Zidovudine Dosage

Usual Adult Dose for HIV Infection

Oral: 300 mg orally every 12 hours or 200 mg orally every 8 hours

IV: 1 mg/kg by IV infusion over 1 hour, every 4 hours around the clock, for a total daily dose of 5 to 6 mg/kg; maximum of 200 mg/dose

Duration: Therapy should be continued for as long as the patient tolerates, or until the patient is switched to another antiretroviral agent.

Usual Adult Dose for Nonoccupational Exposure

300 mg orally every 12 hours or 200 mg orally every 8 hours, in combination with efavirenz plus (lamivudine or emtricitabine) or lopinavir-ritonavir plus (lamivudine or emtricitabine)

Prophylaxis should be initiated as soon as possible, preferably within 72 hours of exposure.

Duration: 28 days

Usual Adult Dose for Occupational Exposure

300 mg orally every 12 hours or 200 mg orally every 8 hours
Prophylaxis should begin promptly, preferably within 1 to 2 hours postexposure.

Duration: Generally 28 days; however, the exact duration of therapy may differ based on the institution's protocol

Usual Adult Dose for Reduction of Perinatal Transmission of HIV

Maternal dosing: 100 mg orally 5 times a day until start of labor; however, most authorities would also consider the standard oral dosages of 300 mg every 12 hours or 200 mg every 8 hours

During labor and delivery: 2 mg/kg by IV infusion over 1 hour followed by a continuous IV infusion of 1 mg/kg/hr until clamping of the umbilical cord

Therapy should begin at 14 to 34 weeks gestation. Neonates should also be treated for 6 weeks. Despite the use of this regimen, transmission to infants may still occur in some cases.

Usual Pediatric Dose for HIV Infection

Oral:
4 weeks to less than 18 years:
Based on body weight:
4 to less than 9 kg: 12 mg/kg orally twice a day or 8 mg/kg orally 3 times a day
9 to less than 30 kg: 9 mg/kg orally twice a day or 6 mg/kg orally 3 times a day
30 kg or more: 300 mg orally twice a day or 200 mg orally 3 times a day

Based on body surface area: 240 mg/m2 orally twice a day or 160 mg/m2 orally 3 times a day

The dosage calculated by body weight may not be the same as the dosage calculated by body surface area in some cases.

IV infusion:
6 weeks to 12 years:
Intermittent: 120 mg/m2 IV every 6 hours
Continuous: 20 mg/m2 IV per hour

13 years or older: 1 mg/kg by IV infusion over 1 hour, every 4 hours around the clock, for a total daily dose of 5 to 6 mg/kg; maximum of 200 mg/dose

Usual Pediatric Dose for Reduction of Perinatal Transmission of HIV

Premature infants:
Oral: 2 mg/kg orally every 12 hours
IV: 1.5 mg/kg IV every 12 hours

Increase dosage frequency to every 8 hours at 4 weeks of age in neonates less than 30 weeks gestation at birth and at 2 weeks of age in neonates 30 to less than 35 weeks gestation at birth.

Full-term infants, 0 to 6 weeks:
Oral: 2 mg/kg orally every 6 hours
IV: 1.5 mg/kg IV every 6 hours

Oral treatment with zidovudine syrup should start at 8 to 12 hours after birth and should continue through 6 weeks of age. IV zidovudine may be administered to neonates unable to receive oral dosing and should be infused over 30 minutes.

Renal Dose Adjustments

CrCl 14 mL/min or less:
Oral: 100 mg orally every 6 to 8 hours
IV: 1 mg/kg IV every 6 to 8 hours; maximum of 200 mg/dose

Liver Dose Adjustments

Mild to moderate impaired hepatic function or liver cirrhosis:
Oral: Data not available

IV: Data not available; since zidovudine is primarily eliminated by hepatic metabolism, a reduction in the daily dose may be necessary in these patients

Dose Adjustments

Doses should be titrated on an individual basis according to patient tolerance and clinical condition. Lower doses or a brief interruption of therapy should be considered for those who develop bone marrow toxicity or other severe adverse reaction.

In patients with HIV-induced dementia, higher doses (up to 1200 mg/day orally) have been used and may offer some benefit in the management of neurological symptoms. Higher doses may also be more effective in treating HIV-related thrombocytopenia.

Precautions

For the purposes of drug toxicity monitoring and dosage adjustment, a complete blood count as well as renal and hepatic function tests should be performed at baseline and every 3 months thereafter over the entire duration of therapy.

Zidovudine may cause bone marrow toxicity, most commonly neutropenia and anemia, particularly in patients with advanced symptomatic HIV disease. Hematologic toxicities appear to be associated with bone marrow reserve prior to therapy and to dose and duration of treatment. Zidovudine should be used with extreme caution in patients with bone marrow suppression indicated by a granulocyte count below 1000 cells/mm3 or hemoglobin less than 9.5 g/dL. Routine blood counts are recommended, and generally should occur more frequently in patients with advanced disease. If bone marrow toxicity occurs, a dose adjustment, dosage interruption, or discontinuation of zidovudine therapy and/or blood transfusions may be necessary.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretroviral agents. Risk factors for lactic acidosis may include female gender, obesity, and prolonged nucleoside exposure. Caution is recommended in patients with risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment should be suspended in patients who develop clinical or laboratory signs of lactic acidosis or hepatotoxicity.

Exacerbation of anemia has been observed with concomitant use of zidovudine and ribavirin. Coadministration of zidovudine and ribavirin is not recommended. Coadministration of zidovudine with interferon alfa with or without ribavirin in HIV/HCV coinfected patients may precipitate hepatic decompensation, fatal in some cases. Patients receiving interferon alfa with or without ribavirin and zidovudine should be closely monitored for treatment-associated toxicities including neutropenia, anemia, and hepatic decompensation. Discontinuation of zidovudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon alpha, ribavirin, or both should be considered if any of these toxicities occur.

Immune reconstitution syndrome has occurred during combination antiretroviral therapy. Patients responding to therapy may develop an inflammatory response to indolent or residual opportunistic infections and require evaluation and treatment.

Patients with allergies to nuts or soy should be aware that zidovudine oral capsules contain soya lecithin.

Patients with diabetes should be aware that the oral syrup contains sucrose.

Related drugs not for coadministration with zidovudine include abacavir/ lamivudine/zidovudine, and lamivudine-zidovudine, in which zidovudine is one of the active components.

Zidovudine has not been shown to reduce the risk of HIV transmission to others through sexual contact or blood contamination.

The potential for HIV cross-resistance among nucleoside reverse transcriptase inhibitors exists but has not been fully explored. The effect of zidovudine therapy on the activity of subsequently administered nucleoside reverse transcriptase inhibitors has not been fully explored. Selection of antiretroviral agents for a patient's medication regimen should be done carefully and with the assistance of expert consultation.

Pediatric dosages are calculated based on body weight or body surface area. Special vigilance is recommended during calculation of dose, transcription of medication order, dispensing information, and dosing instructions to reduce the risk of medication errors.

Dialysis

Hemodialysis or peritoneal dialysis:
Oral: 100 mg orally every 6 to 8 hours
IV: 1 mg/kg IV every 6 to 8 hours; maximum of 200 mg/dose

Other Comments

Once the patient is able to tolerate oral medication, therapy should be substituted with oral zidovudine.

Zidovudine may be taken without regard to meals.

If a patient is unable to reliably swallow a zidovudine tablet or capsule, then the oral syrup should be used.

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