Usage
- Zidovudine is primarily used in combination with other antiretroviral agents for the treatment of Human Immunodeficiency Virus (HIV) infection in adults and children. It is also used to prevent mother-to-child transmission of HIV during pregnancy, labor, and delivery.
- Pharmacological Classification: Nucleoside Reverse Transcriptase Inhibitor (NRTI) - Antiretroviral.
- Mechanism of Action: Zidovudine inhibits the activity of HIV reverse transcriptase, the enzyme responsible for converting viral RNA into DNA, thus preventing viral replication.
Alternate Names
- Azidothymidine (AZT)
- Brand Names: Retrovir
How It Works
- Pharmacodynamics: Zidovudine, after being intracellularly phosphorylated to its active triphosphate form (zidovudine triphosphate), competes with thymidine triphosphate for incorporation into the viral DNA by the HIV reverse transcriptase, which results in premature chain termination and stops viral DNA synthesis. Zidovudine is less active against HIV-2 than HIV-1 due to reduced phosphorylation to the active triphosphate form.
- Pharmacokinetics:
- Absorption: Well-absorbed orally (bioavailability of 60-70%); peak plasma concentration is reached in 0.5 to 1.5 hours.
- Metabolism: Primarily metabolized in the liver via glucuronidation to an inactive metabolite.
- Elimination: Excreted mostly by the kidneys (70-80% as the glucuronide metabolite, 14% unchanged), small amounts also in the bile. Its half-life is around 1 hour.
- Mode of Action: Acts as a nucleoside analogue reverse transcriptase inhibitor. Intracellularly, it undergoes phosphorylation by cellular enzymes to its active form, zidovudine triphosphate. Zidovudine triphosphate competes with naturally occurring thymidine triphosphate for incorporation into viral DNA by the HIV reverse transcriptase. Its incorporation terminates the viral DNA synthesis.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Zidovudine competitively inhibits viral reverse transcriptase. No known direct receptor interaction or effect on neurotransmitters.
- Elimination Pathways: Primarily renal excretion (both unchanged drug and glucuronide metabolite). Some hepatic metabolism and biliary excretion.
Dosage
Standard Dosage
Adults:
- HIV treatment: 300 mg twice daily in combination with other antiretrovirals or 250mg twice daily.
- Prevention of maternal-fetal transmission: 100 mg five times a day orally from 14 weeks of gestation until the start of labor, then 300 mg orally every three hours during labor until delivery.
- IV administration (when oral administration is not feasible): 1-2 mg/kg every 4 hours.
Children:
- Infants ≥ 4 weeks old weighing 4 kg to <9 kg: 12 mg/kg twice daily.
- Infants ≥ 4 weeks old weighing 9 kg to <30 kg: 9 mg/kg twice daily.
- Children weighing ≥30 kg: Same as adult dose.
- Newborn infants (for prevention of mother-to-child transmission): 2 mg/kg every 6 hours starting 12 hours after birth and continuing through 6 weeks of age.
Special Cases:
- Elderly Patients: Pharmacokinetics not extensively studied; dose adjustment may be required based on renal function.
- Patients with Renal Impairment: Dose reduction needed in severe renal impairment (creatinine clearance < 10 ml/min), 100 mg every 6-8 hours. Hemodialysis and peritoneal dialysis do not significantly affect zidovudine elimination.
- Patients with Hepatic Dysfunction: Zidovudine may accumulate due to decreased glucuronidation; close monitoring and dose adjustment may be necessary.
- Patients with Comorbid Conditions: Dose adjustments may be required based on specific conditions and concurrent medications.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: IV zidovudine may be used temporarily when oral administration is not possible, using the standard IV dosing.
Dosage Adjustments:
- Hematological adverse reactions (e.g., anemia, neutropenia): Dose reduction or interruption may be necessary.
Side Effects
Common Side Effects
- Headache, nausea, vomiting, fatigue, myalgia, insomnia.
Rare but Serious Side Effects
- Lactic acidosis, severe hepatomegaly with steatosis, bone marrow suppression (anemia, neutropenia, pancytopenia), myopathy, myositis.
Long-Term Effects
- Lipodystrophy, lipoatrophy.
Adverse Drug Reactions (ADR)
- Anemia, neutropenia, pancytopenia, lactic acidosis, hepatic dysfunction, myopathy.
Contraindications
- Hypersensitivity to zidovudine.
- Patients with markedly low neutrophil counts (<0.75 x 109/L) or severely low hemoglobin levels (<7.5 g/dL).
Drug Interactions
- Other drugs metabolized by glucuronidation (e.g., probenecid, acetaminophen, indomethacin, lorazepam, morphine): May increase zidovudine concentrations.
- Drugs that suppress bone marrow function (e.g., ganciclovir, interferon-alpha, dapsone, flucytosine, vincristine, vinblastine): Increased risk of myelosuppression.
- Nephrotoxic drugs (e.g., aminoglycosides, amphotericin B): May potentiate zidovudine-induced nephrotoxicity.
- Ribavirin, stavudine, clarithromycin: May increase risk of anemia.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (FDA).
- Fetal Risks: Generally considered safe when used according to the established guidelines for preventing mother-to-child transmission. No consistent evidence of teratogenicity.
- Breastfeeding: Zidovudine is excreted in breast milk. It is generally recommended that HIV-infected mothers do not breastfeed to avoid transmission of the virus to the infant.
Drug Profile Summary
- Mechanism of Action: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
- Side Effects: Headache, nausea, vomiting, fatigue, myalgia, insomnia, lactic acidosis, hepatomegaly with steatosis, bone marrow suppression, myopathy.
- Contraindications: Hypersensitivity to zidovudine, markedly low neutrophil counts or hemoglobin levels.
- Drug Interactions: See detailed Drug Interactions section.
- Pregnancy & Breastfeeding: Category C; use with caution; breastfeeding not recommended for HIV-positive mothers.
- Dosage: See detailed Dosage section.
- Monitoring Parameters: Complete blood counts (CBC), liver function tests (LFTs), renal function tests, HIV viral load, CD4 count.
Popular Combinations
Zidovudine is often used in combination with other antiretroviral medications, such as lamivudine, abacavir, and other NRTIs, NNRTIs, and protease inhibitors, as part of highly active antiretroviral therapy (HAART).
Precautions
- General Precautions: Monitor for hematological toxicity, hepatic dysfunction, and lactic acidosis.
- Specific Populations: See detailed Dosage - Special Cases section.
- Lifestyle Considerations: Alcohol should be avoided or limited due to potential for additive hepatotoxicity.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Zidovudine?
A: See the detailed Dosage section above for specific recommendations for adults, children, and special populations.
Q2: What is the mechanism of action of Zidovudine?
A: Zidovudine is a nucleoside reverse transcriptase inhibitor that prevents HIV replication by inhibiting the activity of reverse transcriptase.
Q3: What are the common side effects of Zidovudine?
A: Common side effects include headache, nausea, vomiting, fatigue, myalgia, and insomnia.
Q4: What are the serious side effects of Zidovudine?
A: Serious side effects include lactic acidosis, severe hepatomegaly with steatosis, bone marrow suppression, myopathy, and myositis.
Q5: What are the contraindications for Zidovudine?
A: Contraindications include hypersensitivity to zidovudine and markedly low neutrophil counts or hemoglobin levels.
Q6: What are the key drug interactions with Zidovudine?
A: Significant interactions can occur with drugs metabolized by glucuronidation, those that suppress bone marrow function, and nephrotoxic drugs.
Q7: Can Zidovudine be used during pregnancy?
A: Zidovudine can be used during pregnancy to prevent mother-to-child transmission of HIV but should be used with caution and under the supervision of a physician.
Q8: Is it safe to breastfeed while taking Zidovudine?
A: Breastfeeding is not recommended for HIV-positive mothers to avoid transmission of the virus to the infant.
Q9: What monitoring parameters are important for patients on Zidovudine?
A: Complete blood counts (CBC), liver function tests (LFTs), renal function tests, HIV viral load, and CD4 count should be regularly monitored.
Q10: How is Zidovudine administered?
A: Zidovudine can be administered orally (capsules, syrup) or intravenously. Intravenous administration is generally reserved for situations where oral intake is not feasible.
