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Fatty acid derivative anticonvulsants
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.
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.
Contact your doctor or health care provider right away if any of these apply to you.
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:
Some MEDICINES MAY INTERACT with valproate. Tell your health care provider if you are taking any other medicines, especially any of the following:
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.
Use valproate as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use 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:
Seek medical attention right away if any of these SEVERE side effects occur:
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.
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.
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.
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.
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.
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:
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
If any of the following symptoms of overdose occur while taking valproic acid, get emergency help immediately:Symptoms of overdose
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
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]
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]
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]
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]
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]
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]
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]
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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