For example, for solutions the key aspects that should be addressed during validation include assurance that the drug substance and preservatives are dissolved. Parameters, such as heat and time should be measured. Also, in-process assay of the bulk solution during and/or after compounding according to predetermined limits are also an important aspects of process validation. For solutions that are sensitive to oxygen and/or light, dissolved oxygen levels would also be an important test. Again, the development data and the protocol should provide limits. Review firm's development data and/or documentation for their justification of the process.
Status Epilepticus: Loading Dose:
Infants, Children: 15 to 20 mg/kg IV in a single or divided doses
Anticonvulsant: Loading Dose:
All ages: 15 to 20 mg/kg orally (based on phenytoin serum concentrations and recent dosing history). The oral loading dose should be given in 3 divided doses administered every 2 to 4 hours.
Anticonvulsant: Maintenance Dose:
(IV or oral) (Note: May initially divided daily dose into 3 doses/day, then adjust to suit individual requirements.)
Less than or equal to 4 weeks: Initial: 5 mg/kg/day in 2 divided doses
Usual: 5 to 8 mg/kg/day IV in 2 divided doses (may require dosing every 8 hours).
Greater than or equal to 4 weeks: Initial: 5 mg/kg/day in 2 to 3 divided doses
Usual: (may require up to every 8 hour dosing)
6 months to 3 years: 8 to 10 mg/kg/day
4 to 6 years: to 9 mg/kg/day
7 to 9 years: 7 to 8 mg/kg/day
10 to 16 years: 6 to 7 mg/kg/day
Phenytoin is extensively bound to serum plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes. Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected.