Depakote 500 mg Tablets

Brand Name

This medication is marketed under the widely recognized brand name Depakote. It’s a pharmaceutical product designed to manage specific neurological and psychiatric conditions, earning a reputation for its effectiveness in treating certain disorders.

International Nonproprietary Name (INN)

The active ingredient in this drug is known by its International Nonproprietary Name (INN) as divalproex sodium. This compound consists of sodium valproate and valproic acid in a 1:1 molar ratio, offering a stable form for therapeutic application.

Forms of Release

Depakote is available in several dosage forms to suit diverse patient needs and preferences. These include delayed-release tablets, extended-release tablets, and delayed-release sprinkle capsules. The delayed-release tablets are offered in strengths of 125 mg, 250 mg, and 500 mg, while the extended-release versions come in 250 mg and 500 mg doses. Sprinkle capsules, ideal for those who struggle with swallowing tablets, are provided in a 125 mg strength. Each formulation is designed to release the active substance at varying rates to optimize therapeutic outcomes.

Composition

The primary active component in this medication is divalproex sodium, which breaks down into valproate ions in the gastrointestinal tract to produce its effects. Alongside this, the drug includes various inactive ingredients that support its stability, absorption, and delivery. Delayed-release tablets may contain microcrystalline cellulose, silicon dioxide, and a coating of hypromellose and titanium dioxide to postpone dissolution until reaching the intestines. Extended-release tablets use a polymer matrix, such as hydroxypropyl methylcellulose, to regulate release, with additional excipients like lactose monohydrate and magnesium stearate. Sprinkle capsules feature divalproex sodium pellets coated with povidone and talc, housed in a gelatin shell. These supplementary components ensure effective delivery into the bloodstream.

Pharmacologic Properties

Pharmacodynamics

This medication primarily influences the central nervous system to achieve its therapeutic effects. The active form, valproate, is thought to boost gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that calms neuronal excitability, possibly by inhibiting GABA transaminase, an enzyme that degrades it. Additionally, Depakote may adjust voltage-gated sodium channels, curbing rapid neuronal firing linked to seizures. This dual action stabilizes brain electrical activity, making it suitable for conditions marked by excessive neural activity. In mood disorders like bipolar disorder, it may temper overactive neural circuits to stabilize mood, while its role in migraine prevention might involve reducing cortical spreading depression, a process tied to migraine initiation.

Pharmacokinetics

The pharmacokinetic behavior of this drug outlines its absorption, distribution, metabolism, and excretion processes. After oral intake, divalproex sodium splits into valproate in the stomach and intestines. Absorption depends on the formulation: delayed-release tablets take effect after passing the stomach, typically within 2 to 4 hours, whereas extended-release tablets offer a gradual release over 24 hours, supporting once-daily dosing. Food might delay absorption slightly but doesn’t significantly change the total amount absorbed. Valproate binds strongly to plasma proteins (about 90%), mainly albumin, and distributes widely, including into the brain. It’s metabolized mostly in the liver through glucuronidation and mitochondrial beta-oxidation, yielding various metabolites, some potentially active. Excretion occurs chiefly via urine, with a half-life of 9 to 16 hours, though this varies in certain groups like the elderly or those with liver issues.

Indications for Use

This medication is prescribed for various conditions involving abnormal neurological activity or mood instability, owing to its ability to effectively regulate brain function across different disorders.

Diseases and Conditions

Depakote is used to treat epilepsy, particularly for controlling complex partial seizures in adults and children over 10, either alone or with other antiepileptic drugs. It’s also approved for simple and complex absence seizures, managing these generalized seizure types. In psychiatric care, it addresses acute manic or mixed episodes in bipolar disorder, easing symptoms like elevated mood, irritability, and impulsivity. Furthermore, the extended-release form is indicated for preventing migraine headaches in adults, lessening their frequency and intensity. Its wide-ranging utility makes it a key option in these treatment areas.

Contraindications

Although effective for many, certain conditions prohibit the use of this drug due to potential severe risks, requiring thorough evaluation before starting treatment.

Conditions Prohibiting Use

This medication is not suitable for patients with known hypersensitivity to divalproex sodium or its components, as reactions could range from mild rashes to severe anaphylaxis. It’s contraindicated in those with liver disease or significant hepatic dysfunction, given its risk of causing hepatotoxicity, including fatal liver failure, especially in children under 2 or those with mitochondrial disorders. Individuals with urea cycle disorders should avoid it due to the danger of hyperammonemic encephalopathy, a potentially deadly condition. Additionally, Depakote is not recommended for migraine prevention in pregnant women or those who might conceive, as it significantly increases the risk of fetal malformations like neural tube defects. Finally, patients with mitochondrial disorders, such as Alpers-Huttenlocher syndrome, should steer clear due to increased liver injury risk.

Method of Administration and Dosage

How to Take

This drug should be taken orally as directed by a healthcare provider, with instructions varying by form. Delayed-release tablets are swallowed whole with water and can be taken with food to lessen stomach discomfort. Extended-release tablets, also taken whole, are usually given once daily, with or without food, though consistent timing improves results. Sprinkle capsules can be swallowed intact or opened and mixed with a small amount of soft food like applesauce, consumed immediately without chewing, followed by water. Crushing or chewing any form should be avoided to maintain the intended release pattern and minimize side effects.

Dosages for Adults and Children

Dosing is tailored to the condition, patient weight, and response. For epilepsy, complex partial seizures start at 10–15 mg/kg/day, increasing by 5–10 mg/kg/week up to 60 mg/kg/day or until controlled; absence seizures begin at 15 mg/kg/day with similar adjustments. In bipolar disorder, initial dosing is 750 mg daily in divided doses for delayed-release tablets, or 25 mg/kg/day for extended-release, adjusted up to 60 mg/kg/day as needed. For migraine prevention, Depakote extended-release starts at 250 mg twice daily, with increases to 1000 mg/day if required. Pediatric doses follow adult guidelines but are weight-based, limited to children over 10 for epilepsy, with careful oversight due to elevated risks.

Dose Adjustment in Specific Conditions

Adjustments are needed in renal or hepatic impairment. In kidney issues, this medication typically requires no major change since little is excreted unchanged in urine, though toxicity monitoring is advised due to altered protein binding. In liver impairment, its use is generally discouraged due to hepatotoxicity risks, but if necessary, doses should be lowered with close liver function checks. Elderly patients may need smaller starting doses due to slower liver metabolism and greater side effect sensitivity, with gradual increases to reduce risks.

Side Effects

Like all medications, this drug can produce a range of side effects from mild to severe, and patients should be aware of these to report and manage them promptly.

Possible Adverse Reactions

Common issues include gastrointestinal upset like nausea, vomiting, diarrhea, and abdominal pain, which often lessen with time or food intake. Neurological effects such as drowsiness, dizziness, and tremors are frequent, especially at higher doses, and may impact daily activities. Weight gain, hair loss, and slight liver enzyme increases are also noted. More serious reactions include hepatotoxicity, marked by jaundice or dark urine, and pancreatitis, signaled by severe abdominal pain with nausea. Blood-related effects like thrombocytopenia can cause bruising or bleeding. Rarely, Depakote may lead to confusion or suicidal thoughts, requiring immediate attention. Regular monitoring and patient awareness are vital for managing these risks.

Overdose

Symptoms of Overdose

Excessive intake of this medication can lead to serious symptoms needing urgent care. These may include deep drowsiness, confusion, or coma from central nervous system depression. Heart-related effects like low blood pressure or rapid heartbeat may occur, along with breathing difficulties in severe cases. Nausea and vomiting are common, while metabolic issues like hyperammonemia or acidosis can worsen the situation. Muscle weakness, tremors, or seizures might appear despite its usual anticonvulsant role, indicating toxic levels disrupting brain function.

First Aid Measures

If an overdose occurs, act quickly. For a conscious patient with recent ingestion, don’t induce vomiting; instead, call emergency services or a poison control center. Keep the airway clear and monitor vital signs until help arrives. In medical settings, gastric lavage might be used if ingestion was within an hour, followed by activated charcoal to limit absorption. Supportive care, including IV fluids and metabolic correction, is essential, with hemodialysis considered in severe cases to remove valproate faster.

Drug Interactions

Effects on Other Medications

This drug can affect how other medications work, requiring careful oversight. It inhibits liver enzymes like CYP2C9, raising levels of drugs such as phenytoin and warfarin, potentially increasing their effects or toxicity. Conversely, enzyme inducers like carbamazepine or rifampin may lower its levels, reducing efficacy. It can also displace protein-bound drugs like aspirin from albumin, increasing their free amounts and side effect risks. Additionally, it interacts with lamotrigine, slowing its breakdown and raising rash risks, necessitating dose tweaks.

Compatibility with Alcohol and Food

Alcohol should be avoided during therapy with Depakote, as it can heighten nervous system depression, causing more drowsiness and coordination issues. It may also strain the liver, adding to hepatotoxic risks. Food doesn’t greatly affect its bioavailability, though meals can ease stomach irritation. High-fat meals might slightly slow absorption of the extended-release form, but this rarely impacts overall effectiveness.

Special Precautions

Use During Pregnancy and Breastfeeding

This medication carries significant risks in pregnancy, especially in the first trimester, with a high chance of birth defects like neural tube issues, facial abnormalities, and cognitive delays in offspring. It’s contraindicated for migraine prevention in pregnant women and should only be used for epilepsy or bipolar disorder if no safer options exist, with strict contraception required for women who could conceive. In breastfeeding, valproate passes into milk in small amounts; though generally safe, infants should be watched for sedation or developmental concerns.

Impact on Driving and Operating Machinery

Depakote may cause drowsiness, dizziness, or blurred vision, affecting the ability to drive or use machinery. Patients should avoid these activities until they know how it impacts them, especially during dose changes when effects are strongest.

Considerations for Elderly and Pediatric Patients

In older adults, this drug requires careful use due to slower liver clearance and higher side effect risks like confusion or falls. Lower starting doses with slow increases and regular liver and kidney checks are advised. In children, it’s approved for epilepsy from age 10, but younger kids, especially under 2, face greater hepatotoxicity risks, particularly with metabolic disorders. Pediatric doses must be weight-based and closely supervised for safety and efficacy.