Zidovudine and Acetaminophen: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Zidovudine
Acetaminophen
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Neutropenia; acetaminophen toxicity (hepatotoxicity)
Interaction Deep Dive
Coadministration of acetaminophen with zidovudine may result in neutropenia or hepatotoxicity681. However, these effects have not been consistently reported 745.
Why it happens (mechanism)
Unknown
Literature reports
6 reports — tap to read
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 1. However, statistical significance was not reported for this interaction. Furthermore, granulocytopenia is associated with the zidovudine treatment itself, as well as with the disease 2. Both drugs undergo glucuronidation in the liver and competitive glucuronide conjugation was suggested as a possible factor inhibiting either drug's metabolism 3. In studies of short-term concurrent use, however, acetaminophen did not increase zidovudine concentrations or decrease zidovudine glucuronidation 45.
b) Although a case of acute acetaminophen-related hepatotoxicity has been described with concurrent use 6, in another case, a patient on long-term acetaminophen began zidovudine therapy and after eight months of concurrent usage experienced no acetaminophen toxicity 7. Malnutrition (perhaps disease-related) resulting in decreased hepatic reserves of glutathione was suggested to be a factor in the case of acetaminophen-associated hepatotoxicity 68.
c) Serum zidovudine and metabolite levels were measured in HIV-infected patients taking regular doses of zidovudine with and without acetaminophen 5. 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 7. 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 1. 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 4.
Common questions
Can I take Zidovudine and Acetaminophen together?
Neutropenia; acetaminophen toxicity (hepatotoxicity) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Zidovudine and Acetaminophen interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Zidovudine or Acetaminophen need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (8)
- 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. DOI
- 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. PubMed
- Morse GD, Lechner JL, Santora JA, et al: Zidovudine update: 1990. DICP 1990; 24:754-760. DOI
- Sattler FR, Ko R, Antoniskis D, et al: Acetaminophen does not impair clearance of zidovudine. Ann Intern Med 1991; 114:937-940. PubMed
- 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.
- Shriner K & Bidwell Goetz M: Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine. Am J Med 1992; 93:94-96. PubMed
- Burger DM, Meenhorst, PL, et al: Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy. Ann Pharmacother 1994; 28:327-330. DOI
- Ameer B: Acetaminophen hepatotoxicity augmented by zidovudine (letter). Am J Med 1993; 95:342. PubMed
Keep reading about Zidovudine
Keep reading about Acetaminophen
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