Depakene

Dosage Forms And Strengths

Depakene (valproic acid) is available as orange-colored soft gelatin capsules of 250 mg valproic acid, bearing the trademark Depakene for product identification, in bottles of 100 capsules and as a red Oral Solution containing the equivalent of 250 mg valproic acid per 5 mL as the sodium salt in bottles of 16 ounces.

Storage And Handling

Depakene (valproic acid) is available as orange-colored soft gelatin capsules of 250 mg valproic acid, bearing the trademark Depakene for product identification, in bottles of 100 capsules (NDC 0074-5681-13), and as a red Oral Solution containing the equivalent of 250 mg valproic acid per 5 mL as the sodium salt in bottles of 16 ounces (NDC 0074-5682-16).

Store capsules at 59-77°F (15-25°C). Store Oral Solution below 86°F (30°C).

Depakote ER: 250 mg is Mfd. by AbbVie LTD, Barceloneta, PR 00617 500 mg is Mfd. by AbbVie Inc., North Chicago, IL 60064 U.S.A. or AbbVie LTD, Barceloneta, PR 00617 For AbbVie Inc., North Chicago, IL 60064 U.S.A. Depakote Tablets: Mfd. by AbbVie LTD, Barceloneta, PR 00617 For AbbVie Inc., North Chicago, IL 60064, U.S.A. Depakote Sprinkle Capsules: AbbVie Inc., North Chicago, IL 60064, U.S.A. Depakene Capsules: Mfd. by Banner Pharmacaps, Inc., High Point, NC 27265 U.S.A. For AbbVie Inc., North Chicago, IL 60064, U.S.A. Depakene Oral solution: Mfd. by AbbVie Inc., North Chicago, IL 60064, U.S.A. OR by DPT Laboratories, Ltd., San Antonio, TX 78215, U.S.A. For AbbVie Inc., North Chicago, IL 60064, U.S.A. Revised: March 2017

Depakene is a prescription medication used to treat seizures and manic episodes in people with bipolar disorder and to prevent migraines. Depakene belongs to a group of drugs called anticonvulsants or anti-epileptic drugs. These work by increasing the amount of certain chemicals in the brain.

This medication comes in capsule and syrup forms. It is usually taken at least 2 times a day. 

Common side effects of Depakene include upset stomach, constipation or diarrhea, nausea, and headache.

Depakene can cause drowsiness, dizziness, or blurred vision. Do not drive or operate heavy machinery until you know how Depakene affects you.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Depakene, there are no specific foods that you must exclude from your diet when receiving Depakote.

Take divalproex exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dosage will vary, depending on the indication and response.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your age

The recommended starting of divalproex for the treatment of complex partial seizures is 10 to 15 mg/kg/day. The dose is increased at 1-week intervals by 5 to 10 mg/kg/day to achieve clinical response. The maximum recommended dosage is 60 mg/kg/day.

The recommended starting dose of divalproex for the treatment of absence seizures is 15 mg/kg/day. The dose is increased at 1-week intervals by 5 to 10 mg/kg/day until seizure control is achieved or side effects are not tolerable. The maximum recommended dosage is 60 mg/kg/day.

Valproic acid affects chemicals in the body that may be involved in causing seizures.

Valproic acid is used to treat various types of seizure disorders. Valproic acid is sometimes used together with other seizure medications.

Valproic acid may also be used for purposes not listed in this medication guide.

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

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.

Depakene (valproic acid) is a carboxylic acid designated as 2-propylpentanoic acid. It is also known as dipropylacetic acid. Valproic acid has the following structure:

Valproic acid (pKa 4.8) has a molecular weight of 144 and occurs as a colorless liquid with a characteristic odor. It is slightly soluble in water (1.3 mg/mL) and very soluble in organic solvents.

Depakene capsules and syrup are antiepileptics for oral administration. Each soft elastic capsule contains 250 mg valproic acid. The syrup contains the equivalent of 250 mg valproic acid per 5 mL as the sodium salt.

Inactive Ingredients

250 mg capsules: corn oil, FD&C Yellow No. 6, gelatin, glycerin, iron oxide, methylparaben, propylparaben, and titanium dioxide.

Oral Solution: FD&C Red No. 40, glycerin, methylparaben, propylparaben, sorbitol, sucrose, water, and natural and artificial flavors.

Common side effects of Depakene include: congenital anomalies, infection, abdominal pain, alopecia, asthenia, drowsiness, nausea, thrombocytopenia, tremor, vomiting, and anorexia. Other side effects include: dyspnea, nystagmus, pharyngitis, tinnitus, depression, fever, peripheral edema, and weight gain. See below for a comprehensive list of adverse effects.

Applies to valproic acid: oral capsule delayed release, oral capsule liquid filled, oral syrup, oral tablet delayed release, oral tablet enteric coated, oral tablet extended release

Along with its needed effects, valproic acid (the active ingredient contained in Depakene) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking valproic acid:

• Black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• confusion
• cough or hoarseness
• crying
• delusions
• dementia
• depersonalization
• diarrhea
• difficult or labored breathing
• dysphoria
• euphoria
• fever or chills
• general feeling of discomfort or illness
• headache
• joint pain
• loss of appetite
• lower back or side pain
• mental depression
• muscle aches and pains
• nausea
• nervousness
• painful or difficult urination
• paranoia
• pinpoint red spots on the skin
• quick to react or overreact emotionally
• rapid weight gain
• rapidly changing moods
• runny nose
• shakiness in the legs, arms, hands, or feet
• shivering
• sleepiness or unusual drowsiness
• sore throat
• sweating
• tightness in the chest
• tingling of the hands or feet
• trembling or shaking of the hands or feet
• trouble sleeping
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting

• Abnormal dreams
• absence of or decrease in body movement
• anxiety
• bloody nose
• bloody or cloudy urine
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in personality
• change in walking and balance
• changes in patterns and rhythms of speech
• chest pain
• chills
• clumsiness or unsteadiness
• cold sweats
• constipation
• darkened urine
• degenerative disease of the joint
• difficult, burning, or painful urination
• difficulty with moving
• discouragement
• dizziness
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• dry mouth
• excessive muscle tone
• fast, irregular, pounding, or racing heartbeat or pulse
• fear
• feeling of warmth or heat
• feeling sad or empty
• flushing or redness of the skin, especially on the face and neck
• frequent urge to urinate
• heavy non-menstrual vaginal bleeding
• hyperventilation
• increased need to urinate
• indigestion
• irritability
• lack of appetite
• lack of coordination
• large, flat, blue or purplish patches in the skin
• leg cramps
• lip smacking or puckering
• loss of bladder control
• loss of interest or pleasure
• loss of strength or energy
• multiple swollen and inflamed skin lesions
• muscle pain or stiffness
• muscle tension or tightness
• normal menstrual bleeding occurring earlier, possibly lasting longer than expected
• pains in the stomach, side, or abdomen, possibly radiating to the back
• passing urine more often
• pounding in the ears
• puffing of the cheeks
• rapid or worm-like movements of the tongue
• rapid weight gain
• restlessness
• seeing, hearing, or feeling things that are not there
• shakiness and unsteady walk
• slurred speech
• small red or purple spots on the skin
• sweating
• swollen joints
• tiredness
• trouble with concentrating
• trouble with speaking
• twitching
• uncontrolled chewing movements
• uncontrolled movements of the arms and legs
• unsteadiness, trembling, or other problems with muscle control or coordination
• vomiting of blood or material that looks like coffee grounds
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking valproic acid:

• Change in consciousness
• fainting
• loss of consciousness
• slow or irregular heartbeat

Some side effects of valproic acid may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• body aches or pain
• change in vision
• congestion
• continuing ringing or buzzing or other unexplained noise in the ears
• hair loss or thinning of the hair
• hearing loss
• heartburn
• impaired vision
• lack or loss of strength
• loss of memory
• problems with memory
• rash
• seeing double
• tender, swollen glands in the neck
• trouble with swallowing
• uncontrolled eye movements
• voice changes
• weight gain
• weight loss

• Absent, missed, or irregular menstrual periods
• back pain
• burning, dry, or itching eyes
• change in taste or bad unusual or unpleasant (after) taste
• coin-shaped lesions on the skin
• cough producing mucus
• cramps
• dandruff
• discharge or excessive tearing
• dry skin
• earache
• excess air or gas in the stomach or intestines
• eye pain
• feeling of constant movement of self or surroundings
• full feeling
• heavy bleeding
• increased appetite
• itching of the vagina or genital area
• itching skin
• loss of bowel control
• neck pain
• oily skin
• pain
• pain during sexual intercourse
• pain or tenderness around the eyes and cheekbones
• passing gas
• rash with flat lesions or small raised lesions on the skin
• redness or swelling in the ear
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• redness, swelling, or soreness of the tongue
• sensation of spinning
• sneezing
• stiff neck
• stopping of menstrual bleeding
• thick, white vaginal discharge with no odor or with a mild odor

Applies to valproic acid: injectable solution, intravenous solution, oral capsule, oral delayed release capsule, oral syrup

Cardiovascular

Common (1% to 10%): Edema, hypertension, hypotension, palpitations, postural hypotension, peripheral edema, tachycardia, vasodilation
Frequency not reported: Bradycardia, cutaneous vasculitis, hematoma formation[Ref]

Psychiatric

Very common (10% or more): Nervousness
Common (1% to 10%): Abnormal dreams, agitation, anxiety, aggression, confusion, depression, emotional lability, hallucinations, insomnia, personality disorder, thinking abnormalities
Rare (less than 0.1%): Abnormal behavior, learning disorder, psychomotor hyperactivity
Frequency not reported: Behavioral deterioration, hostility, psychosis[Ref]

Respiratory

Very common (10% or more): Flu syndrome, respiratory infection
Common (1% to 10%): Bronchitis, dyspnea, epistaxis, increased cough, pharyngitis, pneumonia, rhinitis, sinusitis
Uncommon (0.1% to 1%): Pleural effusion[Ref]

Renal

Rare (less than 0.1%): Reversible Fanconi's syndrome, tubulointerstitial nephritis[Ref]

Dermatologic

Very common (10% or more): Alopecia
Common (1% to 10%): Discoid lupus erythematosus, dry skin, ecchymosis, furunculosis, maculopapular rash, petechia, pruritus, rash, seborrhea
Uncommon (0.1% to 1%): Abnormal hair texture, abnormal hair growth, hair color changes, sweating
Rare (0.01% to 0.1%): Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Very rare (less than 0.01%): Acne, hirsutism
Frequency not reported: Angioedema, generalized pruritus, photosensitivity[Ref]

Endocrine

Uncommon (0.1% to 1%): Hyperandrogenism, syndrome of inappropriate ADH secretion
Rare (less than 0.1%): Hypothyroidism
Frequency not reported: Abnormal thyroid function tests, elevated serum testosterone concentrations, parotid gland swelling[Ref]

Gastrointestinal

Very common (10% or more): Abdominal pain, diarrhea, dyspepsia, gingival disorder, nausea, vomiting
Common (1% to 10%): Constipation, dry mouth, eructation, fecal incontinence, flatulence, gastralgia, gastroenteritis, glossitis, periodontal abscess, hematemesis, stomatitis
Uncommon (0.1% to 1%): Pancreatitis (life-threatening)[Ref]

General

The most commonly reported side effects at the start of therapy include nausea, vomiting, and indigestion; these effects are usually transient. Sedative effects occur most often in patients receiving combination therapy.[Ref]

Genitourinary

Common (1% to 10%): Amenorrhea, cystitis, dysmenorrhea, dysuria, enuresis, metrorrhagia, urinary incontinence, urinary frequency, vaginal hemorrhage, vaginitis
Very rare (less than 0.01%): Gynecomastia
Frequency not reported: Breast enlargement, galactorrhea, polycystic ovary disease[Ref]

Hematologic

Very common (10% or more): Thrombocytopenia
Common (1% to 10%): Anemia, hemorrhage
Uncommon (0.1% to 1%): Leucopenia, pancytopenia
Rare (less than 0.1%): Abnormal coagulation tests (e.g., prolonged prothrombin time, prolonged activated partial thromboplastin time, prolonged thrombin time, prolonged INR), agranulocytosis, bone marrow failure, decreased coagulation factors, including pure red cell aplasia, macrocytosis
Frequency not reported: Aplastic anemia, bone marrow suppression, bruising, eosinophilia, frank hemorrhage, hypofibrinogenemia, anemia including macrocytic with or without folate deficiency, relative lymphocytosis[Ref]

Hepatic

Common (1% to 10%): Increased liver enzymes (particularly early in treatment), liver injury, SGOT increased, SGPT increased
Frequency not reported: Severe liver damage (including hepatic failure sometimes resulting in death), increased serum bilirubin, abnormal changes in other liver function tests[Ref]

Hypersensitivity

Frequency not reported: Allergic reaction, anaphylaxis, hypersensitivity[Ref]

Local

Common (1% to 10%): Injection site pain, injection site reaction
Uncommon (0.1% to 1%): Injection site inflammation[Ref]

Metabolic

Very common (10% or more): Anorexia
Common (1% to 10%): Weight loss/gain, increased appetite, hyponatremia
Rare (less than 0.1%): Hyperammonemia
Frequency not reported: Acute intermittent porphyria, minor elevations of LDH (dose related), decreased carnitine concentrations, hyperglycinemia[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia, arthrosis, leg cramps, myalgia, myasthenia, twitching
Uncommon (0.1% to 1%): Decreased bone mineral density, osteopenia, osteoporosis and fractures on long term therapy
Rare (less than 0.1%): Rhabdomyolysis, systemic lupus erythematosus
Frequency not reported: Bone pain[Ref]

Nervous system

Very common (10% or more): Dizziness, headache, somnolence, tremor
Common (1% to 10%): Abnormal gait, amnesia, catatonic reaction, convulsion, disturbance in attention, dysarthria, extrapyramidal disorder, hypertonia, hypokinesia, incoordination, increased reflexes, memory impairment, nystagmus, paraesthesia, speech disorder, stupor, tardive dyskinesia, taste perversion
Uncommon (0.1% to 1%): Ataxia, coma, encephalopathy, lethargy, reversible parkinsonism
Rare (less than 0.1%): Cognitive disorder, reversible dementia associated with reversible cerebral atrophy
Frequency not reported: Cerebral atrophy, dementia[Ref]

Ocular

Very common (10% or more): Amblyopia/blurred vision, diplopia
Common (1% to 10%): Abnormal vision, conjunctivitis, diplopia, dry eyes, eye pain[Ref]

Oncologic

Rare (less than 0.1%): Myelodysplastic syndrome[Ref]

Other

Very common (10% or more): Asthenia
Common (1% to 10%): Back pain, chills, deafness, ear disorder, ear pain, face edema, fever, malaise, otitis media, tinnitus, vertigo
Frequency not reported: Hypothermia, weakness[Ref]

Some side effects of Depakene may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Depakene affects chemicals in the body that may be involved in causing seizures.

Depakene is used to treat various types of seizure disorders. This medicine is sometimes used together with other seizure medications.

Depakene is also used to treat manic episodes related to bipolar disorder (manic depression), and to prevent migraine headaches.

Depakene may also be used for purposes not listed in this medication guide.

Depakene can cause liver failure that may be fatal, especially in children under age 2 and in people with liver problems caused by certain genetic disorders.

You should not use Depakene if you have liver disease, a urea cycle disorder, or a genetic disorder such as Alpers' disease or Alpers-Huttenlocher syndrome.

Follow your doctor's instructions about taking this medicine if you are pregnant. Depakene may harm an unborn baby, but having a seizure during pregnancy could harm both mother and baby. The benefit of preventing seizures may outweigh any risks to the baby.

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

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).

Do not stop using Depakene without your doctor's advice. Stopping suddenly may cause a serious, life-threatening type of seizure.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Drinking alcohol may increase certain side effects of valproic acid.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired.

Depakene could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.