Valacyclovir

Is valacyclovir safe?

Yes, for nearly everyone it is prescribed for. Valacyclovir, sold as Valtrex and called valaciclovir in the UK, treats cold sores, genital herpes, shingles and chickenpox. It turns into acyclovir in the body, an antiviral used since the early 1980s, and its record is long and clean. In 2024 it filled about 6.9 million US prescriptions (ClinCalc). We score it 88, close to amoxicillin (91) and among the safest medicines we rate.

The one thing that really matters is the kidneys. Valacyclovir leaves the body through them, and when they are weak, from age or disease, a normal dose can build up and cause confusion, hallucinations or kidney injury. The fix is simple: a lower dose. That makes it important for your prescriber to know your kidney function and for you to drink enough water.

What side effects are common

In the trials behind the label, side effects were mostly mild and close to placebo:

Most people taking a short course for a cold sore or a week for shingles notice nothing at all.

Confusion, hallucinations and the kidneys

The label warns that agitation, hallucinations, confusion, seizures and a brain disorder called encephalopathy have been reported, more often in older people and in people with kidney disease given a dose too high for their kidneys. A 2021 review of 119 published cases of acyclovir or valacyclovir neurotoxicity found that 83% had kidney impairment, 57% had end-stage kidney disease, and 60% had been given more than the kidney-adjusted dose. Symptoms began after about three days on average, and three in four people recovered within a week of stopping.

Kidney injury itself is uncommon at normal doses. A study of 76,269 older Ontarians given a short course of acyclovir or valacyclovir found hospital admission for acute kidney injury in 0.27%, the same as with famciclovir, an antiviral with no known kidney toxicity. In older adults who already had chronic kidney disease, though, a 2024 Ontario study found that starting at a higher dose rather than a lower one nearly quadrupled the risk of kidney injury confirmed by blood tests (0.83% against 0.22%), although hospital visits coded for confusion or kidney injury did not clearly rise.

The label gives a dose table by kidney function. For shingles, for example, the usual 1 g three times a day falls to 1 g twice a day, once a day or 500 mg once a day as kidney function drops.

Interactions and the 2025 label change

The current Valtrex label says no clinically significant drug or food interactions are known, which is unusual and part of why it scores well. The caution is with other drugs that can strain the kidneys, and with dehydration.

In November 2025 the FDA-approved label added severe skin reactions as a warning and a contraindicationContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS and AGEP have been reported since approval. They are rare, but a painful rash with blisters or sores in the mouth or eyes means stopping the drug and getting urgent care. The label also warns of a blood clotting disorder (TTP/HUS) seen in trials of 8 g a day, many times the usual dose, in people with advanced HIV or transplants.

Who should be careful

• People over 65, and anyone with kidney disease or on dialysis: the dose must be adjusted.
• People taking other drugs that can harm the kidneys, or who are dehydrated.
• Anyone who has had a severe skin or allergic reaction to valacyclovir or acyclovir.
• People with advanced HIV or a transplant on high doses.

Start treatment early: within 72 hours of a shingles rash (best within 48), at the first tingle of a cold sore, and within a day of a genital herpes recurrence. For shingles pain that lingers, see our page on gabapentin, a common treatment for nerve pain.

How we scored it

Dependence (98), interactions (92) and track record (92) are strong. Serious side effects (85) and overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (82) are slightly lower because the drug builds up when the kidneys are weak, causing the rare neurotoxicity and kidney cases. Regulatory warnings (82) reflects the 2025 severe skin reaction warning, with no boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary or restrictions.