indication

For the treatment of human immunovirus (HIV) infections.

pharmacology

Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

mechanism of action

Zidovudine, a structural analog of thymidine, inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

toxicity

Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD₅₀ is 3084 mg/kg (orally in mice).

biotransformation

Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).

absorption

Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.

half life

0.5-3 hours

route of elimination

As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV

drug interactions

Atovaquone: Atovaquone increases the effect and toxicity of zidovudine

Clarithromycin: Clarithromycin may decrease the serum concentration of zidovudine. Increased myelosuppression in mice has been observed. Consider staggering doses during concomitant therapy and closely monitor response to zidovudine therapy.

Doxorubicin: Additive myelosuppression may occur. Doxorubicin may decrease the efficacy of zidovudine. Concomitant therapy should be avoided.

Ganciclovir: Increased risk of hematologic toxicity. Concomitant therapy should be avoided.

Interferon beta-1b: The interferon increases the effect and toxicity of zidovudine

Methadone: Methadone increases the effect and toxicity of zidovudine

Probenecid: Rash, malaise, myalgia

Ribavirin: Increased risk or severity of anemia. Consider alternate therapy or monitor more closely for anemia.

Rifabutin: The rifamycin decreases levels of zidovudine

Rifampin: Rifampin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifampin is initiated, discontinued or dose changed.

Rifapentine: Rifapentin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifapentin is initiated, discontinued or dose changed.

Stavudine: Zidovudine may decrease the efficacy of stavudine. Concomitant therapy should be avoided.

Tipranavir: Tipranavir decreases the concentration of Zidovudine.

Valganciclovir: The adverse/toxic effects of Zidovudine, a reverse transcriptase inhibitor (nucleoside), may be enhanced by Valganciclovir. There is a significant risk of hematologic toxicity. Concomitant therapy should be avoided.