Zidovudine - Revision history

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Ostermayer: Created page with "Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) — the first antiretroviral approved for HIV (1987). While largely replaced by newer agents for routine HIV treatment, it remains important for '''prevention of maternal-fetal HIV transmission''' (intrapartum IV dosing) and as a component of some neonatal prophylaxis regimens. It is also the only ARV available as an IV formulation.Retrovir (zidovudine) [p..."

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Created page with "Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) — the first antiretroviral approved for HIV (1987). While largely replaced by newer agents for routine HIV treatment, it remains important for '''prevention of maternal-fetal HIV transmission''' (intrapartum IV dosing) and as a component of some neonatal prophylaxis regimens. It is also the only ARV available as an IV formulation.<ref name="RetrovirPI">Retrovir (zidovudine) [p..."

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Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) — the first antiretroviral approved for [[HIV - AIDS (main)|HIV]] (1987). While largely replaced by newer agents for routine HIV treatment, it remains important for '''prevention of maternal-fetal HIV transmission''' (intrapartum IV dosing) and as a component of some neonatal prophylaxis regimens. It is also the only ARV available as an IV formulation.<ref name="RetrovirPI">Retrovir (zidovudine) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.</ref>

==Administration==
*Type: Nucleoside reverse transcriptase inhibitor (NRTI)
*Dosage Forms: 100 mg capsules; 300 mg tablets; 10 mg/mL oral solution (syrup); 10 mg/mL IV injection
*Routes of Administration: Oral, intravenous
*Common Trade Names: Retrovir; also in fixed-dose combinations: Combivir (zidovudine/lamivudine), Trizivir (zidovudine/lamivudine/abacavir)

==Adult Dosing==
*'''HIV treatment:''' 300 mg PO twice daily (or 200 mg PO three times daily)<ref name="RetrovirPI"/>
*'''IV dosing:''' 1 mg/kg IV infused over 1 hour, every 4 hours (~5–6 mg/kg/day) — use when oral not feasible<ref name="RetrovirPI"/>
*'''Intrapartum (prevention of perinatal transmission):'''<ref name="RetrovirPI"/>
**2 mg/kg IV loading dose, then 1 mg/kg/hr continuous infusion until umbilical cord clamped
**Scheduled cesarean: Begin IV 3 hours before surgery
**'''Not required''' if mother is virologically suppressed (HIV RNA <50 copies/mL) and adherent to oral ART<ref name="Medscape">Retrovir (zidovudine). Medscape Drug Reference. Accessed 2025.</ref>
*May take with or without food

==Pediatric Dosing==
*'''Neonatal prophylaxis:''' Weight-based dosing starting within 6–12 hours of birth; typically 4 mg/kg PO BID (≥35 weeks gestational age) for 4–6 weeks<ref name="RetrovirPI"/>
*'''Higher-risk neonates:''' Combined with nevirapine and/or lamivudine per current perinatal guidelines
*'''HIV treatment (children ≥4 weeks):''' Weight-based or BSA-based dosing (e.g., 240 mg/m² PO BID); consult pediatric ID<ref name="RetrovirPI"/>

==Special Populations==
===[[Drug pregnancy categories|Pregnancy Rating]]===
*Formerly Category C; extensively studied in pregnancy<ref name="RetrovirPI"/>
*Landmark ACTG 076 trial demonstrated reduced perinatal HIV transmission from 25% to 8% with zidovudine prophylaxis
*Crosses the placenta; neonatal plasma concentrations approximate maternal levels at delivery<ref name="RetrovirPI"/>
*Antiretroviral Pregnancy Registry: 1-800-258-4263

===Lactation risk===
*Excreted in human milk; women with HIV should not breastfeed (risk of HIV transmission)<ref name="RetrovirPI"/>

===Renal Dosing===
*Adult: CrCl <15 mL/min or on hemodialysis/peritoneal dialysis: '''100 mg PO q6–8h''' (or 1 mg/kg IV q6–8h)<ref name="RetrovirPI"/>
**Hemodialysis has negligible effect on zidovudine removal (but enhances removal of its glucuronide metabolite)
*Pediatric: Insufficient specific data

===Hepatic Dosing===
*Adult: Insufficient data to recommend dose adjustment; zidovudine is primarily hepatically metabolized, so concentrations may be increased. Frequent hematologic monitoring is advised<ref name="RetrovirPI"/>
*Pediatric: Not studied

==Contraindications==
*Allergy to class/drug
*Potentially life-threatening hypersensitivity reactions reported (including anaphylaxis)
*Do '''not''' combine with stavudine (d4T) — antagonistic antiviral interaction<ref name="RetrovirPI"/>

==Adverse Reactions==
===Serious===
*'''Hematologic toxicity''' (the defining toxicity): Severe anemia, neutropenia, pancytopenia, aplastic anemia — risk increases with advanced HIV disease, prolonged use, and pre-existing bone marrow suppression<ref name="RetrovirPI"/>
*'''Lactic acidosis with hepatic steatosis''' (NRTI class effect; including fatal cases) — presents with nausea, vomiting, abdominal pain, fatigue, dyspnea, elevated lactate<ref name="RetrovirPI"/>
*Hepatotoxicity (including hepatic failure)
*Myopathy/rhabdomyolysis with prolonged use (related to mitochondrial toxicity)<ref name="StatPearls">Zidovudine. ''StatPearls''. NCBI Bookshelf. Updated 2023.</ref>
*[[Immune reconstitution syndrome|Immune reconstitution inflammatory syndrome (IRIS)]]
*[[Stevens-Johnson syndrome]]

===Common===
*Headache, malaise, fatigue, nausea, vomiting, anorexia<ref name="RetrovirPI"/>
*Macrocytosis (MCV elevation — nearly universal and can serve as an indirect marker of adherence)<ref name="StatPearls"/>
*Insomnia
*Nail pigmentation (bluish-brown discoloration)
*Lipoatrophy (subcutaneous fat loss — NRTI class effect, particularly with thymidine analogs)

==Pharmacology==
*Half-life: ~0.5–3 hours (plasma); intracellular triphosphate half-life ~3–4 hours<ref name="StatPearls"/>
*Metabolism: Hepatic glucuronidation (UGT) to inactive GZDV metabolite (~74% of dose); minor renal excretion of unchanged drug (~14%)<ref name="StatPearls"/>
*Excretion: ~14% unchanged in urine, ~74% as glucuronide metabolite in urine; remainder in feces<ref name="RetrovirPI"/>

==Mechanism of Action==
Zidovudine is a thymidine analog that is phosphorylated intracellularly to its active form, zidovudine triphosphate (ZDV-TP). ZDV-TP competes with natural thymidine triphosphate for incorporation into growing HIV DNA by reverse transcriptase. Once incorporated, it acts as a chain terminator because it lacks the 3'-hydroxyl group needed for DNA chain elongation, halting proviral DNA synthesis.<ref name="RetrovirPI"/> It has no clinically significant activity against HIV-2.<ref name="StatPearls"/>

==Comments==
*'''ED role — intrapartum dosing:''' The most common reason an ED or L&D physician will encounter zidovudine is for '''IV intrapartum prophylaxis''' in an HIV+ woman presenting in labor. Know the loading dose (2 mg/kg IV) and infusion (1 mg/kg/hr). However, if the patient is on suppressive ART with an undetectable viral load and no adherence concerns, IV zidovudine is no longer required<ref name="Medscape"/>
*'''Hematologic monitoring pearl:''' If a patient on zidovudine presents with fatigue, pallor, dyspnea, or recurrent infections, '''check a CBC immediately''' — severe anemia (may require transfusion) and neutropenia are the dose-limiting toxicities. Dose reduction or discontinuation may be needed at Hgb <7.5 g/dL or ANC <750<ref name="RetrovirPI"/>
*'''Macrocytosis as adherence marker:''' An elevated MCV (often >100 fL) is nearly universal on zidovudine and does not require workup. Conversely, a normal MCV in a patient supposedly taking zidovudine may suggest non-adherence<ref name="StatPearls"/>
*'''Lactic acidosis:''' NRTI class effect. Suspect in patients with unexplained nausea, vomiting, abdominal pain, dyspnea, fatigue, and elevated lactate/anion gap. Discontinue zidovudine immediately and provide supportive care<ref name="RetrovirPI"/>
*'''Drug interactions:''' Avoid combining with stavudine (antagonistic), doxorubicin (antagonistic), and ribavirin (worsens anemia). Trimethoprim and probenecid increase zidovudine levels; use caution with other myelosuppressive agents (ganciclovir, TMP-SMX, dapsone)<ref name="RetrovirPI"/>
*Overdose: Exposures up to 50 grams reported; symptoms include fatigue, headache, vomiting, and hematologic disturbances. No specific antidote; supportive care. Hemodialysis does not effectively remove zidovudine but enhances clearance of its metabolite<ref name="RetrovirPI"/>

==See Also==
*[[HIV - AIDS (main)]]
*[[HIV post-exposure prophylaxis]]
*[[Immune reconstitution syndrome]]
*[[Emtricitabine/tenofovir]]

==References==
{{reflist|2}}
[[Category:Pharmacology]]

← Older revision		Revision as of 09:15, 22 March 2026
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	Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) — the first antiretroviral approved for [[HIV - AIDS (main)\|HIV]] (1987). While largely replaced by newer agents for routine HIV treatment, it remains important for ~~'''~~prevention of maternal-fetal HIV transmission~~'''~~ (intrapartum IV dosing) and as a component of some neonatal prophylaxis regimens. It is also the only ARV available as an IV formulation.<ref name="RetrovirPI">Retrovir (zidovudine) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.</ref>		Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) — the first antiretroviral approved for [[HIV - AIDS (main)\|HIV]] (1987). While largely replaced by newer agents for routine HIV treatment, it remains important for prevention of maternal-fetal HIV transmission (intrapartum IV dosing) and as a component of some neonatal prophylaxis regimens. It is also the only ARV available as an IV formulation.<ref name="RetrovirPI">Retrovir (zidovudine) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.</ref>

	==Administration==		==Administration==
Line 8:		Line 8:

	==Adult Dosing==		==Adult Dosing==
	*~~'''~~HIV treatment:~~'''~~ 300 mg PO twice daily (or 200 mg PO three times daily)<ref name="RetrovirPI"/>		*HIV treatment: 300 mg PO twice daily (or 200 mg PO three times daily)<ref name="RetrovirPI"/>
	*~~'''~~IV dosing:~~'''~~ 1 mg/kg IV infused over 1 hour, every 4 hours (~5–6 mg/kg/day) — use when oral not feasible<ref name="RetrovirPI"/>		*IV dosing: 1 mg/kg IV infused over 1 hour, every 4 hours (~5–6 mg/kg/day) — use when oral not feasible<ref name="RetrovirPI"/>
	*~~'''~~Intrapartum (prevention of perinatal transmission):~~'''~~<ref name="RetrovirPI"/>		*Intrapartum (prevention of perinatal transmission):<ref name="RetrovirPI"/>
	**2 mg/kg IV loading dose, then 1 mg/kg/hr continuous infusion until umbilical cord clamped		**2 mg/kg IV loading dose, then 1 mg/kg/hr continuous infusion until umbilical cord clamped
	**Scheduled cesarean: Begin IV 3 hours before surgery		**Scheduled cesarean: Begin IV 3 hours before surgery
	**~~'''~~Not required~~'''~~ if mother is virologically suppressed (HIV RNA <50 copies/mL) and adherent to oral ART<ref name="Medscape">Retrovir (zidovudine). Medscape Drug Reference. Accessed 2025.</ref>		**Not required if mother is virologically suppressed (HIV RNA <50 copies/mL) and adherent to oral ART<ref name="Medscape">Retrovir (zidovudine). Medscape Drug Reference. Accessed 2025.</ref>
	*May take with or without food		*May take with or without food

	==Pediatric Dosing==		==Pediatric Dosing==
	*~~'''~~Neonatal prophylaxis:~~'''~~ Weight-based dosing starting within 6–12 hours of birth; typically 4 mg/kg PO BID (≥35 weeks gestational age) for 4–6 weeks<ref name="RetrovirPI"/>		*Neonatal prophylaxis: Weight-based dosing starting within 6–12 hours of birth; typically 4 mg/kg PO BID (≥35 weeks gestational age) for 4–6 weeks<ref name="RetrovirPI"/>
	*~~'''~~Higher-risk neonates:~~'''~~ Combined with nevirapine and/or lamivudine per current perinatal guidelines		*Higher-risk neonates: Combined with nevirapine and/or lamivudine per current perinatal guidelines
	*~~'''~~HIV treatment (children ≥4 weeks):~~'''~~ Weight-based or BSA-based dosing (e.g., 240 mg/m² PO BID); consult pediatric ID<ref name="RetrovirPI"/>		*HIV treatment (children ≥4 weeks): Weight-based or BSA-based dosing (e.g., 240 mg/m² PO BID); consult pediatric ID<ref name="RetrovirPI"/>

	==Special Populations==		==Special Populations==
Line 32:		Line 32:

	===Renal Dosing===		===Renal Dosing===
	*Adult: CrCl <15 mL/min or on hemodialysis/peritoneal dialysis: ~~'''~~100 mg PO q6–8h~~'''~~ (or 1 mg/kg IV q6–8h)<ref name="RetrovirPI"/>		*Adult: CrCl <15 mL/min or on hemodialysis/peritoneal dialysis: 100 mg PO q6–8h (or 1 mg/kg IV q6–8h)<ref name="RetrovirPI"/>
	**Hemodialysis has negligible effect on zidovudine removal (but enhances removal of its glucuronide metabolite)		**Hemodialysis has negligible effect on zidovudine removal (but enhances removal of its glucuronide metabolite)
	*Pediatric: Insufficient specific data		*Pediatric: Insufficient specific data
Line 43:		Line 43:
	*Allergy to class/drug		*Allergy to class/drug
	*Potentially life-threatening hypersensitivity reactions reported (including anaphylaxis)		*Potentially life-threatening hypersensitivity reactions reported (including anaphylaxis)
	*Do ~~'''~~not~~'''~~ combine with stavudine (d4T) — antagonistic antiviral interaction<ref name="RetrovirPI"/>		*Do not combine with stavudine (d4T) — antagonistic antiviral interaction<ref name="RetrovirPI"/>

	==Adverse Reactions==		==Adverse Reactions==
	===Serious===		===Serious===
	*~~'''~~Hematologic toxicity~~'''~~ (the defining toxicity): Severe anemia, neutropenia, pancytopenia, aplastic anemia — risk increases with advanced HIV disease, prolonged use, and pre-existing bone marrow suppression<ref name="RetrovirPI"/>		*Hematologic toxicity (the defining toxicity): Severe anemia, neutropenia, pancytopenia, aplastic anemia — risk increases with advanced HIV disease, prolonged use, and pre-existing bone marrow suppression<ref name="RetrovirPI"/>
	*'''Lactic acidosis with hepatic steatosis''' (NRTI class effect; including fatal cases) — presents with nausea, vomiting, abdominal pain, fatigue, dyspnea, elevated lactate<ref name="RetrovirPI"/>		*'''Lactic acidosis with hepatic steatosis''' (NRTI class effect; including fatal cases) — presents with nausea, vomiting, abdominal pain, fatigue, dyspnea, elevated lactate<ref name="RetrovirPI"/>
	*Hepatotoxicity (including hepatic failure)		*Hepatotoxicity (including hepatic failure)
Line 70:		Line 70:

	==Comments==		==Comments==
	*~~'''~~ED role — intrapartum dosing:~~'''~~ The most common reason an ED or L&D physician will encounter zidovudine is for ~~'''~~IV intrapartum prophylaxis~~'''~~ in an HIV+ woman presenting in labor. Know the loading dose (2 mg/kg IV) and infusion (1 mg/kg/hr). However, if the patient is on suppressive ART with an undetectable viral load and no adherence concerns, IV zidovudine is no longer required<ref name="Medscape"/>		*ED role — intrapartum dosing: The most common reason an ED or L&D physician will encounter zidovudine is for IV intrapartum prophylaxis in an HIV+ woman presenting in labor. Know the loading dose (2 mg/kg IV) and infusion (1 mg/kg/hr). However, if the patient is on suppressive ART with an undetectable viral load and no adherence concerns, IV zidovudine is no longer required<ref name="Medscape"/>
	*'''Hematologic monitoring pearl:''' If a patient on zidovudine presents with fatigue, pallor, dyspnea, or recurrent infections, '''check a CBC immediately''' — severe anemia (may require transfusion) and neutropenia are the dose-limiting toxicities. Dose reduction or discontinuation may be needed at Hgb <7.5 g/dL or ANC <750<ref name="RetrovirPI"/>		*'''Hematologic monitoring pearl:''' If a patient on zidovudine presents with fatigue, pallor, dyspnea, or recurrent infections, '''check a CBC immediately''' — severe anemia (may require transfusion) and neutropenia are the dose-limiting toxicities. Dose reduction or discontinuation may be needed at Hgb <7.5 g/dL or ANC <750<ref name="RetrovirPI"/>
	*~~'''~~Macrocytosis as adherence marker:~~'''~~ An elevated MCV (often >100 fL) is nearly universal on zidovudine and does not require workup. Conversely, a normal MCV in a patient supposedly taking zidovudine may suggest non-adherence<ref name="StatPearls"/>		*Macrocytosis as adherence marker: An elevated MCV (often >100 fL) is nearly universal on zidovudine and does not require workup. Conversely, a normal MCV in a patient supposedly taking zidovudine may suggest non-adherence<ref name="StatPearls"/>
	*'''Lactic acidosis:''' NRTI class effect. Suspect in patients with unexplained nausea, vomiting, abdominal pain, dyspnea, fatigue, and elevated lactate/anion gap. Discontinue zidovudine immediately and provide supportive care<ref name="RetrovirPI"/>		*'''Lactic acidosis:''' NRTI class effect. Suspect in patients with unexplained nausea, vomiting, abdominal pain, dyspnea, fatigue, and elevated lactate/anion gap. Discontinue zidovudine immediately and provide supportive care<ref name="RetrovirPI"/>
	*~~'''~~Drug interactions:~~'''~~ Avoid combining with stavudine (antagonistic), doxorubicin (antagonistic), and ribavirin (worsens anemia). Trimethoprim and probenecid increase zidovudine levels; use caution with other myelosuppressive agents (ganciclovir, TMP-SMX, dapsone)<ref name="RetrovirPI"/>		*Drug interactions: Avoid combining with stavudine (antagonistic), doxorubicin (antagonistic), and ribavirin (worsens anemia). Trimethoprim and probenecid increase zidovudine levels; use caution with other myelosuppressive agents (ganciclovir, TMP-SMX, dapsone)<ref name="RetrovirPI"/>
	*Overdose: Exposures up to 50 grams reported; symptoms include fatigue, headache, vomiting, and hematologic disturbances. No specific antidote; supportive care. Hemodialysis does not effectively remove zidovudine but enhances clearance of its metabolite<ref name="RetrovirPI"/>		*Overdose: Exposures up to 50 grams reported; symptoms include fatigue, headache, vomiting, and hematologic disturbances. No specific antidote; supportive care. Hemodialysis does not effectively remove zidovudine but enhances clearance of its metabolite<ref name="RetrovirPI"/>