Side Effects of Valtrex (valacyclovir)

Valtrex (valacyclovir) is a type of antiviral drug called a nucleoside analog which is active against the herpes viruses. It is used to treat infections with shingles (herpes zoster), genital herpes (herpes simplex genitalis), and cold sores (herpes labialis). 

Valtrex stops the spread of herpes virus in the body by preventing the replication of viral DNA that is necessary for viruses to multiply. Valtrex is actually a “prodrug,” in that it is not active itself. Rather, it is converted to acyclovir in the body, and it is the acyclovir that is active against the viruses. (Acyclovir itself is available as a topical, oral and intravenous medication.) 

Valtrex, therefore, is active against the same viruses as acyclovir, but Valtrex has a longer duration of action than acyclovir, and, therefore, can be taken fewer times each day.

Common side effects of Valtrex include:

• headache,
• nausea,
• vomiting,
• abdominal pain,
• cold symptoms,
• increased liver enzymes,
• reduction of white blood cells,
• diarrhea,
• rash,
• joint pain, and
• dizziness.

Serious side effects of Valtrex include:

• agitation,
• hallucinations,
• confusion,
• delirium,
• depression,
• increased heart rate,
• seizures,
• encephalopathy (a disorder of the brain),
• decreased number of blood platelets,
• increased heart rate, and
• high blood pressure (hypertension).

Drug interactions of Valtrex include:

• probenecid and cimetidine, which may reduce the kidney's clearance of Valtrex, leading to higher concentrations in the blood. This may lead to side effects of Valtrex. 

There has been no adequate evaluation of Valtrex in pregnant women. The incidence of birth defects in women taking acyclovir is about the same as in the general population. Valtrex should only be used during pregnancy when the benefits to the mother outweigh risks to the fetus. 

It is unknown if Valtrex is excreted into breast milk. Among women taking acyclovir, concentrations of acyclovir in breast milk are about four times higher than in the mother's blood. The safety of Valtrex in breastfeeding infants has not been established. Methods other than breastfeeding should be considered if Valtrex must be taken while nursing.

The side effect profile of Valtrex is similar to that of acyclovir (Zovirax).

Common side effects are:

• Headache
• Nausea
• Vomiting
• Abdominal pain
• Cold symptoms
• Increased liver enzymes
• Reduction of white blood cells

Other important side effects are:

• Diarrhea
• Rash
• Joint pain
• Dizziness

More serious side effects include central nervous system side effects which are more likely to happen in the elderly, for example:

• Agitation
• Hallucinations
• Confusion
• Delirium
• Depression
• Increased heart rate (tachycardia)
• Seizures
• Encephalopathy (a disorder of the brain)
• Decreased number of blood platelets
• Increased heart rate
• High blood pressure (hypertension)

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome.
• Acute Renal Failure.
• Central Nervous System Effects.

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.

Clinical Trials Experience In Adult Subjects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Cold Sores (Herpes Labialis)

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%). The frequencies of abnormal ALT (greater than 2 x ULN) were 1.8% for subjects receiving Valtrex compared with 0.8% for placebo. Other laboratory abnormalities (hemoglobin, white blood cells, alkaline phosphatase, and serum creatinine) occurred with similar frequencies in the 2 groups.

Genital Herpes

Initial Episode

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%). For the incidence of laboratory abnormalities see Table 2.

Recurrent Episodes

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%). For the incidence of laboratory abnormalities see Table 2.

Suppressive Therapy

Suppression of Recurrent Genital Herpes in Immunocompetent Adults

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%). For the incidence of laboratory abnormalities see Table 2.

Suppression of Recurrent Genital Herpes in HIV-1−Infected Subjects

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%). Post-randomization laboratory abnormalities that were reported more frequently in valacyclovir subjects versus placebo included elevated alkaline phosphatase (4%, 2%), elevated ALT (14%, 10%), elevated AST (16%, 11%), decreased neutrophil counts (18%, 10%), and decreased platelet counts (3%, 0%), respectively.

Reduction of Transmission

In a clinical trial for the reduction of transmission of genital herpes, the adverse reactions reported by subjects receiving Valtrex 500 mg once daily (n = 743) or placebo once daily (n = 741), respectively, included headache (29%, 26%), nasopharyngitis (16%, 15%), and upper respiratory tract infection (9%, 10%).

Herpes Zoster

In 2 clinical trials for the treatment of herpes zoster, the adverse reactions reported by subjects receiving Valtrex 1 gram 3 times daily for 7 to 14 days (n = 967) or placebo (n = 195), respectively, included nausea (15%, 8%), headache (14%, 12%), vomiting (6%, 3%), dizziness (3%, 2%), and abdominal pain (3%, 2%). For the incidence of laboratory abnormalities see Table 2.

Table 2. Incidence (%) of Laboratory Abnormalities in Herpes Zoster and Genital Herpes Trial Populations

Clinical Trials Experience In Pediatric Subjects

The safety profile of Valtrex has been studied in 177 pediatric subjects aged 1 month to less than 18 years. Sixty-five of these pediatric subjects, aged 12 to less than 18 years, received oral tablets for 1 to 2 days for treatment of cold sores. The remaining 112 pediatric subjects, aged 1 month to less than 12 years, participated in 3 pharmacokinetic and safety trials and received valacyclovir oral suspension. Fifty-one of these 112 pediatric subjects received oral suspension for 3 to 6 days. The frequency, intensity, and nature of clinical adverse reactions and laboratory abnormalities were similar to those seen in adults.

Pediatric Subjects Aged 12 To Less Than 18 Years (Cold Sores)

In clinical trials for the treatment of cold sores, the adverse reactions reported by adolescent subjects receiving Valtrex 2 grams twice daily for 1 day, or Valtrex 2 grams twice daily for 1 day followed by 1 gram twice daily for 1 day (n = 65, across both dosing groups), or placebo (n = 30), respectively, included headache (17%, 3%) and nausea (8%, 0%).

Pediatric Subjects Aged 1 Month To Less Than 12 Years

Adverse events reported in more than 1 subject across the 3 pharmacokinetic and safety trials in children aged 1 month to less than 12 years were diarrhea (5%), pyrexia (4%), dehydration (2%), herpes simplex (2%), and rhinorrhea (2%). No clinically meaningful changes in laboratory values were observed.

Postmarketing Experience

In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of Valtrex. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Valtrex.

General

Facial edema, hypertension, tachycardia.

Allergic

Acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria.

Central Nervous System (CNS) Symptoms

Aggressive behavior; agitation; ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy; mania; and psychosis, including auditory and visual hallucinations, seizures, tremors.

Eye

Visual abnormalities.

Gastrointestinal

Diarrhea.

Hepatobiliary Tract And Pancreas

Liver enzyme abnormalities, hepatitis.

Renal

Renal failure, renal pain (may be associated with renal failure).

Hematologic

Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS.

Skin

Erythema multiforme, rashes including photosensitivity, alopecia.

No clinically significant drug-drug or drug-food interactions with Valtrex are known.