Depakote (divalproex sodium)
Depakote® is a medication that is used to treat symptoms of seizure and bipolar disorders, as well as to prevent migraine headaches. Depakote should not be taken by pregnant women as it has been linked to serious birth defects including spina bifida, cleft palate, low intellectual functioning, and facial abnormalities. It is available by prescription in 125mg, 250mg, and 500mg tablets.
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
The FDA has issued a black box warning (.pdf) (the strictest warning category) for Depakote, as it can cause pancreatitis in children and adults and can result in liver failure. Symptoms of liver problems include jaundice (yellowing of the skin and eyes), loss of appetite, stomach pain, and back pain. It is most likely to cause liver problems during the first six months of use.
Children less than two years of age with certain medical conditions (including congenital disorders, and severe seizure disorders) who are taking more than one medication for seizures are at increased risk of experiencing potentially dangerous side effects. Children with intellectual disabilities or any form of cognitive impairment (difficulty thinking or learning) should also not take divalproex sodium.
In Pregnant and Nursing Mothers
Depakote has been listed by the FDA as a Category D pregnancy risk for treating epilepsy and mania, and is known to cause serious birth defects when taken by pregnant women. The FDA has also categorized the drug as a Category X pregnancy risk (fda.gov) for the treatment of migraines, as the benefits of the medication do not outweigh the risks (valproic acid should not be taken by pregnant women for the treatment of migraine headaches). Some of the birth defects associated with divalproex sodium include polydactyly (extra fingers or toes), cleft palate, spinal cord malformations such as spina bifida (a condition where the bones of the spine don’t develop normally), skull abnormalities, facial deformations, low intellectual functioning (low IQ), congenital heart defects, such as a hole in the heart, and neural tube defects. Babies born to mothers that take valproic acid during their first 12 weeks of pregnancy have a 1 in 20 chance of being born with a neural tube defect. These infants are also four times more likely to be born with major malformations.
Despite being considered safe by The American Academy of Pediatrics and the World Health Organization (WHO), the FDA suggests women who are breastfeeding should consult their doctor before taking the drug as it can pass into breast milk (.pdf).
In People with Bipolar Disorder
The FDA has warned that people with bipolar disorder who take Depakote are at increased risk for depression and suicidal thoughts and behaviors.
Other Side Effects
Less severe side effects of Depakote include bruising easily, dizziness, joint weakness, abnormal bleeding, changes in menstrual periods, difficulty breathing, loss of consciousness, fever, hives, confusion, fatigue, nausea, and vomiting.
Several lawsuits are linked to the drug’s manufacturer, Abbot Laboratories, due to illegal promotion for off-label uses. Lawsuits have also been filed with the makers of this medication as a result of birth defects from prenatal exposure to valproic acid, and for not providing sufficient warnings of the risks associated with fetal exposure, such as spina bifida and low intellectual functioning.
In 2015, a Saint Louis jury awarded the family of a young girl born with several birth defects, including spina bifida, $38 million. The jury decided that Abbot Laboratories did not provide sufficient warning of the elevated risk of birth defects in babies born to women that were taking Depakote while pregnant. In 2012, the manufacturer paid $1.6 billion in a settlement because it promoted valproate to nursing homes for unapproved uses, including for the treatment of agitation in elderly patients with dementia, schizophrenia, depression, and anxiety. In 2011, Abbot Laboratories was required to pay $1.6 billion to settle claims that it illegally marketed the drug for off-label purposes that have not been approved by the FDA (washingtonpost.com).
Abbot Laboratories and its subdivision Abbvie continue to deal with accusations of racketeering. In April 2015, the U.S. Court of Appeals in Chicago reversed a district court’s earlier dismissal of a putative class action lawsuit brought by Sidney Hillman Health Center of Rochester and others that claimed the manufacturers conducted a scheme to have them and other third-parties pay for Depakote prescriptions to treat non-FDA approved conditions in violation of the Racketeering and Corrupt Organizations Act (RICO) (dailyreportingsuite.com).
Regardless of the number of legal issues surrounding Depakote, valproic acid is included on the World Health Organization's List of Essential Medicines, a list of what the organization considers to be the most vital medications in the healthcare industry.
FDA Safety Alerts
On May 6, 2013, the FDA issued the Safety Communication linked below, warning that women should not take Depacon, Stavzor, Depakene, Depakote, Depakote ER, Depakote CP, or any of the generic forms of these drugs to treat migraine headaches, as these drugs can cause decreased IQ scores in children who were exposed prenatally. The risk category was changed from D, with the benefit outweighing the risk, to X, with the benefit clearly not. (fda.gov)
In July, 2000, Abbot Laboratories issued the below “Important Drug Warning”, indicating that children and adults taking Depakote Tablets, Depakote ER Tablets, Depakon injections, Depakene Capsules and Syrup, and Depakote Sprinkle Capsules are at an increased risk for developing life-threatening pancreatitis. Symptoms can develop quickly after first use or over years of use, and include abdominal pain, nausea, vomiting, and trouble eating. (.pdf).
In June, 2002, Abbott also alerted healthcare professionals and their patients that there had been reports of hyperammonemic encephalopathy in people that took Depakote who also had a urea cycle disorder, particularly ornithine transcarbamylase deficiency (UCD is a group of rare genetic abnormalities). People with UCD have difficulty producing urea, a substance that controls levels of ammonia in the body. Signs of hyperammonemic encephalopathy include changes in mental status, loss of energy, and vomiting. Some of these cases were fatal. People with UCD and people who are suspected of having UCD should not take valproate. This warning includes Depakote Tablets, Depakote ER Tablets (divalproex sodium), Depakene Capsules and Syrup, Depakon injections (valproate sodium), and Depakote Sprinkle Capsules (.pdf).
FDA Labeling Changes
As of March, 2015, the U.S. Food and Drug Administration has issued several labeling changes to Depakote packaging, which makes note of adverse reactions, precautions, and other warnings. These changes are summarized below:
Depakote causes changes in hair and eye color, as well as changes in the endocrine system, including elevated testosterone and male patterns of body hair in women.
Serious birth defects resulting from prenatal exposure to valproic acid have also been reported such as neural tube defects, skull abnormalities, heart defects, and limb defects. These babies were exposed to the drug because their mothers were taking Depakote while pregnant. During this time, the FDA also reported bleeding disorders such as dose-related thrombocytopenia, decreases in other cell lines and myelodysplasia, and issues with blood clotting.
A multiorgan hypersensitivity reaction, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), was included in this release of warnings for Depakote. Symptoms of DRESS include fever, rash, lymphadenopathy (a lymph-node disease), and hepatitis. These reactions are very serious and can be fatal.
Depakote can also affect the musculoskeletal system. People taking Depakote are at risk for decreased bone mineral density, bone fractures, osteoporosis, and osteopenia (reduced bone mass- like a less severe form of osteoporosis).
The FDA released a new Black Box Warning (the most serious category of warnings) as individuals that take Depakote who also have a mitochondrial disease are at increased risk of acute liver failure and death. This includes people taking valproate with hereditary neurometabolic syndromes resulting from DNA mutations involving the mitochondrial DNA Polymerase γ (POLG) gene (such as those with Alpers Huttenlocher Syndrome). People (especially children that are younger than two years old) should not take Depakote if they could have a mitochondrial disease, even if they haven't been officially diagnosed. Most of these fatalities have occurred in children and adolescents.
Depakote shouldn’t be taken by women who plan to conceive unless not doing so would result in permanent injury or death, and should not be taken for epilepsy (a seizure disorder) by women who are pregnant or plan to become pregnant if their conditions may be treated with other medications. This labeling change was added after evidence was found of babies being born with birth defects, such as structural and cardiovascular abnormalities, including low IQ and spina bifida.
Depakote is used in the treatment of seizure disorders (including complex partial seizures and simple and complex absence seizures) and to prevent migraine headaches. It is also used to treat manic episodes related to bipolar disorder and is often combined with SSRI’s (selective serotonin reuptake inhibitors) to treat bipolar depression. It has been the most widely prescribed antiepileptic drug worldwide (jcs.biologists.org).
Valproic acid was developed by B.S. Burton in France in 1882 to be used as an organic solvent, and approved in France for the treatment of epilepsy in 1967. Also known as 2-Propylvaleric acid, and marketed under the trade name Depakote, it was first approved in the United States by the FDA in 1983 to treat epilepsy. In 1995, the drug was approved by the FDA to treat bipolar disorder, and in 1996 to prevent chronic migraines. Today, Depakote is still one of the most commonly prescribed medications for seizure disorders, bipolar disorder, and migraine headaches.
How It Works
Depakote works to balance chemicals in the body by increasing the amount of GABA (gamma-aminobutyric acid), a neurotransmitter that helps to control the nervous system and is categorized as an anticonvulsant and a mood stabilizer. Other forms include Depakote CP and Depakote ER. The prescription comes in three doses: 125 mg, 250 mg, and 500 mg. Generic names include divalproex sodium, valproic acid, and valproate. Stavzor, Convulex, Epilim, Valparin, Depakene, Depacon, and Valproic are some of the other brand names for valproic acid. Once changed into a usable form in the body, valproic acid is called valproate.
Drugs That May Adversely React With Depakote & Related Drugs
According to the National Alliance for Mental Illness (NAMI), Depakote should not be taken in combination with certain antidepressants, such as phenelzine, nortriptyline, and amitriptyline. It is also noted that some antibiotics do not interact well with valproate, such as doripenem and imipenem, and that certain seizure medications are not safe to combine with Depakote. Phenobarbital (also used to treat epilepsy), phenytoin, and topiramate are some of these medications. Also mentioned is high-dose aspirin, which should not be taken with divalproex sodium. Antihistamines and alcohol can increase medication side effects, such as drowsiness, and should be avoided when taking Depakote (nami.org).
Physicians Total Care, Inc.
Rebel Distributors Corp
Lake Erie Medical & Surgical Supply Dba Quality Care Products Llc
Login To Your Free Account