Azt

Zidovudin, Retrovir™; component of Trizivir™, Combivir™ Approved dose: 250 or 300 mg BID

Metabolism: Glucuronidation pathway, Elimination: renal

Drugs

Interactions

Comments

NRTIs

D4T [1-3]

Antagonism

Avoid combination.

NNRTIs

No significant interaction

Antibiotics

Atovaquone

AZT T 35 % ± 23 %

Monitor for AZT side-effects.

Clarithromycin [4]

AZT 1 10-25 %

Take 2 - 4 h apart,

monitor for AZT efficacy.

Cotrimoxazol [2]

Haematotoxicity T

Dapsone [5]

Haematotoxicity T

Antiepileptics

Fosphenytoin, pheny-

Clearance of AZT | 30 % and

Monitor for AZT side-effects,

toin [2]

phenytoin Tl

TDM of phenytoin.

Valproic acid [2]

AZT T 79 %

Monitor for AZT side-effects.

Antifungal drugs

Fluconazole [2]

AZT T 74 %

Monitor for AZT side-effects.

Antimalarials

Pyrimethamine [2]

Increased hematotoxicity T

Antiviral Drugs

Acyclovir [7]

Case report: profound lethargy

Cidofovir [8]

Increased hematotoxicity T

See: Probenecid.

Foscarnet [6]

Increased risk of anaemia T (less

risky than with ganciclovir)

Ganciclovir [9-10],

Increased hematotoxicity T

Avoid combination. Theo-

Valganciclovir

retical alternative:

Foscarnet + AZT.

Ganciclovir +DDI.

Interferon [11]

Increased hematotoxicity T

If necessary, reduce AZT

dose.

Ribavirin [12]

In vitro AZT-antagonism, in vivo

Avoid combination.

case reports of increased viral load,

increased risk of mitochondrial

toxicity (e.g. lactic acidosis)

Cytotoxic drugs

Doxorubicin [2] and a

Increased hematotoxicity T

Avoid combination or con-

lot of other cytotoxic

trol haemogram closely.

drugs.

Monitor kidney function.

Substitution

Methadone [14] AZT | 41 % Monitor for AZT side-effects.

Substitution

Methadone [14] AZT | 41 % Monitor for AZT side-effects.

Uricosuric drug

Probenecid [13]

Monitor for AZT side-effects. Take 50% of AZT dose when combined with cidofovir and probenecid.

References i. 2.

Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2004.

Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

Product information: Retrovir™. Glaxo Smithkline.

Polis MA, Piscitelli SC, Vogel S, et al. Chlarithromycin lowers plasma zidovudine levels in persons with HIV-infection. Antimicrob Agents Chemother 1997; 41: 1709-14. http://www.amedeo.com/lit.php?id=9257746

US Department of Health and Human Services (DHHS) and National Institutes of Health (NIH). The living document: Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Retrieved April 14, 2004. www.aidsinfo.nih.gov. Foscavir™. Astra Zeneca.

Cooper DA, Pehrson PO, Pedersen C, et al. The efficacy and safety of zidovudine alone or as co-therapy with acyclovir for the treatment of AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group. AIDS 1993; 7: 197-207. http://www.amedeo.com/lit.php?id=8096703

Bach MC. Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS [letter]. N Engl J Med 1987; 317: 547. http://www.amedeo.com/lit.php?id=3468354

Hochster H, Dieterich D, Bozzette S, et al. Toxicity of combined ganciclovir and zidovudine for cyto-megalovirus disease associated with AIDS. Ann Intern Med 1990; 113: 111-7. http://www.amedeo.com/lit.php?id=2163228

Cimoch PJ, Lavelle J, Pollard R, et al. Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine and probenecid in HIV-infected subjects. JAIDS 1998; 17: 227-34. http://www.amedeo.com/lit.php?id=9495222

Ruedy J, Schlechter M, Montaner JS. Zidovudine for early HIV-infection: who, when, and how? Ann Intern Med 1990; 112: 721-3.

Sim SM, Higgard PG, Sales SD, et al. Effect of ribavirin on zidovudine efficacy and toxicity in vitro: a concentration-dependent interaction. AIDS Res Hum Retr 1998; 14: 1661-7.

Kornhauser DM, Petty BG, Hendrix CW, et al. Probenecid and zidovudine metabolism. Lancet 1989; 2: 473-5. http://www.amedeo.com/lit.php?id=2570186

Antoniou T, Lin-in Tseng. Interactions between recreational drugs and antiretroviral agents. Ann Pharmacother 2002; 36: 1598-613. http://www.amedeo.com/lit.php?id=12243611

Roszko PJ, Curry K, Brazina B, et al. Standard doses of efavirenz, zidovudine, tenofovir, and didano-sine may be given with tipranavir/ritonavir. Abstract 865, 2nd IAS 2003, Paris. http://www.aegis.com/conferences/2ndIASHIVPT /865.html

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