Zidovir, Zidovudine

Introduction to Zidovir (Zidovudine)

Overview of Zidovir and its Clinical Significance

Zidovir, containing the active ingredient zidovudine, is a cornerstone antiretroviral medication used in the management of human immunodeficiency virus type 1 (HIV-1) infection. By interfering with viral replication, it reduces viral load, preserves immune function, and enhances quality of life in individuals living with HIV. Its role extends beyond treatment, playing a key part in HIV prevention protocols.

History of Zidovudine Development and Approval

Originally synthesized in the 1960s as a potential anticancer compound, zidovudine's antiviral properties were later identified, leading to its approval in 1987 as the first antiretroviral drug for HIV. Its rapid integration into clinical practice transformed the outlook for HIV patients worldwide.

Therapeutic Classification

Zidovir belongs to the pharmacological class known as Nucleoside Reverse Transcriptase Inhibitors (NRTIs). These agents target the reverse transcriptase enzyme, essential for viral replication, halting the progression of the infection at a molecular level.

Global Brand Names and Generic Availability

Zidovudine is marketed under various brand names such as Retrovir, Azidothymidine (AZT), and Zidovir. Widely available in generic form, it ensures affordable access in both developed and resource-limited settings.

Medical Uses of Zidovir (Zidovudine)

FDA-Approved Uses

• Treatment of HIV-1 infection in adults and adolescents: Administered as part of combination antiretroviral therapy to suppress viral load and enhance immune function.
• Treatment of HIV-1 infection in pediatric patients: Age-appropriate dosing to manage infection and prevent disease progression.
• Prevention of maternal-fetal HIV transmission: Administered during pregnancy and labor to significantly reduce vertical transmission risk.
• Post-exposure prophylaxis (PEP): Used in occupational exposure cases, such as needlestick injuries, to prevent HIV infection.

Off-Label Uses

• Management of HIV-associated thrombocytopenia to improve platelet counts.
• Adjunctive therapy in resistant HIV strains within combination regimens.
• Investigational use against other retroviral infections beyond HIV.

How Zidovir (Zidovudine) Works

Mechanism of Action

Zidovudine is phosphorylated intracellularly into its active triphosphate form, which competes with natural nucleosides for incorporation into viral DNA. Once integrated, it causes premature DNA chain termination, blocking viral replication.

Inhibition of Viral Replication

By halting reverse transcription, zidovudine disrupts the essential step of converting viral RNA into DNA, thereby preventing the establishment of proviral DNA in host cells.

Pharmacodynamics and Pharmacokinetics

The drug demonstrates rapid oral absorption, with extensive distribution into bodily tissues, including the central nervous system. Zidovudine undergoes hepatic metabolism and renal excretion, necessitating dose adjustments in certain patient populations.

Resistance Profile

Resistance can develop through point mutations in the reverse transcriptase gene. Cross-resistance with other NRTIs may occur, highlighting the importance of combination therapy.

Composition and Formulations

• Active ingredient: Zidovudine.
• Dosage forms: Tablets, capsules, oral solution, and intravenous injection.
• Inactive ingredients: May include excipients such as cellulose, magnesium stearate, and coloring agents.
• Strengths: Commonly available in 100 mg, 300 mg tablets, and 10 mg/mL oral solution.

Dosage and Administration Guidelines

General Adult Dosage

Standard adult dosing involves 300 mg twice daily, often in combination with other antiretrovirals.

Dosage in Combination Therapy

Integrated into fixed-dose combinations or individualized regimens to maximize efficacy and minimize resistance.

Pediatric Dosage

• Administered according to weight-based calculations.
• Oral solutions facilitate accurate dosing in infants and children.

Pregnancy and Labor Dosage

Special dosing schedules during pregnancy and intrapartum administration are designed to significantly reduce the risk of HIV transmission to the newborn.

Dose Adjustments

• Renal impairment: Dose reduction may be required.
• Hepatic impairment: Caution and potential adjustment based on liver function tests.
• Hematologic toxicity: Dose modification or temporary discontinuation may be necessary.

Possible Side Effects of Zidovir (Zidovudine)

Common Side Effects

• Headache
• Nausea and vomiting
• Fatigue
• Gastrointestinal discomfort
• Muscle pain and mild anemia

Serious Side Effects

• Severe anemia and neutropenia
• Myopathy and muscle weakness with prolonged use
• Lactic acidosis with hepatomegaly and steatosis
• Immune reconstitution syndrome

Drug Interactions with Zidovir (Zidovudine)

• Interactions with other antiretrovirals such as stavudine and ribavirin, which may antagonize effects.
• Increased hematologic toxicity risk when combined with agents like ganciclovir or interferon-alpha.
• Considerations in hepatic metabolism pathways, including CYP450 interactions.
• Alcohol may exacerbate hepatotoxic effects and should be consumed with caution.

Warnings and Precautions

Risk of Hematologic Toxicity and Regular Blood Monitoring

Zidovudine therapy carries a well-recognized risk of hematologic complications, including anemia and neutropenia. These effects are more likely in advanced HIV disease or in patients with pre-existing bone marrow suppression. Regular complete blood count (CBC) assessments are critical to detect abnormalities early, enabling timely intervention such as dose adjustment or therapy interruption.

Hepatic Toxicity and Risk of Lactic Acidosis

Hepatotoxicity, characterized by elevated transaminases and hepatomegaly with steatosis, can occur. Zidovudine may also precipitate lactic acidosis, a rare but potentially fatal condition caused by mitochondrial toxicity. Patients should be monitored for symptoms such as persistent nausea, vomiting, abdominal pain, and unexplained fatigue.

Myopathy Risk with Prolonged Use

Chronic administration of zidovudine has been linked to the development of myopathy, presenting as muscle weakness and pain. This condition is thought to arise from mitochondrial damage in muscle tissue and warrants consideration in patients reporting neuromuscular symptoms.

Special Caution in Patients with Hepatitis Co-infection

Individuals co-infected with hepatitis B or C viruses are at increased risk of hepatic decompensation during antiretroviral therapy. Close liver function monitoring is essential, and dosage modifications may be required to prevent further hepatic injury.

Monitoring Parameters During Therapy

• Complete blood count at baseline and periodically
• Liver function tests at regular intervals
• Creatine kinase levels in patients with muscle symptoms
• Serum lactate in symptomatic individuals

Contraindications for Zidovir Use

Known Hypersensitivity to Zidovudine or Formulation Components

Patients with documented hypersensitivity reactions to zidovudine or any excipients should not receive the drug due to the risk of severe allergic responses.

Severe Anemia or Bone Marrow Suppression

Zidovudine should be avoided in patients with profoundly low hemoglobin or significant bone marrow suppression, as it may exacerbate hematologic deficits.

Previous History of Significant Lactic Acidosis During NRTI Therapy

A history of lactic acidosis related to nucleoside analogue treatment is a contraindication due to the heightened risk of recurrence.

Careful Administration Guidelines

Use in Patients with Pre-existing Hematologic Disorders

Special care is required in those with baseline anemia, leukopenia, or other hematologic abnormalities, with more frequent monitoring advised.

Renal or Hepatic Dysfunction Management

In renal impairment, zidovudine clearance is reduced, necessitating dosage adjustments. Patients with hepatic impairment require careful monitoring for toxicity and altered drug metabolism.

Long-term Therapy Safety Monitoring

Extended use mandates vigilance for cumulative toxicities, including myopathy, lipodystrophy, and mitochondrial dysfunction.

Polypharmacy Management in HIV Patients

Given the frequent use of complex regimens, potential drug-drug interactions should be reviewed regularly to prevent additive toxicities or reduced therapeutic efficacy.

Special Population Considerations

Administration to Elderly Patients

Age-related changes in organ function may increase susceptibility to adverse effects. Lower starting doses and cautious titration are advisable, accompanied by routine monitoring.

Dose Adjustments and Monitoring

Renal and hepatic function tests should guide ongoing dosage modifications in elderly patients to avoid accumulation and toxicity.

Administration to Pregnant and Nursing Women

Zidovudine has demonstrated efficacy in reducing mother-to-child HIV transmission when used during pregnancy and labor. It is generally considered safe for use during pregnancy under medical supervision.

Breastfeeding Considerations and HIV Transmission Prevention

In settings where safe alternatives exist, breastfeeding is generally discouraged in HIV-positive mothers to eliminate postnatal transmission risk, regardless of zidovudine use.

Administration to Children and Infants

Weight-based dosing ensures accuracy in pediatric populations. Liquid formulations facilitate administration in infants and small children, with regular growth and development assessments recommended during therapy.

Overdosage and Emergency Management

Symptoms of Zidovudine Overdose

Acute overdose may present with pronounced fatigue, headache, nausea, hematologic suppression, and in severe cases, lactic acidosis.

Recommended Treatment and Supportive Care

There is no specific antidote. Management includes symptomatic and supportive measures, close clinical observation, and laboratory monitoring. Hemodialysis may partially remove the drug.

Prognosis Following Overdose Incidents

With prompt intervention, recovery is typically complete. However, severe complications such as lactic acidosis may be life-threatening without immediate care.

Storage and Handling Precautions

Recommended Storage Temperature and Light Protection

Store zidovudine tablets and oral solutions at controlled room temperature, away from excessive heat and moisture. Protect from direct light to preserve potency.

Shelf-life and Stability of Oral and Injectable Formulations

Oral formulations generally remain stable until the manufacturer’s expiration date if stored correctly. Injectable preparations should be used within specified time frames after opening or reconstitution.

Safe Disposal Practices for Expired or Unused Medication

Expired or unused zidovudine should be disposed of through pharmaceutical take-back programs or according to local hazardous waste disposal guidelines to prevent environmental contamination and accidental ingestion.

Zidovir, Zidovudine FAQ