Divalproex Sodium-Valproic Acid (Depakote®)
- Depakene® - immediate release
- Syrup: 250 mg/5mL (there is 250 mg in one teaspoonful)
- Capsules: 250 mg
- Depakote®/Depakote® ER– both are enteric-coated and slow release; Depakote® ER releases more slowly than Depakote®.
- Depakote® tablets: 125 mg, 250 mg, 500 mg
- Depakote® sprinkle capsules: 125 mg
- Depakote® ER tablets: 250 mg, 500 mg
- Stavzor®– delayed release
- Capsules: 125 mg, 250 mg, 500
- Divalproex sodium, valproate, valproic acid [commonly referred to as valproate to include all formulations]
Note: For the purpose of this document, the medication will be referred to as valproate to avoid confusion. Even though valproate is available in different names, strengths and formulations all provide the same active medicine. (See below for what you need to know about the different forms).
What is divalproex sodium and what does it treat?
Valproate is a medication that works in the brain to treat bipolar disorder. It is approved for the treatment of seizures (epilepsy) in adults and children; migraine headaches and acute mania associated with bipolar. Bipolar disorder involves episodes of depression and/or mania.
A depressive episode, or depression, occurs when a person experiences several of the following symptoms at the same time: "low" or depressed mood (for example, sad, empty, tearful), decreased interest in most or all activities, changes in appetite (usually decreased), changes in sleep (usually poor sleep), loss of energy, feeling worthless/guilty/hopeless/helpless, psychomotor agitation or retardation (i.e., thoughts/movements speeding up or slowing down), difficulty concentrating, and thoughts of death (suicidal thinking).
A manic episode, or mania, is when a person experiences several of the following symptoms at the same time: “high” or irritable mood, very high self esteem, decreased need for sleep, pressure to keep talking, racing thoughts, being easily distracted, and frequently involved in activities with large risk for bad consequences (for example, excessive buying sprees).
Bipolar disorder is a brain disorder (mental illness) that exposes people to these mood changes over the course of time. Bipolar disorder affects more than two million Americans each year, but patients with this disorder can lead fulfilling lives when they receive proper treatment. Unfortunately, many people with this illness do not receive treatment.
What is the most important information I should know about divalproex sodium?
Do not stop taking valproate or change your dose without first talking to your healthcare provider.
Valproate is used for long-term treatment of bipolar disorder.
Do not stop taking valproate even when you feel better. Only your healthcare provider can determine the length of valproate treatment that is right for you.
Missing doses of valproate may increase your risk for a relapse in your mood symptoms.
In order for valproate to work properly, it should be taken every day as ordered by your healthcare provider.
Periodically, your healthcare provider may ask you to provide a blood sample to make sure the appropriate level of medication is in your body and to assess for side effects, such as changes in blood counts.
Are there specific concerns about divalproex sodium and pregnancy?
If you are planning on becoming pregnant, notify your healthcare provider to best manage your medications. People living with bipolar disorder who wish to become pregnant face important decisions. This is a complex decision since untreated bipolar disorder has risks to the fetus as well as the mother. It is important to discuss with your doctor and caregivers.
See warnings at the end of this sheet for specific risks.
The American Academy of Pediatrics committee on medications in breast-feeding lists valproate as “compatible” with breast-feeding.
What should I discuss with my healthcare provider before taking divalproex sodium?
- Symptoms that are most bothersome to you about your condition
- If you have thoughts of suicide
- Medications you have taken in the past to treat bipolar disorder, whether they were effective or caused any adverse effects
- Any psychiatric or medical problems you may have
- All other medications you are currently taking (including over the counter products, herbal and nutritional supplements) and any medication allergies you have
- Other non-medication treatment you are receiving (such as psychotherapy (i.e., talk therapy) or substance abuse treatment). Your provider can explain how these different treatments work with the medication.
- If you are pregnant, plan to become pregnant, or are breast-feeding
- If you smoke, drink alcohol or use illegal drugs
How should I take divalproex sodium?
Valproate is available in many different forms (e.g., liquid, sprinkle capsules and long-acting tablets) and usually is taken 1-3 times a day depending on the dosage form.
Valproate tablets should be swallowed whole, not crushed or chewed.
The contents of Depakote Sprinkle® capsules may be sprinkled on a small amount of soft food (such as applesauce or pudding) and swallowed immediately. The contents should not be crushed or chewed.
While the dose usually ranges from 1000 and 2500 mg daily, your healthcare provider will determine the dose that is right for you based upon your response and your blood level.
What happens if I miss a dose of divalproex sodium?
If you miss a dose of valproate, take it as soon as you remember it. If it is close to your next dose, wait until then to take the medication and skip the missed dose. Do not double your next dose or take more than your prescribed dose. Discuss any missed doses with your healthcare provider
What should I avoid while taking divalproex sodium?
Avoid drinking alcohol or using illegal drugs while you are taking valproate. They may decrease the benefits (i.e., worsen your symptoms) and increase adverse effects (e.g., sedation, dizziness).
What happens if I overdose with divalproex sodium?
If an overdose occurs call your doctor or 911. You may need urgent medical care. You may also contact the poison control center at 1 (800) 222-1222.
Overdosing with valproate may lead to dizziness, poor coordination, drowsiness, tremor, confusion, nausea, and vomiting. In severe cases, seizures, coma and death can occur.
A specific antidote for valproate does not exist.
What are possible side effects of divalproex sodium?
Common Side Effects
Nausea, diarrhea, drowsiness, and dizziness and weight gain
Rare Side Effects
Valproate may cause an increase in your blood levels of ammonia. If this happens, you may get confused, disoriented, or have difficulty thinking. It may also cause a decrease in the levels of platelets in your blood. If this happens, you may notice that you bruise easier than normal. Blood tests can be used to check the amount of ammonia and platelets in your blood and ensure safety of this medication.
Liver problems, which are rarely severe, may develop on valproate especially in the first six months of treatment. This is most common in young children taking valproate and other anticonvulsants for epilepsy. Pancreatitis and decreased blood counts are also rare but serious side effects. Blood tests to monitor blood counts, as well as liver and pancreas function are an important part of treatment with valproate, in order to make sure that you are safe. A fever or rash may be seen within the first few weeks of treatment. If you develop a fever, rash or itching soon after starting valproate contact your health care provider immediately.
Long-term use of valproate may lead to some hair loss. Speak to your healthcare provider if you experience this side effect.
Stopping valproate quickly may lead to having a seizure. Do not stop taking valproate without discussing it with your healthcare provider.
Talk with your healthcare provider if you experience side effects that are bothersome to you.
Are there any risks for taking divalproex sodium for long periods of time?
To date, there are no known problems associated with long term use of valproate. It is a safe and effective medication when used as directed.
What other medications may interact with divalproex sodium
- Medications that may decrease levels of valproate in the body: phenytoin (Dilantin®), carbamazepine (Tegretol®/Carbatrol®/Equetro®), rifampin (Rifadin®), or phenobarbital
- Avoid taking high doses of aspirin (for example, 325 mg three or more times a day) to treat fever or pain. Aspirin can interfere with valproate and increase valproate blood levels significantly. If you are taking a baby aspirin 81 mg or aspirin 325 mg once a day for your heart, this should not interfere with valproate.
- Valproate may increase the levels of some medications such as amitriptyline (Elavil®) and anti-seizure medications such as phenytoin (Dilantin®), carbamazepine (Tegretol®/Carbatrol®/Equetro®), and especially lamotrigine (Lamictal®).
- Combining valproate with a medication called topiramate (Topamax®) may also increase ammonia levels in your blood. If this happens, you may get confused, disoriented, or have difficulty thinking.
How long does it take for divalproex sodium to work?
It is very important to tell your doctor how you feel during the first few weeks after you start taking valproate. It will probably take several weeks to see big enough changes in your symptoms to decide if valproateis the right medication for you.
Mood stabilizer treatment is generally needed lifelong for persons with bipolar disorder. Your doctor can best discuss the duration of treatment you need based on your symptoms and course of illness.
Liver problems or hepatic failure, which is rarely severe, may develop on valproate especially in the first six months of treatment. This is most common in young children (<2 years of age) taking valproate and other anticonvulsants for epilepsy. Your doctor will conduct blood tests to monitor your liver at regular intervals. If you experience right-sided stomach pain, severe nausea/vomiting, facial swelling, yellowing of the skin, and pale stools, these may be signs of liver problems. If you experience any of these symptoms, contact your healthcare provider immediately.
Pancreatitis (inflammation of the pancreas) is also a rare but serious side effects. If you experience severe belly pain, nausea, vomiting, and not feeling hungry contact your doctor immediately.
Exposure to valproate during the first three months of pregnancy is associated with increased risk of spinal cord defects (e.g., spina bifida) in the fetus. Bleeding, liver problems, developmental delays and other birth defects have also been reported. In order to decrease this risk, exposure to valproate during the first three months should be avoided if possible. Valproate can also cause vitamin K deficiency in the baby, which will increase the risk of bleeding. If valproate is used during pregnancy, close monitoring of fetal serum levels is recommended and a vitamin K supplement may be necessary.
FDA Alert, July 2011. Recently, the Food and Drug Administration (FDA) warned that children who experienced prenatal exposure to valproate may have affected information processing capabilities. The FDA is encouraging any woman who becomes pregnant while receiving valproate to enroll in the North American Antiepileptic Drug Pregnancy Registry (1 (888) 233-2334).
Provided by College of Psychiatric and Neurologic Pharmacists, January 2012
Reviewed by Ken Duckworth, M.D., NAMI Medical Director