phenytoin sodium: clinical use

Prescribing considerations

• Maintain continuity of the manufacturer's product when phenytoin is used for epilepsy; plan and monitor unavoidable switches.
• Phenytoin has a narrow therapeutic margin and non-linear pharmacokinetics, so small exposure changes can cause disproportionate concentration changes.
• Review interactions whenever medicines, supplements, enteral feeds, smoking or alcohol exposure change.
• Avoid abrupt withdrawal unless urgent substitution is required for a serious hypersensitivity reaction.
• Consider HLA-B*1502 testing before initiation in patients of Han Chinese or Thai ancestry, and in other higher-risk Asian populations.
• Interpret total concentrations cautiously in renal or hepatic impairment, hypoalbuminaemia and hyperbilirubinaemia; an unbound concentration may be more informative.

Contraindications and cautions

• Hypersensitivity to phenytoin, another hydantoin or a product excipient.
• For selected injections: sinus bradycardia, sinoatrial block, second- or third-degree atrioventricular block, or Adams–Stokes syndrome.
• Intra-arterial injection must be avoided because the solutions are highly alkaline.
• For the selected ADVANZ injection: concomitant delavirdine.

Monitoring

• Consider baseline full blood count, liver function, renal profile and vitamin D.
• Routine plasma-level monitoring is not required for every stable patient; consider it for suspected toxicity, adherence concerns, loss of seizure control, interactions, product or formulation changes, pregnancy, organ failure or status epilepticus.
• Periodically consider liver function, renal profile and vitamin D, guided by clinical risk.
• Monitor folate during long-term treatment and when folic acid is introduced or withdrawn.
• During intravenous administration, continuously monitor ECG and blood pressure, observe respiration and ensure resuscitation facilities are available.
• Assess long-term bone-health risk and symptoms of haematological, hepatic, dermatological or neurological toxicity.

Clinical pharmacology

Phenytoin is highly protein-bound, is mainly metabolised through CYP2C9 and CYP2C19, and has saturable hepatic metabolism. It induces several drug-metabolising enzymes and primarily limits repetitive neuronal firing through sodium-channel stabilisation.

Formulation and product differences

• Selected oral products include film-coated tablets and hard capsules; formulation or manufacturer changes may alter exposure and should be planned carefully.
• Phenytoin sodium products are not necessarily biologically equivalent to products containing phenytoin base.
• Selected injections are highly alkaline hospital preparations containing ethanol and propylene glycol; they carry important cardiac and local-tissue risks.
• Intravenous phenytoin must not be mixed with dextrose-containing solutions because precipitation can occur.

Capsule

Route: Oral

Strengths: 25 mg, 50 mg, 100 mg, 300 mg

Tablet

Route: Oral

Strengths: 100 mg