Acyclovir Topical and Zidovudine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Zidovudine
Acyclovir Topical
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
Increased lethargy and fatigue
Interaction Deep Dive
In a patient previously taking acyclovir (250 mg every 8 hours) for severe herpetic stomatitis, the addition of zidovudine resulted in lethargy and fatigue. However, it has been demonstrated that acyclovir does not alter the disposition of zidovudine143.
Why it happens (mechanism)
Unknown
Literature reports
3 reports — tap to read
a) Concomitant administration of acyclovir and zidovudine has been reported to result in severe drowsiness and lethargy in a 30-year-old patient with Pneumocystis pneumonia. The patient developed a fever while on cotrimoxazole therapy, which persisted despite discontinuation. Intravenous acyclovir therapy (250 mg every eight hours) was begun for the treatment of herpes simplex infection which occurred during the febrile episode. Zidovudine therapy (200 mg PO every 4 hours) was started 3 days after acyclovir therapy. Within 1 hour the patient demonstrated fatigue and lethargy and was barely able to stay awake. Improvement was seen when acyclovir was switched to the oral form (200 mg every 4 hours). Discontinuation of acyclovir resulted in a return to baseline alertness. Rechallenge confirmed these effects 1.
b) A regimen of zidovudine and acyclovir was administered to eight patients with AIDS or AIDS-related complex. The pharmacokinetics of the two drugs were independent of each other. Six of the patients received the drug combination for at least 10 weeks; all had increased numbers of T4 lymphocytes and two of three assessable patients had reversal of anergy. Two patients, P24 antigen-positive at entry, became negative with treatment. The authors suggest that this drug combination can be tolerated in patients with severe HIV infection 2.
c) A Phase I study of zidovudine (500 mg daily) plus acyclovir (2 g or 4 g daily) was performed in asymptomatic patients infected with HIV to investigate pharmacokinetics, safety, tolerance, and immunologic effects of the combination. Pharmacokinetic analysis on 20 patients over a 24-week period showed no drug interaction. The combination was generally well tolerated, and hematologic parameters remained stable through 24 weeks. There were no significant changes in total lymphocytes, T4 lymphocyte, overall skin test reactivity, or ability to culture virus from peripheral blood 3.
Common questions
Can I take Acyclovir Topical and Zidovudine together?
Increased lethargy and fatigue Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acyclovir Topical and Zidovudine interaction?
It is rated minor. Usually limited clinical impact.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Acyclovir Topical 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 (4)
- Bach MC: Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS (letter). N Engl J Med 1987; 316:547. DOI
- Surbone A, Yarchoan R, McAtee N, et al: Treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex with a regimen of 3'-azido-2',3'-dideoxythymidine (azidothymidine or zidovudine) and acyclovir. Ann Intern Med 1988; 108:534-540. DOI
- Hollander H, Lifson AR, Maha M, et al: Phase I study of low-dose zidovudine and acyclovir in asymptomatic human immunodeficiency virus seropositive individuals. Am J Med 1989; 87:628-632. DOI
- Morse GD, Lechner JL, Santora JA, et al: Zidovudine update: 1990. DICP 1990; 24:754-760. PubMed
Keep reading about Zidovudine
Keep reading about Acyclovir Topical
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