How often to monitor phenytoin (Dilantin) levels?

From the Guidelines

Phenytoin levels should be monitored every 6-12 months in stable patients, but more frequently in specific situations such as after starting therapy, changing doses, or in pregnant patients, as supported by general clinical practice guidelines 1. When initiating phenytoin therapy, it is crucial to monitor levels closely, typically within 7-10 days after starting therapy or changing doses, to ensure therapeutic levels are achieved without risking toxicity 1. In pregnant patients, more frequent monitoring is necessary, typically every 3-4 months, due to altered metabolism that can affect phenytoin levels 1. Additionally, levels should be checked immediately if toxicity is suspected or if seizures occur despite therapy, as this could indicate subtherapeutic levels or the development of resistance 1. Other situations that warrant more frequent monitoring include changes in medications that might affect phenytoin metabolism, significant weight changes, or the development of medical conditions like liver or kidney disease that can alter drug clearance 1. The therapeutic range for phenytoin is generally considered to be between 10-20 mcg/mL, with levels above this range increasing the risk of side effects such as nystagmus, ataxia, and cognitive impairment 1. Regular monitoring is particularly important for phenytoin due to its non-linear kinetics, where small dose changes can lead to disproportionate changes in blood levels, and its narrow therapeutic window, where the difference between an effective dose and a toxic dose is small 1. Key factors to consider in monitoring phenytoin levels include:

• The timing of level checks in relation to dose administration
• The patient's clinical response, including seizure control and presence of side effects
• Any changes in the patient's condition or concomitant medications that could affect phenytoin metabolism or clearance 1.

From the FDA Drug Label

Serum concentrations should be monitored in changing from Dilantin (extended phenytoin sodium capsules, USP to Prompt Phenytoin Sodium Capsules, USP, and from the sodium salt to the free acid form. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum level is usually 10–20 mcg/mL When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out. Patients with a history of renal or liver disease should not receive the oral loading regimen. Initially, one gram of Dilantin (extended phenytoin sodium capsules, USP) is divided into three doses (400 mg, 300 mg, 300 mg) and administered at two-hour intervals Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations.

The monitoring of phenytoin levels should be done:

• When changing the dosage form or brand of phenytoin
• When switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa
• In some cases, for optimal dosage adjustments
• With frequent serum level determinations when using a loading dose
• At intervals of seven to ten days when adjusting the dosage, as it may take this amount of time to achieve steady-state blood levels 2

From the Research

Monitoring Phenytoin Levels

To determine how often to monitor phenytoin levels, several factors must be considered, including the patient's plasma albumin concentration, potential drug interactions, and the presence of liver disease.

• Plasma Albumin Concentration: The study 3 suggests that total phenytoin levels can be misleading in patients with low plasma albumin concentrations, as they may not accurately reflect the free (unbound) phenytoin concentrations. In such cases, direct measurement of free phenytoin concentrations or calculation of adjusted phenytoin levels using the Sheiner-Tozer equation may be necessary.
• Drug Interactions: Phenytoin can interact with other medications, such as valproic acid, which can displace phenytoin from plasma protein binding sites and inhibit its metabolism, leading to increased free phenytoin concentrations 4, 5. Therefore, patients taking these medications may require more frequent monitoring of phenytoin levels.
• Liver Disease: Patients with liver disease may require adjusted phenytoin dosing due to altered drug metabolism 6. In these cases, more frequent monitoring of phenytoin levels may be necessary to avoid toxicity.
• Seizure Control: The frequency of monitoring phenytoin levels may also depend on the patient's response to treatment, with more frequent monitoring required for patients with poor seizure control 7.

Overall, the frequency of monitoring phenytoin levels should be individualized based on the patient's specific clinical circumstances, including plasma albumin concentration, potential drug interactions, liver disease, and response to treatment.