Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).

Uses for Zidovudine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients; used in conjunction with other antiretrovirals.

Used with another NRTI (dual NRTIs) in conjunction with an HIV integrase strand transfer inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens.

Dual NRTI option of zidovudine and lamivudine no longer recommended for initial treatment regimens in nonpregnant antiretroviral-naive HIV-infected adults and adolescents (greater toxicity than currently recommended dual NRTI options), but is recommended as an alternative (not a preferred) dual NRTI option for initial treatment regimens in antiretroviral-naive pregnant women.

For initial treatment in antiretroviral-naive pediatric patients, experts state that zidovudine and lamivudine (or emtricitabine) is a preferred dual NRTI option for use in neonates, infants, and children <12 years of age and an alternative dual NRTI option in adolescents ≥12 years of age with sexual maturity rating (SMR) 3.

Do not use dual NRTI option of zidovudine and stavudine at any time (in vitro and in vivo antagonistic antiretroviral effects reported).

Lamivudine/zidovudine fixed combination can be used in adults, adolescents, and pediatric patients weighing ≥30 kg when dual NRTI option of zidovudine and lamivudine is indicated; used in conjunction with other antiretrovirals.

Abacavir/lamivudine/zidovudine fixed combination can be used in adults, adolescents, and pediatric patients weighing ≥40 kg; used alone as a complete treatment regimen or in conjunction with other antiretrovirals. Data limited regarding use in patients with baseline viral loads >100,000 copies/mL.

Triple NRTI regimen of abacavir, lamivudine, and zidovudine not recommended in antiretroviral-naive or antiretroviral experienced patients (inferior antiretroviral activity).

Prevention of Perinatal HIV Transmission

Prevention of maternal-fetal transmission of HIV in certain pregnant HIV-infected women and in neonates born to HIV-infected women (HIV-exposed neonates).

Prophylaxis in pregnant HIV-infected women (i.e., intrapartum IV zidovudine prophylaxis regimen); indicated based on degree of risk of perinatal HIV transmission near time of delivery.

Prophylaxis in neonates born to HIV-infected women; zidovudine prophylaxis used alone in neonates at low risk of HIV acquisition or in conjunction with nevirapine prophylaxis in those at higher risk.

Empiric HIV therapy^{† [off-label]} in neonates born to HIV-infected women; used in 3-drug empiric regimen (zidovudine, lamivudine, and nevirapine) for prevention of perinatal HIV transmission in neonates at highest risk of HIV acquisition.

Pregnant HIV-infected women: Multiple-drug antiretroviral regimens are standard of care in the US for treatment of HIV infection in pregnant women and for prevention of perinatal HIV transmission. In addition, to further decrease risk of perinatal HIV transmission, experts recommend that all pregnant HIV-infected women with plasma HIV-1 RNA levels >1000 copies/mL (or unknown HIV-1 RNA levels) near delivery receive an intrapartum IV zidovudine prophylaxis regimen initiated at onset of labor (or 3 hours before scheduled cesarean delivery) and continued until delivery. Intrapartum IV zidovudine prophylaxis regimen may be considered in pregnant HIV-infected women with plasma HIV-1 RNA levels of 50–999 copies/mL near time of delivery, but not necessary in those with plasma HIV-1 RNA levels ≤50 copies/mL during late pregnancy and near time of delivery if receiving antiretroviral treatment and there are no concerns related to maternal adherence to the treatment regimen.

HIV-exposed neonates: Experts recommend that all neonates born to HIV-infected women (HIV-exposed neonates) receive an antiretroviral regimen (either prophylaxis or empiric HIV therapy) initiated as soon as possible after birth (within 6–12 hours) and continued through 4–6 weeks of age. Select antiretroviral prophylaxis regimen or empiric HIV treatment regimen based on likelihood of perinatal HIV transmission. HIV-exposed neonates at low risk of HIV acquisition (i.e., infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen) may receive a 4-week zidovudine prophylaxis regimen used alone. HIV-exposed neonates at higher risk of HIV acquisition (e.g., those born to HIV-infected women who did not receive antepartum or intrapartum antiretrovirals, received only intrapartum antiretrovirals, or received antepartum and intrapartum antiretrovirals with suboptimal viral suppression near delivery) should receive 2-drug prophylaxis regimen (6-week zidovudine prophylaxis and 3-dose nevirapine prophylaxis). Alternatively, those at highest risk can receive 3-drug empiric HIV therapy regimen (zidovudine, lamivudine, and nevirapine).

Maternal and neonatal regimens recommended for prevention of perinatal HIV transmission in the US may differ from those used in other countries (e.g., resource-limited countries).

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding antiretroviral treatment of pregnant HIV-infected women and their infants and prevention of perinatal HIV transmission.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. Several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs) also recommended. Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as fixed combination emtricitabine/tenofovir DF); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine), or zidovudine and emtricitabine.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure^{† [off-label]} (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when that exposure represents a substantial risk for HIV transmission.

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF). These experts state preferred nPEP regimen in adults and adolescents ≥13 years of age with impaired renal function (Cl_cr ≤59 mL/minute) is either raltegravir or dolutegravir used in conjunction with zidovudine and lamivudine.

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.

Zidovudine Dosage and Administration

Administration

Administer orally or by intermittent or continuous IV infusion.

Do not administer by rapid IV infusion or injection or by IM injection.

When used for treatment of HIV infection, administer by IV infusion only until oral zidovudine can be substituted.

Oral Administration

Administer capsules, tablets, or oral solution orally without regard to meals.

Use oral solution in children who cannot reliably swallow intact capsules or tablets.

Lamivudine/zidovudine: Administer orally twice daily without regard to meals. Do not use in pediatric patients weighing <30 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), patients with hepatic impairment, or patients who experience dose-limiting adverse effects.

Abacavir/lamivudine/zidovudine: Administer orally twice daily without regard to meals. Do not use in pediatric patients weighing <40 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), or patients with hepatic impairment (contraindicated in those with moderate or severe hepatic impairment).

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

Zidovudine concentrate for IV infusion containing 10 mg/mL must be diluted prior to administration. Withdraw appropriate dose from the vial and dilute in 5% dextrose injection to provide a solution containing ≤4 mg/mL.

Rate of Administration

Intermittent IV infusions in adults: Infuse over 60 minutes.

Intermittent IV infusions in neonates: Infuse over 30 minutes.

Intrapartum IV prophylaxis regimen in pregnant HIV-infected women: Give initial dose by IV infusion over 60 minutes, then give by continuous IV infusion at a rate of 1 mg/kg per hour.

Dosage

Pediatric Patients

Treatment of HIV Infection

Dosage in pediatric patients is based on weight or, alternatively, body surface area (BSA). To avoid medication errors, use extra care in calculating dose, transcribing medication order, dispensing prescription, and providing dosage instructions.

Dosage in pediatric patients should not exceed adult dosage.

Treatment of HIV Infection in Neonates† [off-label]

Premature neonates (gestational age <30 weeks): 2 mg/kg twice daily from birth to 4 weeks of age; 3 mg/kg twice daily from 4 weeks to 8–10 weeks of age; 12 mg/kg twice daily beginning at >8–10 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 2 mg/kg twice daily from birth to 2 weeks of age; 3 mg/kg twice daily from 2 weeks to 6–8 weeks of age; 12 mg/kg twice daily beginning at >6–8 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 4 mg/kg twice daily from birth to 4 weeks of age and 12 mg/kg twice daily in those >4 weeks of age. Alternatively, when simplified weight-based dosage of oral solution containing 10 mg/mL used, experts recommend 10 mg (1 mL) twice daily in those weighing 2 to <3 kg, 15 mg (1.5 mL) twice daily in those weighing 3 to <4 kg, and 20 mg (2 mL) twice daily in those weighing 4 to <5 kg.

Premature neonates (gestational age <30 weeks): 1.5 mg/kg twice daily from birth to 4 weeks of age; 2.3 mg/kg twice daily from 4 weeks to 8–10 weeks of age; 9 mg/kg twice daily beginning at >8–10 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 1.5 mg/kg twice daily from birth to 2 weeks of age; 2.3 mg/kg twice daily from 2 weeks to 6–8 weeks of age; 9 mg/kg twice daily beginning at >6–8 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 3 mg/kg twice daily from birth until 4 weeks of age; 9 mg/kg in those >4 weeks of age.

Treatment of HIV Infection in Infants and Children

Infants and children ≥4 weeks of age weighing ≥4 kg: See Table 1.

Alternatively, if BSA used to calculate dosage for pediatric patients ≥4 weeks of age, manufacturer recommends 240 mg/m² twice daily or 160 mg/m² 3 times daily. Some experts recommend 180–240 mg/m² every 12 hours.

Lamivudine/zidovudine in children and adolescents weighing ≥30 kg: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily.

Abacavir/lamivudine/zidovudine in children and adolescents weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.

Prevention of Perinatal HIV Transmission

Prophylaxis in Neonates Born to HIV-infected Women

Premature neonates (gestational age <30 weeks): 2 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 3 mg/kg twice daily at 4 weeks of age and continue until 4–6 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 2 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 3 mg/kg twice daily at 2 weeks of age and continue until 4–6 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 4 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); continue until 4–6 weeks of age. Alternatively, when simplified weight-based dosage of oral solution containing 10 mg/mL used, experts recommend 10 mg (1 mL) twice daily in those weighing 2 to <3 kg, 15 mg (1.5 mL) twice daily in those weighing 3 to <4 kg, and 20 mg (2 mL) twice daily in those weighing 4 to <5 kg.

Neonates: Manufacturer recommends 2 mg/kg every 6 hours initiated within 12 hours of birth and continued through 6 weeks of age.

Although 4-week zidovudine prophylaxis regimen may be used alone in HIV-exposed neonates at low risk of HIV acquisition (i.e., infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen), 6-week zidovudine prophylaxis regimen used in conjunction with a 3-dose nevirapine prophylaxis regimen (2-drug prophylaxis regimen) recommended for those at higher risk.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Premature neonates (gestational age <30 weeks): 1.5 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 2.3 mg/kg twice daily at 4 weeks of age and continue until 4–6 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 1.5 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 2.3 mg/kg twice daily at 2 weeks of age and continue until 4–6 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 3 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); continue until 4–6 weeks of age.

Neonates: Manufacturer recommends 1.5 mg/kg every 6 hours initiated within 12 hours of birth and continued through 6 weeks of age.

Although 4-week zidovudine prophylaxis regimen may be used alone in HIV-exposed neonates at low risk of HIV acquisition (i.e., infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen), 6-week zidovudine prophylaxis regimen used in conjunction with a 3-dose nevirapine prophylaxis regimen recommended for those at higher risk.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Empiric HIV Therapy in Neonates Born to HIV-infected Women† [off-label]

Recommended empiric HIV therapy regimen consists of zidovudine, lamivudine, and nevirapine initiated as soon as possible after birth (within 6–12 hours); used in HIV-exposed neonates considered at highest risk of HIV acquisition. (See Prevention of Perinatal HIV Transmission under Uses.)

Zidovudine dosage for empiric HIV therapy in neonates Born to HIV-infected women is the same as that recommended for prophylaxis in neonates born to HIV-infected women. (See Prophylaxis in Neonates Born to HIV-infected Women under Dosage and Administration.)

Optimal duration of empiric HIV therapy in HIV-exposed neonates unknown. Many experts recommend that 3-drug empiric regimen be continued for 6 weeks; others discontinue nevirapine and/or lamivudine if results of neonate's HIV nucleic acid amplification test (NAAT) are negative, but recommend continuing zidovudine for 6 weeks.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Adults

Treatment of HIV Infection

Oral

Zidovudine: 300 mg twice daily. Experts state usual dosage can be given as 300 mg twice daily or 200 mg 3 times daily.

Lamivudine/zidovudine in adults weighing ≥30 kg: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily.

Abacavir/lamivudine/zidovudine in adults weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.

IV

Zidovudine: 1 mg/kg every 4 hours.

Prevention of Perinatal HIV Transmission

HIV-infected Pregnant Women

2 mg/kg given by IV infusion over 60 minutes (initiated at start of labor or 3 hours before scheduled cesarean delivery) followed by 1 mg/kg per hour given by continuous IV infusion until delivery.

Indicated in pregnant HIV-infected women depending on plasma HIV-1 RNA levels near time of delivery. (See Prevention of Perinatal HIV Transmission under Uses.)

If oral zidovudine is part of current antiretroviral treatment regimen, substitute with IV zidovudine until after delivery; continue other antiretrovirals in the woman’s treatment regimen on schedule as much as possible during labor.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)†

Oral

Zidovudine: 300 mg twice daily. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV [PEP] under Uses).

Lamivudine/zidovudine: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily. Use in conjunction with a recommended INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)†

Oral

Zidovudine: Adjust dosage based on degree of renal impairment. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.

nPEP not recommended if exposed individual seeks care >72 hours after exposure.

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Zidovudine in infants and children ≥4 weeks of age: Maximum 600 mg daily.

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Zidovudine: Data insufficient to recommend dosage adjustments for patients with hepatic impairment or liver cirrhosis.

Lamivudine/zidovudine: Do not use in patients with hepatic impairment.

Abacavir/lamivudine/zidovudine: Do not use in patients with hepatic impairment; contraindicated in those with moderate or severe hepatic impairment.

IV

Zidovudine: Data insufficient to recommend dosage adjustments for patients with hepatic impairment or liver cirrhosis.

Renal Impairment

Treatment of HIV Infection

Oral

Zidovudine in adults maintained on hemodialysis or peritoneal dialysis or with severe renal impairment (Cl_cr <15 mL/minute): 100 mg every 6–8 hours.

Lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.

Abacavir/lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.

IV

Zidovudine in adults maintained on hemodialysis or peritoneal dialysis or with severe renal impairment (Cl_cr <15 mL/minute): 1 mg/kg every 6–8 hours.

Geriatric Patients

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Contraindications

• Zidovudine: History of potentially life-threatening hypersensitivity reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) to the drug or any ingredient in the formulation.

• Lamivudine/zidovudine: History of hypersensitivity to lamivudine or zidovudine.

• Abacavir/lamivudine/zidovudine: Positive for HLA-B*5701 allele; history of hypersensitivity to abacavir, lamivudine, or zidovudine; moderate or severe hepatic impairment.

Warnings/Precautions

Warnings

Hematologic Effects

Hematologic toxicity (including neutropenia and severe anemia) reported, especially in patients with advanced HIV-1 disease. Pancytopenia reported; pancytopenia usually reversible following discontinuation of zidovudine.

Determine CBCs and indices of anemia (e.g., hemoglobin, mean corpuscular volume) prior to and monitor frequently during zidovudine therapy, especially in patients with advanced HIV disease. Some experts recommend measuring CBCs with differentials 2–8 weeks after initiation of zidovudine treatment and every 3–6 months thereafter.

Use with caution in patients who have bone marrow compromise evidenced by granulocyte count <1000 cells/mm³ or hemoglobin <9.5 g/dL.

Substantial anemia (hemoglobin <7.5 g/dL or >25% reduction from baseline) and/or neutropenia (granulocyte count <750/mm³ or >50% reduction from baseline) may require dose interruption until there is evidence of bone marrow recovery. Dose interruption does not necessarily eliminate need for transfusion. If bone marrow recovery occurs following dose interruption, reinitiation may be appropriate using adjunctive measures (e.g., epoetin alfa), depending on hematologic indices and patient tolerance.

Musculoskeletal Effects

Myopathy and myositis with pathologic changes, similar to that produced by HIV-1 disease, has been associated with long-term zidovudine use.

Myalgia, musculoskeletal pain, arthralgia, back pain, generalized pain, muscle spasm, and tremor also reported.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving nucleoside analogs, including zidovudine. Reported most frequently in women; obesity also may be a risk factor. Has been reported in patients with no known risk factors.

Use particular caution in patients with known risk factors for liver disease.

Discontinue zidovudine if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of markedly increased serum aminotransferase concentrations).

HIV-infected Patients Coinfected with HCV

Exacerbation of anemia reported in patients coinfected with HIV and HCV receiving zidovudine, interferon alfa, and ribavirin concomitantly. (See Specific Drugs under Interactions.)

Hepatic decompensation, sometimes fatal, reported in patients coinfected with HIV and HCV receiving antiretroviral therapy concomitantly with interferon alfa with or without ribavirin. (See Specific Drugs under Interactions.)

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, angioedema, Stevens-Johnson syndrome, and toxic epidermal necrolysis, reported rarely.

A packaging component of zidovudine concentrate for IV infusion (i.e., vial stoppers) contains dry natural rubber (a latex derivative) which may cause allergic reactions in latex-sensitive individuals.

Other Warnings and Precautions

Use of Fixed Combinations

Lamivudine/zidovudine, abacavir/lamivudine/zidovudine: Consider cautions, precautions, contraindications, and interactions associated with each drug in the fixed combination. Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, pediatric patients, geriatric patients) for each drug.

Lipodystrophy

Zidovudine has been associated with lipoatrophy (loss of subcutaneous fat); incidence and severity related to cumulative exposure to the drug. Fat loss, which is most evident in the face, limbs, and buttocks, may be only partially reversible and improvement may take months to years after switching to an antiretroviral regimen that does not contain zidovudine. Regularly assess patients for signs of lipoatrophy. If fat loss suspected, switch to an alternative antiretroviral regimen if feasible.

Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance, reported with antiretroviral agents. Mechanisms and long-term consequences of adipogenic effects unknown; causal relationship not established.

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; however, time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Available data from the pregnancy registry indicate no difference in overall risk of birth defects among infants born to women who received zidovudine during pregnancy compared with US background rate for major birth defects.

Experts state that zidovudine and lamivudine is an alternative dual NRTI option for initial treatment regimens in antiretroviral-naive pregnant women.

Lactation

Zidovudine distributed into human milk.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Well tolerated in neonates and children. However, usual zidovudine dosage used in full-term neonates may be excessive in premature neonates. (See Pediatric Dosage under Dosage and Administration.)

Major adverse effects reported in children are similar to those reported in adults and include bone marrow toxicity resulting in anemia and/or neutropenia.

Lamivudine/zidovudine: Do not use in pediatric patients weighing <30 kg.

Abacavir/lamivudine/zidovudine: Do not use in pediatric patients weighing <40 kg.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults. No substantial differences in response relative to younger adults identified.

Use with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Zidovudine: Monitor frequently for hematologic toxicities since hepatic impairment increases plasma concentrations of zidovudine and may increase risk of adverse hematologic effects.

Lamivudine/zidovudine: Do not use in patients with impaired hepatic function.

Abacavir/lamivudine/zidovudine: Do not use in patients with impaired hepatic function; contraindicated in those with moderate or severe hepatic impairment.

Renal Impairment

Zidovudine: Dosage adjustments recommended in patients maintained on hemodialysis or peritoneal dialysis or with severe renal impairment (Cl_cr <15 mL/minute). (See Renal Impairment under Dosage and Administration.)

Lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.

Abacavir/lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.

Common Adverse Effects

Headache, malaise, fever, cough, GI effects (anorexia, nausea, vomiting).

Administration

Administer orally or by intermittent or continuous IV infusion.

Do not administer by rapid IV infusion or injection or by IM injection.

When used for treatment of HIV infection, administer by IV infusion only until oral zidovudine can be substituted.

Oral Administration

Administer capsules, tablets, or oral solution orally without regard to meals.

Use oral solution in children who cannot reliably swallow intact capsules or tablets.

Lamivudine/zidovudine: Administer orally twice daily without regard to meals. Do not use in pediatric patients weighing <30 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), patients with hepatic impairment, or patients who experience dose-limiting adverse effects.

Abacavir/lamivudine/zidovudine: Administer orally twice daily without regard to meals. Do not use in pediatric patients weighing <40 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), or patients with hepatic impairment (contraindicated in those with moderate or severe hepatic impairment).

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

Zidovudine concentrate for IV infusion containing 10 mg/mL must be diluted prior to administration. Withdraw appropriate dose from the vial and dilute in 5% dextrose injection to provide a solution containing ≤4 mg/mL.

Rate of Administration

Intermittent IV infusions in adults: Infuse over 60 minutes.

Intermittent IV infusions in neonates: Infuse over 30 minutes.

Intrapartum IV prophylaxis regimen in pregnant HIV-infected women: Give initial dose by IV infusion over 60 minutes, then give by continuous IV infusion at a rate of 1 mg/kg per hour.

Dosage

Pediatric Patients

Treatment of HIV Infection

Dosage in pediatric patients is based on weight or, alternatively, body surface area (BSA). To avoid medication errors, use extra care in calculating dose, transcribing medication order, dispensing prescription, and providing dosage instructions.

Dosage in pediatric patients should not exceed adult dosage.

Treatment of HIV Infection in Neonates† [off-label]

Premature neonates (gestational age <30 weeks): 2 mg/kg twice daily from birth to 4 weeks of age; 3 mg/kg twice daily from 4 weeks to 8–10 weeks of age; 12 mg/kg twice daily beginning at >8–10 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 2 mg/kg twice daily from birth to 2 weeks of age; 3 mg/kg twice daily from 2 weeks to 6–8 weeks of age; 12 mg/kg twice daily beginning at >6–8 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 4 mg/kg twice daily from birth to 4 weeks of age and 12 mg/kg twice daily in those >4 weeks of age. Alternatively, when simplified weight-based dosage of oral solution containing 10 mg/mL used, experts recommend 10 mg (1 mL) twice daily in those weighing 2 to <3 kg, 15 mg (1.5 mL) twice daily in those weighing 3 to <4 kg, and 20 mg (2 mL) twice daily in those weighing 4 to <5 kg.

Premature neonates (gestational age <30 weeks): 1.5 mg/kg twice daily from birth to 4 weeks of age; 2.3 mg/kg twice daily from 4 weeks to 8–10 weeks of age; 9 mg/kg twice daily beginning at >8–10 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 1.5 mg/kg twice daily from birth to 2 weeks of age; 2.3 mg/kg twice daily from 2 weeks to 6–8 weeks of age; 9 mg/kg twice daily beginning at >6–8 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 3 mg/kg twice daily from birth until 4 weeks of age; 9 mg/kg in those >4 weeks of age.

Treatment of HIV Infection in Infants and Children

Infants and children ≥4 weeks of age weighing ≥4 kg: See Table 1.

Alternatively, if BSA used to calculate dosage for pediatric patients ≥4 weeks of age, manufacturer recommends 240 mg/m² twice daily or 160 mg/m² 3 times daily. Some experts recommend 180–240 mg/m² every 12 hours.

Lamivudine/zidovudine in children and adolescents weighing ≥30 kg: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily.

Abacavir/lamivudine/zidovudine in children and adolescents weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.

Prevention of Perinatal HIV Transmission

Prophylaxis in Neonates Born to HIV-infected Women

Premature neonates (gestational age <30 weeks): 2 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 3 mg/kg twice daily at 4 weeks of age and continue until 4–6 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 2 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 3 mg/kg twice daily at 2 weeks of age and continue until 4–6 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 4 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); continue until 4–6 weeks of age. Alternatively, when simplified weight-based dosage of oral solution containing 10 mg/mL used, experts recommend 10 mg (1 mL) twice daily in those weighing 2 to <3 kg, 15 mg (1.5 mL) twice daily in those weighing 3 to <4 kg, and 20 mg (2 mL) twice daily in those weighing 4 to <5 kg.

Neonates: Manufacturer recommends 2 mg/kg every 6 hours initiated within 12 hours of birth and continued through 6 weeks of age.

Although 4-week zidovudine prophylaxis regimen may be used alone in HIV-exposed neonates at low risk of HIV acquisition (i.e., infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen), 6-week zidovudine prophylaxis regimen used in conjunction with a 3-dose nevirapine prophylaxis regimen (2-drug prophylaxis regimen) recommended for those at higher risk.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Premature neonates (gestational age <30 weeks): 1.5 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 2.3 mg/kg twice daily at 4 weeks of age and continue until 4–6 weeks of age.

Premature neonates (gestational age 30 to <35 weeks): 1.5 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); increase to 2.3 mg/kg twice daily at 2 weeks of age and continue until 4–6 weeks of age.

Full-term neonates (gestational age ≥35 weeks): 3 mg/kg twice daily initiated as soon as possible after birth (within 6–12 hours); continue until 4–6 weeks of age.

Neonates: Manufacturer recommends 1.5 mg/kg every 6 hours initiated within 12 hours of birth and continued through 6 weeks of age.

Although 4-week zidovudine prophylaxis regimen may be used alone in HIV-exposed neonates at low risk of HIV acquisition (i.e., infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen), 6-week zidovudine prophylaxis regimen used in conjunction with a 3-dose nevirapine prophylaxis regimen recommended for those at higher risk.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Empiric HIV Therapy in Neonates Born to HIV-infected Women† [off-label]

Recommended empiric HIV therapy regimen consists of zidovudine, lamivudine, and nevirapine initiated as soon as possible after birth (within 6–12 hours); used in HIV-exposed neonates considered at highest risk of HIV acquisition. (See Prevention of Perinatal HIV Transmission under Uses.)

Zidovudine dosage for empiric HIV therapy in neonates Born to HIV-infected women is the same as that recommended for prophylaxis in neonates born to HIV-infected women. (See Prophylaxis in Neonates Born to HIV-infected Women under Dosage and Administration.)

Optimal duration of empiric HIV therapy in HIV-exposed neonates unknown. Many experts recommend that 3-drug empiric regimen be continued for 6 weeks; others discontinue nevirapine and/or lamivudine if results of neonate's HIV nucleic acid amplification test (NAAT) are negative, but recommend continuing zidovudine for 6 weeks.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Adults

Treatment of HIV Infection

Oral

Zidovudine: 300 mg twice daily. Experts state usual dosage can be given as 300 mg twice daily or 200 mg 3 times daily.

Lamivudine/zidovudine in adults weighing ≥30 kg: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily.

Abacavir/lamivudine/zidovudine in adults weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.

IV

Zidovudine: 1 mg/kg every 4 hours.

Prevention of Perinatal HIV Transmission

HIV-infected Pregnant Women

2 mg/kg given by IV infusion over 60 minutes (initiated at start of labor or 3 hours before scheduled cesarean delivery) followed by 1 mg/kg per hour given by continuous IV infusion until delivery.

Indicated in pregnant HIV-infected women depending on plasma HIV-1 RNA levels near time of delivery. (See Prevention of Perinatal HIV Transmission under Uses.)

If oral zidovudine is part of current antiretroviral treatment regimen, substitute with IV zidovudine until after delivery; continue other antiretrovirals in the woman’s treatment regimen on schedule as much as possible during labor.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)†

Oral

Zidovudine: 300 mg twice daily. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV [PEP] under Uses).

Lamivudine/zidovudine: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily. Use in conjunction with a recommended INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)†

Oral

Zidovudine: Adjust dosage based on degree of renal impairment. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.

nPEP not recommended if exposed individual seeks care >72 hours after exposure.

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Zidovudine in infants and children ≥4 weeks of age: Maximum 600 mg daily.

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Zidovudine: Data insufficient to recommend dosage adjustments for patients with hepatic impairment or liver cirrhosis.

Lamivudine/zidovudine: Do not use in patients with hepatic impairment.

Abacavir/lamivudine/zidovudine: Do not use in patients with hepatic impairment; contraindicated in those with moderate or severe hepatic impairment.

IV

Zidovudine: Data insufficient to recommend dosage adjustments for patients with hepatic impairment or liver cirrhosis.

Renal Impairment

Treatment of HIV Infection

Oral

Zidovudine in adults maintained on hemodialysis or peritoneal dialysis or with severe renal impairment (Cl_cr <15 mL/minute): 100 mg every 6–8 hours.

Lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.

Abacavir/lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.

IV

Zidovudine in adults maintained on hemodialysis or peritoneal dialysis or with severe renal impairment (Cl_cr <15 mL/minute): 1 mg/kg every 6–8 hours.

Geriatric Patients

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

The following drug interactions are based on studies using zidovudine. When lamivudine/zidovudine or abacavir/lamivudine/zidovudine is used, consider interactions associated with each drug in the fixed combination.

Specific Drugs