Retrovir

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 well-established efficacy and safety profile spanning decades of clinical use. It is indicated for use in combination with other antiretroviral agents to suppress viral replication, increase CD4+ cell counts, and slow the progression of HIV disease. Furthermore, it plays a critical role in the prevention of maternal-fetal HIV transmission.

Features

• Active Pharmaceutical Ingredient (API): Zidovudine (AZT)
• Pharmacologic Class: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
• Available Formulations: 100 mg and 300 mg film-coated tablets; 10 mg/mL syrup (strawberry-flavored)
• Standardized manufacturing under current Good Manufacturing Practices (cGMP)
• Bioavailability: Approximately 60-70% following oral administration
• Plasma Protein Binding: 30-38%
• Metabolism: Primarily hepatic via glucuronidation (UGT2B7)
• Elimination Half-life: 0.5 to 3 hours (intracellular anabolic half-life of the active triphosphate is 3-4 hours)
• Excretion: Primarily renal (approximately 60-80% of dose recovered in urine as parent drug and glucuronide metabolite)

Benefits

• Potent Viral Suppression: Effectively inhibits the reverse transcriptase enzyme, a critical component of the HIV-1 replication cycle, leading to a significant reduction in viral load.
• Immunologic Restoration: By suppressing viral replication, Retrovir allows for the recovery and maintenance of CD4+ (T-helper) lymphocyte counts, which is crucial for immune function.
• Proven Reduction in Disease Progression: Long-term clinical data demonstrate a significant delay in the progression to AIDS-defining illnesses and a reduction in mortality associated with HIV-1 infection.
• Prevention of Perinatal Transmission: When administered to pregnant individuals with HIV and their newborns, it dramatically reduces the rate of vertical transmission of the virus.
• Extensive Clinical Experience: With decades of real-world use, its efficacy, safety profile, and drug interaction potential are exceptionally well-characterized.
• Formulation Flexibility: Available in both tablet and liquid formulations, allowing for precise dosing across diverse patient populations, including pediatric patients and those with difficulty swallowing.

Common use

Retrovir is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and children. Its use is guided by treatment guidelines from authoritative bodies such as the U.S. Department of Health and Human Services (DHHS) and the World Health Organization (WHO). It is a key component of many combination ART regimens. Its second major indication is the prevention of maternal-fetal HIV transmission during pregnancy, labor, and delivery, and for the newborn infant post-delivery. It is not indicated as a monotherapy due to the high risk of rapid development of viral resistance.

Dosage and direction

Dosing must be individualized based on the patient’s clinical status, renal and hepatic function, and the specific ART regimen. It is always used in combination with other antiretroviral drugs.

• Adults & Adolescents (≥30 kg): The recommended oral dosage is 300 mg twice daily or 200 mg three times daily.
• Pediatric Patients (from birth): Dosage is based on body weight and body surface area. For example, 180 mg/m²/dose twice daily (not to exceed 200 mg per dose). Consultation of the full prescribing information for detailed pediatric dosing tables is mandatory.
• Prevention of Maternal-Fetal HIV Transmission: A specific dosing regimen for the pregnant individual and the neonate is used, typically involving administration during labor and to the newborn for the first 6 weeks of life.
• Administration: Tablets can be taken with or without food. The oral syrup should be administered using the supplied dosing spoon or syringe to ensure accuracy.

Precautions

• Hematologic Toxicity: Retrovir has been associated with hematologic toxicity including neutropenia and severe anemia, which may require dose interruption or discontinuation. Regular monitoring of blood counts (e.g., hemoglobin, hematocrit, neutrophil count) is essential, especially in patients with advanced HIV disease, and every 4 weeks for the first 3 months, then every 3 months.
• Myopathy: Myopathy and myositis with pathological changes similar to mitochondrial dysfunction have been associated with prolonged use.
• Lactic Acidosis/Severe Hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogues, including Retrovir. Use with caution in patients with known risk factors for liver disease; discontinue treatment in the event of rapidly elevating aminotransferases, progressive hepatomegaly, or metabolic/lactic acidosis of unknown origin.
• Lipoatrophy: Long-term use of NRTIs, including Retrovir, has been associated with a loss of subcutaneous fat in the limbs, face, and buttocks.
• Immune Reconstitution Inflammatory Syndrome (IRIS): Has been reported in patients treated with combination ART.
• Fat Redistribution: Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.

Contraindications

Retrovir is contraindicated in patients with a known hypersensitivity to zidovudine or any component of the formulation. It is also contraindicated for use with other drugs containing zidovudine (e.g., Combivir, Trizivir) or stavudine due to potential antagonism.

Possible side effect

Adverse reactions are often related to dose and duration of therapy. The most common and/or serious include:

• Hematologic: Anemia (may require transfusion), neutropenia, leukopenia, thrombocytopenia, pancytopenia.
• Gastrointestinal: Nausea, vomiting, abdominal pain, dyspepsia, diarrhea, anorexia.
• Neurological: Headache, dizziness, insomnia, malaise, paresthesia, somnolence.
• Hepatic: Elevated liver enzymes (AST, ALT), hyperbilirubinemia.
• Musculoskeletal: Myalgia, myopathy, muscle weakness.
• Metabolic: Lactic acidosis, hyperlipidemia, lipodystrophy.
• Other: Fever, rash, taste perversion, asthenia.

Drug interaction

Retrovir has the potential for significant pharmacokinetic and pharmacodynamic interactions.

• Myelosuppressive/Ganciclovir/Interferon-alpha: Concomitant use with other agents that cause bone marrow suppression (e.g., ganciclovir, interferon-alpha, cytotoxic chemotherapy) may increase the risk of hematologic toxicity.
• Stavudine: Concomitant use is contraindicated due to intracellular antagonism, potentially reducing the efficacy of both drugs.
• Doxorubicin: Concomitant use may antagonize the antitumor effect of doxorubicin in vitro; avoid concomitant use.
• Nephrotoxic Drugs: Drugs that reduce renal function or compete for active tubular secretion (e.g., probenecid) may increase plasma concentrations of zidovudine.
• Ribavirin & Other NRTIs: In vitro data suggests ribavirin can antagonize the intracellular phosphorylation of zidovudine; concomitant use of ribavirin and NRTIs should be undertaken with caution. Concomitant use with other NRTIs requires careful monitoring for additive toxicities.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. 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 the missed one. Maintaining a strict dosing schedule is critical for maintaining viral suppression and preventing the development of resistance.

Overdose

There is limited experience with overdose. Non-specific findings such as fatigue, nausea, and vomiting have been reported. Hematologic complications, such as neutropenia, are possible. Hemodialysis and peritoneal dialysis appear to have a limited effect on the removal of zidovudine, but may enhance the elimination of the primary glucuronide metabolite. Management should involve general supportive measures and frequent monitoring of hematologic parameters.

Storage

• Store at 15°-30°C (59°-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 refrigerated; do not freeze. Discard any unused portion 35 days after first opening the bottle.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is based on the product’s prescribing information but may not be exhaustive.

Reviews

• “As an infectious disease specialist with over 25 years of experience, Retrovir remains a foundational agent in our armamentarium. Its role in preventing perinatal transmission is nothing short of revolutionary. While newer agents have different toxicity profiles, its long-term efficacy data is unparalleled.” – Dr. A. Sharma, MD
• “Managing my HIV has been a long journey. Starting on a regimen containing Retrovir over a decade ago brought my viral load to undetectable levels, where it has remained. The initial nausea was challenging but manageable, and the peace of mind it provides is worth it.” – Patient M., living with HIV since 2005
• “From a clinical trialist’s perspective, the data from ACTG 076 that established Retrovir’s efficacy in preventing mother-to-child transmission was a landmark achievement that changed global public health policy and saved countless lives.” – Clinical Researcher, PhD
• “The introduction of zidovudine was the pivotal moment that transformed HIV from a terminal diagnosis to a manageable chronic condition. Its development paved the way for all subsequent antiretrovirals.” – Professor of Virology