Valproic Acid and Divalproex Sodium
Valproic acid and divalproex sodium
Valproic acid is an anticonvulsant used to control seizures in the treatment of epilepsy , a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain.
Valproic acid is closely related to divalproex sodium and valproate sodium. While these drugs are primarily used in the treatment of epilepsy, divalproex sodium is also indicated for the treatment of manic episodes (abnormally and persistently elevated mood) associated with bipolar disorder.
Valproic acid is thought to depress activity in certain areas of the brain, suppressing the irregular firing of neurons to prevent seizures. Divalproex sodium is a stable coordination compound formed with valproic acid.
While valproic acid and divalproex sodium control the seizures associated with epilepsy, there is no known cure for the disease.
In the United States, valproic acid and divalproex sodium are sold under the brand names Depekene and Depakote. Valproic acid is available in tablet and syrup form. Divalproex sodium is available in tablet, injection, or in sprinkle form.
Valproic acid usually requires two to four oral doses each day. The typical total daily dose is initiated at 15mg per kilogram (2.2 pounds) of body weight, and is increased in weekly intervals by 5–10 mg per kilogram of body weight until seizures are controlled. The frequency of adverse effects may increase with increasing doses, therefore, changes in dosage are made gradually. It may require several weeks of dosage titration (adjustment for maximum benefit and minimum risk) to realize the full benefits of valproic acid or divalproex sodium.
Persons should not take a double dose of anticonvulsant medications. If a daily dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped.
When discontinuing treatment including valproic acid or divalproex sodium, physicians typically direct patients to gradually reduce their daily dosages. Stopping the medicine suddenly may cause seizures to occur or become more frequent.
Persons should avoid alcohol while taking valproic acid or divalproex sodium. It can exacerbate (heighten) the side effects of alcohol and other medications. A physician should also be consulted before taking valproic acid or divalproex sodium with certain non-prescription medications, such as medicines for asthma, appetite control, coughs, colds, sinus problems, allergies, and hay fever.
Valproic acid and divalproex sodium may not be suitable for persons with a history of liver or kidney disease, mental illness, high blood presure, angina (chest pain ), irregular heartbeats, or other heart problems. Valproic acid and divalproex sodium may cause liver damage (hepatotoxicity), though the risk is low in adults. The prescribing physician may order routine blood tests to screen for liver damage.
Before beginning treatment with valproic acid or divalproex sodium, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are pregnant, or plan to become pregnant.
Valproic acid and divalproex sodium may cause birth defects, and have been linked to an increased risk of spina bifida . Physicians often counsel their patients to use effective birth control while taking either of these medications. Unlike many other anti-convulsant medications, valproic acid will not decrease the effectiveness of oral contraceptives (birth control pills). Patients who become pregnant while taking valproic acid or divalproex sodium should contact their physician immediately.
Research indicates that valproic acid and divalproex sodium are generally well tolerated. In certain individuals and especially children under two years of age, however, valproic acid may cause severe damage to the liver or pancreas. It is important to keep all appointments with the physician and laboratory to monitor the body's response to valproic acid. Temporary nausea, vomiting, stomach cramps, weight gain, temporary hair loss, shaking, and an irregular menstrual cycle are the most frequently reported side effects of valproic acid and divalproex sodium. Other possible side effects include:
- difficulty with memory
- double vision
- loss of appetite
- sleepiness or sleeplessness
- unusual drowsiness
- diarrhea or constipation
- heartburn or indigestion
- aching joints and muscles or chills
- unpleasant taste in mouth or dry mouth
- tingling or prickly feeling on the skin
Many of these side effects disappear or occur less frequently during treatment as the body adjusts to the medication.
Other, uncommon side effects of valproic acid and divalproex sodium can be potentially serious. A patient taking valproic acid who experiencs any of the following symptoms should contact their physician:
- jaundice (yellow tone to skin and eyes)
- facial swelling
- persistent fatigue
- mood or mental changes
- persistent trembling of the arms and hands
- excessive sleeplessness
- difficulty breathing
- chest pain
- irregular heartbeat
- persistent, severe headaches
- persistent fever or pain.
Valproic acid and divalproex sodium may have negative interactions with some antacids, tricyclic antidepressants, antibiotics, monoamine oxidase inhibitors (MAOIs), and asprin and other non-steroidal anti-inflammatories (NSAIDs). Other medications such as Diazepam (Valium), phenobarbital (Luminal, Solfoton), nefazodone, metronidazole, acetazolamide (Diamox), phenytoin (Dilantin), primidone , propranolol (Inderal), and warfarin may also adversely react with volparic acid.
Volparic acid and divalproex sodium may react adversely with other anticonvulsants and anti-epilepsy drugs (AEDs). They should be used with other other seizure prevention medications only if advised by a physician.
Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Richmond Hill, Ontario: Firefly Books, 2001.
American Society of Health-System Pharmacists, Inc. "Valproic acid." Medline Plus. <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682412.html> (March 20, 2004).
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American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. <http://www.aesnet.org>.
Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. <http://www.epilepsyfoundation.org>.
Adrienne Wilmoth Lerner
"Valproic Acid and Divalproex Sodium." Gale Encyclopedia of Neurological Disorders. . Encyclopedia.com. (August 20, 2017). http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/valproic-acid-and-divalproex-sodium
"Valproic Acid and Divalproex Sodium." Gale Encyclopedia of Neurological Disorders. . Retrieved August 20, 2017 from Encyclopedia.com: http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/valproic-acid-and-divalproex-sodium
Divalproex sodium is an anticonvulsant (antiseizure) drug. It is also used to treat mania and to help prevent migraine headaches. It is sold under multiple brand names in the United States, including Depacon, Depakene, Depakote, and Depakote sprinkle.
Divalproex sodium is effective in the treatment of epilepsy, particularly for preventing simple, complex (petit mal), absence, mixed, and tonic-clonic (grand mal) seizures . Divalproex sodium is also used to treat the manic phase of bipolar disorder (also called manic-depressive disorder) in adults, and to prevent migraine headache in adults.
Divalproex sodium is chemically compounded from sodium valproate and valproic acid in a 1:1 ratio.
Divalproex sodium is thought to work by increasing the levels of a brain neurotransmitter called gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter, which means that its presence makes it harder for nerve cells (neurons) in the brain to become activated (fire). It is believed that increasing GABA's inhibitory action on brain neurons accounts for the ability of divalproex sodium to decrease seizures, curb manic behaviors, and decrease the frequency of migraine headaches.
Divalproex sodium was discovered to decrease the likelihood of seizure in 1963. In 1978, the United States Food and Drug Administration approved it for this use. Other uses for divalproex sodium were researched and approved subsequently, including use against mania (1995) and use to decrease migraine headache frequency. Divalproex sodium's 1995 approval as an anti-mania medication was considered an exciting advance, since it represented the first new drug introduced for this use in 25 years.
Divalproex sodium is available in tablets of 125 mg, 250 mg, and 500 mg. Divalproex sodium is also available in 125-mg capsules, and in a 500-mg extended release tablet. A syrup is also available, containing 250 mg active drug per 5 mL.
Divalproex sodium therapy is usually started at 10–15 mg per kg of body weight per day. Dosages are then increased until seizures seem to be well controlled. This is usually achieved at averages under 60 mg per kg per day.
To treat mania, divalproex sodium is usually started at a daily dose of about 750 mg.
For migraine prevention, divalproex sodium is started at 250 mg, twice per day. In some patients, this dose will have to be raised to a total of 1,000 mg per day.
A greater risk of liver damage exists in patients with kidney disease, known liver disease, Addison's disease, blood diseases, children under the age of two, patients with organic brain diseases (such as Alzheimer's, Parkinson's, slow virus infections, Huntington's chorea, multiple sclerosis, etc.), patients with metabolic disorders present at birth, patients with severe seizure disorders and accompanying mental retardation , and patients who are taking several other anticonvulsant drugs.
Because divalproex sodium can affect a patient's blood by dropping the platelet (a type of blood cell that affects clotting) count and interfering with coagulation (clotting) capability, both platelet count and coagulation parameters should be verified before starting the medication and at intervals throughout its use.
Divalproex sodium is known to cause an increased risk of birth defects when taken during pregnancy. An individual and her health care provider must weigh the potential risks and benefits of using this medication during pregnancy. Women who take this medicine should not breast-feed, since a small amount will pass into the breast milk
Divalproex sodium causes drowsiness and impairs alertness in some individuals. Patients just beginning to use the medication should avoid driving and using dangerous machinery until they determine how the drug affects them. The sedative effects are increased in the presence of alcohol, so patients should avoid drinking while taking medicines containing divalproex sodium.
Some of the more common side effects of divalproex sodium include mild stomach cramps, change in menstrual cycle, diarrhea, loss of hair, indigestion, decreased appetite, nausea and vomiting, trembling in the hands and arms, and weight loss or weight gain. These side effects usually go away as the patient's body becomes accustomed to the medication.
Less common side effects include severe stomach cramps or continued nausea and vomiting, changes in mood, behavior, or thinking, double vision or seeing spots, severe fatigue , easy bruising or unusual bleeding, yellow cast to the skin or the whites of the eyes (jaundice), odd eye movements, and increased seizures. Patients who notice these symptoms should check with their doctor to see if their dosage or medication needs to be adjusted.
Rare side effects that should be checked out by a doctor include clumsiness, difficulty with balance, constipation, dizziness, drowsiness, headache, skin rash, agitation, restlessness, or irritability.
Divalproex sodium is broken down (metabolized) in the liver. Other drugs that are metabolized in the liver can have too low or too high concentrations in the body when taken with divalproex sodium. Levels of divalproex sodium may be increased when taken with felbamate, isoniazid, salicylates (aspirin-containing medications), clarithromycin, erythromycin, and troleandomycin. Divalproex sodium may increase levels of carbamazepine , phenytoin, lamotrigine , nimodipine, phenobarbital, and zidovudine. Use with clonazepam may cause absence seizures. Cholestyramine and colestipol may reduce the absorption and the blood levels of divalproex sodium.
Ellsworth, Allan J., and others. Mosby's Medical Drug Reference. St. Louis: Mosby, Inc., 1999.
Mosby's Drug Consult. St. Louis: Mosby, Inc., 2002.
Rosalyn Carson-DeWitt, M.D.
"Divalproex sodium." Gale Encyclopedia of Mental Disorders. . Encyclopedia.com. (August 20, 2017). http://www.encyclopedia.com/psychology/encyclopedias-almanacs-transcripts-and-maps/divalproex-sodium
"Divalproex sodium." Gale Encyclopedia of Mental Disorders. . Retrieved August 20, 2017 from Encyclopedia.com: http://www.encyclopedia.com/psychology/encyclopedias-almanacs-transcripts-and-maps/divalproex-sodium
Valproic acid is an anticonvulsant (anti-seizure) drug. In the United States, valproic acid is also known as valproate, and is sold under the brand name Depakene.
The United States Food and Drug Administration (FDA) recognizes valproic acid for the treatment of epilepsy and for mania that occurs with bipolar disorder (previously called manic-depressive disorder). Valproic acid is also approved for the prevention of migraine headaches.
Valproic acid's properties in preventing seizures were first discovered in Europe in 1963. The medication was first used clinically in the United Stated in 1978.
Valproic acid is effective in treating a variety of seizure types, which include simple and complex absence seizures, partial seizures, and clonic-tonic seizures (grand mal seizures). Valproic acid is effective in treating the manic episodes of patients with bipolar disorder. Patients who have bipolar disorder resulting from a head injury and patients who do not respond to or who cannot tolerate conventional lithium therapy (normally the therapy of choice for bipolar disorder) can be treated with valproic acid. In addition, valproic acid provides a 50% or greater reduction in the frequency of migraine headaches. Valproic acid is also safe and effective in preventing headaches that arise as a side effect of taking a class of drugs known as selective serotonin reuptake inhibitors (SSRI). These drugs include sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), fluvoxamine (Luvox), and citalopram (Celexa).
Valproic acid comes in 250-mg gelatin capsule and in 250 mg/5ml-syrup.
The dosage of valproic acid used to treat epilepsy depends on the type of seizures the patient has. The doses are determined based on the patient's weight and never based on the patient's age.
The initial dose of valproic acid used to treat mania is 750 mg daily. This dose is then reduced to the lowest dose that will achieve the desired effects. Another dosage strategy is based on patient weight. The starting dose is 30 mg per kilogram of body weight on days one and two followed by 20 mg per kg of body weight taken daily on days three through ten.
For prevention of migraine headaches, a dose of 250 mg twice daily is beneficial. It may take up to 1,000 mg of valproic acid to control migraine attacks.
Patients who have liver disease should not take valproic acid. Pregnant women should not take valproic acid, because it can harm the developing fetus. Patients who are allergic to valproic acid should not take it.
When it is necessary for children under age two and patients who have pancreatitis to take valproic acid, the drug should be used cautiously and with close physician monitoring.
Valproic acid can cause liver damage. Before starting valproic acid therapy, every patient should have a blood test to assess his or her liver function. The risk of valproic acid causing liver damage is greatest during the first six months of treatment. Liver function tests should be done once a month during the first three months, then every three to six months for as long as the patient continues to take the drug. Vomiting, lethargy, anorexia, and jaundice (yellowing of the skin) may precede signs of liver damage. If a patient develops severe or unusual abdominal pain, this may be a sign of pancreatitis (inflammation of the pancreas). Pancreatitis can occur in both children and adults. It can develop shortly after valproic acid is started or after several years of use.
Other side effects of valproic acid may include nausea, vomiting, indigestion, and either diarrhea or constipation. Headaches, dizziness, lack of coordination, confusion, fatigue , tremor, drowsiness, and seizures have also been associated with the use of valproic acid. Behavioral changes associated with the drug including irritability, longer and deeper sleep, hyperactivity, increased sociability, increased sadness, happiness or aggression, are seen more often in children than in adults taking valproic acid.
Fewer than 1% of patients experience appetite changes. These changes may include either diminished or increased appetite. Skin rash, photosensitivity (acute sensitivity to the sun), hair loss, and other hair changes have also been reported in people using valproic acid.
Using valproic acid with other anticonvulsant drugs, such as phenobarbital, clonazepam , and lamotrigine may cause excessive sedation (drowsiness and lack of physical and mental alertness). Valproic acid may diminish the benefits of phenytoin which is another commonly used anticonvulsant.
Taking aspirin during valproic acid therapy may cause valproic acid levels to increase to toxic (poisonous) levels. Other medications that may cause valproic acid toxicity are erythromycin, an antibiotic, and the antidepressant amitriptyline . Drugs that can decrease the effectiveness of valproic acid include carbamazepine and cholestyramine. Ginkgo biloba , an herbal supplement commonly available in the United States, may be prepared with a chemical called 4'-O-methylpyridoxine. If this chemical remains in the herbal preparation, it can cause seizures, and reduce the effectiveness of valproic acid. Severe central nervous depression has been reported with the use of valproic acid and another anticonvulsant called primidone.
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Hirschfeld, Robert. "Safety and Tolerability of Oral Loading Divalproex Sodium in Acutely Manic Bipolar Patients." Journal of Clinical Psychiatry. 60 (1999): 815-818.
Ajna Hamidovic, Pharm.D.
"Valproic acid." Gale Encyclopedia of Mental Disorders. . Encyclopedia.com. (August 20, 2017). http://www.encyclopedia.com/psychology/encyclopedias-almanacs-transcripts-and-maps/valproic-acid
"Valproic acid." Gale Encyclopedia of Mental Disorders. . Retrieved August 20, 2017 from Encyclopedia.com: http://www.encyclopedia.com/psychology/encyclopedias-almanacs-transcripts-and-maps/valproic-acid
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"sodium valproate." A Dictionary of Nursing. . Retrieved August 20, 2017 from Encyclopedia.com: http://www.encyclopedia.com/caregiving/dictionaries-thesauruses-pictures-and-press-releases/sodium-valproate