ZIDOVUDINE

Clinical safety rating: safe

Human studies have proved safety

How it works

Nucleoside reverse transcriptase inhibitor; phosphorylated to zidovudine triphosphate, which competes with endogenous thymidine triphosphate and incorporates into viral DNA, causing chain termination.

What the body does with it

Metabolism	Hepatic glucuronidation via UGT2B7 to inactive metabolite; also metabolized by CYP3A4 to minor extent.
Excretion	Renal excretion of unchanged drug accounts for 14-18%; major metabolite is 5'-glucuronide (GZDV) excreted renally (60-80% of dose). Fecal excretion <2%.
Half-life	Terminal elimination half-life is 0.5-3 hours (mean 1.1 hours). Intracellular triphosphate half-life is 3-4 hours. Clinically relevant for twice-daily dosing.
Protein binding	30-38% bound to plasma albumin.
Volume of Distribution	Vd 1.6 L/kg (range 1.1-2.2 L/kg), indicating extensive distribution into total body water and tissues, including CSF (CSF:plasma ratio ~0.6).
Bioavailability	Oral: 60-70% (range 52-75%).
Onset of Action	Oral: Reduces HIV RNA within 1-2 weeks; IV: Peak plasma levels immediately.
Duration of Action	Oral: Suppresses viral replication for 8-12 hours; requires twice-daily dosing to maintain efficacy. IV: Duration similar to oral.

Classification & Brands

Dosing & administration

300 mg orally twice daily or 200 mg orally three times daily; alternatively 1 mg/kg intravenously every 4 hours (total 6 mg/kg/day).

Dosage form	SOLUTION
Renal impairment	CrCl <15 mL/min: 300 mg orally once daily; hemodialysis or peritoneal dialysis: 100 mg orally every 6-8 hours.
Liver impairment	Child-Pugh class A: no adjustment; Child-Pugh class B or C: reduce dose by 50% or increase dosing interval.
Pediatric use	Neonates (birth to 4 weeks): 2 mg/kg orally every 6 hours or 1.5 mg/kg intravenously every 6 hours; Children (4 weeks to 18 years): 240 mg/m² orally every 12 hours or 120 mg/m² intravenously every 6 hours; maximum 300 mg per dose.
Geriatric use	No specific dose adjustment; use with caution due to age-related renal impairment; monitor hematologic parameters.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.

Breastfeeding	Zidovudine is excreted in human milk with a milk-to-plasma ratio (M/P) of approximately 0.7. Breastfeeding is contraindicated in HIV-positive mothers to avoid postnatal transmission; no data on effects in HIV-negative infants.
Teratogenic Risk	Zidovudine is classified as FDA Pregnancy Category C. First trimester: crosses placenta; no increased risk of major malformations in human studies, but animal data show late fetal resorption. Second and third trimesters: well-tolerated; associated with transient anemia and neutropenia in neonates; prophylactic use reduces vertical transmission from 25% to 8%.

Warnings & precautions

■ FDA Black Box Warning

Hematologic toxicity (neutropenia, severe anemia), particularly in advanced HIV disease; myopathy; lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal.

Side Effect Profile

Common Effects	Anemia
Serious Effects

Absolute Contraindications

["Hypersensitivity to zidovudine or any component","Life-threatening allergic reaction to zidovudine","Neutrophil count <750 cells/mm³ or hemoglobin <7.5 g/dL (relative, caution)"]

Clinical Precautions

Precautions

["Monitor hematologic parameters (hemoglobin, neutrophil count) frequently","Risk of lactic acidosis/hepatomegaly with steatosis; discontinue if suspected","Lipodystrophy and metabolic abnormalities","Immune reconstitution syndrome","Possible myopathy with prolonged use"]

Clinical Tips & Counseling

Drug interactions

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