVUDINE tablet contains the following nonmedicinal ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl methylcellulose, indigotine aluminium lake 12% to 14%, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol and titanium dioxide.

What dosage forms it comes in:

Each blue-green coloured modified oval shaped, biconvex film-coated tablets with engraved “APO” on one side and “ALZ” on the other side contains 300 mg of abacavir (as abacavir sulfate), 150 mg of lamivudine and 300 mg of zidovudine. Available in bottles of 60 tablets.

Important Information on Hypersensitivity Reactions

If you get two or more of the following groups of symptoms while taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet contact your doctor immediately to find out if you should stop taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet:

A list of these symptoms is on the Warning Card provided by your pharmacist. You should carry this Warning Card with you at all times. If you notice these symptoms while taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE call your doctor immediately. Your doctor may advise you to stop taking APO-ABACAVIR-LAMIVUDINE-

ZIDOVUDINE Tablet.

If you stop APO-ABACAVIR-LAMIVUDINE-

ZIDOVUDINE Tablet because of a serious allergic reaction, never take APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet or any other medicine containing abacavir (such as ZIAGEN, KIVEXA or TRIUMEQ) again, regardless of whether you have the HLA-B*5701 gene variation or not. Within hours you may experience a life threatening lowering of your blood pressure or death. If you stop APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet for any other reason, even for a few days, and you are not allergic to APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet, talk with your doctor before taking it again. Taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet again may cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before.

If your healthcare provider tells you that you can take APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet, again, start taking it when you are around medical help or people who can call a doctor if you need one.

Occasionally, reactions have developed in people who start taking abacavir again, and had only one symptom on the Warning Card before they stopped taking it.

If you are hypersensitive to APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablet, return all your unused APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE Tablets for safe disposal. Ask your doctor or pharmacist for advice.

Before you use APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, talk to your doctor or pharmacist:

• About all your medicines and medical conditions
• If you have kidney or liver disease (including hepatitis B or C)
• If you are taking interferon or ribavirin
• If you have had previous use of any NRTI class medicine
• If you have been tested and know whether or not you have a gene variation called HLA- B*5701

• If you are pregnant, or planning to become pregnant, breastfeeding or planning to breastfeed

• About all the medicines you are taking including vitamins, herbal supplements and nonprescription drugs.

Other Special Warnings

Your blood sugar levels (glucose) or levels of fats (lipids) in your blood may increase with HIV treatment. Your doctor may order blood tests for you.

The class of medicines to which APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE belongs (NRTIs), can cause a condition called lactic acidosis (excess of lactic acid in your blood), together with an enlarged liver. Symptoms of lactic acidosis include feeling of weakness, loss of appetite, sudden unexplained weight loss, upset stomach and difficulty breathing or rapid breathing. This rare but serious side effect occurs more often in women. If you have liver disease you may also be more at risk of getting this condition. While you are being treated with APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, your doctor will monitor you closely for any signs that you may be developing lactic acidosis.

Zidovudine, one of the three active ingredients in APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, may also cause a decrease in certain types of blood counts (including red blood cells, white blood cells and platelets) and an increase in certain liver enzymes.

Zidovudine can affect the production of red blood cells, resulting in anemia. If this happens, the symptoms are tiredness and shortness of breath. Less commonly, the production of a certain type of white blood cell may be reduced which can make you more prone to infections. Your doctor may want you to have a blood test from time to time to check the blood cell count.

If you have a hepatitis B infection, you should not stop APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE without instructions from your doctor, as you may have a recurrence of your hepatitis. This may occur due to suddenly stopping the active ingredient lamivudine in APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE.

Some HIV medicines including abacavir 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 and diabetes, tell your doctor. Do not stop taking your medication unless you are advised to do so by your doctor.

You may continue to develop other infections and other illnesses associated with HIV disease. You should therefore keep in regular contact with your doctor while taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE.

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE helps to control your condition but is not a cure for HIV infection. You will need to take it every day. Unless you suspect you are having an allergic reaction with APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, do not stop taking your medicine without first talking to your doctor.

Treatment with APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE has not been shown to reduce the risk of passing HIV infection on to others by sexual contact or by blood transfer. You should continue to use appropriate precautions to prevent this.

Use of this medicine during pregnancy and breastfeeding:

If you are pregnant, or planning to become pregnant soon, you must inform your doctor before taking any medicine. The safe use of APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE in pregnancy has not been established. Your doctor will decide whether you should continue to be treated with APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE if you are pregnant. If you take APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE while you are pregnant, talk to your doctor about how you can be included in the Antiretroviral Pregnancy Registry.

Babies and infants exposed to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) during pregnancy or labour show minor temporary increases in blood levels of lactate. The clinical importance of these temporary increases is unknown.

These findings do not affect current recommendations to use antiretroviral therapy in pregnant women to prevent transmission of HIV to their babies. There have been very rare reports of disease that affect the neonatal (babies) nervous system such as delayed development and seizures. The long term effects of APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE are not known.

It is recommended that HIV infected women do not breastfeed their infants under any circumstances in order to avoid transmission of HIV from mother to child. All three of the active substances in APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE are likely to be found in breast milk.

You are recommended not to breastfeed your baby while taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE.

Remember: This medicine is for you. Never give it to someone else. It may harm them even if their symptoms are the same as yours.

INTERACTIONS WITH THIS MEDICATION

Some drugs may change the usefulness and safety of APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE. It is important that your doctor knows about all your medicines so that you get the best possible treatment. Tell your doctor about all your medicines, including vitamin supplements, herbal remedies or homeopathic remedies, including those you have bought yourself.

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE should not be taken with stavudine or emtricitabine.

It is important to tell your doctor or pharmacist about all the medicines listed below or any that you are taking or have recently taken, including those you have bought yourself:

• Phenytoin, valproic acid, oxazepam, lorazepam
• Acetylsalicylic acid
• Codeine, morphine, methadone, rifampicin, indomethacine, ketoprofen, naproxen, cimetidine, clofibrate, Isoprinosine, probenecid
• Pentamine, pyrimethamine, co-trimoxazole, dapsone, atovaquone, amphotericin, flucytosine, interferon
• Vincristine, vinblastine, adriamycin and doxorubicin
• Clarithromycin
• Fluconazole
• Ganciclovir
• Retinoids
• Methadone
• Trimethoprim sulphamethoxazole (co- trimoxazole)
• Interferon and/or ribavirin
• Sorbitol-containing medicines (usually liquids) used regularly

If you are taking methadone, your doctor may need to adjust your methadone dose, as abacavir increases the rate at which methadone leaves your body. This is unlikely to affect most methadone users.

In men, alcohol does increase the amount of abacavir in your blood. However, the meaning of this is unknown. This interaction had not been studied in women.

PROPER USE OF THIS MEDICATION

Usual dose:

Take APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE exactly as your doctor has advised you, and try not to miss any doses. The usual dose is one tablet twice a day. Swallow the tablet whole with water. APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE can be taken with or without food. APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE is a set (fixed) dose combination of abacavir sulfate, lamivudine and zidovudine and therefore cannot be dose-reduced. If you have kidney or liver problems or if you weigh less than 40 kg, then your medicine may be changed to the separate medicines, ZIAGEN, 3TC and RETROVIR (AZT). If you are unsure about how to take it, ask your doctor or pharmacist. The use of abacavir-lamivudine-zidovudine has not been established in patients less than 18 years of age, and in elderly patients (> 65 years).

If you are also taking clarithromycin, your doctor may advise you to take this medication at least 2 hours before or 2 hours after APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, to avoid a drug interaction.

Overdose:

Missed Dose:

It is important to take this medicine as prescribed to ensure you get maximum benefit. If you forget to take a dose, take it as soon as you remember, and then continue as before. Do not take a double dose to make up for forgotten individual doses.

If you stopped taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE:

If you stop taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE because of side effects or illness, you must contact your doctor before restarting to make sure that symptoms of a hypersensitivity reaction have not been missed. In some cases your doctor will ask you to restart APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE under direct medical supervision or in a place where you will be able to get ready access to medical care if needed.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Like all medicines, APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE can have side effects. When treating HIV infection, it is not always possible to tell whether some of the undesirable effects that occur are caused by APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, by other medicines you are taking at the same time or by the HIV infection. For this reason it is very important that you inform your doctor about any changes in your health.

A hypersensitivity reaction (serious allergic reaction) has been reported in patients who have been treated with abacavir. This is described in the section on Hypersensitivity Reaction (under WARNINGS AND PRECAUTIONS) in the beginning of this leaflet. It is important that you read and understand the information about this serious reaction.

APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE contains three active ingredients. Therefore, all side effects that have been reported in patients taking these medicines separately may also occur in patients taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE. The most common side effects reported for these active ingredients (abacavir, lamivudine and zidovudine) are in bold text:

• Nausea, vomiting, stomach pain, diarrhea, loss of appetite, flatulence and indigestion.
• Headache, dizziness, numbness, tingling sensation or sensation of weakness in the limbs, convulsions (fits), difficultly sleeping, tiredness, anxiety, depression, general feeling of being unwell.
• Cough, breathlessness.
• Disease of heart muscle (cardiomyopathy)
• Joint pain, muscle pain and inflammation, including rare reports of breakdown of muscle tissue.
• Fatigue, fever, malaise and lethargy. Taste changes, chills, urinary frequency, enlargement of the breasts in men, chest pain, flu-like symptoms.
• Nail and skin colour changes, patchy colour changes in the mouth, rash, very rare reports of serious skin reactions, itching, sweating and hair loss.
• Liver disorders such as an enlarged liver, fatty liver and jaundice. Temporary increases in certain substance (enzymes) produced by the liver. Inflammation of the pancreas.
• Anemia (low red blood cell count) and neutropenia/leucopenia (low white blood cell count) have been reported. If the production of red blood cells is reduced you may have symptoms of tiredness or breathlessness. A reduction in your white blood cell count can make you more prone to infection.

• Reduction in platelets (blood cells important for blood clotting) has been reported. If you have a low platelet count you may notice that you bruise more easily.

  Treatment with APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE or other medicines that contain zidovudine may cause a loss of fat from legs, arms and face (lipoatrophy). Your doctor should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your legs, arms, and face. When these signs occur, your doctor will assess if APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE should be stopped and your HIV treatment changed. If you stop taking APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE, it may take several months to see any lost fat return. You may not regain all of your lost body fat.

  Changes to your immune system (Immune Reconstitution Inflammatory Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time.

  Autoimmune disorders (when the immune system attacks healthy body tissue), may also occur after you start taking medicines for HIV infection. Examples of this include: Grave's disease (which affects the thyroid gland), Guillain-Barre syndrome (which affects the nervous system), polymyositis (which affects the muscles), or autoimmune hepatitis (which affects the liver). Autoimmune disorders may occur many months after the start of treatment. Look for any other symptoms such as:

  • High temperature (fever), redness, rash or swelling
  • Fatigue

  • Joint or muscle pain

    • Numbness or weakness beginning in the hands and feet and moving up towards the trunk of the body
  • Palpitations (chest pain) or rapid heart rate
  • Yellowing of the eyes and skin

If you notice these or any symptoms of inflammation or infection, tell your doctor immediately.

Inflammation in the pancreas (pancreatitis) has been observed in patients treated with abacavir, lamivudine and zidovudine, although it was not clear whether this was due to the medicine or the HIV infection itself (See Side Serious Side Effects table). If your doctor detects clinical signs, symptoms or lab tests suggestive of pancreatitis, they will stop treatment with APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE immediately.

Always tell your doctor or pharmacist if any of the side effects mentioned becomes severe or troublesome, or if you notice any other side effects not listed in this leaflet.

HOW TO STORE IT

Store APO-ABACAVIR-LAMIVUDINE-

ZIDOVUDINE Tablets between 15°C and 30°C.

As with all medicines, keep APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE out of the reach and sight of children.

Do not take your medicine after the expiry date shown on the bottle and the carton.

Reporting Side Effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

• Visiting the Web page on Adverse Reaction Reporting (https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html) for information on how to report online, by mail or by fax; or

MORE INFORMATION

If you want more information about APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes this Consumer Information by visiting the Health Canada website (https://health-products.canada.ca/dpd-bdpp/index-eng.jsp). Find the Consumer Information on the manufacturer’s website http://www.apotex.ca/products, or by calling 1-800-667-4708.

Last revised: October 3, 2019

INFORMATION FOR PRESCRIBERS:

A copy of the warning card included with the APO-ABACAVIR-LAMIVUDINE-ZIDOVUDINE carton is shown below.