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zidovudine; azidothymidine; AZT (Retrovir)

Tradenames: Retrovir, AZT. Indications: 1) treatment of HIV infection 2) for inclusion in all HAART regimens [5] Dosage: 1) may be administered with or without food 2) 200 mg PO TID or 300 mg PO BID 3) 100 mg PO every 4 hours, including night dose if symptomatic 4) doses of 300-400 mg daily are appropriate in patients with severe renal dysfunction 5) 1-2 mg/kg IV infused over 1 hour every 4 hours 6) children: 3 months to 13 years a) 90-180 mg/m2 (max 200 mg) PO every 6 hours b) 1-2 mg/kg IV infused over 1 hour every 4 hours 7) 1000 mg/day if thrombocytopenic Capsule: 100 mg. Tabs: 300 mg. Syrup: 50 mg/5 mL (240 mL). Injection: 10 mg/mL (20 mL) Dosage adjustment in renal failure: creatinine clearance dosage > 50-90 mL/min 200 mg PO TID or 300 mg PO BID 10-50 mL/min 200 mg PO TID or 300 mg PO BID < 10 mL/min* 100 mg PO TID * same dose for hemodialysis Pharmacokinetics: 1) rapidly absorbed after oral administration 2) elimination 1/2life is approximately 1.1-1.4 hours (1.4-3 hours ESRD) 3) rapidly converted to a metabolite which is eliminated mainly through the kidneys 4) AZT penetrates the blood brain barrier into the CSF Adverse effects: 1) common (> 10%) - anemia, leukopenia, severe headache, insomnia, nausea 2) less common (1-10%) - hyperpigmentation of nails (bluish-brown) 3) uncommon (< 1%) - hepatotoxicity, anorexia, myopathy*, weakness, tenderness, neurotoxicity, confusion, mania, seizures, bone marrow suppression, granulocytopenia, thrombocytopenia, pancytopenia, cholestatic hepatitis 4) other - bone marrow suppression: - granulocytopenia - anemia - GI intolerance - asthenia - myalgia - abdominal pain - syndrome of lactic acidosis, hepatic failure & pancreatitis - cardiomyopathy - lipodystrophy [5] * An HIV-associated myositis is also described Drug interactions: 1) acyclovir: in combination may lead to neurotoxicity 2) ganciclovir in combination a) increased risk of neutropenia b) increased levels of AZT 3) interferon-alpha: may increase the risk of hematologic toxicity 4) probenecid: increases AZT concentration 5) AZT increases levels of atovaquone 6) increased risk of bone marrow toxicity in combination with: a) flucytosine b) trimethoprim/sulfamethoxazole 7) do not use with stavudine [5] Laboratory: 1) specimen: a) serum, plasma (heparin, EDTA), whole blood, urine b) stable for 1 hour at 20-60 degrees C c) stable for 60 days at -20 degrees C 2) methods: a) serum/plasma: HPLC, RIA, FPIA, DPV b) urine: HPLC c) whole blood: DPV 3) interferences: a) RIA/FPIA: cross reactivity with zidovudine-glucuronide b) DPV: lipemia c) AZT may interfere with antimicrobial sensitivity testing d) metronidazole may interfere with beta-hydroxyethyl- theophylline used as an internal standard in HPLC 4) macrocytosis is often marked (used to assess compliance) Mechanism of action: 1) thymidine analog 2) inhibits HIV reverse transcriptase 3) promotes platelet production [5] 4) inhibits platelet destruction [5] 5) AZT has antimicrobial activity against Enterobacteriaceae 6) transported by SLC28A1

Interactions

drug interactions drug adverse effects of antiretroviral agents

Related

Acquired Immuno-Deficiency Syndrome (HIV infection stage 3, AIDS) HIV-associated myositis

General

nucleoside reverse transcriptase inhibitor (NRTI)

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 1-1.5 HOURS therapeutic-range 150-270 NG/ML protein-binding 30% pregnancy-category C safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 17. American College of Physicians, Philadelphia 1998, 2006, 2015
  6. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  7. Sanford Guide to antimicrobial therapy 2001

Component-of

abacavir/lamivudine/zidovudine (Trizivir) lamivudine/nevirapine/zidovudine lamivudine/zidovudine (Combivir)