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Valproic acid Side Effects

Medically reviewed by Drugs.com. Last updated on Aug 1, 2023.

Applies to valproic acid: oral capsule delayed release, oral capsule liquid filled, oral solution, oral syrup, oral tablet delayed release, oral tablet extended release.

Warning

Oral route (Capsule, Delayed Release)

Hepatotoxicity (some cases fatal), usually occurring during the first 6 months of treatment, has been reported in patients receiving valproate and its derivatives. Children younger than 2 years and patients with hereditary mitochondrial disease are at a considerably increased risk of developing fatal hepatotoxicity. Use is contraindicated in patients with known mitochondrial disorders caused by mitochondrial DNA polymerase gamma (POLG) mutations and in children younger than 2 years in which mitochondrial disorder is clinically suspected. Failure of other anticonvulsants is the only indication for valproate use in patients older than 2 years with hereditary mitochondrial disease. Perform POLG mutation screening as clinically indicated. Monitor patients closely and perform liver function tests prior to therapy and at frequent intervals thereafter, especially during the first 6 months. Valproate can impair cognitive development with prenatal exposure and produce major congenital malformations, particularly neural tube defects (eg, spina bifida), and neurodevelopmental disorders. Valproate is contraindicated for prophylaxis of migraine headaches in pregnant women and in women of childbearing potential who are not using effective contraception. Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. In such situations, effective contraception should be used. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. Cases have occurred shortly after initiation as well as several years after use. If pancreatitis is diagnosed, valproate should ordinarily be discontinued.

Oral route (Syrup; Capsule, Liquid Filled)

Hepatotoxicity (some cases fatal), usually occurring during the first 6 months of treatment, has been reported in patients receiving valproate and its derivatives. Children younger than 2 years and patients with hereditary mitochondrial disease are at a considerably increased risk of developing fatal hepatotoxicity. Use is contraindicated in patients with known mitochondrial disorders caused by mitochondrial DNA polymerase gamma (POLG) mutations and in children younger than 2 years in which mitochondrial disorder is clinically suspected. Failure of other anticonvulsants is the only indication for valproate use in patients older than 2 years with hereditary mitochondrial disease. Perform POLG mutation screening as clinically indicated. Monitor patients closely and perform liver function tests prior to therapy and at frequent intervals thereafter, especially during the first 6 months. Valproate can impair cognitive development with prenatal exposure and produce major congenital malformations, particularly neural tube defects (eg, spina bifida). Valproate is contraindicated for prophylaxis of migraine headaches in pregnant women and women of childbearing potential who are not using effective contraception. Valproate should not be administered to a woman of childbearing potential unless other medications have failed or are otherwise unacceptable. Effective contraception should be used in such situations. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. Cases have occurred shortly after initiation as well as several years after use. If pancreatitis is diagnosed, valproate should ordinarily be discontinued.

Oral route (Tablet, Delayed Release; Capsule, Delayed Release; Tablet, Extended Release)

Hepatotoxicity (some cases fatal), usually occurring during the first 6 months of treatment, has been reported in patients receiving valproate and its derivatives. Children younger than 2 years and patients with hereditary mitochondrial disease are at a considerably increased risk of developing fatal hepatotoxicity. For these patients under 2 years, valproate sodium should be used with extreme caution as a sole agent. Use is contraindicated in patients with known mitochondrial disorders caused by mitochondrial DNA polymerase gamma (POLG) mutations and in children younger than 2 years in which mitochondrial disorder is clinically suspected. Failure of other anticonvulsants is the only indication for divalproex sodium in patients older than 2 years with hereditary mitochondrial disease. Perform POLG mutation screening as clinically indicated. Monitor patients closely and perform liver function tests prior to therapy and at frequent intervals thereafter, especially during the first 6 months. Valproate can impair cognitive development with prenatal exposure and produce major congenital malformations, particularly neural tube defects (eg, spina bifida). Valproate is contraindicated for prophylaxis of migraine headaches in pregnant women and women of childbearing potential who are not using effective contraception. Valproate should not be administered to a woman of childbearing potential unless other medications have failed or are otherwise unacceptable. Effective contraception should be used in such situations. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. Cases have occurred shortly after initiation as well as several years after use. If pancreatitis is diagnosed, valproate should ordinarily be discontinued.

Serious side effects of Valproic acid

Along with its needed effects, valproic acid may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking valproic acid:

More common

Less common

Incidence not known

Get emergency help immediately if any of the following symptoms of overdose occur while taking valproic acid:

Symptoms of overdose

Other side effects of Valproic acid

Some side effects of valproic acid may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

Incidence not known

For Healthcare Professionals

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

Cardiovascular

Common (1% to 10%): Edema, hypertension, hypotension, palpitations, postural hypotension, peripheral edema, tachycardia, vasodilation

Frequency not reported: Bradycardia, cutaneous vasculitis, hematoma formation[Ref]

Psychiatric

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

Postmarketing reports: Emotional upset, disturbance in-attention[Ref]

Respiratory

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]

Renal

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

Dermatologic

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

Postmarketing reports: Nail and nail bed disorders[Ref]

Endocrine

Uncommon (0.1% to 1%): Hyperandrogenism, syndrome of inappropriate ADH secretion

Rare (less than 0.1%): Hypothyroidism

Very rare (less than 0.01%): Gynecomastia

Frequency not reported: Abnormal thyroid function tests, elevated serum testosterone concentrations, parotid gland swelling, breast enlargement, galactorrhea,[Ref]

Gastrointestinal

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]

General

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]

Genitourinary

Common (1% to 10%): Amenorrhea, cystitis, dysmenorrhea, dysuria, enuresis, metrorrhagia, urinary incontinence, urinary frequency, vaginal hemorrhage, vaginitis

Frequency not reported: Polycystic ovary disease

Post marketing reports: Irregular menses, secondary amenorrhea, azoospermia, aspermia, decreased sperm count, decreased spermatozoa motility, male infertility, and abnormal spermatozoa morphology, urinary tract infection[Ref]

Hematologic

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

Postmarketing reports: Relative lymphocytosis, macrocytosis, agranulocytosis, acute intermittent porphyria, Fanconi's syndrome[Ref]

Hepatic

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]

Hypersensitivity

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

Local

Common (1% to 10%): Injection site pain, injection site reaction

Uncommon (0.1% to 1%): Injection site inflammation[Ref]

Metabolic

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]

Musculoskeletal

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

Postmarketing reports: Fractures, weakness[Ref]

Nervous system

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, paraesthesia, 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

Postmarketing reports: Paradoxical convulsion, parkinsonism[Ref]

Ocular

Very common (10% or more): Amblyopia/blurred vision, diplopia

Common (1% to 10%): Abnormal vision, conjunctivitis, diplopia, dry eyes, eye pain[Ref]

Oncologic

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

Other

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, hearing loss[Ref]

References

1. Product Information. Depakene (valproic acid). Abbott Pharmaceutical. 2001.

2. Product Information. Depacon (valproic acid). Abbott Pharmaceutical. 2001.

3. Cerner Multum, Inc. UK Summary of Product Characteristics.

4. Cerner Multum, Inc. Australian Product Information.

5. Product Information. Valproate Sodium (valproic acid). West Ward Pharmaceutical Corporation. 2017.

6. Product Information. Valproic Acid (valproic acid). Upsher-Smith Laboratories Inc. 2017.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.