Clinical TopicsNeurologyPatient SafetyPharmacologyWorkplace Management

Phenytoin: Keep patients in the range and out of danger


For more than 70 years, we’ve used phenytoin (Dilantin) to control seizures—and with good reason. The drug of choice for tonic-clonic seizures and tonic-clonic status epilepticus, phenytoin also treats complex partial seizures and prevents and treats neurosurgical-related seizures. Plus, phenytoin is cost-effective, making it a good choice for hospital formularies and discharge prescriptions for uninsured and underinsured patients.
Like any drug, phenytoin can cause adverse effects, some of them serious. But if you know the in’s and out’s of phenytoin and monitor your patient closely, you can make sure he or she receives the therapeutic benefits and avoids the risks.

Out of range
The therapeutic range for serum phenytoin levels is 10 to 20 mg/dL, but achieving and maintaining a level in this range can be challenging. Several factors—including the patient’s albumin level and other medications—can make the phenytoin level quickly slip out of range, resulting in breakthrough seizures or toxicity.
Up to 90% of phenytoin binds to proteins, leaving only 10% to enter the blood and achieve the desired effect. Patients with low albumin levels need dosage adjustments to avoid toxicity.
Many drugs interact with phenytoin. Some—including diazepam, isoniazid, and cimetidine—compete with it for protein-binding sites, causing higher plasma phen­y­toin levels. Others—including folic acid, carbamaze­pine, and phenobarbital—decrease the availability of phenytoin, posing the risk of breakthrough seizures.
Phenytoin is metabolized by hepatic enzyme systems, which become increasingly saturated at levels between 10 and 12 mg/dL. When a patient’s plasma phenytoin level is in this narrow range, a prescriber must make dosage increases with caution because the level can rise dramatically. (See Phenytoin safety measures in pdf format by clicking the download now button.)

Administering parenteral phenytoin
Because of the poor water solubility of phenytoin, the parenteral formulation has a highly alkaline medium. The medium, which consists of 40% propylene glycol and 10% alcohol, may lead to cardiovascular and local adverse effects. Never infuse parenteral phenytoin at a rate greater than 50 mg/minute because of the risk of hypotension and arrhythmias. Patients who are hemodynamically unstable or have cardiovascular disease are particularly susceptible to these effects. To minimize cardiovascular risks, many hospitals recommend an infusion rate of 20 to 25 mg/minute.
Parenteral phenytoin can also cause soft-tissue injury to the hand or forearm. Called purple glove syndrome, the injury is characterized by edema, discoloration, and pain. In severe cases, compartment syndrome can develop, and a fasciotomy and even amputation may be needed. To reduce the risk of purple glove syndrome, dilute phenytoin with normal saline solution to a concentration of less than 6.7 mg/mL. In many hospitals, the limit is 5 mg/mL, and the drug must be infused into a large vein using the largest bore catheter possible, at least 18G. A central venous access line is preferred. Always administer phenytoin using a 0.22-micron in-line filter and infusion pump.

An I.V. alternative
Parenteral fosphenytoin (Cerebyx), a water-soluble prodrug of phenytoin, is a safe alternative to parenteral phenytoin. Like all prodrugs, it’s an inactive form of the drug that becomes active in the body. Though this prodrug poses less risk of cardiovascular complications and purple glove syndrome, it’s significantly more expensive.
Typically, you’ll see fosphenytoin prescribed when central venous access or access via an 18G catheter isn’t possible or when a patient is hemodynamically unstable or has a history of adverse effects from phen­y­toin infusions. Make sure you know your facility’s policy regarding phenytoin and fosphenytoin.

Administering enteral phenytoin
When hospitalized patients achieve therapeutic levels with parenteral phenytoin, the prescriber switches to an enteral formulation, such as a suspension, capsule, or chewable tablet. Some of these patients may be receiving enteral nutrition, which can reduce phenytoin absorption, causing subtherapeutic drug levels. This reduced absorption may develop because the acidic enteral formula reduces the solubility of phenytoin or because phenytoin binds to proteins in the enteral formula.
To ensure absorption, hold intermittent tube feedings for 1 to 2 hours before and after the phenytoin dose. For ease of administration, most patients receiving enteral nutrition are given the suspension formulation via their feeding tube. If giving phenytoin through a feeding tube, flush it with 20 mL of water or normal saline solution before and after giving the drug.
What if your patient needs continuous feedings? Depending on his or her nutritional status and the degree of seizure control, the prescriber may order a different enteral feeding formula, increase the phenytoin dosage, or replace phenytoin with an anticonvulsant that’s not affected by enteral feedings.

Keeping control
Parenteral or enteral phenytoin can effectively control your patient’s seizures. But the patient’s phenytoin level must stay in the therapeutic range, and several forces can push it out. That’s why you need to administer the drug skillfully and monitor phenytoin levels frequently.

Selected references
Bader MK, Littlejohns LR, eds. AANN Core Curriculum for Neuroscience Nursing. 4th ed. St. Louis, MO: W.B. Saunders; 2004.
Bazil CW, Morrell MJ, Peldey TA. Epilepsy. In Rowland LP, ed. Merritt’s Neurology. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
Evidence-based medicine guidelines. Fosphenytoin utilization. Use of fosphenytoin (Cerebyx) and intravenous phenytoin (Dilantin) in adult patients. Accessed November 10, 2008.
Fisher R, Long L, White I. Guide to the Care of the Patient with Seizures: AANN Reference Series for Clinical Practice. Glenview, IL: AANN; 2004.
Lehne R. Pharmacology for Nursing Care. 5th ed. Philadelphia, PA: W.B. Saunders; 2004.

Susan Tocco is a Neuroscience Clinical Nurse Specialist at Orlando Regional Medical Center in Florida.

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