Valproic acid Side Effects

Some side effects of valproic acid may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to valproic acid: oral capsule, oral delayed release capsule, oral syrup

Seek emergency medical attention if the person taking this medicine has nausea, vomiting, upper stomach pain, or loss of appetite, low fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). These symptoms may be early signs of liver damage. Some of these symptoms may also be early signs of pancreatitis.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Get emergency medical help if you have any of these signs of an allergic reaction while taking valproic acid: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these other serious side effects:

• unexplained weakness with vomiting and confusion or fainting;

• easy bruising or bleeding, blood in your urine;

• fever, chills, body aches, swollen glands, flu symptoms;

• urinating less than usual;

• hallucinations (seeing things that aren't there);

• extreme drowsiness, lack of coordination;

• double vision or back-and-forth movements of the eyes; or

• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects of valproic acid may include:

• mild drowsiness or weakness;

• diarrhea, constipation, upset stomach;

• changes in your menstrual periods;

• enlarged breasts;

• tremor (shaking);

• hair loss;

• weight changes;

• vision changes; or

• unusual or unpleasant taste in your mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to valproic acid: injectable solution, oral capsule, oral delayed release capsule, oral syrup

Gastrointestinal

Gastrointestinal side effects have been reported frequently and include nausea, vomiting, and indigestion (in up to 16% of patients), especially with initiation of therapy and rapid increases in dose. Life threatening pancreatitis has been reported to occur anywhere from shortly after initial use to after several years of use. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Hyperamylasemia has occurred in up to 20% of patients and has rarely presented as clinical pancreatitis (usually one to six months after initiation of therapy).

Severe nausea, emesis, and anorexia may be due to valproate-induced hyperammonemia or hepatitis. Adverse gastrointestinal effects may be attenuated by administering doses with food. Increased appetite and weight gain occur in approximately one half of treated patients.

Hepatic

Hepatic side effects including transient dose-dependent elevations of serum transaminases, amylase, and ammonia have been reported in up to 44% of treated patients. Dose-related hepatitis and a case of nonalcoholic liver disease have also been reported.

Some clinicians recommend monitoring liver function tests at baseline, then monthly during the first 6 months of therapy and every 3 months thereafter. Prompt withdrawal of valproic acid is recommended if significant hepatic dysfunction occurs.

Risk factors for valproic acid-associated hepatitis are young age (particularly age less than 2 years old), poor nutritional status, mental retardation, underlying metabolic disease, and concomitant use of other anticonvulsant medications. Characteristic pathological features include microvesicular steatosis.

Mild elevations in transaminases and amylase may be managed by dose reductions.

Nervous system

Neurologic side effects including drowsiness, ataxia, and hand tremor have been reported. Cases of encephalopathy (manifested by stupor, coma, hallucinations or affective changes) and chorea have also been reported. Valproate may inhibit urea synthesis resulting in hyperammonemia, which has been associated with encephalopathy, delirium, and ataxia in rare cases. Reversible sensorineural hearing loss associated with valproic acid has been reported rarely. Two cases of extrapyramidal disorders have been reported in association with valproic acid therapy. A case of truncal weakness and respiratory failure has also been associated with valproic acid therapy.

A clinical observational study has reported that valproic acid is associated with cognitive decline in HIV-infected individuals.

Loss of seizure control may indicate associated hepatitis.

Hematologic

Hematologic side effects including rare cases of reversible thrombocytopenia associated with antiplatelet antibodies and bone marrow suppression have been reported.

Some clinicians recommend monitoring complete blood counts (including platelet counts) at baseline, then monthly for three months, and every three months thereafter.

Data from a study of 265 patients strongly suggests a causal relationship between rising plasma valproic acid levels and reduced platelet counts, with additional risk factors including female gender and lower baseline platelet counts.

Dermatologic

Valproic acid has been associated with stomatitis and cutaneous leukoclastic vasculitis. A case of psoriasiform eruption has been reported in a patient receiving valproic acid.

The mechanism of valproic acid induced alopecia is believed to be telogen shedding. This is believed to appear within three months of the initiation of valproic acid therapy. Alopecia does not appear to be dose related. Limited data have reported that supplements with a zinc and selenium-containing vitamin may be useful in the prevention of valproic acid associated alopecia.

Dermatologic side effects including transient alopecia (2.6% to 12%), thinning of the hair, hair color changes, hair texture changes, and rare rashes have been reported. Valproic acid has been implicated in producing Stevens-Johnson syndrome and toxic epidermal necrolysis.

Cardiovascular

Cardiovascular side effects including peripheral edema have been reported rarely.

Renal

Valproate-induced Fanconi's syndrome has been reported more often in children than in adults.

Renal side effects including several cases of Fanconi's syndrome have been reported.

Endocrine

Valproate therapy has been associated with polycystic ovaries, elevated serum testosterone concentrations and menstrual disturbances. One study has suggested that 80% of women treated with valproic acid before the age of 20 have polycystic ovaries or hyperandrogenism.

Endocrine side effects including a variety of adverse reproductive endocrine disorders have been reported in epileptic women taking valproic acid.

Respiratory

Respiratory side effects including a case of eosinophilic pleural effusion have been reported.

Immunologic

Immunologic side effects have been reported including a case of bone marrow suppression in a girl who received high dose valproic acid.

Other

Other side effects including a case of valproate-withdrawal induced migraine has been reported.

Musculoskeletal

Musculoskeletal side effects including decreased bone mass and increased bone turnover have been reported.

Hypersensitivity

Hypersensitivity side effects including a case of hypersensitivity syndrome have been reported.

General

General side effects including hypothermia have been reported.

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