Depakote Sprinkles

Name: Depakote Sprinkles

Dosing & Uses

Dosage Forms & Strengths

Dosages expressed as valproic acid equivalents

tablet, delayed-release (Depakote)

  • 125mg
  • 250mg
  • 500mg

tablet, extended-release (Depakote ER)

  • 250mg
  • 500mg

capsule (Depakote Sprinkles)

  • 125mg

Mania

Indicated for treatment of manic episodes associated with bipolar disorder

Depakote initial dose: 750 mg/day PO in divided doses

Depakote ER initial dose: 25 mg/kg PO once daily Increase as rapidly as possible to achieve the lowest therapeutic dose that provides desired clinical effect or plasma concentration

Not to exceed 60 mg/kg/day

Epilepsy

Complex partial seizures: Indicated as monotherapy and adjunctive therapy for complex partial seizures that occur either in isolation or in association with other types of seizures

Simple and complex absence seizures: Also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

10-15 mg/kg/day PO initially; may increase by 5-10 mg/kg/week to achieve optimal clinical response; not to exceed 60 mg/kg/day

Depakote: If daily dose >250 mg, give as divided dose

Migraine Prophylaxis

Indicated for prophylaxis of migraine headaches; there is no evidence of use for acute treatment

Depakote initial dose: 250 mg PO BID for 1 week

Depakote ER initial dose: 500 mg PO qDay for 1 week

May increase dose up to 1000 mg/day if needed

Dosage Modifications

Conversion to monotherapy: Decrease concomitant antiepilepsy drug dosage ~25% q2weeks

Renal impairment

  • No adjustment necessary; protein binding is reduced and may cause measurement of total valproate concentrations to be inaccurate

Hepatic impairment

  • Administer lower doses
  • Contraindicated in severe impairment

Dosing Considerations

Monitor LFT's

Conversion from Depakote to Depakote ER: Administered Depakote ER once daily using a dose 8-20% higher than the total daily dose of Depakote

Therapeutic range

  • Low serum albumin levels may cause an increase in unbound drug (while total concentration may appear normal)
  • Epilepsy: 50-100 mcg/mL total valproate
  • Mania: 50-125 mcg/mL total valproate; maximum concentrations generally achieved within 14 days

Administration

Swallow whole, do not chew or crush

Capsules may be opened and sprinkled on spoonful of soft food immediately before administration

If dose is skipped, do not double next dose

Depakote or Depakote Sprinkles: If daily dose >250 mg, give as divided dose

Depakote ER: Administer once daily

Dosage Forms & Strengths

Dosages expressed as valproic acid equivalents

tablet, delayed-release (Depakote)

  • 125mg
  • 250mg
  • 500mg

tablet, extended-release (Depakote ER)

  • 250mg
  • 500mg

capsule (Depakote Sprinkles)

  • 125mg

Epilepsy

Complex partial seizures: Indicated as monotherapy and adjunctive therapy for complex partial seizures that occur either in isolation or in association with other types of seizures

Simple and complex absence seizures: Also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

<10 years: Safety and efficacy not established

10-15 mg/kg/day PO initially; may increase by 5-10 mg/kg/week to achieve optimal clinical response; not to exceed 60 mg/kg/day

Dosage Modifications

Conversion to monotherapy: Decrease concomitant antiepilepsy drug dosage ~25% q2weeks

Renal impairment

  • No adjustment necessary; protein binding is reduced and may cause measurement of total valproate concentrations to be inaccurate

Hepatic impairment

  • Administer lower doses
  • Contraindicated in severe impairment

Dosing Considerations

Monitor LFT's

Conversion from Depakote to Depakote ER: Administered Depakote ER once daily using a dose 8-20% higher than the total daily dose of Depakote

Therapeutic range

  • Low serum albumin levels may cause an increase in unbound drug (while total concentration may appear normal)
  • Epilepsy: 50-100 mcg/mL total valproate
  • Mania: 50-125 mcg/mL total valproate; maximum concentrations generally achieved within 14 days

Administration

Swallow whole, do not chew or crush

Capsules may be opened and sprinkled on spoonful of soft food immediately before administration

If dose is skipped, do not double next dose

Depakote or Depakote Sprinkles: If daily dose >250 mg, give as divided dose

Depakote ER: Administer once daily

Warnings

Black Box Warnings

Hepatotoxicity

  • Hepatic failure resulting in fatalities has occurred
  • Children younger than 2 years are at increased risk for fatal hepatotoxicity, particularly patients on multiple anticonvulsants, as well as those with congenital metabolic disorders, severe seizure disorders accompanied by mental retardation, or organic brain disease
  • Increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA polymerase-gamma (POLG) gene (eg, Alpers Huttenlocher Syndrome)
  • If used in children with these conditions, it should be administered with extreme caution as a sole agent
  • Hepatotoxicity usually occurs during the first 6 months of treatment and may be preceded by malaise, weakness, lethargy, facial edema, anorexia, and vomiting

Teratogenicity

  • Do not use in women of childbearing age unless the drug is essential to the management of the medical condition; all non-pregnant women of childbearing potential should use effective birth control if taking valproate products (see Contraindications and Pregnancy sections)
  • May cause neural tube defects
  • Children exposed in utero have increased risk for lower cognitive test scores compared with those exposed in utero to other antiseizure medications
  • Alternative medications that have a lower risk for adverse birth outcomes should be considered
  • Patients should not stop taking valproate without talking to a health-care professional
  • Women should use effective contraception while taking valproate derivatives

Pancreatitis

  • Cases of life-threatening pancreatitis have been reported in children and adults
  • Some cases have been described as hemorrhagic with a rapid progression from initial symptoms to death

Contraindications

Hypersensitivity

Liver disease, significant hepatic impairment

Urea cycle disorders

Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase-gamma (POLG; eg, Alpers-Huttenlocher Syndrome) and children <2 years of age who are suspected of having a POLG-related disorder

Migraine headache prevention in women who are pregnant or plan to become pregnant

Cautions

Probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations exceed 110 mcg/mL in females and 135 mcg/mL in males

Hepatotoxic (age <2 years, higher risk of fatal hepatotoxicity); see Black Box Warnings

POLG mutations; see Contraindications and Black Box Warnings

Discontinue if hyperammonemia/encephalopathy occurs; check ammonia level if emesis occurs or if the patient displays lethargy or abnormal behavior; evaluate patient for urea cycle disorder (see Contraindications) or hepatotoxicity (see Black Box Warnings);

Pancreatitis, including fatalities reported (see Black Box Warnings)

Hypothermia has been reported during valproate therapy with or without associated hyperammonemia; this adverse reaction can also occur in patients using concomitant topiramate

In utero exposure increases risk for poor cognitive outcomes and anatomical malformations, compared with 3 other common AEDs (carbamazepine, lamotrigine, phenytoin); see Black Box Warnings

Potential for thrombocytopenia, porphyria, and multiorgan hypersensitivity reaction (also known as drug reaction with eosinophilia and systemic symptoms or DRESS)

May produce false-positive urine ketone test and alter TFTs

Reversible cerebral and cerebellar atrophy reported; monitor motor and cognitive function routinely and assess for signs and symptoms of brain atrophy

May cause CNS depression and impair physical or mental abilities

Somnolence in the elderly can occur; divalproex dosage should be increased slowly and with regular monitoring for fluid and nutritional intake

Not for administration to post-traumatic seizure prophylaxis in patients with acute head trauma (increased mortality reported when used)

Pregnancy & Lactation

Pregnancy Category: D for seizures or manic episodes associated with bipolar disorder that are unresponsive to other treatments

Pregnancy category: X for migraine headache prevention

Results from epidemiologic studies concluded that children born to women who take valproate sodium or related products (valproic acid, divalproex sodium) during pregnancy have an increased risk for lower cognitive test scores, compared with children exposed to other antiseizure medications during pregnancy

Known to cause neural tube defects; evidence suggests that folic acid supplementation prior to conception and during the first trimester decreases risk for congenital neural tube defects

Lactation: Excreted in breast milk; use caution (AAP and ACOG say compatible)

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Patient Handout

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Commonly used brand name(s)

In the U.S.

  • Depakene
  • Depakote
  • Depakote DR
  • Depakote ER
  • Depakote Sprinkles
  • Stavzor

In Canada

  • Alti-Valproic

Available Dosage Forms:

  • Capsule, Delayed Release
  • Syrup
  • Capsule, Liquid Filled
  • Tablet, Extended Release
  • Tablet, Enteric Coated
  • Tablet, Delayed Release

Therapeutic Class: Antimanic

Pharmacologic Class: Histone Deacetylase Inhibitor

Chemical Class: Valproic Acid (class)

Uses For Depakote Sprinkles

Valproic acid is used to treat certain types of seizures (epilepsy). This medicine is an anticonvulsant that works in the brain tissue to stop seizures.

Valproic acid is also used to treat the manic phase of bipolar disorder (manic-depressive illness), and helps prevent migraine headaches.

This medicine is available only with your doctor's prescription.

Before Using Depakote Sprinkles

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of valproic acid in children. However, safety and efficacy have not been established in children with epilepsy younger than 10 years of age, and in children with migraine younger than 12 years of age. Because of valproic acid's toxicity, use in children younger than 2 years of age requires extreme caution.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of valproic acid in the elderly. However, elderly patients are more likely to have unwanted effects (eg, tremors or unusual drowsiness), which may require an adjustment in the dose for patients receiving valproic acid.

Pregnancy

Pregnancy Category Explanation
All Trimesters X Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Calcifediol
  • Cisplatin
  • Doripenem
  • Ertapenem
  • Estradiol
  • Ethinyl Estradiol
  • Imipenem
  • Lamotrigine
  • Meropenem
  • Mestranol
  • Orlistat
  • Primidone
  • Propofol
  • Sodium Oxybate
  • Vorinostat
  • Warfarin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acyclovir
  • Aspirin
  • Betamipron
  • Carbamazepine
  • Cholestyramine
  • Clomipramine
  • Erythromycin
  • Ethosuximide
  • Felbamate
  • Fosphenytoin
  • Ginkgo
  • Lopinavir
  • Lorazepam
  • Mefloquine
  • Nimodipine
  • Nortriptyline
  • Olanzapine
  • Oxcarbazepine
  • Panipenem
  • Phenobarbital
  • Phenytoin
  • Rifampin
  • Rifapentine
  • Risperidone
  • Ritonavir
  • Rufinamide
  • Topiramate
  • Valacyclovir
  • Zidovudine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Congenital metabolism disorders (born with a disease that affects metabolism) or
  • Mental retardation with severe seizure disorders—Use with caution. May increase risk for more serious side effects.
  • Depression, or history of or
  • Mental illness, or history of or
  • Pancreatitis (inflammation of the pancreas) or
  • Thrombocytopenia (low platelet count)—Use with caution. May make these conditions worse.
  • Liver disease or
  • Mitochondrial disorder, including Alpers-Huttenlocher syndrome (genetic disorder) or
  • Urea cycle disorder (genetic disorder)—Should not be used in patients with these conditions.

Proper Use of valproic acid

This section provides information on the proper use of a number of products that contain valproic acid. It may not be specific to Depakote Sprinkles. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a Medication Guide and patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

Swallow the delayed-release capsules and oral capsules whole with a full glass of water. Do not split, crush, or chew it. You may take this medicine with food to decrease stomach upset.

Measure the oral liquid medicine with a marked measuring spoon, oral syringe, or medicine cup.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage forms (capsules, delayed-release capsules, and solution):
    • For seizures:
      • Adults and children 10 years of age or older—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 10 to 15 milligrams (mg) per kilogram (kg) of body weight per day. Your doctor may gradually increase your dose every week by 5 to 10 mg per kg of body weight if needed. However, the dose is usually not more than 60 mg per kg of body weight per day. If the total dose a day is greater than 250 mg, it is usually divided into smaller doses and taken two or more times during the day.
      • Children younger than 10 years of age—Use and dose must be determined by your doctor.
  • For oral dosage form (delayed-release capsules):
    • For mania:
      • Adults—At first, 750 milligrams (mg) once a day, usually divided in smaller doses. Your doctor may increase your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For migraine:
      • Adults—At first, 250 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1000 mg a day.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Depakote Sprinkles

It is very important that your doctor check your progress closely while you are using this medicine to see if it is working properly and to allow for a change in the dose. Blood tests may be needed to check for any unwanted effects.

Using this medicine while you are pregnant (especially during first trimester) can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

It is very important to take folic acid before getting pregnant and during early pregnancy to lower chances of harmful side effects to your unborn baby. Ask your doctor or pharmacist for help if you are not sure how to choose a folic acid product.

Liver problems may occur while you are using this medicine, and some may be serious. Check with your doctor right away if you are having more than one of these symptoms: abdominal or stomach pain or tenderness, clay-colored stools, dark urine, decreased appetite, fever, headache, itching, loss of appetite, nausea and vomiting, skin rash, swelling of the feet or lower legs, unusual tiredness or weakness, or yellow eyes or skin.

Valproic acid may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you notice any of these side effects, tell your doctor right away.

Valproic acid may cause serious allergic reactions affecting multiple body organs (eg, liver or kidney). Check with your doctor right away if you have the following symptoms: a fever, dark urine, headache, rash, stomach pain, swollen lymph glands in the neck, armpit, or groin, unusual tiredness, or yellow eyes or skin.

Pancreatitis may occur while you are using this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Check with your doctor right away if fever, sore throat, rash, ulcers in the mouth, nosebleeds, bleeding gums, swollen glands, or small red or purple spots on the skin occur. These could be symptoms of a serious blood problem.

Check with your doctor right away if you are having unusual drowsiness, dullness, tiredness, weakness or feelings of sluggishness, changes in mental status, low body temperature, or vomiting. These may be symptoms of a serious condition called hyperammonemic encephalopathy.

Valproic acid may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Do not stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping completely. This may help prevent worsening of seizures and reduce the possibility of withdrawal symptoms.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for seizures (eg, barbiturates), muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

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