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valproic acid (bulk)
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valproic acid (bulk) Overview

Valproic acid (VPA, valproate), an acidic chemical compound, has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. VPA is a liquid at room temperature, but it can be reacted with a base such as sodium hydroxide to form the salt sodium valproate, which is a solid.

The acid, salt, or a mixture of the two (valproate semisodium) are marketed under a number of different brand names, including: Depakote, Epilim, Valparin, Valpro, Vilapro and Stavzor. It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Adverse effects

The most common adverse effects of valproic acid are digestive complaints like diarrhoea, nausea, vomiting and indigestion; vision problems like seeing double or lazy eye; hormonal disturbances (increased testosterone production in females and menstrual irregularities), hair loss, memory problems, weight gain, infections, low platelet count (which can make one bleed more easily), infection, dizziness, drowsiness, tremor and headache. Less common, yet serious side effects include liver damage, brittle bones (becomes far more common with long-term use), polycystic ovaries, movement disorders (which may be irreversible like tardive dyskinesia), psychiatric/neurologic disturbances like hallucinations, anxiety and confusion; swollen pancreas, low body temperature and potentially life-threatening blood abnormalities.

Pregnancy

Valproate causes birth defects; exposure during pregnancy is associated with about three times as many major anomalies as usual, mainly spina bifida and, more rarely, with several other defects, possibly including a "valproate syndrome". Characteristics of this valproate syndrome include facial features that tend to evolve with age, including trigonocephaly, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, anteverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth.

Mechanism of action

Although the mechanism of action of valproate is not fully understood,it has recently been shown to protect against a seizure-induced reduction in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) as a potential therapeutic mechanism.In addition, its anticonvulsant effect has been attributed to the blockade of voltage-dependent sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).

History

Valproic acid was first synthesized in 1882 by B.S. Burton as an analogue of valeric acid, found naturally in valerian. Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats.   

VALPROIC ACID (BULK) WARNING

Rarely, this medication has caused serious (sometimes fatal) liver problems, usually within the first 6 months of starting treatment. Laboratory tests should be performed before you start treatment and periodically during treatment, especially within the first 6 months, to monitor this side effect.

The risk of serious liver problems is increased in children younger than 2 years, especially if they have an inherited metabolic disorder, severe seizure disorder with mental retardation, organic brain disease, or if they take more than one seizure medication. Talk with the doctor about the risks and benefits of using this medication in children younger than 2 years.

Due to an increased risk for liver problems, people with certain inherited metabolic disorders (such as Alpers-Huttenlocher syndrome) should not use this medication. Children younger than 2 years who might have these disorders should not use this medication. Children older than 2 years who might have these disorders should be closely monitored during treatment with valproic acid. Talk to your doctor for details.

This medication has rarely caused severe (sometimes fatal) disease of the pancreas (pancreatitis). This may occur at any time during treatment and can quickly worsen.

Tell your doctor right away if you develop symptoms of liver problems or pancreatitis such as unusual tiredness, weakness, swelling of the face, stomach/abdominal pain, loss of appetite, or vomiting.

Taking this medication during pregnancy can cause birth defects and may lower your child's IQ. Women of childbearing age should discuss the risks and benefits of this medication, other treatment options, and use of reliable forms of birth control with their doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately talk to your doctor. If you are taking valproic acid only to prevent migraine headaches, this medication must not be used during pregnancy. If you are taking valproic acid to treat seizures or mental/mood disorders, do not stop taking this medication unless directed by your doctor. Untreated seizures and mental/mood disorders are serious conditions that can harm both a pregnant woman and her unborn baby.

VALPROIC ACID (BULK) USES

This medication is used to treat seizure disorders, mental/mood conditions (such as manic phase of bipolar disorder), and to prevent migraine headaches. It works by restoring the balance of certain natural substances (neurotransmitters) in the brain.
How to use valproic acid oral

Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking valproic acid and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor. You may take it with food if stomach upset occurs. Swallow the capsule whole. Do not crush or chew the capsule, which can irritate the mouth or throat.

Dosage is based on your age, weight, medical condition, and response to therapy. Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day to keep the amount of medication in your blood constant.

If this medication is used for seizures, do not stop taking it without consulting your doctor. Your condition may become worse if the drug is suddenly stopped. Your dose may need to be gradually decreased.

This medication does not relieve acute migraine headaches. Take other medications as directed by your doctor for acute attacks.

Inform your doctor if your condition does not improve.

VALPROIC ACID (BULK) SIDE EFFECTS

Diarrhea, dizziness, drowsiness, hair loss, blurred/double vision, change in menstrual periods, ringing in the ears, shakiness (tremor), unsteadiness, weight changes may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these serious side effects occur: signs of infection (e.g., fever, persistent sore throat).

Tell your doctor immediately if any of these unlikely but serious side effects occur: chest pain, easy bruising/unexplained bleeding, fast/slow/irregular heartbeat, swelling of hands/feet, uncontrolled eye movement (nystagmus), feeling cold/shivering, rapid breathing, loss of consciousness.

A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor immediately if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: dark urine, persistent nausea/vomiting, severe stomach/abdominal pain, yellowing eyes or skin.

Severe (sometimes fatal) brain disorder (encephalopathy) has rarely occurred, particularly in patients with certain metabolic disorders (urea cycle disorders). Tell your doctor immediately if you develop unexplained weakness, vomiting, or sudden mental/mood changes (such as confusion).

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

VALPROIC ACID (BULK) PRECAUTIONS

Before taking valproic acid, tell your doctor or pharmacist if you are allergic to it; or to divalproex or valproate sodium; or if you have any other allergies. This product may contain inactive ingredients (such as peanut oil), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, pancreatitis, certain metabolic disorders (such as urea cycle disorders, Alpers-Huttenlocher syndrome), alcohol abuse, bleeding problems, brain disease (dementia), kidney disease, low body water (dehydration), poor nutrition.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This drug may make you dizzy or drowsy or cause blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.

Older adults may be more sensitive to the side effects of this drug, especially drowsiness, dizziness, unsteadiness, or tremor. Drowsiness, dizziness, unsteadiness can increase the risk of falling.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. See also Warning section.

This medication passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

VALPROIC ACID (BULK) INTERACTIONS

Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain antidepressants (e.g., amitriptyline, nortriptyline, phenelzine), certain benzodiazepines (e.g., clonazepam, diazepam), certain antibiotics (carbapenems such as doripenem, imipenem), guanfacine, mefloquine, other medications for seizure (e.g., carbamazepine, ethosuximide, felbamate, lamotrigine, phenobarbital, phenytoin, rufinamide, topiramate), rifampin, vorinostat, warfarin, zidovudine.

Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually these dosages are 81-325 milligrams per day), should be continued. Consult your doctor or pharmacist if you are using aspirin for any reason.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: antihistamines that cause drowsiness (e.g., diphenhydramine), medicine for sleep (e.g., sedatives), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., phenothiazines such as chlorpromazine), tranquilizers.

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about the safe use of those products.

This drug may affect certain lab tests (e.g., urine ketones). Make sure laboratory personnel and your doctors know you use this medication.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

VALPROIC ACID (BULK) OVERDOSE

If overdose is suspected, contact a poison control center or emergency room immediately. Symptoms of overdose may include: excessive drowsiness, coma, irregular/slowed/skipped heart beats (heart block).

NOTES:

Do not share this medication with others.

Laboratory and/or medical tests (e.g., drug levels, liver function tests, complete blood counts, clotting tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE:

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE:

Store at room temperature between 59-77 degrees F (15-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised January 2014. Copyright(c) 2014 First Databank, Inc.

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