phenytoin: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
phenytoin: clinical details
Prescribing considerations
- Use a consistent manufacturer's preparation for epilepsy and review any proposed switch.
- Phenytoin has a narrow therapeutic index, nonlinear pharmacokinetics and extensive interaction potential.
- It is ineffective for absence seizures and is not indicated for seizures caused by hypoglycaemia or other metabolic disturbances.
- Review pregnancy potential, contraception and pregnancy plans before and during treatment.
Contraindications and cautions
- Hypersensitivity to phenytoin, another hydantoin or a product excipient.
- Concomitant delavirdine because of potential loss of antiviral response and resistance.
- Exercise particular caution with hepatic or renal impairment, hypoalbuminaemia, hyperbilirubinaemia and known reduced-function CYP2C9 variants.
- Consider HLA-B*1502 testing in patients with relevant Asian ancestry before initiation.
Monitoring
- Consider baseline full blood count, liver function, renal profile and vitamin D assessment.
- Consider periodic renal profile, vitamin D and liver-function monitoring according to individual risk.
- Plasma concentration monitoring is not routinely required when stable, but is useful for suspected toxicity, non-adherence, loss of seizure control, interactions, pregnancy, organ failure or formulation changes.
- Interpret total concentrations cautiously when protein binding is reduced; a free concentration may be more informative.
- Monitor oral health, bone health, mood and symptoms of blood, skin or liver disorders.
Clinical pharmacology
Phenytoin is highly protein-bound and mainly metabolised through CYP2C9 and CYP2C19. Its metabolism is saturable, so small changes in exposure can cause disproportionate changes in blood concentration. It also induces multiple hepatic drug-metabolising enzymes.
Formulation and product differences
- The selected suspension and chewable tablets contain phenytoin free acid; some other formulations contain phenytoin sodium and are not necessarily bioequivalent.
- Infatabs must be chewed before swallowing.
- The suspension must be shaken vigorously and accurately measured.
- Clinical review and concentration monitoring are advised when changing formulation or manufacturer.
phenytoin preparations and strengths
Oral suspension
Route: Oral
Strengths: 30 mg/5 mL
phenytoin interactions
Phenytoin has many clinically important interactions because other treatments can alter its concentration and it strongly induces liver enzymes.
Hormonal contraceptives
Phenytoin can reduce contraceptive effectiveness; discuss an appropriate alternative method.
Azole antifungals, macrolides and co-trimoxazole
Some can raise phenytoin concentrations and increase toxicity risk.
St John's wort
It can lower phenytoin concentrations and reduce seizure control; concomitant use should be avoided.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.