Zidovudine

Aka: Zidovudine, Retrovir, ZDV, AZT

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II. Indications

  1. HIV Infection
    1. Replaced in the U.S. by other nRTIs

III. Mechanism

  1. Nucleoside Reverse Transcriptase Inhibitor
  2. Thymidine analogue
    1. Interferes with viral reverse transcriptase and elongation of the viral DNA chain (as with other nRTIs)

IV. Pharmacokinetics

  1. Well absorbed from the Gastrointestinal Tract
  2. Glucuronidase added in the liver
  3. Excreted by the Kidney
  4. Crosses the blood-brain barrier and the placenta

V. Efficacy

  1. Delays the progression to AIDS and late HIV
  2. Increases CD4 Counts
  3. Suppresses viral replication in mild HIV (CD4 200-500)
  4. Resistance develops 6 months into therapy

VI. Dosing

  1. Taken as part of combination therapy with other Antiretrovirals
  2. Not to be used as HIV monotherapy (including in pregnancy)
  3. Adult (or child weight >30 kg)
    1. Zidovudine 300 mg orally twice daily OR
    2. Zidovudine 1 mg/kg IV over 1 hour every 4 hours
  4. Pregnancy - Prevention of vertical transmission
    1. First, starting at 14 weeks gestation: Take 100 mg orally five times daily until labor
    2. Peripartum, during labor
      1. Load 2 mg/kg total body weight IV over 1 hour
      2. Maintain 1 mg/kg/hour until Umbilical Cord clamped
  5. Child (age >=4 weeks and weight >=4 kg)
    1. Weight 4 to 9 kg: 4 mg/kg orally twice daily
    2. Weight 9 to 30 kg: 9 mg/kg orally twice daily
    3. Weight >30 kg: 300 mg orally twice daily (adult dosing)
  6. Infant - Prevention of vertical transmission
    1. Start within 12 hours of delivery
      1. Continue until age 6 weeks (four weeks if maternal sustained viral suppression on HAART)
    2. Original FDA approved protocol
      1. Give 2 mg/kg (using syringe with 0.1 ml markers) orally every 6 hours
      2. Alternatively, give 1.5 mg/kg IV over 30 min every 6 hours
    3. Off Label dosing
      1. Gestational age >35 weeks: Give 4 mg orally twice daily
      2. See other references for dosing Gestational age <35 weeks
  7. Renal Dosing (Adults with Creatinine Clearance <15 ml/min or Hemodialysis)
    1. Take 100 mg orally every 8 hours OR
    2. Take 300 mg orally once daily OR
    3. Give 1 mg/kg IV every 6 to 8 hours

VII. Adverse effects: General

  1. See nRTI for adverse effects attributed to the class
  2. Toxicity limits use as first-line nRTI (other agents are preferred)
  3. Short term
    1. Headache
    2. Myalgia
    3. Malaise
    4. Fatigue
    5. Insomnia
    6. Nausea or Vomiting
    7. Bloating
    8. Dyspepsia
  4. Long term
    1. Nail and Oral Mucosa Hyperpigmentation
    2. Myopathy

VIII. Adverse Effects: Major Toxicities

  1. Hepatitis
  2. Myopathy
  3. Bone Marrow suppression
    1. Anemia (Macrocytosis) (7% late, 1.8% early)
    2. Leukopenia (Neutropenia) (37% late, 4% early)
  4. Management of toxicity
    1. Interrupt treatment
      1. Results in reversal of Anemia and Neutropenia
    2. Specific Therapy
      1. Anemia: Give Erythropoietin
      2. Neutropenia: Give growth factors
    3. Persistent Anemia or Neutropenia
      1. Change therapy

IX. Safety

  1. Avoid in Lactation
  2. Pregnancy
    1. Alternative nRTI in pregnancy
    2. Pregnancy registry exists

X. Monitoring

  1. Advanced disease: Complete Blood Count each month
  2. Early disease: Complete Blood Count every 2-3 months

XI. Drug Interactions

  1. CMV Prophylaxis agents (Ganciclovir or Valganciclovir)
    1. Increased Bone Marrow suppression risk
  2. Nevirapine
    1. Increased Granulocytopenia risk (esp. children)

XII. Resources

  1. Zidovudine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca9f0c57-fc8b-4da4-a987-0fc52b7fd4f4

XIII. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (1998) Med Lett Drugs Ther 40(1041):115 [PubMed]
  3. (2009) Treat Guidel Med Lett 7(78): 11-22 [PubMed]
  4. Reust (2011) Am Fam Physician 83(12): 1443-51 [PubMed]

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Related Studies

Ontology: Zidovudine (C0043474)

Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (CHV) an antiviral drug used in the treatment of AIDS
Definition (NCI_NCI-GLOSS) A drug that inhibits the human immunodeficiency virus (HIV) that causes AIDS. It is a type of systemic antiviral.
Definition (NCI) A synthetic dideoxynucleoside. After intracellular phosphorylation to its active metabolite, zidovudine inhibits DNA polymerase, resulting in the inhibition of DNA replication and cell death. This agent also decreases levels of available pyrimidines. (NCI04)
Definition (MSH) A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
Definition (CSP) synthetic thymidine analog that inhibits replication of some retroviruses, including human immunodeficiency virus; used in the management of AIDS or HIV infection.
Definition (PDQ) A synthetic dideoxynucleoside. After intracellular phosphorylation to its active metabolite, zidovudine inhibits DNA polymerase, resulting in the inhibition of DNA replication and cell death. This agent also decreases levels of available pyrimidines. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40121&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40121&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C947" NCI Thesaurus)
Concepts Nucleic Acid, Nucleoside, or Nucleotide (T114) , Pharmacologic Substance (T121)
MSH D015215
SnomedCT 27479000, 387151007
LNC LP16744-2, MTHU013874
English 3' Azido 2',3' Dideoxythymidine, 3'-Azido-2',3'-Dideoxythymidine, Antiviral AZT, Azidothymidine, AZT (Antiviral), AZT Antiviral, AZT, Antiviral, Zidovudine, zidovudine, Thymidine, 3'-azido-3'-deoxy-, 3' Azido 3' deoxythymidine, 3'-Azido-3'-deoxythymidine, 3'-azido-3'-deoxythymidine, azidodeoxythymidine, ZIDOVUDINE, azidothymidine (AZT) (medication), azidothymidine (AZT), Zidovudine [Chemical/Ingredient], azt, zdv, compound s, zidovudine (AZT), s compound, Compound S, 1-(3-Azido-2,3-dideoxy-beta-D-ribofuranosyl)-5-methylpyrimidine-2,4-(1H,3H)-dione, antiviral zidovudine, zidovudine (medication), AZT, AZT - Azidothymidine, Zidovudine product, Zidovudine (product), Zidovudine (substance), azidothymidine, ZDV
German Azidothymidin, 3-Azido-2,3-Dideoxythymidin, 3'-Azido-2',3'-Dideoxythymidin, AZT (Antiviral), AZT, antiviral, 3'-Azido-3'-Deoxythymidin, AZT (Antivirusmittel), 3-Azido-3-Deoxythymidin, Zidovudin
Swedish Zidovudin
Czech azidothymidin, zidovudin
Finnish Tsidovudiini
Russian AZIDOTIMIDIN, ZIDOVUDIN, AZT (ANTIVIRUSNYI), AZT (АНТИВИРУСНЫЙ), АЗИДОТИМИДИН, ЗИДОВУДИН
Japanese アジドチミジン, アジドデオキシチミジン, レトロビル, ジドブジン, 3'-アジド-3'-デオキシチミジン
Polish Azydotymidyna, Zidowudine, Zydowudyna, AZT przeciwwirusowa, AZT
Spanish azidotimidina, zidovudina (producto), zidovudina (sustancia), zidovudina, AZT, Azidotimidina, AZT (Antiviral), Zidovudina
French AZT, Azidothymidine, Zidovudine
Italian Zidovudina
Portuguese Azidotimidina, AZT (Antiviral), Zidovudina
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Retrovir (C0699576)

Concepts Pharmacologic Substance (T121) , Nucleic Acid, Nucleoside, or Nucleotide (T114)
MSH D015215
German Retrovir
English retrovir, Retrovir
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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