Retrovir (Zidovudine)

BEFORE you use RETROVIR (AZT) talk to your doctor or pharmacist if:

• you are allergic to any ingredient in this medicine.
• you have bone marrow problems (low blood cell counts).
• you have hepatomegaly (enlarged liver), hepatitis (inflamed liver) or other known risk factors for liver disease.
• you have kidney disease.
• you are taking other drugs
• you are pregnant or breastfeeding.
• your baby or infant was exposed to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) during pregnancy or labour.
• you are taking ribavirin as it could cause or worsen anemia (symptoms of tiredness, shortness of breath).
• Your doctor will advise whether you should stop taking RETROVIR (AZT).

Illness associated with HIV infection, including other infections, may still happen. Therefore, it is very important to keep appointments with your doctor and to report any change in your health as it occurs.

RETROVIR (AZT) has been extensively studied in humans for limited periods of time. Studies have shown that treatment will benefit your health. However, the effectiveness and overall safety of RETROVIR (AZT) is unknown beyond the length of time for which it has been studied.

The effectiveness and overall safety of RETROVIR (AZT) in women, intravenous drug users, and ethnic minorities are not different than that observed in white males.

Solution for Infusion:

The rubber stopper of the RETROVIR (AZT) intravenous vials contains latex. Tell your doctor if you are allergic to latex.

Use of This Medication During Pregnancy and Breast Feeding:

Before you use RETROVIR (AZT), talk to your doctor or pharmacist if you are pregnant, planning to become pregnant, or become pregnant while taking RETROVIR (AZT). It is not known if RETROVIR (AZT) can harm your unborn child. You and your doctor will need to decide if taking RETROVIR (AZT) is right for you. If you take RETROVIR (AZT) while you are pregnant, talk to your doctor about how you can be included in the Antiretroviral Pregnancy Registry.

For pregnant women who are considering the use of RETROVIR (AZT) during pregnancy for the prevention of HIV-transmission to their infants, it is important to understand that transmission may still occur in some cases (about 8%) despite using RETROVIR (AZT). The long-term safety in treated fetuses, neonates, or infants has not been established.

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.

There have been very rare reports of diseases that affect the nervous system such as delayed development and seizures.

These findings do not affect current recommendations to use antiretroviral therapy in pregnant women to prevent transmission of HIV to their babies.

HIV-infected women should not breast-feed in order to prevent transmission of HIV to a child who may not yet be infected. The ingredients in RETROVIR (AZT) can also pass into your breast-milk.

Side-effects of RETROVIR (AZT) include nausea, vomiting, fever, headache, stomach pain, loss of appetite, muscle pain, low white blood cell count (neutropenia or leucopenia), decrease in the number of cells involved in blood clotting (thrombocytopenia) or in all kinds of blood cells (pancytopenia), reduction in the number of red blood cells (pure red cell aplasia), failure of the bone marrow to produce new blood cells (aplastic anaemia), an increase in lactic acid, feeling depressed or anxious, dizziness, not being able to sleep, tingly feelings in the skin (pins and needles), not being able to concentrate, feeling drowsy, seizures, disease of the heart muscle, cough, intestinal gas, changes in the colour of the nails, skin, or the skin inside the mouth, taste disturbance, indigestion, skin rash (red, raised or itchy skin), sweating, passing urine more often, enlarged breasts in men, general aches and pain, chills, chest pain, flu-like feeling. If these become bothersome, consult your doctor.

Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time, or you could develop an autoimmune disease in which your immune system reacts against your own body (e.g. Graves' disease (which affects the thyroid gland), Guillain-Barré syndrome (which affects the nervous system) or polymyositis (which affects the muscles) and it may develop at any time, sometimes months later after the start of HIV therapy). Sometimes symptoms can be severe, so if you develop high temperature (fever), joint or muscle pain, redness, rash, swelling, or fatigue or any new symptoms contact your doctor straight away.

An important but reversible side-effect of RETROVIR (AZT), particularly in patients with more severe disease, can be a decrease in certain types of blood counts (including red blood cells, white blood cells and platelets) and increase in certain liver enzymes. Since a reduction in these cells can directly affect your health, it is important to have your blood tested as often as your doctor requests it. In some cases, it may be necessary to adjust the dose of the drug, temporarily discontinue the drug, give a blood transfusion, or stop the drug altogether.

It is important to understand that although these blood effects can occur at any stage, they are much more common in advanced disease and in patients who start RETROVIR (AZT) therapy late in their illness.

Contact your doctor if you experience muscle weakness, shortness of breath, symptoms of hepatitis or pancreatitis (which include very severe stomach cramps) or any other unexpected adverse events while being treated with RETROVIR (AZT).

This is not a complete list of side effects. For any unexpected effects while taking RETROVIR (AZT), contact your doctor or pharmacist.

Some drugs may change the usefulness and safety of RETROVIR (AZT). It is therefore very important that you tell your doctor before you decide to take any new drugs, even if these are available without a prescription.

Drugs that may interact with RETROVIR (AZT) include: atovaquone, bone marrow suppressive agents/cytotoxic agents, clarithromycin, fluconazole, ganciclovir, interferon-alpha, lamivudine, methadone, phenytoin, probenecid, stavudine, valproic acid, and others such as trimethoprim-sulfamethoxazole, pyrimethamine, acyclovir and rifampin.

For patients receiving combination therapy with RETROVIR (AZT) and zalcitabine, it is important to understand that the major toxicity of zalcitabine is peripheral neuropathy. Pancreatitis is another serious and potentially life-threatening toxicity that has been reported in less than 1% of patients treated with zalcitabine alone. Symptoms of peripheral neuropathy include tingling, burning, pain, or numbness in the hands or feet. Symptoms of pancreatitis include abdominal pain, nausea and vomiting. These symptoms should be promptly reported to your physician. Since the development of peripheral neuropathy seems to be dose-related to zalcitabine, you should follow your physician's instructions regarding the prescribed dose. The long-term effects of zalcitabine in combination with RETROVIR (AZT) are presently unknown. If you are a female of child-bearing age, you should use effective contraception while using zalcitabine.

An additional precaution is that some other drugs may change the usefulness and safety of RETROVIR (AZT).

Usual dose:

You should be counselled about the use of RETROVIR (AZT).

It is important to take RETROVIR (AZT) exactly as prescribed. Altering the dose without the direct advice of your physician is unwise, as is sharing your medication with others.

Oral Administration:

Adults and Adolescents 30 kg and Over:

The recommended total oral daily dose of RETROVIR (AZT) is 600 mg per day in divided doses in combination with other antiretroviral agents. Suggested Dosing Regimens:

• Capsules: three 100 mg RETROVIR (AZT) capsules every 12 hours; OR two 100 mg RETROVIR (AZT) capsules every 8 hours.
• Syrup: 6 teaspoonfuls (30 mL) RETROVIR (AZT) syrup every 12 hours; OR 4 teaspoonfuls (20 mL) RETROVIR (AZT) syrup every 8 hours.

Children (≥4 kg):

The recommended oral dose in children weighing ≥4 kg

Children should be assessed for the ability to swallow capsules. If a child has difficulty in swallowing a RETROVIR (AZT) capsule, the RETROVIR (AZT) syrup formulation should be prescribed.

RETROVIR (AZT) Syrup is available for dosing children who weigh less than 30 kg. RETROVIR (AZT) Syrup should be used to provide accurate dosage when capsules are not appropriate.

Alternatively, dosing for RETROVIR can be based on body surface area (BSA) for each child. The usual dose of RETROVIR is 480 mg/m2per day, divided equally into two or three doses per day. In some cases the dose calculated by mg for each kg will not be the same as that calculated by BSA.

Children (<4 kg):

Available data are insufficient to propose specific dosing recommendations for children weighing <4 kg.

Solution for Infusion:

Adults and Adolescents 30 kg and Over:

The recommended dose is 1 to 2 mg/kg administered as a 1 hour infusion every 4 hours around the clock (6 times daily). RETROVIR (AZT) solution for infusion is administered intravenously at a constant rate over 1 hour. Rapid infusion or bolus injection should be avoided. RETROVIR (AZT) solution for infusion should not be given intramuscularly.

If you are also taking clarithromycin, your doctor may advise you to take this medication at least 2 hours before or 2 hours after RETROVIR(AZT), to avoid a drug interaction.

Children:

The recommended dose of RETROVIR (AZT) I.V. Injection in children 3 months to 12 years of age is 120 mg/m2 every 6 hours, infused over 1 hour (480 mg/m2 per day). Do not exceed 160 mg for any individual dose.

Prevention of Maternal-Fetal HIV Transmission:

The recommended dosing regimen for administration to pregnant women (>14 weeks of pregnancy) and their newborn infant is:

• Maternal Dosing: 100 mg orally 5 times per day until the start of labour. During labour and delivery, intravenous RETROVIR (AZT) should be administered at 2 mg/kg (total body weight) over 1 hour followed by a continuous intravenous infusion at 1 mg/kg/h (total body weight) until clamping of the umbilical cord.
• Infant Dosing: 2 mg/kg of oral solution every 6 hours starting within 12 hours after birth and continuing through 6 weeks of age. Infants unable to receive oral dosing may be administered RETROVIR (AZT) intravenously at 1.5 mg/kg, infused over 30 minutes, every 6 hours.

Overdose:

If you are concerned that you may have taken too much RETROVIR, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.