ZIDOVUDINE
Clinical safety rating: safe
Human studies have proved safety
Nucleoside reverse transcriptase inhibitor; phosphorylated to zidovudine triphosphate, which competes with endogenous thymidine triphosphate and incorporates into viral DNA, causing chain termination.
| 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. |
| Molecular Weight | 267.24 |
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. |
| 1st trimester | Zidovudine is recommended for use in pregnancy for prevention of mother-to-child transmission of HIV. It is generally considered safe during the first trimester; however, risks and benefits must be weighed. Animal studies have shown some embryotoxicity at high doses, but human data do not indicate an increased risk of major congenital anomalies. |
| 2nd trimester | Zidovudine is continued for prevention of HIV vertical transmission. No specific safety concerns beyond continued monitoring for maternal and fetal effects such as anemia. |
| 3rd trimester | Zidovudine is recommended for intrapartum prophylaxis and for the newborn. Extensive use in third trimester has not shown teratogenic effects; however, transient neonatal anemia and neutropenia have been reported. Monitoring of blood counts is advised. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| Placental transfer | Zidovudine crosses the placenta efficiently, achieving fetal plasma concentrations approximately 50-100% of maternal concentrations. This property is utilized for prevention of perinatal HIV transmission. |
■ FDA Black Box Warning
Hematologic toxicity (neutropenia, severe anemia), particularly in advanced HIV disease; myopathy; lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal.
| Common Effects | Anemia |
| Serious Effects |
Hypersensitivity to zidovudine or any component of the formulationLife-threatening reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) to zidovudineSevere anemia or neutropenia (absolute neutrophil count <750 cells/mm³ or hemoglobin <7.5 g/dL) as a relative contraindication; absolute contraindication if significant pre-existing bone marrow suppression not due to HIV
| 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 |
| Food/Dietary |
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| Breastfeeding | Zidovudine is excreted into human breast milk in concentrations lower than maternal serum. In HIV-infected women, breastfeeding is contraindicated to avoid postnatal transmission of HIV. Therefore, use of zidovudine during breastfeeding is not recommended for HIV-positive mothers. |
| Lactation Rating | L3 (Moderately Safe) in the absence of HIV; however, breastfeeding contraindicated due to HIV transmission risk. |
| 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%. |
| Fetal Monitoring | Maternal: Complete blood count (CBC) with differential every 2 weeks for first month, then monthly; renal and hepatic function tests. Fetal/neonatal: Monitor for anemia and neutropenia via CBC at birth; assess for mitochondrial dysfunction (lactic acidosis). |
| Fertility Effects | No significant adverse effects on human fertility reported in clinical studies. Animal studies showing no impairment of fertility. Limited data on ovarian reserve; theoretical concern for mitochondrial toxicity but not confirmed. |
| Take with food if gastrointestinal upset occurs. No significant food interactions. Avoid grapefruit juice as it may increase drug levels via CYP3A4 inhibition. |
| Clinical Pearls | Monitor for macrocytic anemia and neutropenia, especially in advanced HIV. Dose adjustment required in renal impairment (CrCl <15 mL/min). Can cause lactic acidosis with hepatosteatosis, particularly in obese patients on prolonged therapy. Avoid concurrent use with stavudine due to antagonism. Use with caution in patients with hepatic impairment. |
| Patient Advice | Take zidovudine exactly as prescribed; do not miss doses. · Report any signs of anemia (fatigue, pallor) or infection (fever, sore throat). · Notify your doctor immediately if you experience unexplained muscle pain, abdominal pain, nausea, or vomiting. · Avoid alcohol due to increased risk of liver toxicity. · Do not stop treatment without consulting your doctor. |