Acetaminophen And Codeine and Zidovudine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Zidovudine
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.
Your pain medicine contains acetaminophen (the same active ingredient found in Tylenol), combined with codeine. The other medicine, zidovudine (Retrovir), is used to treat HIV. When these are taken together over a long time, there is a chance of two problems: a drop in a type of white blood cell that fights infection (called neutropenia), and extra stress on the liver.
The good news is that these effects have not been seen in everyone, and they mostly matter with regular, ongoing use rather than a single dose. Please talk with your pharmacist or doctor about how long you will be taking these together. Your care team can watch your blood counts and liver, and choose the safest plan for you.
Effect: Concurrent acetaminophen (here combined with codeine) and zidovudine may increase risk of neutropenia and hepatotoxicity. Direction is additive/overlapping toxicity, not a clear enzyme induction/inhibition effect; the precise mechanism is unknown.
- Onset: delayed (associated with chronic/multiple-dose exposure)
- Evidence: probable, though effects have not been consistently reported
- Severity: moderate
Management: Avoid chronic or repeated-dose acetaminophen in patients on zidovudine; consider aspirin or ibuprofen as alternatives where appropriate. If used together chronically, monitor CBC/WBC (neutrophil count) and LFTs, especially in malnourished patients.
What happens
Neutropenia; acetaminophen toxicity (hepatotoxicity)
Interaction Deep Dive
When acetaminophen is given together with zidovudine, the combination may lead to neutropenia or hepatotoxicity681. Nevertheless, such outcomes have not been reported consistently745.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medications as prescribed unless your care team tells you otherwise, but do raise this combination with your pharmacist or doctor, especially if you expect to use the acetaminophen/codeine product for more than a few days.
- The concern applies mainly to regular, ongoing acetaminophen use, not a one-time dose.
- Your team may suggest a different pain reliever (such as aspirin or ibuprofen) if that is appropriate for you.
- If both are continued together, your team may monitor your blood counts and liver function more closely, particularly if you are underweight or poorly nourished.
Do not stop either medicine on your own; let your care team guide any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
6 reports — tap to read
a) The literature contains contradictory accounts regarding interactions between acetaminophen and zidovudine. In a double-blind, placebo-controlled study of zidovudine, neutropenia was noted, and it appeared more often in participants who were taking zidovudine and acetaminophen at the same time 1. Statistical significance for this interaction was not reported, however. In addition, granulocytopenia occurs with zidovudine therapy itself and with the disease 2. Both agents are glucuronidated in the liver, and competitive glucuronide conjugation was proposed as a possible mechanism that might inhibit metabolism of either drug 3. In investigations of short-term concurrent administration, though, acetaminophen neither raised zidovudine concentrations nor lowered zidovudine glucuronidation 45.
b) While one instance of acute acetaminophen-related hepatotoxicity has been reported during concurrent use 6, in another instance a patient already on long-term acetaminophen started zidovudine therapy and, after eight months of concurrent use, had no acetaminophen toxicity 7. Malnutrition (possibly related to the disease) leading to reduced hepatic glutathione reserves was proposed as a contributing factor in the case of acetaminophen-associated hepatotoxicity 68.
c) Serum concentrations of zidovudine and its metabolite were assessed in HIV-infected patients receiving regular zidovudine doses both with and without acetaminophen 5. In every patient, serum zidovudine and metabolite levels were comparable whether or not acetaminophen was given. Short-term acetaminophen use at moderate doses below 3.5 grams per day does not raise serum zidovudine levels.
d) A 43-year-old man with HIV-1 infection had been using acetaminophen (together with codeine and diazepam) for over three years when he started zidovudine therapy 7. He took 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 may have sped up zidovudine absorption, no other effect on zidovudine pharmacokinetics was observed. In this case, zidovudine showed no apparent effect on acetaminophen pharmacokinetics.
e) In a double-blind, placebo-controlled trial of oral zidovudine involving 282 AIDS/ARC patients, myelosuppression was greater among participants receiving zidovudine and acetaminophen concurrently than among those receiving zidovudine alone 1. Bone marrow suppression was not increased in patients taking zidovudine together with aspirin compared with those on zidovudine only. However, statistical significance and supporting data were not reported for patients using zidovudine concurrently with other drugs.
f) In a study of 27 patients with AIDS or AIDS-related complex, acetaminophen did not affect the clearance of zidovudine. Acetaminophen was given as 325 mg to 650 mg for three to seven days. Zidovudine was given at a dose of 200 mg every four hours. Acetaminophen impaired neither the clearance of zidovudine nor the formation of the zidovudine glucuronide conjugate 4.
Common questions
Can I take Acetaminophen And Codeine and Zidovudine together?
Regular, long-term use of acetaminophen (in your codeine product) alongside zidovudine may raise the risk of low white blood cells and liver stress, so check with your pharmacist or doctor about how long you'll take them together and whether an alternative pain reliever fits you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Zidovudine 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 is the Acetaminophen And Codeine and Zidovudine interaction managed?
Keep taking both medications as prescribed unless your care team tells you otherwise, but do raise this combination with your pharmacist or doctor, especially if you expect to use the acetaminophen/codeine product for more than a few days. The concern applies mainly to regular, ongoing acetaminophen use, not a one-time dose. Your team may suggest a different pain reliever (such as aspirin or ibupr… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Zidovudine 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. PubMed
- 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. PubMed
- 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. PubMed
- Ameer B: Acetaminophen hepatotoxicity augmented by zidovudine (letter). Am J Med 1993; 95:342. PubMed
Keep reading about Acetaminophen And Codeine
Keep reading about Zidovudine
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