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Acyclovir Side Effects

In Summary

More frequently reported side effects include: nausea, phlebitis, vomiting, and inflammation at injection site. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to acyclovir: buccal mucosa tablet

In addition to its needed effects, some unwanted effects may be caused by acyclovir. In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking acyclovir:

Less common:
  • Canker sores
  • pain in the gums
  • sores, ulcers, or white spots on the tongue or inside the mouth

Minor Side Effects

Some of the side effects that can occur with acyclovir may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common:
  • Flushing or redness of the skin
  • rash
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
  • unusually warm skin

For Healthcare Professionals

Applies to acyclovir: buccal tablet, compounding powder, intravenous powder for injection, intravenous solution, oral capsule, oral suspension, oral tablet


Gastrointestinal side effects have been the most frequently reported side effects, and include nausea, vomiting, abdominal pain, and diarrhea.

Nausea and vomiting have been reported with oral and intravenous administration, and have preceded neurotoxicity and nephrotoxicity. Gagging and anorexia have also been reported.[Ref]


Renal side effects have included renal failure, renal pain (may be associated with renal failure), elevated blood urea nitrogen, elevated serum creatinine, and hematuria. Renal effects generally are transient and resolve over several days following discontinuation of therapy; however fatal renal failure has occurred. Renal damage is most commonly due to crystallization of the drug in the renal tubules. Acute tubular necrosis and interstitial nephritis have also been reported.[Ref]

Transient renal dysfunction has been reported with both oral and intravenous acyclovir therapy. Crystallization of the drug in renal tubules is thought to be the mechanism for the development of renal dysfunction, based on findings of crystalluria in several case reports and at least one prospective study.

Elderly or renally impaired patients are at greater risk for developing neurotoxicity and further deterioration in renal function.[Ref]

Nervous system

Nervous system side effects have included aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, delirium, delusions, disorientation, dizziness, EEG changes, abnormal cerebrospinal fluid findings, encephalopathy, focal neurological signs, hallucinations, headache, insomnia, irritability, lightheadedness, major depression, mania, myoclonus, obtundation, paresthesia, psychosis, seizure, somnolence, tremors, and Cotard's syndrome. Neurotoxicity generally develops early in acyclovir treatment and has most commonly been reported in patients with renal failure, the elderly, and in patients following bone marrow transplant. It is thought to be associated with high serum concentrations of acyclovir. Guillain Barre syndrome has been reported in at least one patient receiving acyclovir prophylaxis following allogeneic marrow transplantation.[Ref]

Acyclovir neurotoxicity is almost exclusively seen in patients with renal failure. These patients may have longstanding chronic renal failure or acute failure associated with acyclovir. Although more commonly seen with intravenous administration of larger doses, neurotoxicity has also been reported in patients receiving oral doses of acyclovir. Following discontinuation of acyclovir, mental status recovers within about a week. Several patients with chronic renal failure exhibiting neurotoxicity improved dramatically following hemodialysis. In one study of renal transplant patients receiving oral acyclovir therapy, one patient developed neurotoxicity, manifested as disorientation, confusion and myoclonus. The symptoms responded to a decrease in dosage. Three other case reports have also described neurologic symptoms, including visual hallucinations, delusions, mania, tremors, myoclonus and EEG changes, which improved following discontinuation of intravenous acyclovir. Rechallenge in one case using a lower dosage resulted in no sequelae.[Ref]


Local adverse effects associated with intravenous administration of acyclovir have included inflammation or phlebitis at the injection site. Phlebitis is more common when concentrated solutions (greater than 7 mg/mL) are administered. Skin eruptions have been reported at venipuncture sites and tissue necrosis has occurred after infiltration into extravascular tissues.[Ref]


Cardiovascular side effects have included hypotension.[Ref]


Dermatologic side effects have included alopecia, erythema multiforme, hives, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, and urticaria.[Ref]


Hematologic and lymphatic side effects have included anemia, disseminated intravascular coagulation, hemolysis, leukocytoclastic vasculitis, leukocytosis, leukopenia, lymphadenopathy, neutropenia, neutrophilia, thrombocytosis, thrombocytopenia, and pancytopenia.[Ref]


Hepatic side effects have included elevated liver function tests, hepatitis, hyperbilirubinemia, and jaundice.[Ref]


Hypersensitivity reactions have included anaphylaxis.[Ref]


Ocular side effects have included visual abnormalities.[Ref]


Musculoskeletal side effects reported have included myalgia and dysarthria.[Ref]


Other side effects have included angioedema, fever, malaise, pain, fatigue, peripheral edema, and increased lactate dehydrogenase.[Ref]


Genitourinary side effects have included crystalluria.[Ref]


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Not all side effects for acyclovir may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

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