zidovudine; azidothymidine; AZT (Retrovir)
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Introduction
Tradenames: Retrovir, AZT.
Indications
- treatment of HIV infection
- for inclusion in all HAART regimens[5]
Dosage
- may be administered with or without food
- 200 mg PO TID or 300 mg PO BID
- 100 mg PO every 4 hours, including night dose if symptomatic
- doses of 300-400 mg daily are appropriate in patients with severe renal dysfunction
- 1-2 mg/kg IV infused over 1 hour every 4 hours
- children: 3 months to 13 years
- 1000 mg/day if thrombocytopenic
Capsule: 100 mg.
Tabs: 300 mg.
Dosage adjustment in renal failure
Table
| 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
- rapidly absorbed after oral administration
- elimination 1/2life is approximately 1.1-1.4 hours (1.4-3 hours ESRD)
- rapidly converted to a metabolite which is eliminated mainly through the kidneys
- AZT penetrates the blood brain barrier into the CSF
elimination via liver
elimination via kidney
1/2life = 1-1.5 hours
protein binding = 30 %
Adverse effects
- common (> 10%)
- anemia, leukopenia, severe headache, insomnia, nausea
- less common (1-10%)
- hyperpigmentation of nails (bluish-brown)
- uncommon (< 1%)
- other
- bone marrow suppression:
- 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
- acyclovir: in combination may lead to neurotoxicity
- ganciclovir in combination
- increased risk of neutropenia
- increased levels of AZT
- interferon-alpha: may increase the risk of hematologic toxicity
- probenecid: increases AZT concentration
- AZT increases levels of atovaquone
- increased risk of bone marrow toxicity in combination with:
- do not use with stavudine[5]
Laboratory
- specimen:
- methods:
- interferences:
- RIA/FPIA: cross reactivity with zidovudine-glucuronide
- DPV: lipemia
- AZT may interfere with antimicrobial sensitivity testing
- metronidazole may interfere with beta-hydroxyethyl- theophylline used as an internal standard in HPLC
- macrocytosis is often marked (used to assess compliance)
Mechanism of action
- thymidine analog
- inhibits HIV reverse transcriptase
- promotes platelet production[5]
- inhibits platelet destruction[5]
- AZT has antimicrobial activity against Enterobacteriaceae
- transported by SLC28A1
More general terms
Additional terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 17. American College of Physicians, Philadelphia 1998, 2006, 2015
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
- ↑ Sanford Guide to antimicrobial therapy 2001