Zidovudine

This medication may also cause muscle problems (myopathy). Seek immediate medical attention if you develop symptoms of myopathy (such as wasting or decrease in muscle size, muscle weakness/pain/tenderness, weight loss).

Rarely, zidovudine has caused a severe (sometimes fatal) liver and blood problem (lactic acidosis). Tell your doctor immediately if you develop symptoms of liver problems (persistent nausea, stomach/abdominal pain, dark urine, yellowing eyes/skin) or lactic acidosis (rapid breathing, drowsiness, muscle aches).

Treatment Of HIV-1

RETROVIR, a nucleoside reverse transcriptase inhibitor, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Prevention Of Maternal-Fetal HIV-1 Transmission

RETROVIR is indicated for the prevention of maternal-fetal HIV-1 transmission [see DOSAGE AND ADMINISTRATION]. The indication is based on a dosing regimen that included 3 components:

1. antepartum therapy of HIV-1-infected mothers
2. intrapartum therapy of HIV-1-infected mothers
3. post-partum therapy of HIV-1-exposed neonate

Points to consider prior to initiating RETROVIR in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:

• In most cases, RETROVIR for prevention of maternal-fetal HIV-1 transmission should be given in combination with other antiretroviral drugs.
• Prevention of HIV-1 transmission in women who have received RETROVIR for a prolonged period before pregnancy has not been evaluated.
• Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of therapy with RETROVIR during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of antiretroviral therapy for their own health may consider delaying use; this indication is based on use after 14 weeks gestation.

WARNING: RISK OF HEMATOLOGICAL TOXICITY, MYOPATHY, LACTIC ACIDOSIS 

• Hematologic toxicity including neutropenia and severe anemia have been associated with the use of zidovudine.
• Symptomatic myopathy associated with prolonged use of zidovudine.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues including zidovudine. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. 

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

The following drug interactions are based on studies using zidovudine.1 Drug interaction studies not performed using lamivudine/zidovudine or abacavir/lamivudine/zidovudine.227 229 When fixed combinations are used, consider interactions associated with each drug in the fixed combination.227 229

Specific Drugs

Storage

Oral

Zidovudine: 15–25°C; protect from moisture.1

Zidovudine: 15–25°C.1

Zidovudine: 15–25°C.1

Lamivudine/zidovudine (Combivir): 2–30°C.227

Abacavir/lamivudine/zidovudine (Trizivir): 25°C (may be exposed to 15–30°C).229

Parenteral

Zidovudine: 15–25°C; protect from light.231

After dilution in 5% dextrose, physically and chemically stable for 24 hours when stored at room temperature and for 48 hours when refrigerated at 2–8°C.231

To minimize risk of microbial contamination, administer diluted solutions within 8 hours if stored at room temperature or within 24 hours if refrigerated.231

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Admixture in biologic or colloidal fluids (e.g., blood products, protein solutions) not recommended.231

Along with its needed effects, a medicine 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:

• Fever, chills, or sore throat
• pale skin
• unusual tiredness or weakness

• Abdominal or stomach discomfort
• confusion
• convulsions (seizures)
• diarrhea
• fast, shallow breathing
• general feeling of discomfort
• loss of appetite
• mood or mental changes
• muscle pain, tenderness, weakness, or cramping
• nausea
• shortness of breath
• sleepiness

Some side effects 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:

• Difficulty having a bowel movement (stool)
• general feeling of discomfort or illness
• headache (severe)
• lack or loss of strength
• muscle soreness
• trouble with sleeping
• vomiting
• weight loss

• Bluish-brown colored bands on nails
• changes in skin color

• Acid or sour stomach
• belching
• burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• heartburn
• indigestion
• muscle or bone pain
• sensation of pins and needles, stabbing pain
• stomach cramps
• stomach pain
• yellow eyes or skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adults - Treatment of HIV-1 Infection

Oral Dosing

The recommended oral dose of Zidovudine capsules is 300 mg twice daily in combination with other antiretroviral agents.

Pediatric Patients (Aged 4 Weeks to Less than 18 Years)

Healthcare professionals should pay special attention to accurate calculation of the dose of Zidovudine capsules, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.

Prescribers should calculate the appropriate dose of Zidovudine capsules for each child based on body weight (kg) and should not exceed the recommended adult dose.

Before prescribing Zidovudine capsules, children should be assessed for the ability to swallow capsules. If a child is unable to reliably swallow a Zidovudine capsule, the Zidovudine syrup formulation should be prescribed.

The recommended oral dosage in pediatric patients aged 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when capsules are not appropriate.

Alternatively, dosing for Zidovudine capsules can be based on body surface area (BSA) for each child. The recommended oral dose of Zidovudine capsules is 480 mg per m2 per day in divided doses (240 mg per m2 twice daily or 160 mg per m2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.

Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (greater than 14 weeks of pregnancy) and their neonates is:

Maternal Dosing

100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous Zidovudine should be administered at 2 mg per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord.

Neonatal Dosing

Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered Zidovudine intravenously. See Table 2.

Patients with Severe Anemia and/or Neutropenia

Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm3 or reduction greater than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoietin level and patient tolerance.

Patients with Renal Impairment

In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours. [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment

There are insufficient data to recommend dose adjustment of Zidovudine capsules in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].

Zidovudine Capsules USP, 100 mg are white/white size ‘3’ hard gelatin capsules imprinted with ‘D’ on white cap and ‘01’ on white body with black edible ink.

Antiretroviral Agents

Stavudine

Concomitant use of Zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated in vitro.

Nucleoside Analogues Affecting DNA Replication

Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of Zidovudine against HIV-1; concomitant use of such drugs should be avoided.

Doxorubicin

Concomitant use of Zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated in vitro.

Hematologic/Bone Marrow Suppressive/Cytotoxic Agents

Coadministration of ganciclovir, interferon alfa, ribavirin, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of Zidovudine.

Acute overdoses of Zidovudine have been reported in pediatric patients and adults. These involved exposures up to 50 grams. No specific symptoms or signs have been identified following acute overdosage with Zidovudine apart from those listed as adverse events such as fatigue, headache, vomiting, and occasional reports of hematological disturbances. Patients recovered without permanent sequelae. Hemodialysis and peritoneal dialysis appear to have a negligible effect on the removal of Zidovudine while elimination of its primary metabolite, 3′-azido-3′-deoxy-5′-O-β-D-glucopyranuronosylthymidine (GZDV), is enhanced. If overdose occurs, the patient should be monitored for evidence of toxicity and given standard supportive treatment as required.

Potentially life-threatening hypersensitivity to zidovudine or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Neutrophil count <750/mm3 or hemoglobin <7.5 g/dL (4.65 mmol/L)

Refer to adult dosing.

Solution for injection should be removed from the vial and diluted with D5W to a concentration ≤4 mg/mL.

Oral: Administer around-the-clock to promote less variation in peak and trough serum levels; may be administered without regard to meals

IV: Avoid rapid infusion or bolus injection. Do not administer IM

Infuse over 1 hour; infuse over 30 minutes in neonates; in pregnant women, infuse loading dose over 1 hour followed by continuous infusion.

IV: Store undiluted vials at 15°C to 25°C (59°F to 77°F). Protect from light. When diluted in D5W, solution is physically and chemically stable for 24 hours at room temperature and 48 hours if refrigerated at 2°C to 8°C (36°F to 46°F). Attempt to administer diluted solution within 8 hours if stored at room temperature or 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F) to minimize potential for microbial-contaminated solutions (vials are single-use and do not contain preservative).

Tablets, capsules, syrup: Store at 15°C to 25°C (59°F to 77°F). Protect capsules from moisture.