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Valproic acid Side Effects

In Summary

Commonly reported side effects of valproic acid include: congenital anomalies, infection, abdominal pain, asthenia, drowsiness, nausea, tremor, vomiting, alopecia, diarrhea, dizziness, flu-like symptoms, thrombocytopenia, and anorexia. Other side effects include: dyspnea, pharyngitis, tinnitus, abnormality in thinking, amnesia, ataxia, bronchitis, constipation, depression, fever, nystagmus, peripheral edema, weight gain, and weight loss. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to valproic acid: oral capsule delayed release, oral capsule liquid filled, oral syrup, oral tablet delayed release, oral tablet enteric coated, oral tablet extended release

As well as its needed effects, valproic acid may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking valproic acid, check with your doctor immediately:

More common:
  • Black, tarry stools
  • bleeding gums
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • blood in the urine or stools
  • confusion
  • cough or hoarseness
  • crying
  • delusions
  • dementia
  • depersonalization
  • diarrhea
  • difficult or labored breathing
  • dysphoria
  • euphoria
  • fever or chills
  • general feeling of discomfort or illness
  • headache
  • joint pain
  • loss of appetite
  • lower back or side pain
  • mental depression
  • muscle aches and pains
  • nausea
  • nervousness
  • painful or difficult urination
  • paranoia
  • pinpoint red spots on the skin
  • quick to react or overreact emotionally
  • rapid weight gain
  • rapidly changing moods
  • runny nose
  • shakiness in the legs, arms, hands, or feet
  • shivering
  • sleepiness or unusual drowsiness
  • sore throat
  • sweating
  • tightness in the chest
  • tingling of the hands or feet
  • trembling or shaking of the hands or feet
  • trouble sleeping
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • vomiting
Less common:
  • Abnormal dreams
  • absence of or decrease in body movement
  • anxiety
  • bloody nose
  • bloody or cloudy urine
  • blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • change in personality
  • change in walking and balance
  • changes in patterns and rhythms of speech
  • chest pain
  • chills
  • clumsiness or unsteadiness
  • cold sweats
  • constipation
  • darkened urine
  • degenerative disease of the joint
  • difficult, burning, or painful urination
  • difficulty with moving
  • discouragement
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • dry mouth
  • excessive muscle tone
  • fast, irregular, pounding, or racing heartbeat or pulse
  • fear
  • feeling of warmth or heat
  • feeling sad or empty
  • flushing or redness of the skin, especially on the face and neck
  • frequent urge to urinate
  • heavy non-menstrual vaginal bleeding
  • hyperventilation
  • increased need to urinate
  • indigestion
  • irritability
  • lack of appetite
  • lack of coordination
  • large, flat, blue or purplish patches in the skin
  • leg cramps
  • lip smacking or puckering
  • loss of bladder control
  • loss of interest or pleasure
  • loss of strength or energy
  • multiple swollen and inflamed skin lesions
  • muscle pain or stiffness
  • muscle tension or tightness
  • normal menstrual bleeding occurring earlier, possibly lasting longer than expected
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • passing urine more often
  • pounding in the ears
  • puffing of the cheeks
  • rapid or worm-like movements of the tongue
  • rapid weight gain
  • restlessness
  • seeing, hearing, or feeling things that are not there
  • shakiness and unsteady walk
  • slurred speech
  • small red or purple spots on the skin
  • sweating
  • swollen joints
  • tiredness
  • trouble with concentrating
  • trouble with speaking
  • twitching
  • uncontrolled chewing movements
  • uncontrolled movements of the arms and legs
  • unsteadiness, trembling, or other problems with muscle control or coordination
  • vomiting of blood or material that looks like coffee grounds
  • yellow eyes or skin

If any of the following symptoms of overdose occur while taking valproic acid, get emergency help immediately:

Symptoms of overdose:
  • Change in consciousness
  • fainting
  • loss of consciousness
  • slow or irregular heartbeat

Minor Side Effects

Some valproic acid side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common:
  • Acid or sour stomach
  • belching
  • body aches or pain
  • change in vision
  • congestion
  • continuing ringing or buzzing or other unexplained noise in the ears
  • hair loss or thinning of the hair
  • hearing loss
  • heartburn
  • impaired vision
  • lack or loss of strength
  • loss of memory
  • problems with memory
  • rash
  • seeing double
  • tender, swollen glands in the neck
  • trouble with swallowing
  • uncontrolled eye movements
  • voice changes
  • weight gain
  • weight loss
Less common:
  • Absent, missed, or irregular menstrual periods
  • back pain
  • burning, dry, or itching eyes
  • change in taste or bad unusual or unpleasant (after) taste
  • coin-shaped lesions on the skin
  • cough producing mucus
  • cramps
  • dandruff
  • discharge or excessive tearing
  • dry skin
  • earache
  • excess air or gas in the stomach or intestines
  • eye pain
  • feeling of constant movement of self or surroundings
  • full feeling
  • heavy bleeding
  • increased appetite
  • itching of the vagina or genital area
  • itching skin
  • loss of bowel control
  • neck pain
  • oily skin
  • pain
  • pain during sexual intercourse
  • pain or tenderness around the eyes and cheekbones
  • passing gas
  • rash with flat lesions or small raised lesions on the skin
  • redness or swelling in the ear
  • redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
  • redness, swelling, or soreness of the tongue
  • sensation of spinning
  • sneezing
  • stiff neck
  • stopping of menstrual bleeding
  • thick, white vaginal discharge with no odor or with a mild odor

For Healthcare Professionals

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


The most commonly reported side effects at the start of therapy include nausea, vomiting, and indigestion; these effects are usually transient. Sedative effects occur most often in patients receiving combination therapy.[Ref]


Very common (10% or more): Abdominal pain, diarrhea, dyspepsia, gingival disorder, nausea, vomiting
Common (1% to 10%): Constipation, dry mouth, eructation, fecal incontinence, flatulence, gastralgia, gastroenteritis, glossitis, periodontal abscess, hematemesis, stomatitis
Uncommon (0.1% to 1%): Pancreatitis (life-threatening)[Ref]

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, or through the use of delayed-release valproic acid.[Ref]


Common (1% to 10%): Increased liver enzymes (particularly early in treatment), liver injury, SGOT increased, SGPT increased
Frequency not reported: Severe liver damage (including hepatic failure sometimes resulting in death), increased serum bilirubin, abnormal changes in other liver function tests[Ref]

Prompt withdrawal of valproic acid is recommended if significant hepatic dysfunction occurs. Mild elevations in transaminases and amylase may be managed by dose reductions.

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.[Ref]

Nervous system

Loss of seizure control may indicate associated hepatitis.

Rarely, encephalopathy with or without fever has developed shortly after the introduction of valproate monotherapy without evidence of hepatic dysfunction or inappropriately high plasma valproate levels. There have been fatalities in patients with hyperammonemic encephalopathy, particularly in patients with underlying urea cycle disorders.

Rare cases of lethargy occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported. Encephalopathy and coma have very rarely been observed. These cases have often been associated with too high a starting dose or too rapid a dose escalation or concomitant use of other anticonvulsants, e.g., phenobarbital or topiramate. They have usually been reversible on withdrawal of treatment or reduction of dosage.[Ref]

Very common (10% or more): Dizziness, headache, somnolence, tremor
Common (1% to 10%): Abnormal gait, amnesia, catatonic reaction, convulsion, disturbance in attention, dysarthria, extrapyramidal disorder, hypertonia, hypokinesia, incoordination, increased reflexes, memory impairment, nystagmus, paresthesia, speech disorder, stupor, tardive dyskinesia, taste perversion
Uncommon (0.1% to 1%): Ataxia, coma, encephalopathy, lethargy, reversible parkinsonism
Rare (less than 0.1%): Cognitive disorder, reversible dementia associated with reversible cerebral atrophy
Frequency not reported: Cerebral atrophy, dementia[Ref]


Common (1% to 10%): Edema, hypertension, hypotension, palpitations, postural hypotension, peripheral edema, tachycardia, vasodilation
Frequency not reported: Bradycardia, cutaneous vasculitis, hematoma formation[Ref]


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. Hair regrowth normally begins within 6 months, although the hair may become curlier than previously.

Serious skin reactions have been reported with concomitant administration of lamotrigine and valproate.[Ref]

Very common (10% or more): Alopecia
Common (1% to 10%): Discoid lupus erythematosus, dry skin, ecchymosis, furunculosis, maculopapular rash, petechia, pruritus, rash, seborrhea
Uncommon (0.1% to 1%): Abnormal hair texture, abnormal hair growth, hair color changes, sweating
Rare (0.01% to 0.1%): Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Very rare (less than 0.01%): Acne, hirsutism
Frequency not reported: Angioedema, generalized pruritus, photosensitivity[Ref]


Uncommon (0.1% to 1%): Hyperandrogenism, syndrome of inappropriate ADH secretion
Rare (less than 0.1%): Hypothyroidism
Frequency not reported: Abnormal thyroid function tests, elevated serum testosterone concentrations, parotid gland swelling[Ref]

One study has suggested that 80% of women treated with valproic acid before the age of 20 have polycystic ovaries or hyperandrogenism.[Ref]


Common (1% to 10%): Amenorrhea, cystitis, dysmenorrhea, dysuria, enuresis, metrorrhagia, urinary incontinence, urinary frequency, vaginal hemorrhage, vaginitis
Very rare (less than 0.01%): Gynecomastia
Frequency not reported: Breast enlargement, galactorrhea, polycystic ovary disease[Ref]


Very common (10% or more): Thrombocytopenia
Common (1% to 10%): Anemia, hemorrhage
Uncommon (0.1% to 1%): Leucopenia, pancytopenia
Rare (less than 0.1%): Abnormal coagulation tests (e.g., prolonged prothrombin time, prolonged activated partial thromboplastin time, prolonged thrombin time, prolonged INR), agranulocytosis, bone marrow failure, decreased coagulation factors, including pure red cell aplasia, macrocytosis
Frequency not reported: Aplastic anemia, bone marrow suppression, bruising, eosinophilia, frank hemorrhage, hypofibrinogenemia, anemia including macrocytic with or without folate deficiency, relative lymphocytosis[Ref]

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.

Isolated findings of a reduction in blood fibrinogen and/or an increase in prothrombin time have been reported, particularly with high doses. Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigations.[Ref]


Frequency not reported: Allergic reaction, anaphylaxis, hypersensitivity[Ref]


Common (1% to 10%): Injection site pain, injection site reaction
Uncommon (0.1% to 1%): Injection site inflammation[Ref]


Very common (10% or more): Anorexia
Common (1% to 10%): Weight loss/gain, increased appetite, hyponatremia
Rare (less than 0.1%): Hyperammonemia
Frequency not reported: Acute intermittent porphyria, minor elevations of LDH (dose related), decreased carnitine concentrations, hyperglycinemia[Ref]

Cases of isolated and moderate hyperammonemia without change in liver function tests may occur, are usually transient and should not cause treatment discontinuation. However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness. Valproate should be discontinued if these symptoms occur.[Ref]


Common (1% to 10%): Arthralgia, arthrosis, leg cramps, myalgia, myasthenia, twitching
Uncommon (0.1% to 1%): Decreased bone mineral density, osteopenia, osteoporosis and fractures on long term therapy
Rare (less than 0.1%): Rhabdomyolysis, systemic lupus erythematosus
Frequency not reported: Bone pain[Ref]


Very common (10% or more): Amblyopia/blurred vision, diplopia
Common (1% to 10%): Abnormal vision, conjunctivitis, diplopia, dry eyes, eye pain[Ref]


Rare (less than 0.1%): Myelodysplastic syndrome[Ref]


Aggression, agitation, disturbance in attention, abnormal behavior, psychomotor hyperactivity, and learning disorder has been primarily observed in the pediatric population.

In offspring of women exposed to valproate during pregnancy there have been reports of developmental delay, autism and/or autism spectrum disorder.[Ref]

Very common (10% or more): Nervousness
Common (1% to 10%): Abnormal dreams, agitation, anxiety, aggression, confusion, depression, emotional lability, hallucinations, insomnia, personality disorder, thinking abnormalities
Rare (less than 0.1%): Abnormal behavior, learning disorder, psychomotor hyperactivity
Frequency not reported: Behavioral deterioration, hostility, psychosis[Ref]


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

Rare (less than 0.1%): Reversible Fanconi's syndrome, tubulointerstitial nephritis[Ref]


Very common (10% or more): Flu syndrome, respiratory infection
Common (1% to 10%): Bronchitis, dyspnea, epistaxis, increased cough, pharyngitis, pneumonia, rhinitis, sinusitis
Uncommon (0.1% to 1%): Pleural effusion[Ref]


Very common (10% or more): Asthenia
Common (1% to 10%): Back pain, chills, deafness, ear disorder, ear pain, face edema, fever, malaise, otitis media, tinnitus, vertigo
Frequency not reported: Hypothermia, weakness[Ref]


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It is possible that some side effects of valproic acid may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

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