rufinamide: clinical use

Prescribing considerations

• Initiation should be by a paediatric or neurology specialist experienced in epilepsy.
• Review concomitant valproate, hormonal contraception, CYP3A4 substrates and medicines with a narrow therapeutic window.
• Assess hepatic function, personal or family history of short-QT syndrome, swallowing or enteral-tube needs, and formulation excipients.
• Plan gradual withdrawal rather than abrupt cessation.
• Use clinical judgement and involve the patient or carer when switching manufacturer because rufinamide is classified as switch-with-caution.

Contraindications and cautions

• Hypersensitivity to rufinamide, triazole derivatives or product excipients.
• The oral suspension should not be used in hereditary fructose intolerance because it contains sorbitol.
• Brown & Burk tablets should not be used in specified rare hereditary disorders affecting galactose or lactose handling.
• Use in severe hepatic impairment is not recommended; use cautiously in mild or moderate impairment.
• Exercise particular caution where further QT shortening could present a risk.

Monitoring

• Seizure frequency, seizure types and any occurrence of status epilepticus.
• Rash and systemic hypersensitivity features, including hepatic involvement.
• Somnolence, dizziness, ataxia, gait disturbance and falls.
• Mood, behaviour and suicidal thoughts.
• Appetite, weight and gastrointestinal tolerability.
• Effectiveness or toxicity of clinically important interacting treatments, especially after therapy changes.

Clinical pharmacology

Rufinamide prolongs the inactive state of sodium channels. It is absorbed better with food, has relatively low protein binding and is mainly metabolised by hydrolysis to an inactive derivative rather than through cytochrome P450 metabolism. It induces CYP3A4 to a modest or moderate degree.

Formulation and product differences

• Brown & Burk film-coated tablets contain lactose, are scored into equal halves and may be crushed into water.
• Eisai oral suspension contains sorbitol, parahydroxybenzoates and benzoic acid; it requires vigorous shaking and measurement with the supplied syringe.
• The suspension can be administered through an enteral feeding tube with an appropriate water flush.
• Eisai tablets and oral suspension are bioequivalent; monitor the patient during formulation switches.

Tablet

Route: Oral

Strengths: 100 mg, 200 mg, 400 mg