How Does Acyclovir Make You Feel? A Guide to Sensations and Side Effects

October 9, 2025 •

3 min read

Daily suppressive therapy with acyclovir can reduce the subclinical shedding of the herpes simplex virus (HSV) by as much as 94% [1.8.1]. While highly effective, it's important to understand the full spectrum of how does acyclovir make you feel, from common adjustments to rare but serious reactions.

Quick Summary

Acyclovir can cause a range of feelings, most commonly a general sense of being unwell (malaise), nausea, diarrhea, and headaches [1.2.4]. More serious, though less frequent, effects can include kidney problems and neurological changes like confusion [1.4.3].

Key Points

Common Feelings: The most common feelings are general malaise (feeling unwell), nausea, vomiting, diarrhea, and headache [1.2.4, 1.2.5].
Energy Levels: Acyclovir can cause unusual tiredness, fatigue, or weakness in some individuals [1.2.1, 1.5.1].
Neurological Effects: Rarely, it can cause confusion, agitation, dizziness, hallucinations, or difficulty speaking, particularly in the elderly or those with kidney issues [1.4.1, 1.5.2].
Kidney Health is Key: Staying well-hydrated is crucial to prevent potential kidney injury, a serious side effect marked by decreased urination or back pain [1.4.2, 1.9.3].
Formulation Matters: Oral acyclovir is linked to systemic side effects like nausea, while topical versions cause localized stinging or burning [1.6.1, 1.6.5].
Temporary Effects: For most people, side effects are temporary and may disappear as the body adjusts to the medicine or soon after stopping it [1.11.2].
Patient Ratings: Acyclovir generally has high patient satisfaction, with a Drugs.com rating of 8.2 out of 10, where 77% of users reported a positive experience [1.3.1].

Understanding Acyclovir and Its Purpose

Acyclovir is a powerful antiviral drug primarily used to treat infections caused by the herpes simplex virus (HSV) types 1 and 2, and the varicella-zoster virus (VZV) [1.8.4]. These viruses are responsible for conditions like genital herpes, cold sores, shingles, and chickenpox. Acyclovir works by incorporating itself into the viral DNA, which stops the virus from replicating and spreading within the body [1.8.4]. It is a synthetic purine nucleoside analog, and while it doesn't cure the infections, it is highly effective at managing symptoms, reducing the severity and duration of outbreaks, and, in some cases, preventing future episodes through suppressive therapy [1.8.1, 1.8.4]. It is available in several forms, including oral tablets or capsules, topical creams, and intravenous (IV) injections for more severe cases [1.6.1].

Common Sensations and Side Effects

For many people, taking oral acyclovir may not cause any noticeable side effects. However, when side effects do occur, they are often mild and temporary, resolving as the body adjusts to the medication [1.11.2].

The most frequently reported feelings associated with oral acyclovir include:

General Malaise: A common feeling of general discomfort, weakness, or being unwell is often reported [1.2.4].
Gastrointestinal Issues: Nausea, vomiting, and diarrhea are among the most common side effects [1.2.5]. Taking the medication with food can sometimes help alleviate these symptoms.
Headache: Headaches are another frequently mentioned side effect for those taking oral acyclovir [1.2.5].
Fatigue: Some individuals may experience unusual tiredness or weakness while on the medication [1.2.1, 1.5.1].

Topical acyclovir, applied directly to sores, typically has more localized side effects, such as mild pain, burning, or stinging at the application site [1.6.5]. Intravenous (IV) acyclovir, used in hospital settings, is most associated with inflammation or phlebitis (vein inflammation) at the injection site [1.6.1].

Less Common and Serious Side Effects

While rare, acyclovir can cause more severe side effects that require immediate medical attention. It's crucial to be aware of these potential reactions.

Neurological and Mood Changes

In some cases, acyclovir can affect the central nervous system, leading to a range of neurological and psychological symptoms. Elderly patients and those with pre-existing kidney disease are more susceptible to these effects [1.5.2, 1.4.3]. Symptoms can include:

Confusion, agitation, or aggressive behavior [1.4.1, 1.5.1]
Dizziness and drowsiness [1.5.2]
Hallucinations (seeing or hearing things that are not there) [1.4.2]
Difficulty speaking or slurred speech [1.4.1]
Shakiness, tremors, or unsteady movements [1.4.1]

Kidney-Related Effects

Kidney injury is a significant potential side effect, particularly with IV acyclovir or in patients who are dehydrated or have prior kidney problems [1.4.2, 1.4.3]. Acyclovir can form crystals in the kidneys, potentially leading to damage. Staying well-hydrated by drinking plenty of water is essential to help prevent this. Signs of kidney problems include:

Decreased urination [1.4.1]
Swelling in the hands, feet, or ankles [1.4.2]
Pain in the lower back or side (kidney area) [1.9.3]
Blood in the urine [1.4.1]

Comparison: Acyclovir vs. Valacyclovir

Valacyclovir is a prodrug of acyclovir, meaning it is converted into acyclovir in the body after being ingested [1.7.4]. This allows for less frequent dosing. While their side effect profiles are very similar, some differences exist.


Feature	Acyclovir	Valacyclovir
Common Side Effects	Nausea, malaise, diarrhea, headache [1.2.4, 1.2.5]	Nausea, stomach pain, headache, dizziness [1.7.1]
Dosing Frequency	Typically 3-5 times per day for active outbreaks	Typically 1-2 times per day [1.6.3, 1.7.3]
GI Tolerability	Higher frequency of doses may lead to more gastrointestinal irritation [1.7.3]	Generally better tolerated regarding GI side effects due to lower dosing frequency [1.7.2]
Serious Side Effects	Kidney problems, neurological effects, rare blood disorders [1.4.4, 1.4.5]	Very similar to acyclovir, including kidney problems and neurological effects [1.7.1, 1.7.4]

Conclusion

How acyclovir makes you feel can range from completely normal to experiencing mild, temporary discomforts like nausea and headache [1.2.4, 1.2.5]. Most people tolerate the medication well [1.3.1]. However, it is vital to be aware of the potential for more serious side effects, especially neurological changes and signs of kidney distress [1.4.1, 1.4.2]. Staying hydrated and communicating openly with a healthcare provider about any unusual or persistent symptoms is key to using acyclovir safely and effectively. Side effects are often temporary and may resolve as your body adjusts or after the treatment course is complete [1.11.1, 1.11.2].

For more detailed information, consult a trusted medical source such as MedlinePlus [1.4.1].

Frequently Asked Questions

Yes, unusual tiredness or weakness is a possible side effect of taking acyclovir [1.2.1]. This feeling of fatigue is also described as malaise [1.2.4].

Yes, although less common, acyclovir can cause mood or mental changes like confusion, agitation, aggressive behavior, and even hallucinations [1.4.1, 1.5.5].

For many people, side effects are temporary and may go away during treatment as the body adjusts, or shortly after the medication is stopped [1.11.1, 1.11.2].

The most common side effects are nausea, vomiting, diarrhea, and headache [1.2.5]. A general feeling of discomfort or malaise is also frequently reported [1.2.4].

Dizziness can be a side effect of acyclovir [1.2.4]. It may be more likely in elderly patients [1.5.2]. If dizziness is severe, you should contact your doctor.

Yes, you should contact your doctor immediately. Kidney pain, along with changes in urination, can be a sign of a serious side effect affecting your kidneys [1.4.2, 1.9.3]. Drinking plenty of water can help reduce this risk.

Using alcohol with certain medicines may cause interactions. You should discuss the use of your medicine with alcohol with your healthcare professional [1.10.2].