Zidovudine Injection

RETROVIR is the brand name for zidovudine (formerly called azidothymidine [AZT]), a pyrimidine nucleoside analogue active against HIV. RETROVIR IV (zidovudine injection) Infusion is a sterile solution for intravenous infusion only. Each mL contains 10 mg zidovudine in Water for Injection. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH to approximately 5.5. RETROVIR IV (zidovudine injection) Infusion contains no preservatives.

The chemical name of zidovudine is 3′-azido-3′-deoxythymidine; it has the following structural formula:

Zidovudine is a white to beige, odorless, crystalline solid with a molecular weight of 267.24 and a solubility of 20.1 mg/mL in water at 25°C. The molecular formula is C10H13N5O4.

Do not use this medication if you have ever had an allergic reaction to Retrovir or any medicine that contains zidovudine, including Combivir or Trizivir.

Do not use Retrovir with any other medicine that contains zidovudine or stavudine, including: Combivir, Trizivir, or Zerit.

Some people develop a life-threatening condition called lactic acidosis while using zidovudine. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk.

Zidovudine can also cause severe or life-threatening effects on your liver. Tell your doctor if you have liver disease, especially hepatitis C.

To make sure you can safely use zidovudine, tell your doctor if you have any of these other conditions:

• kidney disease;
• anemia (low red blood cell count);
• an active infection;
• bone marrow suppression; or
• if you have used an HIV medication in the past, such as abacavir (Ziagen), didanosine (Videx), emtricitabine (Atripla, Complera, Emtriva, Truvada), lamivudine (Combivir, Epivir, Epzicom, Trizivir), stavudine (Zerit), tenofovir (Viread), or zidovudine (Retrovir).

FDA pregnancy category C. It is not known whether zidovudine will harm an unborn baby. HIV can be passed to your baby if you are not properly treated during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Take all of your HIV medicines as directed to control your infection.

You should not breast-feed while you are using zidovudine. Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

The adverse events reported during intravenous administration of RETROVIR IV (zidovudine injection) Infusion are similar to those reported with oral administration; neutropenia and anemia were reported most frequently. Long-term intravenous administration beyond 2 to 4 weeks has not been studied in adults and may enhance hematologic adverse events. Local reaction, pain, and slight irritation during intravenous administration occur infrequently.

Adults

The frequency and severity of adverse events associated with the use of RETROVIR are greater in patients with more advanced infection at the time of initiation of therapy.

Table 5 summarizes events reported at a statistically significantly greater incidence for patients receiving RETROVIR orally in a monotherapy study:

Table 5. Percentage (%) of Patients with Adverse Events* in Asymptomatic HIV Infection (ACTG 019)

In addition to the adverse events listed in Table 5, other adverse events observed in clinical studies were abdominal cramps, abdominal pain, arthralgia, chills, dyspepsia, fatigue, hyperbilirubinemia, insomnia, musculoskeletal pain, myalgia, and neuropathy.

Selected laboratory abnormalities observed during a clinical study of monotherapy with oral RETROVIR are shown in Table 6.

Table 6. Frequencies of Selected (Grade 3/4) Laboratory Abnormalities in Patients with Asymptomatic HIV Infection (ACTG 019)

Pediatrics

Study ACTG300: Selected clinical adverse events and physical findings with a ≥ 5% frequency during therapy with EPIVIR 4 mg/kg twice daily plus RETROVIR 160 mg/m2 orally 3 times daily compared with didanosine in therapy-naive ( ≤ 56 days of antiretroviral therapy) pediatric patients are listed in Table 7.

Table 7. Selected Clinical Adverse Events and Physical Findings ( ≥ 5% Frequency) in Pediatric Patients in Study ACTG300

Selected laboratory abnormalities experienced by therapy-naive ( ≤ 56 days of antiretroviral therapy) pediatric patients are listed in Table 8.

Table 8. Frequencies of Selected (Grade 3/4) Laboratory Abnormalities in Pediatric Patients in Study ACTG300

Additional adverse events reported in open-label studies in pediatric patients receiving RETROVIR 180 mg/m2 every 6 hours were congestive heart failure, decreased reflexes, ECG abnormality, edema, hematuria, left ventricular dilation, macrocytosis, nervousness/irritability, and weight loss.

The clinical adverse events reported among adult recipients of RETROVIR may also occur in pediatric patients.

Use for the Prevention of Maternal-Fetal Transmission of HIV

In a randomized, double-blind, placebo-controlled trial in HIV-infected women and their neonates conducted to determine the utility of RETROVIR for the prevention of maternal-fetal HIV transmission, RETROVIR Syrup at 2 mg/kg was administered every 6 hours for 6 weeks to neonates beginning within 12 hours following birth. The most commonly reported adverse experiences were anemia (hemoglobin < 9.0 g/dL) and neutropenia ( < 1,000 cells/mm3). Anemia occurred in 22% of the neonates who received RETROVIR and in 12% of the neonates who received placebo. The mean difference in hemoglobin values was less than 1.0 g/dL for neonates receiving RETROVIR compared to neonates receiving placebo. No neonates with anemia required transfusion and all hemoglobin values spontaneously returned to normal within 6 weeks after completion of therapy with RETROVIR. Neutropenia was reported with similar frequency in the group that received RETROVIR (21%) and in the group that received placebo (27%). The long-term consequences of in utero and infant exposure to RETROVIR are unknown.

Observed During Clinical Practice

In addition to adverse events reported from clinical trials, the following events have been identified during use of RETROVIR in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, potential causal connection to RETROVIR, or a combination of these factors.

Body as a Whole: Back pain, chest pain, flu-like syndrome, generalized pain.

Cardiovascular: Cardiomyopathy, syncope.

Endocrine: Gynecomastia.

Eye: Macular edema.

Gastrointestinal: Constipation, dysphagia, flatulence, oral mucosal pigmentation, mouth ulcer.

General: Sensitization reactions including anaphylaxis and angioedema, vasculitis.

Hemic and Lymphatic: Aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow hypoplasia, pure red cell aplasia.

Hepatobiliary Tract and Pancreas: Hepatitis, hepatomegaly with steatosis, jaundice, lactic acidosis, pancreatitis.

Musculoskeletal: Increased CPK, increased LDH, muscle spasm, myopathy and myositis with pathological changes (similar to that produced by HIV disease), rhabdomyolysis, tremor.

Nervous: Anxiety, confusion, depression, dizziness, loss of mental acuity, mania, paresthesia, seizures, somnolence, vertigo.

Respiratory: Cough, dyspnea, rhinitis, sinusitis.

Skin: Changes in skin and nail pigmentation, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweat, urticaria.

Special Senses: Amblyopia, hearing loss, photophobia, taste perversion.

Urogenital:Urinary frequency, urinary hesitancy.

Read the entire FDA prescribing information for Retrovir IV (Zidovudine Injection)

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Zidovudine is injected into a vein through an IV. You may be shown how to use an IV at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

Zidovudine must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

Each single-use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after preparing your dose.

Mixed medicine must be used within 24 hours if you keep it at room temperature.

You may also store the mixed medicine in a refrigerator, but you must use it within 48 hours.

Do not use zidovudine if it has changed colors or has particles in it. Call your pharmacist for new medication.

Zidovudine injection must be given slowly, and the IV infusion can take up to 1 hour to complete. Zidovudine is usually given 4 times per day until you are able to take the medication orally (by mouth). Follow your doctor's dosing instructions very carefully.

Zidovudine can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store unopened vials of zidovudine at room temperature away from moisture, heat, and light.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Avoid drinking alcohol. It may increase your risk of liver damage or lactic acidosis.

Using this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• doxorubicin;

• ganciclovir;

• interferon alfa (Intron, Infergen);

• ribavirin (Copegus, Moderiba, Rebetol, Ribasphere, RibaTab); or

• drugs that weaken the immune system such as cancer medicine, steroids, and medicines to prevent organ transplant rejection.

This list is not complete. Other drugs may interact with zidovudine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Use zidovudine injection as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of zidovudine injection during treatment.
• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

For all uses of this medicine:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Feeling very tired or weak.
• Muscle pain or weakness.
• Any unexplained bruising or bleeding.
• Change in body fat.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Treating HIV infection:

• This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take zidovudine injection. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start this medicine.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hard stools (constipation).
• Headache.
• Not hungry.
• Upset stomach or throwing up.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.