API Zidovudine

Zidovudine More Info

Zidovudine, also known by its brand name Retrovir, is a first-generation nucleoside reverse transcriptase inhibitor (NRTI). It was the first approved antiretroviral drug for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and remains a core component of combined antiretroviral therapy (cART) regimens worldwide.

Basic Properties

Chemical Formula: C₁₀H₁₃N₅O₄

Molecular Weight: 267.24 g/mol

Physical Appearance: A white to off-white crystalline powder with a slight solubility in water and greater solubility in dimethyl sulfoxide (DMSO) and methanol.

Chemical Alias: Azidothymidine (AZT)

Mechanism of Action

Zidovudine works by mimicking the structure of thymidine, a natural nucleoside required for viral DNA synthesis. Once inside the host cell, it is phosphorylated into its active triphosphate form. This active form competitively inhibits HIV reverse transcriptase—the enzyme that converts the virus’s RNA genome into DNA. By incorporating itself into the growing viral DNA chain, zidovudine terminates DNA synthesis prematurely, thus blocking HIV replication and reducing viral load in the body.

Clinical Uses

HIV Treatment

It is used to treat HIV-1 infection in adults, adolescents, and pediatric patients (including neonates born to HIV-positive mothers). Zidovudine is almost always prescribed in combination with other antiretroviral drugs (e.g., non-nucleoside reverse transcriptase inhibitors, protease inhibitors) to prevent the development of drug resistance.

Perinatal HIV Prevention

Administering zidovudine to HIV-positive pregnant women during pregnancy, labor, and delivery, followed by a short course for the newborn, significantly reduces the risk of mother-to-child HIV transmission.

Dosage and Administration

Adults with normal renal function: The typical oral dose is 300 mg twice daily or 600 mg once daily (extended-release formulation). Intravenous administration is available for patients who cannot take oral medications.

Pediatric patients: Dosage is based on body weight, with formulations including oral syrup and tablets to accommodate different age groups.

Patients with renal or hepatic impairment: Dosage adjustments are required to avoid drug accumulation and side effects.

Side Effects

Hematological Toxicity

The most serious side effect is bone marrow suppression, which can lead to anemia, neutropenia, or thrombocytopenia. Regular blood cell count monitoring is mandatory during treatment, especially in the first 12 weeks.

Gastrointestinal Effects

Common mild side effects include nausea, vomiting, diarrhea, and abdominal pain, which often improve with continued use.

Other Side Effects

Headache, fatigue, myalgia, and elevated liver enzymes may occur. Long-term use has been associated with lipoatrophy (loss of subcutaneous fat) and peripheral neuropathy in some patients.

Contraindications and Precautions

Contraindications: Hypersensitivity to zidovudine or any of its formulation components.

Precautions

Hematological Monitoring: Patients with pre-existing blood disorders (e.g., anemia, neutropenia) require close monitoring, as zidovudine may worsen these conditions.

Renal/Hepatic Impairment: Dose reduction is necessary for patients with moderate to severe kidney or liver dysfunction.

Pregnancy and Lactation: Classified as Pregnancy Category C in some regions; use only if the potential benefit justifies the risk to the fetus. HIV-positive mothers should not breastfeed to prevent viral transmission.

Drug Interactions: Co-administration with other myelosuppressive drugs (e.g., chemotherapy agents) increases the risk of bone marrow suppression. It may also interact with other NRTIs, requiring dosage adjustments.

Market Information

Zidovudine is available in both brand-name (Retrovir) and generic forms, making it affordable and accessible in low- and middle-income countries. It is listed on the WHO Model List of Essential Medicines, highlighting its critical role in global HIV/AIDS management.