Zidovudine an antiretroviral (anti-HIV) drug | NRTI

Zidovudine is an antiretroviral (anti-HIV) drug that is part of the nucleoside reverse transcriptase inhibitor (NRTIs or Nukes) family. It is used together with other antiretroviral to delay the progression of HIV infection. By doing this, your immune system should improve (increase in CD4+ count) and you will be better protected against infections.
Zidovudine does not cure AIDS or completely kill the HIV virus




Zidovudine does not cure AIDS or completely kill the HIV virus, but helps to prevent further damage by slowing down the production of new viruses. Treatment with zidovudine does not reduce the risk of passing infection on to others. You will still be able to pass HIV by sexual contact, by blood transfer or by sharing needles. You should always use appropriate precautions to prevent passing HIV on to others.

Indication




• Treatment of HIV infection when antiretroviral therapy is warranted
• Prevention of human immunodeficiency virus (HIV)infection in newborn
• Prevention of maternal-fetal HIV transmission in HIV positive women
• Low risk newborn whose mother: Has an undetectable viral load at birth (less than 40 copies per mL)
• High risk newborn whose mother: Has detectable viral load at birth; Is not on therapy, presents late/in labour or without testing available; Has HIV infection detected post-partum

Mechanism of action

Following intracellular conversion to its active form, inhibits viral RNA synthesis by inhibiting the enzyme DNA polymerase (reverse transcriptase). Prevents viral replication.

Therapeutic Effects: Virustatic action against selected retroviruses. Slowed progression and decreased sequelae of HIV infection. Decreased viral load and improved CD4 cell counts. Decreased transmission of HIV to infants born to HIV infected mothers

Mechanism of Resistance

Resistance to NRTIs occurs through two mechanisms; decreased incorporation of NRTIs into the viral DNA and increased excision of NRTIs from the viral DNA.

Pharmacodynamics

In vitro IC50 (50% inhibitory concentration) was 0.003 to 0.013mcg/mL and the IC90 (90% inhibitory concentration) was 0.03 to 0.3 mcg/mL.

Pharmacokinetics

Zidovudine is well absorbed and undergoes first-pass hepatic glucuronidation to zidovudine glucuronide. Peak plasma concentrations occur at 0.5-1.0 hour after dosing in the fasted state. Both zidovudine glucuronide and zidovudine are eliminated through renal excretion with tubular secretion contributing to the elimination.

Dosage

100mg capsule (100 capsule bottle)
300mg tablet (60 tablet bottle)
Syrup 50mg/5ml (240mg bottle)

Adult: 300mg twice daily
600mg once a day has been studied. This dose has been shown to have antiviral activity. However, it is less marked and more slowly achieved than 300mg twice a day.

Pediatric

Preterm Infants (below 30 weeks gestational age)
Oral: 2 mg/kg q12h IV: 1.5 mg/kg q12h (Both increased to q8h at four weeks of age)
Preterm Infants (=30 weeks gestational age)
Oral: 2 mg/kg q12h IV: 1.5 mg/kg q12h (Both increased to q8h at two weeks of age)
Neonates (within 12 hours after birth through 6 weeks of age)
Oral: 2 mg/kg q6h IV: 1.5 mg/kg, infused over 30 minutes, q6h
Pediatrics (6 weeks to 12 years)
Oral: 160 mg/m2 q8h IV intermittent: 120 mg/m2 q6h IV continuous: 20 mg/m2/hr

Prevention of Maternal/Fetal Transmission of HIV Infection

PO (Adults above 14 week Pregnant): 100 mg 5 times daily until onset of labor.
IV (Adults during Labor and Delivery): 2 mg/kg over 1 hr., then continuous infusion of 1mg/kg/hr until umbilical cord is clamped.
IV (Infants):1.5mg/kg q 6 hr until able to take PO.
Take with or without food

Precaution

Anemia (usually not observed before six weeks of zidovudine therapy but occasionally occurring earlier), neutropenia (usually not observed before four weeks therapy but sometimes occurring earlier) and leucopenia (usually secondary to neutropenia) can be expected to occur in patients with advanced symptomatic HIV disease receiving zidovudine. These occurred more frequently at higher dosages (1200 to 1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV disease.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of NRTIs.

Adverse Reactions/Side Effects


  • CNS: SEIZURES, headache, weakness, anxiety, confusion,pmental acuity, dizziness, insomnia, mental depression, restlessness, syncope.
  • GI: HEPATOMEGALY (with steatosis), PANCREATITIS, abdominal pain, diarrhea, nausea, anorexia, drug-induced hepatitis, dyspepsia, oral mucosa pigmentation, vomiting.
  • Derm: nail pigmentation.
  • Endo: fat redistribution, gynecomastia.
  • Hemat: anemia, granulocytopenia, pure red-cell aplasia, thrombocytosis.
  • MS: back pain, myopathy.
  • Neuro: tremor.
  • Misc: immune reconstitution syndrome.
Interactions

Drug-Drug: bone marrow depression with other agents having bone marrow– depressing properties, antineoplastics, radiation therapy, or ganciclovir. Neurotoxicity may occur with acyclovir. Toxicity may be increased by concurrent administration of probenecid or fluconazole. Levels are increased by clarithromycin.



Reference
https://www.webmd.com/drugs/2/drug-4386/zidovudine-oral/details
https://aidsinfo.nih.gov/drugs/4/zidovudine/0/patient
https://pubchem.ncbi.nlm.nih.gov/compound/Zidovudine
http://www.antimicrobe.org/drugpopup/zidovudine.htm
https://www.drugbank.ca/drugs/DB00495
https://reference.medscape.com/drug/retrovir-zdv-zidovudine-342639
https://www.medicinesforchildren.org.uk/zidovudine-treatment-hiv-infection
https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0717-97072019000304523

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