Phenytoin / Fosphenytoin

LICENSED INDICATION (§4.1, verbatim): 'Pro-Epanutin is indicated in adults and children aged 5 years and older: for the control of status epilepticus of the tonic-clonic (grand mal) type (see section 4.2); for prevention and treatment of seizures occurring in connection with neurosurgery and/or head trauma; as substitute for oral phenytoin if oral administration is not possible and/or contra-indicated.' PRODUCT SWAP SINCE THE PREVIOUS REVIEW: this page was previously held because the bundle carried only the ORAL tablet SPC (Phenytoin Sodium Milpharm 100 mg) with no parenteral regimen. The bundle now carries the parenteral fosphenytoin SPC that hold asked for, so the dose is published. UNITS — READ BEFORE PRESCRIBING (§4.2, verbatim): 'Throughout all Pro-Epanutin product labelling, the amount and concentration of fosphenytoin is always expressed in terms of phenytoin sodium equivalents (PE)... Pro-Epanutin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE).' Each 10 mL vial contains 500 mg PE; each 2 mL vial contains 100 mg PE. DOSING ERRORS (§4.4, verbatim): 'Pro-Epanutin is marketed in 2 mL and 10 mL vials at a concentration of 50 mg PE/mL... Errors have occurred when the concentration of the vial (50 mg PE/mL) was misinterpreted to mean that the total content of the vial was 50 mg PE, resulting in two- or ten-fold overdoses of Pro-Epanutin. In some cases, overdoses were associated with fatal outcomes, including in children under 5 years of age.' CARDIOVASCULAR RISK (§4.4): use with caution in hypotension and severe myocardial insufficiency; severe reactions including atrial and ventricular conduction depression, ventricular fibrillation, asystole and fatalities have been reported, and hypotension may occur even within recommended doses and rates — a reduction in the rate of administration or discontinuation of dosing may be necessary. Severe cardiac complications have been reported in the elderly, children (especially infants) and gravely ill patients. OTHER LICENSED USES ON THIS LABEL, NOT THIS PAGE'S PRIMARY INDICATION: treatment or prophylaxis of seizures — loading 10 to 15 mg PE/kg by IV infusion or IM injection at 50 to 100 mg PE/minute; temporary substitution for oral phenytoin — the same total daily PE dose and dosing frequency as the oral therapy. ⚠ TRUNCATION: §4.2 was cut off at the source-fetch limit part-way through the paediatric 'treatment or prophylaxis of seizures' maintenance dose. The status epilepticus regimens for adults and for children aged 5 years and older sit ABOVE the cut and are complete, but the label's guidance on DOSE REDUCTION IN THE ELDERLY AND IN RENAL OR HEPATIC IMPAIRMENT, and its Therapeutic Drug Monitoring section, sit below it and were NOT retrieved — do not treat what is recorded here as the complete posology, and do not fill those gaps from memory. §4.4, §4.6 and §4.8 were also truncated.

CHILDREN AGED 5 YEARS AND OLDER ONLY. §4.2, verbatim: 'The safety and efficacy of Pro-Epanutin in children under 5 years has not been established.' The 15 mg PE/kg figure above is the label's own paediatric status epilepticus loading dose and is a PER-DOSE value, so it may be multiplied by body weight. The concentration 50 is milligrams of phenytoin sodium equivalents per mL of UNDILUTED Pro-Epanutin — §4.4, verbatim: 'Pro-Epanutin is marketed in 2 mL and 10 mL vials at a concentration of 50 mg PE/mL.' For IV infusion the drug must then be diluted in 5% glucose or 0.9% sodium chloride to a final concentration of 1.5 to 25 mg PE/mL; Table 6 dilutes the paediatric loading dose to 25 mg PE/mL. ⚠ Fatal ten-fold and two-fold overdoses have occurred, including in children under 5, from misreading '50 mg PE/mL' as the total vial content. Always calculate for the patient's exact body weight and always express the prescription in mg PE. Verify any under-18 dosing against a children's formulary.