Acetaminophen with Zidovudine Interaction Details
Brand Names Associated with Zidovudine
- AZT
- Retrovir®
- ZDV
- Zidovudine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 25, 2024
Interaction Effect
Neutropenia; acetaminophen toxicity (hepatotoxicity)
Interaction Summary
Coadministration of acetaminophen with zidovudine may result in neutropenia or hepatotoxicity[1][2][3]. However, these effects have not been consistently reported [4][5][6].
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Avoid chronic/multiple-dose acetaminophen use in patients on zidovudine therapy. Alternatively, aspirin or ibuprofen should be considered in place of acetaminophen. However, if chronic acetaminophen and zidovudine are to be given concurrently, monitor not only white blood count but also liver function tests, particularly in malnourished patients.
Mechanism Of Interaction
Unknown
Literature Reports
A) Conflicting reports on the interactions between acetaminophen and zidovudine have appeared in the literature. Neutropenia was reported in a double-blind, placebo-controlled trial of zidovudine , with a higher frequency of neutropenia apparently occurring in subjects taking concurrent zidovudine and acetaminophen [3]. However, statistical significance was not reported for this interaction. Furthermore, granulocytopenia is associated with the zidovudine treatment itself, as well as with the disease [7]. Both drugs undergo glucuronidation in the liver and competitive glucuronide conjugation was suggested as a possible factor inhibiting either drug's metabolism [8]. In studies of short-term concurrent use, however, acetaminophen did not increase zidovudine concentrations or decrease zidovudine glucuronidation [5][6].
B) Although a case of acute acetaminophen-related hepatotoxicity has been described with concurrent use [1], in another case, a patient on long-term acetaminophen began zidovudine therapy and after eight months of concurrent usage experienced no acetaminophen toxicity [4]. Malnutrition (perhaps disease-related) resulting in decreased hepatic reserves of glutathione was suggested to be a factor in the case of acetaminophen-associated hepatotoxicity [1][2].
C) Serum zidovudine and metabolite levels were measured in HIV-infected patients taking regular doses of zidovudine with and without acetaminophen [6]. In all patients, serum levels of zidovudine and its metabolite were similar with and without acetaminophen administration. Short-term use of acetaminophen in moderate doses of less than 3.5 grams daily does not increase serum zidovudine levels.
D) A 43-year-old man with HIV-1 infection had used acetaminophen (along with codeine and diazepam) for more than three years when he began zidovudine therapy [4]. He used concurrent zidovudine 100 mg every six hours and acetaminophen 500 mg every four hours for eight months without experiencing zidovudine or acetaminophen toxicity. Although acetaminophen use might have accelerated the absorption of zidovudine, no other effect on zidovudine pharmacokinetics was seen. Zidovudine had no apparent effect on acetaminophen pharmacokinetics in this case.
E) In a double-blind, placebo-controlled trial of oral zidovudine (in 282 AIDS/ARC patients, myelosuppression was greater in participants receiving concurrent zidovudine and acetaminophen compared with those receiving zidovudine alone [3]. Bone marrow suppression was not increased in patients receiving concurrent zidovudine and aspirin compared with subjects on zidovudine only. However, statistical significance and supporting data were not reported for patients taking zidovudine concomitantly with other drugs.
F) In a study of 27 patients with AIDS or AIDS-related complex, acetaminophen did not interfere with the clearance of zidovudine. Acetaminophen was administered as 325 mg to 650 mg for three to seven days. Zidovudine was administered at a dose of 200 mg every four hours. Neither clearance of zidovudine nor formation of zidovudine glucuronide conjugate was impaired by acetaminophen [5].
References
1 ) Shriner K & Bidwell Goetz M: Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine. Am J Med 1992; 93:94-96.
2 ) Ameer B: Acetaminophen hepatotoxicity augmented by zidovudine (letter). Am J Med 1993; 95:342.
3 ) Richman DD, Fischl MA, Grieco MH, et al: The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: a double-blind, placebo-controlled trial. N Engl J Med 1987; 317:192-197.
4 ) Burger DM, Meenhorst, PL, et al: Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy. Ann Pharmacother 1994; 28:327-330.
5 ) Sattler FR, Ko R, Antoniskis D, et al: Acetaminophen does not impair clearance of zidovudine. Ann Intern Med 1991; 114:937-940.
6 ) Steffe EM, King JH, Inciardi JF, et al: The effect of acetaminophen on zidovudine metabolism in HIV-infected patients. J Acquir Immune Defic Syndr 1990; 3:691-694.
7 ) Hewitt RG, Morse GD, Lawrence WD, et al: Pharmacokinetics and pharmacodynamics of Granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex. Antimicrob Agents Chemother 1993; 37:512-522.
8 ) Morse GD, Lechner JL, Santora JA, et al: Zidovudine update: 1990. DICP 1990; 24:754-760.
Zidovudine Overview
-
Zidovudine is used along with other medications to treat human immunodeficiency virus (HIV) infection. Zidovudine is given to HIV-positive pregnant women to reduce the chance of passing the infection to the baby. Zidovudine is in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). It works by decreasing the amount of HIV in the blood. Although zidovudine does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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The prescribing information for each drug, as published on DailyMED, is also used.
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