Zidovudine has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease.
Prolonged use of zidovudine has been associated with symptomatic myopathy.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including with zidovudine and other antiretrovirals. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
Note: Patients should receive IV therapy only until oral therapy can be administered.
Prevention of perinatal HIV transmission: Recommendations for use of intrapartum zidovudine are based on maternal HIV RNA levels near the time of delivery (defined as ≥34 to 36 weeks gestation or 4 to 6 weeks prior to delivery) and other factors. Intrapartum zidovudine IV is recommended when HIV RNA is >1,000 copies/mL or when the HIV RNA level is unknown near delivery. Intrapartum zidovudine IV should also be administered if a lack of adherence is suspected since the last RNA result or when HIV is initially diagnosed during labor. Patients with HIV RNA >1,000 copies/mL should be given zidovudine even in cases of documented zidovudine resistance unless there is a history of hypersensitivity. Intrapartum zidovudine IV is not needed in patients receiving antiretroviral therapy (ART) who have HIV RNA <50 copies/mL near delivery AND who are adherent to their ART regimen. If a fetal scalp electrode is needed during labor, consider the fetal risk of HIV transmission high even if maternal HIV RNA is <50 copies/mL. The decision to administer zidovudine IV intrapartum to patients with HIV RNA ≥50 and ≤1,000 copies/mL near delivery should be made on a case-by-case basis (HHS [perinatal] 2020).
IV (preferred route): During labor and delivery: Loading dose: 2 mg/kg over 1 hour followed by a continuous IV infusion of 1 mg/kg/hour for 2 hours (minimum 3 hours total). For scheduled cesarean delivery, begin IV zidovudine 3 hours before surgery. In cases of unscheduled cesarean delivery due to maternal and fetal indications, consider administering the loading dose then proceeding to delivery. Note: Dosage based on total body weight.
Oral (alternative route): Note: Oral is not the preferred route of administration in the United States as benefits to this approach are unproven. Reserve for use when IV administration is not possible.
Loading dose: 600 mg, then 400 mg every 3 hours (HHS [perinatal] 2020).
HIV-1 infection, treatment: Note: Use in combination with other antiretroviral agents.
Oral: 300 mg twice daily.
IV: 1 mg/kg/dose administered every 4 hours around-the-clock (6 doses daily).
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use) (HHS [nPEP] 2016): Oral:
CrCl ≥60 mL/minute: Zidovudine is not a component of the recommended antiretroviral regimen for these patients.
CrCl <60 and ≥15 mL/minute: 300 mg twice daily in combination with other antiretroviral agents. Initiate therapy within 72 hours of exposure and continue for 28 days.
CrCl <15 mL/minute: Adjust dose based on renal function. Give in combination with other antiretroviral agents. Initiate therapy within 72 hours of exposure and continue for 28 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute:
Oral: 100 mg 3 times daily or 300 mg once daily (HHS [adult] 2019).
IV: 1 mg/kg every 6 to 8 hours.
End-stage renal disease on intermittent hemodialysis (administer dose after dialysis on dialysis days):
Oral: 100 mg 3 times daily or 300 mg once daily (HHS [adult] 2019).
IV: 1 mg/kg every 6 to 8 hours.
Peritoneal dialysis:
Oral: 100 mg every 6 to 8 hours.
IV: 1 mg/kg every 6 to 8 hours.
CRRT: No adjustment needed (Aronoff 2007).
There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied). However, adjustment may be necessary due to extensive hepatic metabolism.
(For additional information see "Zidovudine: Pediatric drug information")
HIV-1 infection, treatment: Use in combination with other antiretroviral (ARV) agents. Gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.
Oral: Note: Although a 3-times-daily dosing regimen is FDA approved, it is rarely used in practice; twice-daily dosing is recommended in the current pediatric HIV guidelines (HHS [pediatric 2020]; HHS [perinatal 2020]).
Infants (postconceptional age [PCA] ≥35 weeks and PNA ≥4 weeks), Children, and Adolescents:
Weight-directed dosing: Oral:
<9 kg: 12 mg/kg/dose twice daily.
9 to <30 kg: 9 mg/kg/dose twice daily.
≥30 kg: 300 mg twice daily.
BSA-directed dosing: Oral: 240 mg/m2/dose every 12 hours, range: 180 to 240 mg/m2/dose every 12 hours (maximum dose: 300 mg/dose).
IV: Note: Use IV route only until oral therapy can be administered:
Infants ≥3 months and Children: 120 mg/m2/dose every 6 hours; maximum dose: 160 mg/dose (Retrovir prescribing information [Canada] 2018).
Adolescents ≥30 kg: 1 to 2 mg/kg every 4 hours around the clock (Retrovir prescribing information [Canada] 2018).
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (HHS [nPEP] 2016): Note: Initiate therapy within 72 hours of exposure and continue for 28 days; use in combination with other antiretroviral agents.
Infants (PCA ≥35 weeks and PNA ≥4 weeks of age) and Children: Oral:
4 to <9 kg: 12 mg/kg/dose twice daily.
9 to <30 kg: 9 mg/kg/dose twice daily.
≥30 kg: 300 mg twice daily.
Adolescents: Oral: 300 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for hematologic toxicity: Consider interruption of therapy for significant anemia (Hgb <7.5 g/dL or >25% decrease from baseline) and/or significant neutropenia (ANC <750 cells/mm3 or >50% decrease from baseline) until evidence of bone marrow recovery occurs; once bone marrow recovers, dose may be resumed using appropriate adjunctive therapy (eg, epoetin alfa) (HHS [pediatric 2020]).
Infants >6 weeks, Children, and Adolescents:
The following adjustments have been recommended (Aronoff 2007): Note: Renally adjusted dose recommendations are based on oral doses of 160 mg/m2/dose every 8 hours and IV dose of 120 mg/m2/dose every 6 hours.
GFR ≥10 mL/minute/1.73 m2: No dosage adjustment required
GFR <10 mL/minute/1.73 m2: Administer 50% of dose every 8 hours
Intermittent hemodialysis (IHD): Administer 50% of dose every 8 hours
Peritoneal dialysis (PD): Administer 50% of dose every 8 hours
Continuous renal replacement therapy (CRRT): No adjustment required
All patients: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment may be necessary due to extensive hepatic metabolism; dosage reduction may be required; use with caution; monitor for hematologic toxicities frequently.
Refer to adult dosing.
Consider dose interruption for significant anemia (hemoglobin <7.5 g/dL or >25% reduction from baseline) and/or neutropenia (granulocyte count <750 cells/mm3 or >50% reduction from baseline) until evidence of recovery. Resumption in dose in combination with adjunctive measures (eg, epoetin alfa) may be appropriate, depending on erythropoietin level and patient tolerance.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Retrovir: 100 mg [contains soybean lecithin]
Generic: 100 mg
Solution, Intravenous [preservative free]:
Retrovir: 10 mg/mL (20 mL)
Syrup, Oral:
Retrovir: 50 mg/5 mL (240 mL) [contains sodium benzoate; strawberry flavor]
Generic: 50 mg/5 mL (240 mL)
Tablet, Oral:
Generic: 300 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Retrovir (AZT): 100 mg [DSC]
Generic: 100 mg
Solution, Intravenous:
Retrovir (AZT): 10 mg/mL (20 mL)
Syrup, Oral:
Retrovir (AZT): 10 mg/mL (240 mL) [contains sodium benzoate]
Oral: Administer without regard to meals.
IV: Avoid rapid infusion or bolus injection. Do not administer IM.
Infuse over 1 hour; in pregnant women, infuse loading dose over 1 hour followed by continuous infusion.
Oral: May be administered without regard to meals; use calibrated measuring device to accurately measure oral liquid dose; for neonatal patients, graduations of 0.1 mL are necessary due to small dose volumes.
Parenteral: IV infusion: Administer over 1 hour; in neonates, dose may be infused over 30 minutes. Do not administer IM; do not administer IV push or by rapid infusion.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends single gloving for administration of intact tablets or capsules. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration. For IV preparation, double gloves, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) are recommended. Double gloving, a gown, and CSTDs are recommended during IV administration (NIOSH 2016). Facilities may perform assessment of some (non-antineoplastic) hazardous drugs to determine if appropriate for alternative containment strategies and handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2017).
HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents
Perinatal HIV-1 transmission, prevention: Prevention of mother to fetus HIV-1 transmission
HIV-1 nonoccupational postexposure prophylaxis (nPEP)
Azidothymidine may be confused with azaTHIOprine, aztreonam
Retrovir may be confused with acyclovir, ritonavir
AZT is an error-prone abbreviation (mistaken as azathioprine, aztreonam)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages noted with oral administration in adults unless otherwise stated. Pediatric adverse event incidences occurred with combination therapy.
>10%:
Central nervous system: Headache (63%), malaise (53%)
Dermatologic: Skin rash (infants, children, & adolescents: 12%)
Gastrointestinal: Nausea (adults: 51%; infants, children, & adolescents: 8%), anorexia (20%), vomiting (adults: 17%; infants, children, & adolescents: 8%)
Hematologic & oncologic: Macrocytosis (infants, children, & adolescents: >50%), anemia (neonates: 22%; infants, children, & adolescents: 4%; adults, grades 3/4: 1%)
Hepatic: Hepatomegaly (infants, children, & adolescents: 11%)
Respiratory: Cough (infants, children, & adolescents: 15%)
Miscellaneous: Fever (infants, children, & adolescents: 25%)
1% to 10%:
Cardiovascular: Cardiac failure (infants, children, & adolescents: <6%), ECG abnormality (infants, children, & adolescents: <6%), edema (infants, children, & adolescents: <6%), left ventricular dilation (infants, children, & adolescents: <6%)
Central nervous system: Hyporeflexia (infants, children, & adolescents: <6%), irritability (infants, children, & adolescents: <6%), nervousness (infants, children, & adolescents: <6%), chills (≥5%), fatigue (≥5%), insomnia (≥5%), neuropathy (≥5%)
Endocrine & metabolic: Weight loss (infants, children, & adolescents: <6%), increased amylase (infants, children, & adolescents, grades 3/4: 3%)
Gastrointestinal: Diarrhea (infants, children, & adolescents: 8%), constipation (6%), stomatitis (infants, children, & adolescents: 6%), abdominal cramps (≥5%), abdominal pain (≥5%), dyspepsia (≥5%), increased serum lipase (infants, children, & adolescents, grades 3/4: 3%)
Genitourinary: Hematuria (infants, children, & adolescents: <6%)
Hematologic & oncologic: Lymphadenopathy (infants, children, & adolescents: 9%), neutropenia (infants, children, & adolescents, grades 3/4: 8%), splenomegaly (infants, children, & adolescents: 5%), thrombocytopenia (infants, children, & adolescents, grades 3/4: 1%)
Hepatic: Increased serum aspartate aminotransferase (infants, children, & adolescents, grades 3/4: 2%), increased serum alanine aminotransferase (infants, children, & adolescents, grades 3/4: 1%),
Neuromuscular & skeletal: Asthenia (9%), arthralgia (≥5%), musculoskeletal pain (≥5%), myalgia (≥5%)
Otic: Ear sign or symptom (infants, children, & adolescents: 7%)
Respiratory: Nasal congestion (infants, children, & adolescents: ≤8%), rhinorrhea (infants, children, & adolescents: ≤8%), abnormal breath sounds (infants, children, & adolescents: ≤7%), wheezing (infants, children, & adolescents: ≤7%)
Frequency not defined:
Local: Injection site reaction (IV), irritation at injection site (IV), pain at injection site (IV)
<1%, postmarketing and/or case reports: Amblyopia, anaphylaxis, angioedema, anxiety, aplastic anemia, autoimmune disease, back pain, cardiomyopathy, chest pain, confusion, decreased mental acuity, depression, diaphoresis, dizziness, drowsiness, dyschromia, dysgeusia, dysphagia, dyspnea, flatulence, flu-like symptoms, Graves disease, Guillain-Barré syndrome, gynecomastia, hearing loss, hemolytic anemia, hepatitis, hepatomegaly with steatosis, hyperbilirubinemia, hypersensitivity reaction, immune reconstitution syndrome, increased creatine phosphokinase, increased lactate dehydrogenase, jaundice, lactic acidosis, leukopenia, lipotrophy, macular edema, mania, muscle spasm, myopathy, myositis, oral mucosa hyperpigmentation, oral mucosa ulcer, pain, pancreatitis, pancytopenia, paresthesia, photophobia, polymyositis, pruritus, pure red cell aplasia, redistribution of body fat, rhabdomyolysis, rhinitis, seizure, sinusitis, Stevens-Johnson syndrome, syncope, toxic epidermal necrolysis, tremor, urinary frequency, urinary hesitancy, urticaria, vasculitis, vertigo
Potentially life-threatening hypersensitivity to zidovudine or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Neutrophil count <750/mm3 or hemoglobin <7.5 g/dL (4.65 mmol/L)
Concerns related to adverse effects:
• Hematologic toxicity: [US Boxed Warning]: Hematologic toxicity, including neutropenia and severe anemia have been reported with use, especially with advanced HIV-1 disease. Toxicity may be related to duration of use and prior bone marrow reserve. Hemoglobin reduction may occur in as early as 2 to 4 weeks; neutropenia usually occurs after 6 to 8 weeks. Pancytopenia has been reported (usually reversible). Use with caution in patients with bone marrow compromise (granulocytes <1,000 cells/mm3 or hemoglobin <9.5 g/dL). Monitor blood counts; dose interruption may be required in patients who develop anemia or neutropenia.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases. Risk may be increased with obesity or in females. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Lipoatrophy: May cause loss of subcutaneous fat, especially in the face, limbs, and buttocks. Lipoatrophy incidence and severity are related to cumulative exposure and may be only partially reversible; improvement may take months to years after switching to a regimen that does not contain zidovudine. Monitor patients for signs of lipoatrophy and consider switching to a non-zidovudine-containing regimen if lipoatrophy occurs.
• Myopathy: [US Boxed Warning]: Prolonged use has been associated with symptomatic myopathy and myositis. Pathological changes observed are similar to that produced by HIV-1 disease.
Disease-related concerns:
• Hepatic impairment: Hematologic toxicity may be increased due to increased serum concentrations in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with CrCl <15 mL/minute; dosage adjustment recommended.
Special populations:
• Newborns: Zidovudine newborn prophylaxis may affect diagnostic virologic assays in HIV-exposed infants. If a virologic assay result is negative while the infant is receiving combination antiretroviral prophylaxis or presumptive HIV therapy, repeat virologic testing should be considered 2 to 6 weeks after cessation of antiretroviral prophylaxis or presumptive HIV therapy (HHS [pediatric 2020]).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
Dosage form specific issues:
• Injection: Latex is used in vial stopper. May cause allergic reactions in latex-sensitive individuals.
Use with caution in patients with ANC <1,000 cells/mm3 or Hgb <9.5 g/dL; consider interruption of therapy for significant anemia (Hgb <7.5 g/dL or reduction >25% of baseline; neonates: Hgb <7 g/dL) or neutropenia (ANC <750 cells/mm3 or reduction >50% from baseline; neonates ANC <500 cells/mm3).
In perinatally HIV-exposed neonates and infants, the sensitivity of diagnostic virologic assays, particularly HIV RNA assays, may be decreased by combination antiretroviral therapy the neonate or infant is receiving. All neonates and infants with perinatal HIV exposure (regardless of risk) should undergo standard virologic testing at PNA 14 to 21 days, 1 to 2 months of life, and 4 to 6 months of life. For neonates and infants at higher risk of perinatal HIV transmission, additional testing is recommended at birth and 2 to 6 weeks after cessation of antiretroviral agents (HHS [perinatal 2020]).
Adverse cardiac effects have been associated with zidovudine therapy. A prospective study of 325 pediatric patients aged 7 to 16 years with perinatally-acquired HIV evaluated associations between previous or current antiretroviral agents and cardiac echocardiogram measures. When comparing patients currently receiving zidovudine (n=107) with those who were not, zidovudine therapy was associated with increased end-systolic wall stress and slightly larger heart size. Longer duration of zidovudine use was associated with higher wall stress. Implications for cardiac outcomes later in life (eg, cardiomyopathy) are unknown (Williams 2018).
Substrate of CYP2A6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor), OAT1/3; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Acemetacin: May enhance the adverse/toxic effect of Zidovudine. Specifically, the risk for hematologic toxicity may be increased. Risk C: Monitor therapy
Acyclovir-Valacyclovir: May enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy
Amodiaquine: Zidovudine may enhance the neutropenic effect of Amodiaquine. Management: Avoid coadministration of zidovudine-containing antiretroviral therapy with amodiaquine when possible. If combined, monitor closely for neutropenia. Risk D: Consider therapy modification
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dexketoprofen: May enhance the adverse/toxic effect of Zidovudine. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DOXOrubicin (Conventional): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Conventional) may diminish the therapeutic effect of Zidovudine. Management: Avoid concomitant use of doxorubicin and zidovudine due to the possibility of reduced zidovudine efficacy and increased myelosuppressive effects. Risk D: Consider therapy modification
DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Management: Avoid concomitant use of doxorubicin and zidovudine. Reduced efficacy of zidovudine is possible based on in vitro data. Also, increased myelosuppressive effects are possible with combined administration. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Fluconazole: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Zidovudine. Specifically, hematologic toxicity may be enhanced. Risk C: Monitor therapy
Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Levomethadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Lopinavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Methadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Nelfinavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of Zidovudine. Risk C: Monitor therapy
Ribavirin (Oral Inhalation): Zidovudine may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Risk D: Consider therapy modification
Ribavirin (Systemic): Zidovudine may enhance the adverse/toxic effect of Ribavirin (Systemic). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended for ribavirin. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Risk D: Consider therapy modification
RifAMPin: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Ritonavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Risk X: Avoid combination
Tenoxicam: May enhance the adverse/toxic effect of Zidovudine. Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Trimethoprim: Zidovudine may enhance the neutropenic effect of Trimethoprim. Trimethoprim may increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Valproate Products: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
The Health and Human Services (HHS) perinatal HIV guidelines consider zidovudine an alternative nucleoside reverse transcriptase inhibitor for patients living with HIV who are not yet pregnant but are trying to conceive.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in patients of all genders who are living with HIV and planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception.
Health care providers caring for couples planning a pregnancy when one or both partners are living with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Zidovudine has a high level of transfer across the human placenta; the placenta also metabolizes zidovudine to the active metabolite.
No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors, such as disease severity, GA at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services (HHS) perinatal HIV guidelines consider zidovudine an alternative nucleoside reverse transcriptase inhibitor (NRTI) for pregnant patients living with HIV who are antiretroviral-naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking zidovudine may continue if viral suppression is effective and the regimen is well tolerated.
The pharmacokinetics of zidovudine are not significantly altered in pregnancy and dosing adjustment is not needed.
Recommendations for use of intrapartum zidovudine are based on maternal HIV RNA levels near the time of delivery (defined as ≥34 to 36 weeks gestation or 4 to 6 weeks prior to delivery) and other factors. Intrapartum zidovudine IV is recommended when HIV RNA is >1,000 copies/mL or when the HIV RNA level is unknown near delivery. Intrapartum zidovudine IV should also be administered if a lack of adherence is suspected since the last RNA result or when HIV is initially diagnosed during labor. Patients with HIV RNA >1,000 copies/mL should be given zidovudine even in cases of documented zidovudine resistance unless there is a history of hypersensitivity. Intrapartum zidovudine IV is not needed in patients receiving ART who have HIV RNA <50 copies/mL near delivery AND who are adherent to their ART regimen. If a fetal scalp electrode is needed during labor, consider the fetal risk of HIV transmission high even if maternal HIV RNA is <50 copies/mL. The decision to administer zidovudine IV intrapartum to patients with HIV RNA ≥50 and ≤1000 copies/mL near delivery should be made on a case-by-case basis.
ART is recommended for all patients who are pregnant and living with HIV to maintain the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART should be continued postpartum for all patients living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant patients who are living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Zidovudine is present in breast milk.
Concentrations of zidovudine in breast milk are similar to those in the maternal serum. Zidovudine has not been detected in the serum of breastfeeding infants exposed only via breast milk.
Maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breastfeeding infants despite maternal therapy. In the United States, where formula is accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients who are living with HIV. Information is available for counseling and managing patients living with HIV who are considering breastfeeding (HHS [perinatal] 2020).
CBC with differential (more frequent monitoring required in patients with poor bone marrow reserve); LFTs; serum creatinine; HIV viral load and CD4 count.
Zidovudine is a thymidine analog which interferes with the HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication; nucleoside reverse transcriptase inhibitor
Note: In general, pharmacokinetic data for pediatric patients >3 months to 12 years of age are similar to data in adult patients.
Absorption: Oral: Well absorbed
Distribution: Significant penetration into the CSF
Vd: 1 to 2.2 L/kg
CSF/plasma ratio:
Infants 3 months to Children 12 years (n=38): Median: 0.68; Range: 0.03 to 3.25
Adults (n=39): Median: 0.6; Range: 0.04 to 2.62
Protein binding: 25% to 38%
Metabolism: Hepatic via glucuronidation to inactive metabolites, including GZDV; extensive first-pass effect
Bioavailability: Oral: Similar for tablets, capsules, and syrup
Neonates <14 days: 89%
Infants 14 days to 3 months: 61%
Infants 3 months to Children 12 years: 65%
Adults: 64% ± 10%
Half-life elimination: Terminal:
Premature neonate: 6.3 hours
Full-term neonates: 3.1 hours
Infants 14 days to 3 months: 1.9 hours
Infants 3 months to Children 12 years: 1.5 hours
Adults: 0.5 to 3 hours (mean 1.1 hours)
Time to peak, serum: 30 to 90 minutes
Excretion:
Oral: Urine (72% to 74% as metabolites, 14% to 18% as unchanged drug)
IV: Urine (45% to 60% as metabolites, 18% to 29% as unchanged drug)
Renal function impairment: Cl is decreased, resulting in an increased half-life and AUC of zidovudine and major metabolite GZDV.
Hepatic function impairment: Clearance is decreased and plasma concentrations are increased.
Capsules (Retrovir Oral)
100 mg (per each): $3.24
Capsules (Zidovudine Oral)
100 mg (per each): $0.80 - $2.02
Solution (Retrovir Intravenous)
10 mg/mL (per mL): $1.75
Syrup (Retrovir Oral)
50 mg/5 mL (per mL): $0.32
Tablets (Zidovudine Oral)
300 mg (per each): $0.23 - $6.02
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