Guidelines for use of Fosphenytoin

---

Guidelines for use of Fosphenytoin Fosphenytoin is a water soluble prodrug of phenytoin which is converted within minutes to phenytoin after IV or IM administration. Each 1.5mg of fosphenytoin is equivalent to 1mg of phenytoin and is expressed as mg phenytoin equivalents (mg PE). It does not require propylene glycol as a solvent to keep it in solution; therefore it lacks the irritant properties to tissues like phenytoin. Also, it may be administered at up to three times the rate of phenytoin, up to 150mg PE/minute. Fosphenytoin is compatible with most IV fluids, including dextrose and saline. Appropriate Indications for Use: Where one of the following indications are not present, standard IV phenytoin should be used. Fosphenytoin should not be used for maintenance therapy in patients able to utilize oral medications. APPROPRIATE in patients who:

• Require phenytoin loading doses, but lack a central line.
• Have no venous access.
• Are hemodynamically unstable ( except in cases of Status Epilepticus the drug may be given at 50mg PE/minute and may produce less hypotension and parathesias than an equivalent dose of phenytoin)
• Are NPO and do not have access in a large IV vein (e.g. antecubital fossa or greater).

Monitoring:

• Continuous EKG monitoring at the discretion of the prescribing physician.
• Blood pressure and respiratory status monitoring required for IV loading doses.
• Phenytoin levels should not be determined for at least 2 hours after completion of IV administration and 4 hours after IM administration.

Determining Fosphenytoin Dose When ordering fosphenytoin order as a mg phenytoin equivalent to avoid confusion For example: 100mg phenytoin = 100mg PE fosphenytoin

• Determine patient's actual body weight in kilograms
• Obtain baseline phenytoin level is patient has recent phenytoin therapy. The therapeuctic level of phenytoin is 10 to 20 mcg/ml for bound and 1 to 2 mcg/ml for unbound.
• Status epilepticus loading dose: 18-20mg PE/kg IV at rate not to exceed 150mg PE/minute. If seizures continue after loading dose then an additional 10mg PE/kg IV can be given.
• Recurrent, repetitive seizures: 15 to 20mg PE/kg at a rate not to exceed 150mg PE/minute or IM in one or two injection sites.
• Maintenance in patients without venous access: same as previous oral phenytoin dose or 4 to 6 mg PE/kg/day administered IM in one or two injection sites or IV.
• Patients with subtherapeutic phenytoin levels: New fosphenytoin dose = (desired level - actual level) x 0.7 x weight in kg given as bolus dose. Weight is based on actual body weight (ABW).

Then to adjust daily dosing: For plasma concentrations less than 7mcg/ml a dosage increase of 100mg/day is recommended For plasma concentrations between 7 and 12 mcg/ml, the dose may be increased by 50mg/day Dose increases when the plasma level is above 16mcg/ml should only be done with caution, as small increases may result in toxicity

• Since phenytoin is metabolized by a saturable enzyme system, serum concentrations are not related linearly to the daily doses and small increases in dose may result in substantial increases in serum levels.

Albumin Levels

• Obtain a baseline level prior to initiation of concurrent phenytoin.
• If adverse effects present, obtain a follow-up albumin every 2 to 3 weeks.
• Where albumin is less than 3.2 and only total concentration is available may ESTIMATE

Concentration Observed Concentration corrected= 0.25 x Albumin conc + 0.1 Patients with Low Serum Albumin

Measured Total Phenytoin Concentration (mcg/ml)	Patient's Serum Albumin (gm/dl)
	3.5	3	2.5	2
	Adjusted Total Phenytoin Concentration (mcg/ml)
5	6	7	8	10
10	13	14	17	20
15	19	21	25	30

Adjusted concentration= Measured total concentration¸ [(0.2 X albumin)+0.1] Patients with Renal Failure (ClCR £ 10ml/min)

Measured Total Phenytoin Concentration (mcg/ml)	Patient's Serum Albumin (gm/dl)
	4.0	3.5	3	2.5	2
	Adjusted Total Phenytoin Concentration (mcg/ml)
5	10	11	13	14	17
10	20	22	25	29	33
15	30	19	21	25	30

Adjusted concentration= Measured total concentration¸ [(0.2 X albumin)+0.1 Toxicity Nystagmus Confusion Dizziness Ataxia Nausea/Vomiting Lethargy