What are the side effects of Valacyclovir (Valtrex)?

From the Guidelines

Valacyclovir is generally well-tolerated, but it can cause side effects such as headache, nausea, and dizziness, and in rare cases, it may lead to more serious conditions like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), particularly in immunocompromised patients 1. The most common side effects of valacyclovir include:

• Headache
• Nausea
• Stomach pain
• Dizziness Some patients may also experience:
• Vomiting
• Diarrhea
• Fatigue More serious but less common side effects include:
• Allergic reactions (rash, itching, swelling)
• Unusual bleeding or bruising
• Yellowing of skin or eyes (jaundice)
• Changes in urination
• Extreme tiredness
• Confusion or seizures It is essential to note that valacyclovir can cause neurological reactions like confusion, hallucinations, or agitation, especially in elderly patients or those with kidney problems 1. Patients with kidney disease may need dose adjustments to prevent side effects, as the medication is eliminated through the kidneys, and the recommended dosage for patients with CKD or ESRD is as follows:
• CrCl 30–49 mL/min: 500 mg–1 g po q12h
• CrCl 10–20 mL/min: 500-1 g mg po q24h
• CrCl <10 mL/min: 500 mg po q24h 1. If severe side effects occur, patients should contact their healthcare provider immediately.

From the FDA Drug Label

The most common adverse reactions reported in at least 1 indication by greater than 10% of adult subjects treated with VALTREX and observed more frequently with VALTREX compared with placebo are headache, nausea, and abdominal pain. The only adverse reaction reported in greater than 10% of pediatric subjects aged less than 18 years was headache In clinical trials for the treatment of cold sores, the adverse reactions reported by subjects receiving VALTREX 2 grams twice daily (n = 609) or placebo (n = 609) for 1 day, respectively, included headache (14%, 10%) and dizziness (2%, 1%). In a clinical trial for the treatment of initial episodes of genital herpes, the adverse reactions reported by greater than or equal to 5% of subjects receiving VALTREX 1 gram twice daily for 10 days (n = 318) or oral acyclovir 200 mg 5 times daily for 10 days (n = 318), respectively, included headache (13%, 10%) and nausea (6%, 6%). In 3 clinical trials for the episodic treatment of recurrent genital herpes, the adverse reactions reported by greater than or equal to 5% of subjects receiving VALTREX 500 mg twice daily for 3 days (n = 402), VALTREX 500 mg twice daily for 5 days (n = 1,136), or placebo (n = 259), respectively, included headache (16%, 11%, 14%) and nausea (5%, 4%, 5%). In a clinical trial for the suppression of recurrent genital herpes infections, the adverse reactions reported by subjects receiving VALTREX 1 gram once daily (n = 269), VALTREX 500 mg once daily (n = 266), or placebo (n = 134), respectively, included headache (35%, 38%, 34%), nausea (11%, 11%, 8%), abdominal pain (11%, 9%, 6%), dysmenorrhea (8%, 5%, 4%), depression (7%, 5%, 5%), arthralgia (6%, 5%, 4%), vomiting (3%, 3%, 2%), and dizziness (4%, 2%, 1%). In HIV-1-infected subjects, frequently reported adverse reactions for VALTREX (500 mg twice daily; n = 194, median days on therapy = 172) and placebo (n = 99, median days on therapy = 59), respectively, included headache (13%, 8%), fatigue (8%, 5%), and rash (8%, 1%).

The side effects of valacyclovir include:

• Headache: reported in 14% to 35% of subjects
• Nausea: reported in 5% to 11% of subjects
• Abdominal pain: reported in 3% to 11% of subjects
• Dizziness: reported in 1% to 4% of subjects
• Fatigue: reported in 8% of HIV-1-infected subjects
• Rash: reported in 8% of HIV-1-infected subjects
• Depression: reported in 7% of subjects
• Arthralgia: reported in 6% of subjects
• Vomiting: reported in 3% of subjects
• Dysmenorrhea: reported in 8% of subjects 2
• Central nervous system effects: such as agitation, hallucinations, confusion, delirium, seizures, and encephalopathy, have been reported in both adult and pediatric patients 2

From the Research

Side Effects of Valacyclovir

• The most common side effect of valacyclovir is neurotoxicity, which can occur mainly in patients with advanced age and impaired renal function 3, 4.
• Symptoms of neurotoxicity include confusion, altered level of consciousness, hallucinations, agitation, and dysarthria 4.
• Valacyclovir can accumulate in patients with renal dysfunction, leading to severe side effects due to the prolonged half-life 3.
• The half-life of valacyclovir can be up to 14 hours in patients with end-stage renal disease, and hemodialysis may be necessary to improve rapid excretion of the drug and promote rapid recovery from neurotoxicity 3.
• Other side effects of valacyclovir may include phlebitis, local irritation, and reversible renal dysfunction 5.

Risk Factors for Side Effects

• Patients with end-stage renal disease are at higher risk of developing neurotoxicity due to valacyclovir 3, 4.
• Advanced age and impaired renal function are also risk factors for neurotoxicity 4.
• Failure to adjust the dose of valacyclovir according to renal function can lead to severe side effects 3, 4.

Treatment and Management

• Discontinuation of valacyclovir is the basis of treatment for neurotoxicity 4.
• Hemodialysis may be necessary in severe cases of neurotoxicity to improve rapid excretion of the drug and promote rapid recovery 3.
• Dose reduction is recommended in patients with impaired renal function to prevent side effects 5.