ZIDOVUDINE (Generic for RETROVIR)

General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-INJECTABLES: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-ORAL TABLETS/CAPSULES/LIQUID: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.

Route-Specific Administration

Oral Administration
-Zidovudine may be taken without regard to meals.
Oral Liquid Formulations
-Use a calibrated spoon, oral syringe, or container to measure the oral solution for accurate dosing. To ensure accurate dosing in neonates, use an appropriate-sized oral syringe with 0.1 mL graduation.



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Do not give intramuscularly.
Intravenous Administration
Dilution
-Withdraw the appropriate dose from the commercially available 10 mg/ml injection solution and dilute in D5W to a concentration not to exceed 4 mg/mL.
-Storage: After dilution, the solution is stable for 24 hours at room temperature and 48 hours if refrigerated at 2 to 8 degrees C (36 to 46 degrees F); however, the FDA-approved product labeling recommends administering the diluted solution within 8 hours if stored at room temperature or within 24 hours if refrigerated to minimize the risk of administering a microbially contaminated solution.

Intravenous Infusion
-Infuse IV over at least 60 minutes or as a continuous infusion; avoid rapid or bolus injection.
-May infuse over 30 minutes in neonates.

Bone marrow suppression resulting in severe anemia and neutropenia is one of the most concerning adverse effects of zidovudine and occurs more frequently in pediatric patients than in adults. Anemia has been reported in 4% of non-neonatal pediatric patients during clinical trials and 22% of neonates who received zidovudine for the prevention of maternal-fetal transmission of HIV. Zidovudine-induced anemia may occur as early as 2 to 4 weeks after treatment initiation. Macrocytosis occurs in the majority of patients. Neutropenia has been reported in 8% of pediatric patients and 21% of neonates. It generally occurs after 6 to 8 weeks of treatment. Mild anemia and neutropenia usually improve with a dosage reduction; more severe cases may respond to erythropoietin or filgrastim injections or transfusions or may require discontinuation of therapy until the bone marrow recovers. Lymphadenopathy (9%) and thrombocytopenia (1%) have also been reported in pediatric patients. Pancytopenia with marrow hypoplasia, aplastic anemia, hemolytic anemia, leukopenia, and pure red cell aplasia have also been reported during postmarketing surveillance.

Myopathy and myositis with pathological changes similar to those produced by human immunodeficiency virus (HIV) have been associated with prolonged zidovudine therapy. These adverse reactions are thought to be due to the effect of zidovudine on mitochondrial DNA polymerase-gamma. Proximal muscle weakness and/or elevations of creatine kinase should alert the clinician to this possible adverse reaction. Onset is insidious, occurring 6 months to 2 years after starting therapy. Discontinuation can provide some improvement, but rapid worsening can occur with rechallenge. Cardiomyopathy also has been reported during postmarketing surveillance; however, infection with HIV is an important cause of dilated cardiomyopathy. In a retrospective study in children with HIV infection, the odds that a cardiomyopathy would develop were 8.4 times greater in children who had previously received zidovudine than in those who had never taken zidovudine, despite correction of the ECHO results for HIV disease severity. In clinical trials of adult patients with HIV, musculoskeletal pain, arthralgia, and myalgia were reported in 5% or more of patients. Other musculoskeletal events reported during postmarketing surveillance include back pain, elevated CPK and LDH concentrations, muscle spasm, rhabdomyolysis, and tremor.

Decreased reflexes, nervousness, and irritability were all reported in less than 6% of pediatric patients during open-label zidovudine trials. Although not specifically reported in pediatric trials, headache is one of the most common adverse effects associated with zidovudine use in adults (reported by more than 50% of patients). Other nervous system reactions noted during adult trials or postmarketing surveillance include dizziness, drowsiness/somnolence, malaise, insomnia, paresthesias, vertigo, anxiety, confusion, depression, loss of mental acuity, mania, peripheral neuropathy, and seizures.

Adverse gastrointestinal effects of zidovudine therapy reported in pediatric patients include nausea and vomiting (8%), diarrhea (8%), stomatitis (6%), and splenomegaly (5%). Although not specifically reported in pediatric patients, anorexia, abdominal pain, abdominal cramps, dyspepsia, and constipation occurred in more than 5% of adults. Other GI adverse events reported during adult clinical trials or postmarketing surveillance include dysphagia, flatulence, oral ulceration, dysgeusia, and oral mucosa pigmentation.

Fever was reported in 25% of pediatric patients during zidovudine clinical trials. Weight loss was reported in less than 6% of pediatric patients during open-label trials. Other adverse events noted during adults trials and/or postmarketing surveillance include asthenia, chest pain (unspecified), chills, fatigue, influenza-like syndrome, generalized pain, and malaise.

Mild forms of hepatomegaly and lactic acidosis are both relatively common in certain pediatric patients taking zidovudine; however, rare cases of serious, even fatal, forms have also occurred. If either of these adverse reactions occur, carefully evaluate the patient to determine the severity of the event. In 1 clinical trial, hepatomegaly occurred in 11% of children. Rarely, lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside reverse transcriptase inhibitors, including zidovudine. Many of these cases have occurred in women. In addition, transient increases in lactic acid concentrations are common in infants exposed to antiretroviral therapy in utero and/or neonatal zidovudine; in most cases, the increase is not clinically significant. In 1 study, 92% of infants (35 of 38) experienced at least 1 elevated serum lactate concentration, and in 10 infants, the concentration reached 5 mmol/L or higher. Elevated lactate concentrations persisted up to 6 months before returning to normal values. The clinical relevance of asymptomatic hyperlactatemia is unknown; therefore, routine monitoring of serum lactate is not recommended for asymptomatic infants. Consider serum lactate measurement for symptomatic infants to assess for potential mitochondrial toxicity. If the serum lactate is more than 5 mmol/L, discontinue antiretroviral prophylaxis and consult a pediatric HIV expert. In addition, elevated hepatic enzymes have occurred in 1% to 2% of pediatric patients taking zidovudine and elevated lipase and amylase (hyperamylasemia) have each been reported in 3%. Other related adverse reactions that have been reported during adult clinical trials or postmarketing surveillance include hepatitis, hyperbilirubinemia, jaundice, and pancreatitis.

Zidovudine has been associated with loss of subcutaneous fat, particularly in the face, limbs, and buttocks. The mechanism by which zidovudine causes lipoatrophy is not known; however, it has been suggested that nucleoside analogs may damage the mitochondria of adipocytes. The incidence and severity of these body fat changes are related to cumulative exposure. Lipodystrophy often accompanies other metabolic complications such as insulin resistance, dyslipidemia, and lactic acidosis. The prevalence of lipodystrophy in pediatric patients treated with HAART has ranged from approximately 20% to 50% in most clinical studies. Older age (preadolescents and adolescents vs. younger children) has also been shown to increase the risk of lipodystrophy. Unlike in adults, most studies in children have not found a higher incidence of lipodystrophy in girls vs. boys. Switching to a non-zidovudine-containing regimen may only partially reverse these changes, and improvement may take months to years to achieve. Regularly assess patients for signs of lipodystrophy. If feasible, therapy should be switched to an alternative regimen.

Adverse reactions reported in less than 6% of pediatric patients receiving zidovudine during open label studies include congestive heart failure, ECG abnormalities, edema, and left ventricular dilation. Syncope was reported during postmarketing surveillance with zidovudine.

Hematuria was noted in less than 6% of pediatric patients during open-label zidovudine trials. Increased urinary frequency and urinary hesitancy were noted in postmarketing reports with zidovudine.

Macular edema, amblyopia, and photophobia have all been reported during postmarketing surveillance with zidovudine.

Rash was reported in 12% of pediatric patients during zidovudine trials. Other dermatologic or hypersensitivity-based reactions noted during postmarketing surveillance include anaphylactoid reactions, angioedema, vasculitis, changes in skin and nail pigmentation (nail discoloration), pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweating (hyperhidrosis), and urticaria.

Cough (15%), abnormal breathing sounds/wheezing (7%), and nasal discharge (rhinorrhea) or nasal congestion (8%) have been reported in pediatric patients during zidovudine clinical trials. Dyspnea, rhinitis, and sinusitis were all noted in postmarketing reports with zidovudine.

Otic adverse events including pain (otalgia), discharge, erythema, or swelling have been reported in 7% of pediatric patients during zidovudine clinical trials. Hearing loss has been noted in postmarketing reports with zidovudine.

Zidovudine is associated with a decrease in vitamin B12 concentrations in HIV infected patients and may lead to vitamin B12 deficiency. Regular monitoring and supplementation may be necessary.

Unplanned antiretroviral therapy interruption may be necessary in specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake (e.g., gastroenteritis or pancreatitis), or drug non-availability. If short-term treatment interruption is necessary (i.e., less than 1 to 2 days), in general, it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption is because of serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered. When the antiretroviral regimen contains drugs with differing half-lives, stopping all drugs simultaneously may result in functional monotherapy of the drug with the longest half-life. For example, after discontinuation, the duration of detectable drug concentrations of efavirenz and nevirapine ranges from less than 1 week to more than 3 weeks. Simultaneously stopping all drugs in a regimen containing these agents may result in functional monotherapy with the NNRTI and may increase the risk of NNRTI-resistant mutations. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.

Zidovudine is contraindicated for use in patients who have potentially life-threatening allergic reactions to any component of the formulation. The vial stoppers of the injection contain dry natural rubber (a latex derivative) which may cause allergic reactions in patients with latex hypersensitivity.

Use zidovudine with caution in patients who have pre-existing bone marrow suppression evidenced by neutropenia (absolute neutrophil count less than 1000/mm3) or anemia (hemoglobin less than 9.5 mg/dL). Zidovudine is known to cause hematologic toxicity, particularly in neonates and those with advanced HIV disease. Hematologic toxicity appears to be related to pretreatment bone marrow reserve and to dose and duration of therapy. Cytotoxic chemotherapy or radiation therapy may also increase the risk of myelosuppression. Monitor blood counts frequently in patients with poor bone marrow reserve, particularly those with advanced HIV. The HIV guidelines recommend monitoring complete blood counts (CBC) with differential at entry to care and before initiating or modifying treatment. For patients started on an antiretroviral regimen containing zidovudine, a follow-up CBC with differential should be obtained after 2 to 8 weeks of treatment, followed by periodic monitoring every 3 to 6 months or as clinically indicated. A complete blood count and differential should be performed in a neonate prior to administration of zidovudine; those with anemia at birth, those exposed in utero to antiretrovirals, or those who are born premature warrant more intensive monitoring due to increased risk of anemia. Consider repeating CBC at 4 weeks in high-risk neonates. Repeat measurement of hemoglobin is required minimally with any signs of anemia, after the completion of the 6-week regimen, and at 12 weeks of age. Severe anemia and/or granulocytopenia may necessitate interruption of therapy, dosage adjustment, discontinuation of zidovudine, and/or blood transfusions until bone marrow recovery is observed. Use of erythropoietin or colony stimulating factors (e.g., GM-CSF, G-CSF) may be necessary in some patients.

Zidovudine is primarily eliminated by hepatic metabolism and concentrations appear to be increased in patients with hepatic disease, which may increase the risk for toxicity. Use zidovudine with caution in patients with hepatic disease or in those with known risk factors for liver disease (i.e., alcoholism); however, cases of hepatotoxicity or lactic acidosis, including fatal cases, have been reported in patients with no risk factors. Adult females appear to be at a higher risk for lactic acidosis; it is not clear whether this increased risk also applies to pediatric females. In addition, obesity may also be a risk factor for nucleoside analog-induced lactic acidosis and hepatotoxicity. Clinicians need to be alert for early diagnosis of this syndrome. Discontinue treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, which may include hepatomegaly and steatosis even in the absence of marked increases in transaminases.

Zidovudine should be used with caution in patients with renal impairment. Zidovudine can accumulate in patients with renal failure (creatinine clearance < 10 ml/min), causing an increased risk of toxicity; dosage adjustment is recommended.

Monitor patients for signs of myopathy and myositis, as they have been reported, along with pathological changes similar to that produced by HIV, with prolonged use of zidovudine.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including zidovudine. During the initial phase of HIV treatment, patients whose immune system responds to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as mycobacterium avium complex (MAC), cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), or tuberculosis (TB)), which may necessitate further evaluation and treatment. In addition, autoimmune disease (including Graves' disease, Guillain-Barre syndrome, and polymyositis) may also develop; the time to onset is variable and may occur months after treatment initiation.

Testing for human immunodeficiency virus (HIV) infection resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform resistance testing prior to initiating or changing any HIV treatment regimen. Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. Therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test results kept in the patient's medical record until they become clinically useful. Additionally, because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. As with all other antiretroviral agents, resistance can develop when zidovudine is used either alone or in combination with other agents. Due to the risk of zidovudine resistance, monotherapy with zidovudine is not recommended outside of the perinatal prophylaxis setting.

Zidovudine solution for injection is only approved for intravenous administration. Do not give zidovudine by intramuscular administration or subcutaneous administration.

Perform hepatitis B virus (HBV) screening in any patient who presents with HIV-infection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection who require treatment for either infection should be started on a fully suppressive antiretroviral regimen that contains NRTIs with activity against both viruses. Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, or tenofovir as the only active agent) due to the risk of developing resistant strains of HIV. The HIV guidelines recommend that coinfected pediatric patients 2 years and older receive an antiretroviral regimen that contains tenofovir in combination with either lamivudine or emtricitabine as the dual NRTI backbone. If tenofovir cannot be used, another agent with anti-HBV activity should be used in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Management of HIV should be continued with the goal of maximal suppression.

Perform hepatitis C virus (HCV) screening in any child whose mother is known to have HCV infection and all HIV-infected adolescents. Treatment of HCV infection in children < 3 years is not usually recommended; however, treatment should be considered for all children >= 3 years and adolescents with hepatitis C and HIV coinfection who have no contraindications to treatment. For antiretroviral-naive adolescent patients with CD4 counts > 500 cells/mm3, consideration may be given to deferring ARV therapy until the hepatitis C treatment regimen has been completed. Conversely, for adolescent patients with CD4 counts < 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on a fully suppressive ARV regimen. All HIV-infected children and adolescents, regardless of HIV and HCV status, should receive standard vaccination with hepatitis A and B vaccines. Additionally, HIV/HCV-coinfected adolescents should be counseled to avoid alcohol.

In utero exposure to antiretroviral agents (ARVs) has been associated with mitochondrial toxicity in newborns. Hyperlactatemia can occur after delivery, but it is transient and asymptomatic in most cases. While routine monitoring of serum lactate is not recommended for all newborns, evaluation for a mitochondrial disorder, including serum lactate measurement, should be considered for those newborns who develop clinical symptoms, particularly neurologic symptoms. In symptomatic infants with significantly abnormal lactate concentrations (more than 5 mmol/L), discontinue ARV prophylaxis and consult a pediatric HIV expert. Data are limited concerning potential toxicities in infants whose mothers received combination ARV therapy. More intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised in these infants. Current clinical guidelines recommend long-term follow-up for all children exposed to ARVs in utero. It is recommended that health care providers who are treating the newborns of HIV-infected women report cases of prenatal ARV exposure to the Antiretroviral Pregnancy Registry (telephone 800-258-4263; fax 800-800-1052); the Antiretroviral Pregnancy Registry is also accessible via the Internet.

Description: Zidovudine (AZT, ZDV) is a thymidine nucleoside analog antiretroviral nucleoside reverse transcriptase inhibitor (NRTI). Introduced in the late 1980's, it was the first antiretroviral agent clinically effective against human immunodeficiency virus type-1 (HIV-1). The drug later made history again when the Pediatric AIDS Clinical Trials Group 076 (PACTG 076) trial demonstrated that zidovudine administration to pregnant women and their newborns could reduce perinatal transmission of HIV by almost 70%. Today, zidovudine continues to be the cornerstone of therapy for the prevention of HIV transmission from mother to infant, and it is one of the few antiretrovirals with data available in neonates < 14 days of age. Due to the development of resistance, zidovudine is not recommended to be given as monotherapy, except when given to prevent maternal-fetal HIV transmission. Bone marrow toxicity (anemia and neutropenia) is relatively common with zidovudine use and occurs more frequently in pediatric patients compared to adults; neonates are at particularly high risk. Zidovudine is FDA-approved for use in pediatric patients as young as neonates.

Initiation of HIV therapy
-Antiretroviral drug resistance testing (preferably genotypic testing) is recommended prior to initiation of therapy in antiretroviral treatment (ART)-naive patients and prior to changing therapy for treatment failure.
-Initiation of treatment immediately or within days after HIV diagnosis is recommended in all pediatric patients, except for patients with cryptococcal meningitis, disseminated Mycobacterium avium complex disease, or Mycobacterium tuberculosis disease. In these patients, initiate treatment for the opportunistic infection first, ahead of ART initiation. The urgency of rapid treatment initiation is especially critical for all patients younger than 1 year, who carry the highest risk of rapid disease progression and mortality. If therapy is deferred for certain circumstances, closely monitor the patient's virologic, immunologic, and clinical status at least every 3 to 4 months. If therapy is deferred, initiate treatment when HIV RNA concentrations increase, CD4 count or percentage values decline (i.e., approaching CDC Stage 2 or 3), the patient develops new HIV-related clinical symptoms, or the ability of the caregiver and patient to adhere to the prescribed regimen has improved.

Place in therapy for HIV
-Zidovudine is recommended for all HIV-exposed neonates to reduce perinatal transmission of HIV. Initiate treatment as close to birth as possible, preferably within 6 to 12 hours. Zidovudine is one of the preferred nucleoside reverse transcriptase inhibitors (NRTIs) to be included as a part of a 2-NRTI backbone regimen for HIV-infected neonates.
-Zidovudine, as part of a 2-NRTI backbone option, is recommended as an alternative therapy for infants and children 1 month and older. The 2-NRTI backbone should be used in combination with a non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), or integrase strand transfer inhibitor (INSTI). Specific recommendations vary depending on age.
-Zidovudine, as part of a 2-NRTI combination, is not recommended as initial therapy for treatment-naive adolescents due to higher toxicity.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human immunodeficiency virus (HIV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Epstein-Barr virus, hepatitis B virus, human T-lymphotropic virus type I (HTLV-I)
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents:
Oral dosage:
Premature Neonates younger than 30 weeks gestation and 0 to 4 weeks*: 2 mg/kg/dose PO twice daily.
Premature Neonates younger than 30 weeks gestation and 4 to 8 weeks*: 3 mg/kg/dose PO twice daily.
Premature Neonates younger than 30 weeks gestation and older than 8 weeks*: 12 mg/kg/dose PO twice daily.
Premature Neonates 30 to 34 weeks gestation and 0 to 2 weeks*: 2 mg/kg/dose PO twice daily.
Premature Neonates 30 to 34 weeks gestation and 2 to 6 weeks*: 3 mg/kg/dose PO twice daily.
Premature Neonates 30 to 34 weeks gestation and older than 6 weeks*: 12 mg/kg/dose PO twice daily.
Neonates 35 weeks gestation and older and 0 to 4 weeks*: 4 mg/kg/dose PO twice daily.
Neonates 35 weeks gestation and older than 4 weeks*: 12 mg/kg/dose PO twice daily.
Infants and Children weighing 4 to 8 kg: 12 mg/kg/dose PO twice daily, or alternatively, 180 to 240 mg/m2/dose PO twice daily. The FDA-approved dose is 12 mg/kg/dose PO twice daily or 8 mg/kg/dose PO 3 times daily, or alternatively, 240 mg/m2/dose PO twice daily or 160 mg/m2/dose PO 3 times daily.
Infants and Children weighing 9 to 29 kg: 9 mg/kg/dose PO twice daily, or alternatively, 180 to 240 mg/m2/dose PO twice daily. The FDA-approved dose is 9 mg/kg/dose PO twice daily or 6 mg/kg/dose PO 3 times daily, or alternatively, 240 mg/m2/dose PO twice daily or 160 mg/m2/dose PO 3 times daily.
Children and Adolescents weighing 30 kg or more: 300 mg PO twice daily, or alternatively, 180 to 240 mg/m2/dose (Max: 300 mg/dose) PO twice daily. The FDA-approved dose is 300 mg PO twice daily or 200 mg PO 3 times daily, or alternatively, 240 mg/m2/dose PO twice daily or 160 mg/m2/dose PO 3 times daily (Max: 600 mg/day).
Intravenous dosage*:
Premature Neonates younger than 30 weeks gestation and 0 to 4 weeks: 1.5 mg/kg/dose IV twice daily.
Premature Neonates younger than 30 weeks gestation and 4 to 8 weeks: 2.25 mg/kg/dose IV twice daily.
Premature Neonates younger than 30 weeks gestation and older than 8 weeks: 9 mg/kg/dose IV twice daily.
Premature Neonates 30 to 34 weeks gestation and 0 to 2 weeks: 1.5 mg/kg/dose IV twice daily.
Premature Neonates 30 to 34 weeks gestation and 2 to 6 weeks: 2.25 mg/kg/dose IV twice daily.
Premature Neonates 30 to 34 weeks gestation and older than 6 weeks: 9 mg/kg/dose IV twice daily.
Neonates 35 weeks gestation and older and 0 to 4 weeks: 3 mg/kg/dose IV twice daily.
Neonates 35 weeks gestation and older than 4 weeks: 9 mg/kg/dose IV twice daily.
Infants and Children: 120 mg/m2/dose IV every 6 hours. Current guidelines do not contain IV dosing for infants and children 4 weeks of age and older.
Adolescents: 120 mg/m2/dose IV every 6 hours. Current guidelines do not contain IV dosing for pediatric patients. The FDA-approved adult dose is 1 mg/kg/dose IV every 4 hours, which is approximately equivalent to 100 mg PO every 4 hours.

For human immunodeficiency virus (HIV) prophylaxis*:
-for human immunodeficiency virus (HIV) prophylaxis* to prevent mother-to-child transmission (MTCT) during breastfeeding:
NOTE: Optional extended zidovudine postnatal prophylaxis may be considered for infants with low risk of HIV acquisition during breastfeeding (mothers with sustained viral suppression) who received only 2 weeks of initial zidovudine prophylaxis after birth.
Oral dosage:
Neonates 37 weeks gestation and older: 4 mg/kg/dose PO twice daily for 4 to 6 weeks total (including initial 2 weeks of zidovudine prophylaxis after birth).
Infants: 4 mg/kg/dose PO twice daily for 4 to 6 weeks total (including initial 2 weeks of zidovudine prophylaxis after birth).
-for human immunodeficiency virus (HIV) prophylaxis* after nonoccupational exposure:
NOTE: Higher risk exposures for which prophylaxis is recommended include exposure of vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood when the source is known to be HIV-positive. Exposures to a source patient with unknown HIV status should be assessed on a case-by-case basis.
Oral dosage:
Infants and Children 4 weeks to 1 year weighing 4 to 8 kg: 12 mg/kg/dose PO twice daily in combination with lamivudine and raltegravir or lopinavir/ritonavir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. Zidovudine in combination with emtricitabine and raltegravir or lopinavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Infants and Children 4 weeks to 1 year weighing 9 kg or more: 9 mg/kg/dose PO twice daily in combination with lamivudine and raltegravir or lopinavir/ritonavir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. Zidovudine in combination with emtricitabine and raltegravir or lopinavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Children 2 to 12 years: 9 mg/kg/dose (Max: 300 mg/dose) PO twice daily in combination with lamivudine and raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in children 2 to 12 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.
Adolescents: 300 mg PO twice daily in combination with lamivudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents with renal dysfunction (CrCl 59 mL/minute or less). Zidovudine and lamivudine doses should be adjusted to degree of renal impairment. Zidovudine in combination with lamivudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

For perinatal human immunodeficiency virus (HIV) prophylaxis:
NOTE: Postpartum chemoprophylaxis with zidovudine is recommended for all HIV-exposed infants to reduce perinatal transmission of HIV.
NOTE: In premature neonates, dosage needs be adjusted during treatment course based on postnatal age.
-for perinatal human immunodeficiency virus (HIV) prophylaxis in neonates at low risk for HIV acquisition:
NOTE: Low-risk neonates include those born of mothers with low risk of perinatal HIV transmission [i.e., receiving and has received at least 10 consecutive weeks of ART during pregnancy, has achieved and maintained viral suppression (defined as at least 2 consecutive tests with HIV RNA less than 50 copies/mL obtained at least 4 weeks apart for the duration of pregnancy), has a viral load less than 50 copies/mL at or after 36 weeks, did not have acute HIV infection during pregnancy, and no concerns related to adherence] and neonates born to mothers with HIV-2 mono-infection.
Oral dosage:
Premature Neonates younger than 30 weeks gestation*: 2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 4 weeks of age. Treat for 4 to 6 weeks.
Premature Neonates 30 to 34 weeks gestation*: 2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 2 weeks of age. Treat for 4 to 6 weeks.
Premature Neonates 35 to 36 weeks gestation: 4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.
Neonates 37 weeks gestation and older: 4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 2 weeks. Prophylaxis may be extended to 4 to 6 weeks for infants who are breastfeeding. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.
Infants: 4 mg/kg/dose PO twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours.
Intravenous dosage:
NOTE: The IV doses are 75% of the oral doses administered at the same interval. Use IV route only until oral therapy can be administered.
Premature Neonates younger than 30 weeks gestation*: 1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 4 weeks of age. Treat for 4 to 6 weeks.
Premature Neonates 30 to 34 weeks gestation*: 1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 2 weeks of age. Treat for 4 to 6 weeks.
Premature Neonates 35 to 36 weeks gestation: 3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.
Neonates 37 weeks gestation and older: 3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 2 weeks. Prophylaxis may be extended to 4 to 6 weeks for infants who are breastfeeding. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.
Infants: 3 mg/kg/dose IV twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours.
-for perinatal human immunodeficiency virus (HIV) prophylaxis in neonates born of mothers who do not meet other low-risk criteria but who have a viral load less than 50 copies/mL at or after 36 weeks gestation:
Oral dosage:
Premature Neonates younger than 30 weeks gestation*: 2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 4 weeks of age. Treat for 4 to 6 weeks.
Premature Neonates 30 to 34 weeks gestation*: 2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 2 weeks of age. Treat for 4 to 6 weeks.
Neonates 35 weeks gestation and older: 4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.
Infants: 4 mg/kg/dose PO twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours.
Intravenous dosage:
NOTE: The IV doses are 75% of the oral doses administered at the same interval. Use IV route only until oral therapy can be administered.
Premature Neonates younger than 30 weeks gestation*: 1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 4 weeks of age. Treat for 4 to 6 weeks.
Premature Neonates 30 to 34 weeks gestation*: 1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 2 weeks of age. Treat for 4 to 6 weeks.
Neonates 35 weeks gestation and older: 3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours), for 4 to 6 weeks. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.
Infants: 3 mg/kg/dose IV twice daily to complete 4 to 6 weeks of therapy. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours.
-for perinatal human immunodeficiency virus (HIV) prophylaxis in neonates at high risk for HIV acquisition:
NOTE: Presumptive therapy with a 3-drug combination antiretroviral (ARV) regimen, consisting of zidovudine, lamivudine, and either nevirapine or raltegravir at treatment doses, is recommended for neonates with presumed HIV exposure (mothers with unknown HIV status who test HIV positive at delivery or postpartum or whose newborns have a positive HIV antibody test) and neonates born to HIV-infected mothers who have not received antepartum ARV treatment, who have received only intrapartum ARV treatment, who have suboptimal viral suppression (defined as at least 2 consecutive tests with HIV RNA less than 50 copies/mL obtained at least 4 weeks apart within 4 weeks of delivery), or who have acute or primary HIV infection during pregnancy or breastfeeding. Consider raltegravir use in the 3-drug combination ARV prophylaxis regimen if the mother has HIV-1 and HIV-2 infection, since HIV-2 is not susceptible to nevirapine. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered for neonates 32 weeks gestation and older based on clinical scenario.
NOTE: The ARV regimen for newborns born to mothers with known or suspected drug resistance should be determined in consultation with a pediatric HIV specialist before delivery or through consultation via the National Perinatal HIV hotline (1-888-448-8765). Additionally, no evidence exists that shows that neonatal prophylaxis regimens customized based on presence of maternal drug resistance are more effective than standard neonatal prophylaxis regimens.
Oral dosage:
Premature Neonates younger than 30 weeks gestation*: 2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 4 weeks of age. Treat for 6 weeks.
Premature Neonates 30 to 34 weeks gestation*: 2 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 3 mg/kg/dose PO twice daily after 2 weeks of age. Treat for 6 weeks in combination with lamivudine and nevirapine (32 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario.
Neonates 35 weeks gestation and older: 4 mg/kg/dose PO twice daily, beginning as soon as possible after birth (preferably within 6 hours). Treat for 6 weeks in combination with lamivudine and either nevirapine or raltegravir (37 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours beginning within 12 hours after birth.
Infants: 4 mg/kg/dose PO twice daily to complete 6 weeks of therapy with lamivudine and either nevirapine or raltegravir at treatment doses for 2 to 6 weeks. If the infant is receiving a 2-drug ARV prophylaxis regimen and received 3 nevirapine doses in the first week of life, continue therapy with zidovudine monotherapy to complete 6 weeks of treatment. The FDA-approved dosage is 2 mg/kg/dose PO every 6 hours.
Intravenous dosage:
NOTE: The IV doses are 75% of the oral doses administered at the same interval. Use IV route only until oral therapy can be administered.
Premature Neonates younger than 30 weeks gestation*: 1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 4 weeks of age. Treat for 6 weeks.
Premature Neonates 30 to 34 weeks gestation*: 1.5 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Increase dose to 2.25 mg/kg/dose IV twice daily after 2 weeks of age. Treat for 6 weeks in combination with lamivudine and nevirapine (32 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario.
Neonates 35 weeks gestation and older: 3 mg/kg/dose IV twice daily, beginning as soon as possible after birth (preferably within 6 hours). Treat for 6 weeks in combination with lamivudine and either nevirapine or raltegravir (37 weeks gestation and older) at treatment doses for 2 to 6 weeks. A 2-drug ARV prophylaxis regimen with 6 weeks of zidovudine and 3 doses of nevirapine (prophylaxis dosage) may also be considered based on clinical scenario. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours beginning within 12 hours after birth.
Infants: 3 mg/kg/dose IV twice daily to complete 6 weeks of therapy with lamivudine and either nevirapine or raltegravir at treatment doses for 2 to 6 weeks. If the infant is receiving a 2-drug ARV prophylaxis regimen and received 3 nevirapine doses in the first week of life, continue therapy with zidovudine monotherapy to complete 6 weeks of treatment. The FDA-approved dosage is 1.5 mg/kg/dose IV every 6 hours.
-for intrapartum dosing for perinatal human immunodeficiency virus (HIV) prophylaxis*:
NOTE: Intrapartum IV zidovudine is recommended for all pregnant patients with HIV infection with HIV RNA concentrations more than 1,000 copies/mL or unknown HIV RNA concentration near the time of delivery (within 4 weeks of delivery). Although not required, intrapartum treatment may also be considered for patients with HIV RNA concentrations 50 to 1,000 copies/mL or if there are concerns regarding adherence to or tolerance of antiretroviral regimen in late pregnancy. Patients with HIV RNA more than 1,000 copies/mL near delivery who have known or suspected zidovudine resistance should still receive intrapartum IV zidovudine unless there is a documented history of hypersensitivity to the drug.
Intravenous dosage:
Pregnant Adolescents: 2 mg/kg/dose IV over 1 hour, followed by 1 mg/kg/hour IV continuous infusion for 2 hours (minimum of 3 hours total). The FDA-approved labeling recommends continuation until clamping of the umbilical cord. Initiate the infusion upon presenting in labor or at least 3 hours before a cesarean delivery. For cases of unscheduled cesarean delivery for both maternal and fetal indications, consideration can be given to administering only the 1-hour loading dose, and not waiting to complete additional administration before proceeding with delivery.

For the treatment of multicentric Castleman's disease* associated with human herpesvirus 8 (HHV-8) infection*:
Oral dosage:
Adolescents: 600 mg PO every 6 hours in combination with valganciclovir or ganciclovir for 7 to 21 days.

Therapeutic Drug Monitoring:
Dosage adjustments based on hematologic parameters
For hemoglobin < 7.5 g/dl or decrease of > 25% of baseline and/or absolute neutrophil count < 750 cells/mm3 or decrease of > 50% from baseline: Consider an interruption of therapy.
For less severe anemia or granulocytopenia: A reduction in the daily dose may be adequate.

Maximum Dosage Limits:
-Neonates
younger than 30 weeks gestation: Safety and efficacy have not been established; however, doses of 4 mg/kg/day PO or 3 mg/kg/day IV for the first 4 weeks, then 6 mg/kg/day PO or 4.5 mg/kg/day IV, have been used off-label.
30 to 34 weeks gestation: Safety and efficacy have not been established; however, doses of 4 mg/kg/day PO or 3 mg/kg/day IV for the first 2 weeks, then 6 mg/kg/day PO or 4.5 mg/kg/day IV, have been used off-label.
35 weeks gestation and older: 8 mg/kg/day PO; 6 mg/kg/day IV.
-Infants
weight 4 to 8 kg: 24 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 9 to 29 kg: 18 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
-Children
weight 4 to 8 kg: 24 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 9 to 29 kg: 18 mg/kg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 30 kg or more: 600 mg/day or 480 mg/m2/day PO; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
-Adolescents
weight less than 30 kg: 18 mg/kg/day or 480 mg/m2/day PO is FDA-approved maximum; however, doses up to 2,400 mg/day PO have been used off-label; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.
weight 30 kg or more: 600 mg/day or 480 mg/m2/day PO is FDA-approved maximum; however, doses up to 2,400 mg/day PO have been used off-label; safety and efficacy of the IV formulation have not been established; however, doses up to 480 mg/m2/day IV have been used off-label.

Patients with Hepatic Impairment Dosing
There are insufficient data to recommend dosage adjustments in patients with hepatic impairment or liver cirrhosis; however, zidovudine is primarily eliminated by hepatic metabolism and elevated concentrations have been noted in patients with hepatic impairment. Monitor closely for hematologic toxicities.

Patients with Renal Impairment Dosing
Infants, Children, and Adolescents*
GFR 10 mL/minute/1.73 m2 or more: No dosage adjustment needed.
GFR less than 10 mL/minute/1.73 m2: Reduce recommended dose by 50%.

Intermittent hemodialysis*
Reduce the recommended dose by 50%.

Peritoneal dialysis*
Reduce the recommended dose by 50%.

Continuous renal replacement therapy (CRRT)*
No dosage adjustment necessary.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Like other nucleoside reverse transcriptase inhibitors (NRTIs), zidovudine inhibits the replication of human and animal retroviruses after first being activated via several phosphorylation steps. Activity is dependent upon intracellular conversion to zidovudine 5'-triphosphate (ZDV-TP). The rate of phosphorylation varies depending on cell type. ZDV-TP inhibits the activity of the HIV reverse transcriptase by both competing for utilization with the natural substrate, deoxythymidine 5'-triphosphate (dTTP), and by incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleoside analog prevents the formation of 5' to 3' phosphodiester linkage essential for DNA chain elongation, and, therefore, viral DNA growth is terminated and production of new virions is inhibited. The active metabolite is also a weak inhibitor of cellular DNA polymerase-alpha and mitochondrial polymerase-gamma and has been reported to be incorporated into DNA cells in vitro. While human DNA polymerase is less susceptible to the effects of ZDV-TP, this mechanism may account for some of the drug's toxicity. The IC50 and IC90 (50% and 90% inhibitory concentrations) of HIV isolates from untreated patients are in the range of 0.003-0.013 mcg/ml and 0.03-0.3 mcg/ml, respectively. In vitro combination studies have shown synergistic activity between zidovudine and other drugs, including other nucleoside analogs, non-nucleoside agents, and cytokines.

Pharmacokinetics: Zidovudine is administered orally and intravenously. The apparent volume of distribution is about 1.6 +/- 0.6 L/kg in adult patients. Protein binding is < 38%. Limited data in children (n = 18, 3 months to 12 years of age) indicate that zidovudine CSF concentrations are highly variable and average about 68% of serum concentrations (range, 3-325%). Zidovudine is primarily eliminated by hepatic metabolism. The major metabolite is GZDV, which is formed by glucuronidation; the AUC for GZDV is roughly 3-fold greater than that of zidovudine. A second metabolite, 3'-amino-3'-deoxythymidine (AMT) has been discovered after single dose intravenous administration of zidovudine. The AUC of AMT is about one-fifth of the zidovudine AUC. Both zidovudine and metabolites are excreted by glomerular filtration and tubular secretion. Approximately 14-18% of the dose is excreted as unchanged drug and 60-74% as GZDV. The elimination half-life of zidovudine ranges from 0.5-3 hours.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
After oral administration, zidovudine is rapidly absorbed; bioavailability is approximately 65%. Peak concentrations are reached 0.5-1.5 hours after oral administration. In adults, zidovudine capsules, tablets, and syrup produce similar exposure (AUC). Food does not significantly affect bioavailability.


-Special Populations
Pediatrics
Premature Neonates
Premature neonates have a significantly slower clearance and longer half-life compared with term neonates. Neonates born at < 30 weeks gestational age (GA) have slower clearance compared to those >= 30 weeks GA. Postnatal age also plays a significant role with more rapid clearance occurring after about 14 days; however, the maturation of clearance is more rapid in those neonates born at >= 30 weeks GA compared to those < 30 weeks GA. In 1 study in premature neonates (n = 15; mean gestational age, 29.4 weeks; mean weight, 1.23 kg), the mean clearance, volume of distribution, and elimination half-life of zidovudine were 2.53 mL/min/kg, 1.59 L/kg, and 7.2 hours, respectively, at a mean age of 5.5 days. At approximately 18 days of age, clearance had almost doubled and elimination half-life was decreased to approximately 4.4 hours.

Neonates and Infants < 3 months
Postnatal age is the most significant factor determining zidovudine clearance, resulting in a prolonged clearance in neonates <= 14 days compared with older neonates and infants. In a pharmacokinetic study of 32 neonates and infants < 3 months (mean gestational age, 38.9 weeks), clearance and elimination half-life were 10.9 mL/min/kg and 3.12 hours, respectively, for neonates <= 14 days of age (n = 26). For neonates > 14 days (n = 6), clearance and elimination half-life were 19 mL/min/kg and 1.87 hours, respectively. Bioavailability was also significantly greater in neonates <= 14 days compared with those > 14 days (89% vs. 61%, respectively). The increased bioavailability is consistent with a decreased first-pass metabolism due to immature hepatic metabolism in neonates.

Infants >= 3 months, Children, and Adolescents
In infants and children 3 months of age and older, clearance and elimination half-life of zidovudine have been reported to be approximately 1.85 L/kg/hr and 1.5 hours, respectively. Although most data indicate no significant differences in zidovudine pharmacokinetics between pediatric age groups > 3 months of age , one large study of 394 infants and children reported a slower clearance in children < 2 years of age compared with older children, which may contribute to the higher rates of hematologic toxicity in young children.

Hepatic Impairment
Pharmacokinetic data are unavailable in pediatric patients with hepatic impairment. Because zidovudine is primarily eliminated through hepatic metabolism, decreased clearance and increased plasma concentrations would be likely in patients with hepatic impairment.

Renal Impairment
Pharmacokinetic data are unavailable in pediatric patients with renal impairment. Zidovudine clearance was reduced in adult patients with renal impairment (mean CrCl 18 ml/min). Dosage adjustments are recommended for children with CrCl < 10 mL/min/1.73 m2.