Retrovir (zidovudine) is a nucleoside reverse transcriptase inhibitor (NRTI) and a cornerstone of antiretroviral therapy (ART) for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection. As the first antiretroviral medication approved by the FDA, it has a robust and extensively documented clinical profile spanning decades. Retrovir is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children. Its primary mechanism of action involves the inhibition of viral reverse transcriptase, thereby halting the replication of the HIV-1 virus. This introduction provides a foundational overview for healthcare professionals managing patients with HIV.

Features

• Active Pharmaceutical Ingredient (API): Zidovudine (AZT).
• Pharmacological Class: Nucleoside Reverse Transcriptase Inhibitor (NRTI).
• Available Formulations: 100 mg and 300 mg film-coated tablets; 10 mg/mL oral syrup.
• Standardized manufacturing process ensuring consistent potency and bioavailability.
• Extensive long-term and short-term clinical trial data supporting its efficacy and safety profile.
• Included on the World Health Organization’s Model List of Essential Medicines.

Benefits

• Potent Viral Suppression: Effectively reduces HIV-1 RNA viral load, a critical marker for disease progression.
• Immunological Restoration: Contributes to the increase and maintenance of CD4+ (T-helper) cell counts, restoring immune function.
• Proven Reduction in Mortality: Long-term use is associated with a significant decrease in HIV-related morbidity and mortality.
• Prevention of Maternal-Fetal Transmission: A key component in regimens to reduce the risk of HIV-1 transmission from mother to child during pregnancy, labor, and delivery.
• Flexible Dosing Options: Availability of both tablet and syrup formulations allows for tailored dosing across diverse patient populations, including pediatric cases.
• Extensive Clinical Experience: Decades of real-world use provide a deep understanding of its long-term benefits and management of associated risks.

Common use

Retrovir is used as part of a combination antiretroviral therapy (cART) regimen for the management of HIV-1 infection. It is never used as monotherapy due to the high risk of rapid development of viral resistance. Its use is central to treatment-naïve patients initiating therapy and remains an option for treatment-experienced patients as part of a optimized background regimen. A critical non-treatment application is the prevention of perinatal transmission of HIV-1. Pregnant individuals with HIV-1 are administered Retrovir (often intravenously during labor) to significantly reduce the viral load and lower the risk of transmission to the neonate, who may also receive a prophylactic course post-delivery.

Dosage and direction

Dosing must be individualized based on the patient’s clinical status, renal and hepatic function, and other concomitant medications.

• Adults: The recommended oral dosage is 300 mg twice daily or 200 mg three times daily.
• Pediatric Patients (aged 4 weeks to 18 years): Dosage is based on body surface area or body weight and must be calculated precisely. The recommended dose is 240 mg/m² twice daily (maximum 300 mg per dose) or 4 mg/kg twice daily (for neonates). The oral syrup is typically used for this population.
• Prevention of Maternal-Fetal HIV Transmission:
  • Pregnant Patient ( >14 weeks gestation): 100 mg orally five times daily until the start of labor.
  • During Labor and Delivery: 2 mg/kg IV over 1 hour, followed by a continuous IV infusion of 1 mg/kg/hour until umbilical cord clamping.
  • Neonate: 2 mg/kg orally every 6 hours starting within 12 hours after birth and continuing through 6 weeks of age.
• Administration: Tablets can be taken with or without food. The oral syrup should be administered using the supplied measuring cup for accuracy.

Precautions

• Hematologic Toxicity: Retrovir has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV disease. Frequent blood monitoring is mandatory (see below).
• Myopathy: Prolonged use has been associated with symptomatic myopathy and myositis.
• Lactic Acidosis: Fatal cases of lactic acidosis and severe hepatomegaly with steatosis have been reported with NRTIs, including Retrovir. Use with caution in patients with known risk factors for liver disease.
• Exacerbation of Hepatitis B and C: In patients co-infected with Hepatitis B or C, hepatic decompensation, including fatal cases, has been reported. Monitor hepatic function.
• Lipoatrophy: Long-term use of Retrovir has been associated with a loss of subcutaneous fat in the limbs, face, and buttocks.
• Monitoring Requirements: Baseline and frequent monitoring of complete blood count (CBC) with differential (e.g., every 4 weeks for the first 3 months, then every 3 months) and blood chemistries, including liver function tests, is essential.

Contraindications

Retrovir is contraindicated in patients with:

• A history of a life-threatening hypersensitivity reaction (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the formulation.
• Potentially fatal adverse reactions to other NRTI agents.
• Severe hepatic impairment (use is not recommended due to lack of data and increased risk of toxicity).
• Co-administration with stavudine (d4T), due to antagonistic antiviral effects.

Possible side effect

Adverse reactions are often linked to dosage and duration of therapy. Common and serious side effects include:

• Very Common (≥1/10): Headache, nausea, vomiting, asthenia, malaise, insomnia.
• Common (≥1/100 to <1/10): Anemia, neutropenia, leukopenia, dizziness, anorexia, abdominal pain, diarrhea, myalgia, fever.
• Uncommon (≥1/1,000 to <1/100): Thrombocytopenia, pancytopenia (with marrow hypoplasia), hyperpigmentation of nails and skin, myopathy, paresthesia, dyspnea, cough.
• Rare (<1/1,000): Lactic acidosis, severe hepatomegaly with steatosis, hepatic failure, pancreatitis, convulsions.

Drug interaction

Retrovir is primarily metabolized by glucuronidation. Concomitant use with drugs that affect this pathway requires caution.

• Increased Retrovir Exposure: Ganciclovir, valganciclovir, and other myelosuppressive agents can increase the risk of hematologic toxicity.
• Decreased Retrovir Exposure: Drugs that induce UDP-glucuronosyltransferase (UGT) enzymes, such as rifampicin, can decrease zidovudine plasma concentrations, potentially reducing efficacy. Dose adjustment may be necessary.
• Increased Exposure of Other Drugs: Retrovir may increase plasma concentrations of phenytoin and methadone, requiring monitoring.
• Antagonistic Effects: Concurrent use with stavudine (d4T) is contraindicated as they compete for intracellular activation.
• Additive Toxicities: Use with other drugs that cause neutropenia, anemia, nephrotoxicity, or pancreatitis may increase the risk of these adverse effects.

Missed dose

• If a dose is missed, it should be taken as soon as the patient remembers.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped.
• The patient should not take a double dose to make up for a missed one.
• Instruct patients on the critical importance of adherence to the prescribed dosing schedule to maintain effective viral suppression and prevent the development of resistance.

Overdose

• Signs and Symptoms: Reported events in cases of overdose include nausea, vomiting, lethargy, and hematologic disturbances. Other findings may include hepatic dysfunction, lactic acidosis, and neurological symptoms such as seizures.
• Management: There is no specific antidote for Retrovir overdose. Treatment consists of standard supportive measures, including continuous ECG monitoring due to the potential for electrolyte imbalances. Hemodialysis and peritoneal dialysis are not effective in eliminating zidovudine, but enhanced elimination by glucuronidation may be of some benefit. Gastric lavage or activated charcoal may be considered if ingestion was recent.

Storage

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Keep the bottle tightly closed to protect from moisture.
• Retain in the original container.
• The oral syrup may be stored at room temperature or under refrigeration. Do not freeze.
• Keep out of reach of children and pets.

Disclaimer

This information is intended for educational purposes for healthcare professionals and is not a substitute for professional medical advice, diagnosis, or treatment. The prescribing physician should be consulted for diagnosis and treatment of any and all medical conditions. The author does not endorse any specific tests, physicians, products, or procedures. Full prescribing information, including boxed warnings, should be reviewed before initiating therapy with Retrovir.

Reviews

• “The Concorde trial and subsequent long-term follow-up studies cemented Retrovir’s role in changing HIV from a fatal diagnosis to a manageable chronic condition. While newer agents offer improved side effect profiles, its efficacy and role in PMTCT are undeniable.” – Infectious Disease Specialist, 20+ years experience
• “Managing hematologic parameters requires vigilance, especially in advanced patients. However, in the correct combination regimen, it remains a powerful and reliable tool in our arsenal. The availability of a pediatric formulation is invaluable.” – Clinical Pharmacist, HIV Clinic
• “The landmark ACTG 076 study was a watershed moment, proving that Retrovir could drastically reduce perinatal transmission. This application alone has saved hundreds of thousands of children from HIV infection globally.” – OB/GYN specializing in HIV
• “While we now have NRTIs with better mitochondrial toxicity profiles, understanding the long-term data and management of side effects with zidovudine is fundamental knowledge for any HIV treater.” – Clinical Researcher, HIV Therapeutics