Zidovudine

Zidovudine Uses, Dosage, Side Effects, Food Interaction and all others data.

Zidovudine is converted intracellularly to zidovudine triphosphate, which inhibits replication of retroviruses, including HIV, by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

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.

Trade Name Zidovudine
Availability Prescription only
Generic Zidovudine
Zidovudine Other Names Azidothymidine, Zidovudina, Zidovudine, Zidovudinum
Related Drugs Biktarvy, Truvada, tenofovir, ritonavir, abacavir, emtricitabine, lamivudine, Complera, Atripla, Stribild
Weight 50mg/5ml, , 10mg/ml, 100mg, 300mg
Type Tablet, Syrup, Oral, Intravenous, Intravenous Solution, Oral Capsule, Oral Syrup, Oral Tablet, Oral/injection, Capsule
Formula C10H13N5O4
Weight Average: 267.2413
Monoisotopic: 267.096753929
Protein binding

30-38%

Groups Approved
Therapeutic Class Drugs for HIV / Anti-retroviral drugs
Manufacturer Cipla Limited, Essential Drugs Company Ltd, Aurobindo Pharma - Milpharm Ltd, , Kimia Farma
Available Country India, Bangladesh, United Kingdom, United States, Indonesia
Last Updated: September 19, 2023 at 7:00 am
Zidovudine
Zidovudine

Uses

Zidovudine, a nucleoside reverse transcriptase inhibitor, is used for combination with other antiretroviral agents for the treatment of HIV-1 infection.Prevention Of Maternal-Fetal HIV-1 Transmission Zidovudine is used for the prevention of maternal-fetal HIV-1 transmission. The indication is based on a dosing regimen that included 3 components:

  • Antepartum therapy of HIV-1–infected mothers
  • Intrapartum therapy of HIV-1–infected mothers
  • Post-partum therapy of HIV-1–exposed neonate

Points to consider prior to initiatingZidovudine in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:

  • In most cases,Zidovudine for prevention of maternal-fetal HIV-1 transmission should be given in combination with other antiretroviral drugs.
  • Prevention of HIV-1 transmission in women who have receivedZidovudine for a prolonged period before pregnancy has not been evaluated.
  • Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of therapy withZidovudine during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of antiretroviral therapy for their own health may consider delaying use; this indication is based on use after 14 weeks’ gestation.

Zidovudine is also used to associated treatment for these conditions: HIV Transmission, Human Immunodeficiency Virus (HIV) Infections, Perinatal HIV transmission

How Zidovudine works

Zidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ.

Dosage

Zidovudine dosage

Prophylaxis of HIV infection in neonates:

  • Child:2 mg/kg 6 hrly, starting within 12 hr after birth and continuing for 6 wk.

HIV infection:

  • Adult:250 mg or 300 mg bid, in combination with other antiretroviral agents.
  • Child:As soln: 4 to <9 kg: 12 mg/kg bid; 9 to <30 kg: 9 mg/kg bid; ≥30 kg: 250 mg or 300 mg bid. As cap/tab: 8-13 kg: 100 mg bid; 14-21 kg: 100 mg in the morning, 200 mg in the evening; 22-30 kg: 200 mg bid; ≥30 kg: 250 mg or 300 mg bid. Alternatively (based on BSA), 480 mg/m2daily in 2-3 divided doses. Doses are given in combination with other antiretroviral agents.

Prophylaxis of maternal-fetal HIV transmission:

  • Adult:100 mg 5 times daily, starting on the 14th wk of gestation until the start of labour.

May be taken with or without food.

Side Effects

Dizziness, headache, malaise, myalgia, GI symptoms (e.g. abdominal pain, diarrhoea, nausea, vomiting), anorexia, immune reconstitution syndrome, lipodystrophy, metabolic abnormalities, mitochondrial dysfunction, osteonecrosis; raised liver enzymes, creatine phosphokinase; hyperbilirubinaemia, myalgia, myositis. Rarely, aplastic anaemia, pure red cell aplasia, pancytopenia, thrombocytopenia, rhabdomyolysis, cardiomyopathy, convulsions, pancreatitis.

Toxicity

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

Precaution

Severe renal and hepatic impairment. Childn. Pregnancy.

Interaction

Decreased plasma concentration with rifampicin resulting in partial or total loss of efficacy of zidovudine. Increased risk of anaemia with ribavirin in patients co-infected with HCV. Antagonistic effect with stavudine or doxorubicn. Increased plasma level with probenecid, atovaquone, valproic acid, fluconazole, or methadone. May alter phenytoin blood levels. Increased adverse effect with potentially nephrotoxic or myelosuppressive drugs (e.g. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine, doxorubicin). Reduced absorption with clarithromycin.

Food Interaction

  • Take with or without food. The administration of zidovudine with food causes a 28% reduction in the Cmax but does not affect the AUC.

[Minor] Food may have variable effects on the oral bioavailability of zidovudine.

Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration.

In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast.

In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state.

In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting.

Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected.

The clinical significance of these alterations, if any, is unknown.

The product labeling states that zidovudine may be taken with or without food.

Volume of Distribution

Apparent volume of distribution, HIV-infected patients, IV administration = 1.6 ± 0.6 L/kg

Elimination Route

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

Elimination half life, HIV-infected patients, IV administration = 1.1 hours (range of 0.5 - 2.9 hours)

Clearance

  • 0.65 +/- 0.29 L/hr/kg [HIV-infected, Birth to 14 Days of Age]
  • 1.14 +/- 0.24 L/hr/kg [HIV-infected, 14 Days to 3 Months of Age]
  • 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12 Years of Age]. The transporters, ABCB1, ABCC4, ABCC5, and ABCG2 are involved with the clearance of zidovudine.

Elimination Route

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.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Hypersensitivity; abnormally low neutrophil counts (<0.75 x 109/L) or Hb levels (<7.5 g/dL or 4.65 mmol/L); newborn infants with hyperbilirubinaemia requiring treatment other than phototherapy, or with increased transaminase levels >5 times the ULN. Lactation. Concomitant use with interferon alfa (with or witho ribavirin) in HIV and hepatitis B or C virus co-infected patients.

Special Warning

Renal Impairment:

  • ESRD maintained on haemodialysis or peritoneal dialysis: 100 mg 6-8 hrly.
  • CrCl <10-15 mL/min: 100 mg 6-8 hrly.

Hepatic Impairment: Dose reduction may be needed.

Acute Overdose

Symptoms: Vomiting, CNS effects (e.g. fatigue, dizziness, drowsiness, lethargy, confusion), haematologic effects (e.g. anaemia, decreased Hb). Bone marrow hypoplasia, mild ataxia, tonic-clonic seizure and increased serum concentration of AST and ALT may also occur. Management: Supportive and symptomatic treatment. Induce emesis and admin activated charcoal to prevent further absorption of unrecovered drug.

Interaction with other Medicine

Store between 15-25° C.

Innovators Monograph

You find simplified version here Zidovudine

Zidovudine contains Zidovudine see full prescribing information from innovator Zidovudine Monograph, Zidovudine MSDS, Zidovudine FDA label

FAQ

What is Zidovudine used for?

Zidovudine is used along with other medications to treat human immunodeficiency virus (HIV) infection.

How is Zidovudine administered?

Zidovudine injection Infusion is administered intravenously at a constant rate over 1 hour.

What is the side effect of Zidovudine?

Headache, nausea, vomiting, trouble sleeping, or loss of appetite may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects.

Is Zidovudine still used?

Zidovudine is still used in combination with other ARVs for the treatment of HIV.

Is Zidovudine safe in pregnancy?

Zidovudine was well tolerated by mothers and infants; there was no difference in pregnancy-related side effects between the treatment groups.

Is Zidovudine safe during breastfeeding?

Zidovudine has been well studied during breastfeeding. Milk levels are low and most breastfed infants do not have detectable blood levels. Some breastfed infants have developed anemia during maternal therapy.

How do I know if Zidovudine is working?

You will need to have regular blood tests to check how well your medicines are working. It is important that you continue to take Zidovudine and your other antiretroviral treatment regularly.

Who should not take Zidovudine?

You should not use Zidovudine if you are allergic to it.You may develop lactic acidosis, a dangerous build-up of lactic acid in your blood. This may be more likely if you have other medical conditions, if you've taken HIV medication for a long time, or if you are a woman. Ask your doctor about your risk.

Is Zidovudine an antibiotic?

Zidovudine also has antibacterial properties, though not routinely used in clinical settings.

How can I use Zidovudine?

Zidovudine usually taken twice a day by adults and two to three times a day by infants and children. Infants 6 weeks of age and younger may take Zidovudine every 6 hours.

Can I drink alcohol with Zidovudine?

Avoid drinking alcohol.Zidovudine may increase your risk of liver damage or lactic acidosis.

Can I take Zidovudine for a long time?

Long-term use of Zidovudine can cause muscle weakness, or loss of muscle tissue similar to "wasting syndrome" caused by HIV.

How does Zidovudine work?

Zidovudine works by inhibiting the enzyme reverse transcriptase that HIV uses to make DNA and therefore decreases replication of the virus.

*** Taking medicines without doctor's advice can cause long-term problems.
Share