UNIPROEX ER 250

Indications

• Epilepsy (generalized seizures, focal seizures)
• Bipolar disorder (manic episodes)
• Migraine prophylaxis

Dosage

Children: Refer to the BNF for Children for specific dosing information based on the child's age, weight, and condition.

Adults: Refer to the BNF for specific dosing information based on the condition being treated.

Mechanism of action

Divalproex is thought to exert its effects primarily through the inhibition of voltage-gated sodium channels and the enhancement of GABAergic transmission. It increases the levels of GABA, an inhibitory neurotransmitter, which helps to dampen excessive neuronal firing, thus providing anticonvulsant and mood-stabilizing effects. Additionally, it may modulate excitatory neurotransmitter systems.

Pharmacodynamics

Divalproex demonstrates a dose-dependent relationship with its clinical efficacy. The drug's mood stabilizing effects are attributed to the modulation of various neurotransmitter systems, particularly the GABAergic system. Its ability to enhance GABA levels helps in stabilizing mood and controlling seizures. The pharmacodynamic profile also includes a potential influence on the glutamatergic system, contributing to its anticonvulsant properties.

Pharmacokinetics

Divalproex is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically achieved within 1 to 4 hours after oral administration. It is extensively metabolized in the liver, primarily by glucuronidation and beta-oxidation pathways. The elimination half-life ranges from 9 to 16 hours, and it is primarily excreted in urine as metabolites. The drug's pharmacokinetics can be affected by age, liver function, and the presence of other medications.

Contra-indications

• Hypersensitivity to divalproex or any of its components
• Severe hepatic impairment
• Urea cycle disorders

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Weight gain
• Tremor
• Alopecia
• Hepatotoxicity
• Pancreatitis
• Thrombocytopenia
• Sedation
• Drowsiness
• Cognitive impairment

Interactions

• May interact with other antiepileptic drugs, potentially altering their efficacy
• Increased risk of hepatotoxicity when combined with other hepatotoxic agents
• May enhance the effects of warfarin and other anticoagulants

Precautions

• Monitor liver function tests before and during treatment
• Caution in patients with a history of liver disease
• Assess for any signs of pancreatitis
• Caution in patients with a history of suicidal thoughts or behavior

Pregnancy

Divalproex is associated with an increased risk of teratogenic effects, including neural tube defects. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Divalproex is excreted in breast milk. Caution is advised when administering to nursing mothers, as adverse effects on the infant cannot be ruled out.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Divalproex sodium delayed-release tablets
• Divalproex sodium extended-release tablets
• Divalproex sodium oral solution