Depakote Capsules

Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however patients have recovered from valproate levels as high as 2,120 mcg/mL.

In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output.

Naloxone has been reported to reverse the CNS depressant effects of valproate over dosage. Because naloxone could theoretically also reverse the antiepileptic effects of valproate, it should be used with caution in patients with epilepsy.

Divalproex sodium is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0.5 equivalent of sodium hydroxide. Chemically it is designated as sodium hydrogen bis(2-propylpentanoate). Divalproex sodium has the following structure:

Divalproex sodium occurs as a white powder with a characteristic odor.

Depakote Sprinkle Capsules are for oral administration. Depakote Sprinkle Capsules contain specially coated particles of divalproex sodium equivalent to 125 mg of valproic acid in a hard gelatin capsule.

Inactive Ingredients

125 mg Depakote Sprinkle Capsules: cellulosic polymers, D&C Red No. 28, FD&C Blue No. 1 gelatin, iron oxide, magnesium stearate, silica gel, titanium dioxide, and triethyl citrate.

Meets USP Dissolution Test 2.

1. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12 (3):244-252.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Hepatotoxicity

Warn patients and guardians that nausea, vomiting, abdominal pain, anorexia, diarrhea, asthenia, and/or jaundice can be symptoms of hepatotoxicity and, therefore, require further medical evaluation promptly [see Warnings and Precautions (5.1)].

Pancreatitis

Warn patients and guardians that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly [see Warnings and Precautions (5.5)].

Birth Defects and Decreased IQ

Inform pregnant women and women of childbearing potential that use of valproate during pregnancy increases the risk of birth defects and decreased IQ in children who were exposed. Advise women to use effective contraception while using valproate. When appropriate, counsel these patients about alternative therapeutic options. This is particularly important when valproate use is considered for a condition not usually associated with permanent injury or death. Advise patients to read the Medication Guide, which appears as the last section of the labeling [see Warnings and Precautions (5.2, 5.3, 5.4) and Use in Specific Populations (8.1)].

Advise women of childbearing potential to discuss pregnancy planning with their doctor and to contact their doctor immediately if they think they are pregnant.

Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 [see Use in Specific Populations (8.1)].

Suicidal Thinking and Behavior

Counsel patients, their caregivers, and families that AEDs, including Depakote, may increase the risk of suicidal thoughts and behavior and to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to the healthcare providers [see Warnings and Precautions (5.7)].

Hyperammonemia

Inform patients of the signs and symptoms associated with hyperammonemic encephalopathy and to notify the prescriber if any of these symptoms occur [see Warnings and Precautions (5.9, 5.10)].

CNS Depression

Since valproate products may produce CNS depression, especially when combined with another CNS depressant (e.g., alcohol), advise patients not to engage in hazardous activities, such as driving an automobile or operating dangerous machinery, until it is known that they do not become drowsy from the drug.

Multiorgan Hypersensitivity Reactions

Instruct patients that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related and should be reported to the physician immediately [see Warnings and Precautions (5.12)].

Medication Residue in the Stool

Instruct patients to notify their healthcare provider if they notice a medication residue in the stool [see Warnings and Precautions (5.18)].

AbbVie Inc.

North Chicago, IL 60064, U.S.A.

©2017 AbbVie Inc.

Revised: March 2017

03-B502

Administration Guide

DEPAKOTE®

Sprinkle Capsules

DIVALPROEX SODIUM DELAYED RELEASE CAPSULES

DEPAKOTE® Sprinkle Capsules (divalproex sodium delayed release capsules) may be swallowed whole or the capsule contents may be sprinkled onto soft food such as applesauce or pudding.

Serving Suggestions

Depakote® Sprinkle Capsules (divalproex sodium delayed release capsules) provide the medicine that your healthcare provider has prescribed. The sprinkles are flavorless. Soft foods such as applesauce or pudding are best to use for mixing and taking Depakote Sprinkles.

TO ADMINISTER WITH FOOD:

Make sure this medicine is taken exactly as your healthcare provider prescribed it. If you have any questions, please contact your healthcare provider or pharmacist. Keep all of your healthcare provider's appointments as scheduled. Make sure that Depakote Sprinkle Capsules and all other medicines are kept out of the reach of children.

Note

You may see the specially coated particles in Depakote Sprinkle Capsules in stool. If you do, you should inform your healthcare provider.

Ask your healthcare provider or pharmacist about possible side effects with Depakote Sprinkle Capsules.

Store Depakote Sprinkle Capsules below 77°F (25°C).

AbbVie Inc.

North Chicago, IL 60064, U.S.A.

©2017 AbbVie Inc.

Revised: March 2017

03-B502

Do not use divalproex sodium to prevent migraine headaches if you are pregnant.

If you take divalproex sodium for seizures or manic episodes: Do not start or stop taking the medicine during pregnancy without your doctor's advice. Divalproex sodium may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby.

You should not use divalproex sodium if you have liver disease, a urea cycle disorder, or a genetic disorder such as Alpers' disease or Alpers-Huttenlocher syndrome (especially in a child younger than 2 years old).

Divalproex sodium can cause liver failure that may be fatal, especially in children under age 2 and in people with liver problems caused by a genetic mitochondrial (MYE-toe-KON-dree-al) disorder.

Call your doctor at once if the person taking this medicine has signs of liver or pancreas problems, such as: loss of appetite, upper stomach pain (that may spread to your back), ongoing nausea or vomiting, dark urine, swelling in the face, or jaundice (yellowing of the skin or eyes).

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Drink plenty of water while you are taking this medication. Your dose may need to be changed if you do not get enough fluids each day.

You may open the divalproex sodium sprinkle capsule and sprinkle the medicine into a spoonful of pudding or applesauce to make swallowing easier. Swallow this mixture right away.

Do not crush, chew, break, or open a delayed-release or extended-release tablet or capsule. Swallow it whole.

While using divalproex sodium, you may need frequent blood tests.

Wear a medical alert tag or carry an ID card stating that you take divalproex sodium. Any doctor, dentist, or emergency medical care provider who treats you should know that you are taking a seizure medication.

If you need surgery, tell the surgeon ahead of time that you are using divalproex sodium.

Do not stop using divalproex sodium suddenly, even if you feel fine. Stopping suddenly may cause a serious, life-threatening type of seizure. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Common side effects of Depakote Sprinkles include: abdominal pain, asthenia, dizziness, drowsiness, nausea, and anorexia. Other side effects include: abnormality in thinking, alopecia, ataxia, nystagmus, tremor, weight loss, fever, and skin rash. See below for a comprehensive list of adverse effects.