What labs should be monitored for patients on phenytoin (Dilantin)?

Laboratory Monitoring for Phenytoin Therapy

Patients on phenytoin require regular monitoring of serum phenytoin levels, complete blood count, liver function tests (AST/ALT and bilirubin), and albumin levels, with the frequency and specific parameters determined by clinical context and patient risk factors.

Serum Phenytoin Level Monitoring

Timing of Measurements

• Measure trough levels (just before the next dose) to assess steady-state concentrations, as this is the standard approach for therapeutic drug monitoring 1, 2.
• Wait 7-10 days after initiating therapy or any dose change before checking levels, as this is the time required to reach steady state with phenytoin's nonlinear pharmacokinetics 1.
• Checking levels too early (before steady state) is a common pitfall that leads to inappropriate dosing decisions 3.

Therapeutic Range Considerations

• The standard therapeutic range is 10-20 mcg/mL for total phenytoin 1, 4.
• However, in critically ill patients with hypoalbuminemia, unbound (free) phenytoin levels are more accurate than total levels, as phenytoin is 90-95% protein-bound to albumin 2, 5.
• When albumin is low, total phenytoin levels may appear subtherapeutic while unbound levels are actually toxic 5.

When to Monitor Levels

• At baseline after loading dose (if given) 1
• After reaching steady state (7-10 days) 1
• When seizure control is inadequate 3
• When toxicity is suspected (ataxia, nystagmus, cognitive impairment) 2
• When interacting drugs are added or removed 6, 1
• In patients with renal or hepatic disease 1

Baseline and Routine Laboratory Tests

Liver Function Tests

• Measure AST, ALT, and serum bilirubin at baseline in selected high-risk cases including patients with HIV infection, history of liver disease, alcoholism, and pregnancy 6.
• Repeat liver function tests if clinical signs of hepatotoxicity develop (jaundice, abdominal pain, unexplained fatigue) 6.

Complete Blood Count

• Monitor CBC for potential hematologic toxicity, though specific frequency is not rigidly defined in guidelines 1.
• Thrombocytopenia is a rare but serious adverse effect requiring monitoring 6.

Serum Albumin

• Check albumin levels, especially in critically ill patients, as hypoalbuminemia significantly affects phenytoin interpretation 5.
• Low albumin increases free (active) phenytoin even when total levels appear low 5.

Additional Metabolic Parameters

• Monitor serum glucose, as phenytoin may cause increased glucose levels 1.
• Check alkaline phosphatase and GGT, which may be elevated by phenytoin 1.
• Monitor thyroid function (T4), as phenytoin may decrease T4 concentrations 1.

Drug Interaction Monitoring

Critical Drug Level Interactions

• When phenytoin is given with isoniazid, monitor both phenytoin AND phenytoin levels, as isoniazid increases phenytoin concentrations through enzyme inhibition 6.
• For patients taking cycloserine with phenytoin, measure phenytoin levels to ensure therapeutic dosing 6.
• Many drugs alter phenytoin metabolism through CYP450 enzyme induction or inhibition, necessitating more frequent level monitoring when these agents are started or stopped 1.

Clinical Monitoring

Neurological Assessment

• Assess for signs of phenytoin toxicity at each visit: ataxia, nystagmus, tremor, somnolence, and cognitive impairment 7, 2.
• Phenytoin encephalopathy with cerebellar syndrome is a serious adverse effect requiring immediate dose reduction or discontinuation 2.

Cardiovascular Monitoring During IV Administration

• Continuous ECG monitoring is mandatory during IV phenytoin administration for bradycardia, arrhythmias, and heart block 7.
• Monitor blood pressure continuously during infusion for hypotension 7.
• Reduce infusion rate if heart rate decreases by 10 beats/min 7.

Common Pitfalls to Avoid

• Do not check phenytoin levels before steady state (7-10 days), as this leads to inappropriate dose adjustments 1, 3.
• Do not rely solely on total phenytoin levels in hypoalbuminemic patients—calculate or measure free levels 5.
• Do not forget to monitor for drug interactions, as phenytoin has extensive interactions affecting both its own levels and levels of other medications 1.
• Do not overlook subtle signs of chronic toxicity (cognitive decline, balance problems), especially in patients with intellectual disability who may not report symptoms 2.