Frequently Asked Questions

Valproate Sodium

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Depacon

Fatty acid derivative anticonvulsants


Pronunciation

Liver failure and death from liver failure has occurred in patients taking valproate. This has usually occurred within the first 6 months of treatment. Tell your doctor right away if you notice symptoms of liver problems (eg, a general feeling of discomfort, sluggishness, unusual tiredness or weakness, swelling of the face, loss of appetite, vomiting, stomach pain, dark urine, pale stools, or yellowing of the skin or eyes). In patients who have seizures, loss of seizure control may occur. You should have lab tests done before and during treatment to check for liver problems. Be sure to keep all doctor and lab appointments.

Children younger than 2 years old have an increased risk of fatal liver problems, especially if they take more than 1 seizure medicine or have a metabolic disorder, a severe seizure disorder along with mental retardation, or organic brain disease. Discuss any questions or concerns with your doctor.

There is an increased risk of liver failure and death from liver failure in patients who have a genetic liver problem caused by a mitochondrial disorder (eg, Alpers-Huttenlocher syndrome). You may need to have a special genetic test to check for this condition. Certain patients who have known or suspected mitochondrial disorders should not take valproate. Talk with your doctor for more information.

Valproate can cause severe birth defects if it is used during pregnancy. It can also cause the child to have a lower IQ. Do not take valproate to prevent migraine headaches if you are pregnant. If you are pregnant and take valproate for seizures or bipolar disorder, talk to your doctor to decide if you will continue to take valproate.

If you are able to become pregnant, you must use an effective form of birth control while you take valproate. Contact your doctor right away if you become pregnant or think you may be pregnant while taking valproate.

Valproate comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get valproate refilled.

Severe and sometimes fatal pancreas problems (pancreatitis) have occurred with the use of valproate. This has been reported shortly after starting treatment as well as after several years of use. Seek immediate medical attention if you notice any stomach pain, nausea, vomiting, or loss of appetite.


Valproate is used for:

Controlling certain types of seizures in the treatment of epilepsy in patients who are unable to take the oral form of valproate. It may also be used for other conditions as determined by your doctor.

Valproate is an anticonvulsant. It works by increasing a certain chemical in the brain.

Do NOT use valproate if:

  • you are allergic to any ingredient in valproate
  • you have liver problems or a urea cycle disorder
  • you have a genetic liver problem caused by a mitochondrial disorder (eg, Alpers-Huttenlocher syndrome)
  • the patient is younger than 2 years old and has a mitochondrial disorder
  • you are taking valproate to prevent migraine headaches and you are pregnant

Contact your doctor or health care provider right away if any of these apply to you.

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

Before using valproate:

Some medical conditions may interact with valproate. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

  • if you are pregnant, planning to become pregnant, are breast-feeding, or are of childbearing age
  • if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
  • if you have allergies to medicines, foods, or other substances
  • if you have a history of liver problems, cancer, blood disease (eg, low levels of white blood cells, low blood platelet levels), HIV infection, cytomegalovirus (CMV) infection, kidney problems, pancreas problems, low blood albumin levels, or high blood glycine levels
  • if you have a history of metabolic problems, ornithine transcarbamylase deficiency, brain problems (eg, organic brain disease), coma, high blood ammonia or glutamine levels, low body temperature, mental retardation, recurring vomiting and sluggishness, or recurring extreme irritability
  • if you have a history of mental or mood problems, suicidal thoughts or actions, or alcohol abuse or dependence
  • if you have decreased food or fluid intake, or if you are scheduled for surgery
  • if you have a family history of urea cycle disorders or unexplained infant deaths
  • if you take any other medicine for seizures

Some MEDICINES MAY INTERACT with valproate. Tell your health care provider if you are taking any other medicines, especially any of the following:

  • Clonazepam because the risk of seizures may be increased
  • Topiramate because the risk of high ammonium levels and brain problems may be increased
  • Benzodiazepines (eg, diazepam), felbamate, or salicylates (eg, aspirin) because they may increase the risk of valproate's side effects
  • Carbamazepine, carbapenem antibiotics (eg, imipenem), hormonal birth control (eg, birth control pills), hydantoins (eg, phenytoin), mefloquine, or rifampin because they may decrease valproate's effectiveness
  • Anticoagulants (eg, warfarin), barbiturates (eg, phenobarbital, primidone), ethosuximide, lamotrigine, methylphenidate, quetiapine, rufinamide, tolbutamide, tricyclic antidepressants (eg, amitriptyline), or zidovudine because the risk of their side effects may be increased by valproate

This may not be a complete list of all interactions that may occur. Ask your health care provider if valproate may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use valproate:

Use valproate as directed by your doctor. Check the label on the medicine for exact dosing instructions.

  • Valproate is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using valproate at home, a health care provider will teach you how to use it. Be sure you understand how to use valproate. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
  • Do not use valproate if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
  • Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
  • Do not suddenly stop using valproate. Suddenly stopping valproate may cause seizures to occur more often. If you need to stop valproate, your doctor will gradually lower your dose.
  • Valproate works best if it is used at the same time each day.
  • Continue to use valproate even if you feel well. Do not miss any doses.
  • If you miss a dose of valproate, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use valproate.

Important safety information:

  • Valproate may cause dizziness, drowsiness, or vision changes. These effects may be worse if you take it with alcohol or certain medicines. Use valproate with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
  • Check with your doctor before you drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using valproate; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.
  • Patients who take valproate may be at increased risk for suicidal thoughts or actions. The risk may be greater in patients who have had suicidal thoughts or actions in the past. Watch patients who take valproate closely. Contact the doctor at once if new, worsened, or sudden symptoms, such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or any unusual change in mood or behavior, occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.
  • Inflammation of the pancreas is a potentially life-threatening illness associated with valproate. Symptoms include stomach pain, vomiting, or loss of appetite. Contact your doctor at once if any of these symptoms occur.
  • Valproate may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.
  • Tell your doctor or dentist that you use valproate before you receive any medical or dental care, emergency care, or surgery.
  • Certain brain problems have happened with the use of valproic acid products. Sometimes, these problems have led to health problems that may not go away. Discuss any questions or concerns with your doctor.
  • Diabetes patients - Valproate may cause the results of some tests for urine ketones to be wrong. Ask your doctor before you change your diet or the dose of your diabetes medicine.
  • Valproate may interfere with certain lab tests, including thyroid function. Be sure your doctor and lab personnel know you are taking valproate.
  • Lab tests, including complete blood cell counts and liver function, may be performed while you use valproate. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
  • Use valproate with caution in the ELDERLY; they may be more sensitive to its effects, especially drowsiness.
  • Valproate has been shown to cause harm to the fetus. If you may become pregnant, discuss other possible treatment options with your doctor. If a decision is made to take valproate, use effective birth control while you are taking it. Talk with your doctor if you are planning to become pregnant, or if you have questions or concerns about this information.
  • PREGNANCY and BREAST-FEEDING: Valproate has been shown to cause harm to the fetus. If you think you may be pregnant, contact your doctor right away. You will need to discuss the benefits and risks of using valproate while you are pregnant. You and your doctor will need to decide if you will continue to take valproate while you are pregnant. Valproate is found in breast milk. Do not breast-feed while you are using valproate.

Possible side effects of valproate:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Change in appetite; constipation; diarrhea; dizziness; drowsiness; hair loss; headache; indigestion; mild pain or redness at the injection site; nausea; stomach cramps or pain; trouble sleeping; vomiting; weakness; weight changes.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); abnormal thinking; blurred vision or other vision changes; changes in behavior; change in menstrual period; chest pain; chills; confusion; difficulty speaking; difficulty urinating or other urination problems; extreme tiredness; fainting; fast or irregular heartbeat; fever; general body discomfort; hallucinations; hearing loss; involuntary movements of the arms and legs; involuntary movements or chewing movements of the face, jaw, mouth, or tongue; joint or muscle pain or weakness; lack of energy; loss of coordination; memory loss; new or worsening mental or mood changes (eg, aggressiveness, agitation, anxiety, depression, exaggerated feeling of well-being, hostility, impulsiveness, inability to sit still, irritability, panic attacks, restlessness); new or worsening seizures; nosebleed; red, swollen, blistered, or peeling skin; ringing in the ears; severe or persistent nausea, vomiting, or stomach pain; severe or persistent pain; shortness of breath; sore throat; suicidal thoughts or actions; swelling of the arms or legs; swollen lymph nodes; symptoms of liver problems (eg, dark urine, loss of appetite, pale stools, severe stomach pain, yellowing of the skin or eyes); tremor; unusual bleeding or bruising; unusual weakness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of valproate:

Store the undiluted solution of valproate at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Because the product does not contain a preservative, any unused mixed portion should be discarded. Valproate is stable for 24 hours when added to compatible intravenous solutions and stored in glass or polyvinyl chloride (PVC) bags at room temperature between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep valproate out of the reach of children and away from pets.

General information:

  • If you have any questions about valproate, please talk with your doctor, pharmacist, or other health care provider.
  • Valproate is to be used only by the patient for whom it is prescribed. Do not share it with other people.
  • If your symptoms do not improve or if they become worse, check with your doctor.
  • Check with your pharmacist about how to dispose of unused medicine.

This information should not be used to decide whether or not to take valproate or any other medicine. Only your health care provider has the knowledge and training to decide which medicines are right for you. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about valproate. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to valproate. This information is not specific medical advice and does not replace information you receive from your health care provider. You must talk with your health care provider for complete information about the risks and benefits of using valproate.

Issue Date: February 4, 2015
Database Edition 15.1.1.002
Copyright © 2015 Wolters Kluwer Health, Inc.

Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only your health care provider has the knowledge and training to decide which medicines are right for you. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from your health care provider. You must talk with your healthcare provider for complete information about the risks and benefits of using this medicine.

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.

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

Other dosage forms:

  • intravenous solution

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

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

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

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]

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]

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]

Hepatic

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]

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]

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]

Cardiovascular

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

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. 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]

Endocrine

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

Genitourinary

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]

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[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]

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]

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]

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[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]

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[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]

Renal

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

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

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[Ref]

References

1. "Product Information. Stavzor (valproic acid)." Noven Pharmaceuticals, Inc., New York, NY.

2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

3. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical, Abbott Park, IL.

4. Asconape JJ, Penry JK, Dreifuss FE, Riela A, Mirza W "Valproate-associated pancreatitis." Epilepsia 34 (1993): 177-83

5. Wilder BJ, Karas BJ, Penry JK, Asconape J "Gastrointestinal tolerance of divalproex sodium." Neurology 33 (1983): 808-11

6. Caparros-Lefebvre D, Lecomte-Houcke M, Pruvot FR, Declerck N, Paris JC, Petit H "Unusual electronmicroscopic changes in valproate-associated liver failure." Lancet 341 (1993): 1604

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