What are the guidelines for monitoring therapeutic levels of Phenytoin (Dilantin)?

From the Guidelines

Monitoring for phenytoin should prioritize maintaining therapeutic levels between 10-20 mcg/mL, with regular blood level testing and careful observation for side effects and drug interactions. When monitoring phenytoin levels, it is essential to consider the timing of blood draws, with trough levels drawn just before the next dose, and peak levels typically measured after the dose has been absorbed, usually around 1-3 hours after administration, although the provided evidence does not directly address phenytoin monitoring, general principles of therapeutic drug monitoring can be applied 1. Key aspects of monitoring include:

• Regular blood level testing, initially 7-10 days after starting therapy or dose changes, then every 3-6 months for stable patients
• Monitoring for side effects such as nystagmus, ataxia, slurred speech, drowsiness, gingival hyperplasia, hirsutism, and rash
• Checking complete blood count, liver function tests, and albumin levels at baseline and periodically, especially in patients with hypoalbuminemia, renal failure, or liver disease, as phenytoin is highly protein-bound and free levels may need assessment
• Careful titration due to phenytoin's non-linear pharmacokinetics, where small dose changes can cause large concentration changes
• Regular medication reviews to assess for potential drug interactions, given phenytoin's effect on liver enzymes
• Patient education on adherence, side effects, and the importance of consistent timing with meals to maintain steady blood levels. Although the provided study 1 focuses on guidelines for non-tuberculous mycobacterial pulmonary disease, its mention of ensuring therapeutic dose and monitoring renal clearance, especially in at-risk patients, underscores the importance of careful monitoring in vulnerable populations, which can be applied to phenytoin therapy as well.

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.

Monitoring for Phenytoin should include:

• Serum concentration monitoring when changing dosage forms or brands
• Serum blood level determinations for optimal dosage adjustments
• Target serum level: 10-20 mcg/mL
• Frequent serum level determinations when using a loading dose regimen 2

From the Research

Monitoring for Phenytoin

• Phenytoin monitoring is crucial to maintain serum phenytoin levels within the normal therapeutic range, and it can be done by measuring total phenytoin concentration or free phenytoin concentration 3, 4.
• Measuring free phenytoin concentration is more reliable than total phenytoin concentration, especially in patients with hypoalbuminemia, as it reflects the pharmacologically active component of the drug 3, 5.
• The Sheiner-Tozer equation can be used to estimate free phenytoin concentration, but it may not be accurate in all patients, especially those with low plasma albumin or older patients 4, 6.
• Clinical decision support tools can help identify patients who would benefit from adjusted phenytoin calculations or laboratory measurement of free phenytoin 4.
• An algorithm for monitoring phenytoin therapy has been developed, which takes into account the total serum phenytoin and serum albumin ratio 7.
• Monitoring free phenytoin serum concentration, in addition to clinical outcomes, is recommended for phenytoin-dose adjustment in critically ill patients, especially those with hypoalbuminemia 6.

Factors Affecting Phenytoin Monitoring

• Hypoalbuminemia: can lead to increased free phenytoin concentrations, even if total phenytoin concentrations are within the therapeutic range 3, 5, 6.
• Age: older patients may have a lower level of agreement between calculated and measured free phenytoin concentrations 6.
• Plasma albumin concentration: can affect the accuracy of the Sheiner-Tozer equation in estimating free phenytoin concentration 4, 6.
• Drug interactions: can alter free phenytoin concentrations, making monitoring more complex 3.
• Uremia, pregnancy: can also affect free phenytoin concentrations, making monitoring more challenging 3.