How do you monitor carbamazepine and phenytoin blood levels?

Monitoring Carbamazepine and Phenytoin Blood Levels

For carbamazepine, draw trough levels (immediately before the next dose) targeting 4-8 mcg/mL, and for phenytoin, draw levels at steady state (7-10 days after dose changes) targeting 10-20 mcg/mL. 1, 2

Carbamazepine Monitoring

Timing of Blood Draws

• Draw trough levels immediately before the morning dose to avoid the large interindividual variation between peak and trough levels 3
• Peak levels occur 2-4 hours after oral administration but are less reliable for therapeutic monitoring 3
• Wait 4-6 days after any dose adjustment before drawing levels to avoid making decisions based on transient changes 1

Target Therapeutic Range

• Maintain levels between 4-8 mcg/mL for optimal anticonvulsant effect 1
• Peak levels should not exceed 10-12 mcg/mL to avoid adverse effects 3
• Levels above 20 mcg/mL can paradoxically increase seizures (paradoxical intoxication) 4

Baseline and Ongoing Laboratory Monitoring

• Obtain baseline complete blood count (CBC) and liver function tests (LFTs) before initiating therapy 1, 5
• Monitor CBC and LFTs monthly for the first 3 months, then every 3-6 months if stable 1
• More frequent monitoring is required in patients with pre-existing liver disease 1
• Consider HLA-B*15:02 screening before initiation, particularly in patients of Asian descent, to reduce Stevens-Johnson syndrome risk 1, 6

When to Monitor Levels

• Dramatic increase in seizure frequency 5
• Suspected toxicity or non-compliance 5
• When adding or removing interacting medications (isoniazid increases carbamazepine levels; rifampin decreases levels) 7, 5
• During pregnancy, as levels may decrease due to increased metabolism 8

Phenytoin (Dilantin) Monitoring

Timing of Blood Draws

• Wait 7-10 days after any dose change to reach steady state before drawing levels 2
• Levels can be drawn at any time during the dosing interval once steady state is achieved 2
• More frequent monitoring is needed when switching between formulations (extended vs. prompt release, or sodium salt vs. free acid forms) due to the 8% difference in drug content 2

Target Therapeutic Range

• Maintain levels between 10-20 mcg/mL for optimal seizure control 2
• Levels above 20 mcg/mL increase risk of toxicity (ataxia, nystagmus, cognitive impairment) 9

Baseline and Ongoing Laboratory Monitoring

• Measure baseline AST, ALT, and bilirubin in high-risk patients (HIV infection, history of liver disease, alcoholism, pregnancy) 9
• Repeat LFTs if clinical signs of hepatotoxicity develop (jaundice, abdominal pain, unexplained fatigue) 9
• Monitor for thrombocytopenia, a rare but serious adverse effect 9

Clinical Monitoring During Administration

• Continuous ECG monitoring is mandatory during IV phenytoin administration for bradycardia, arrhythmias, and heart block 9
• Assess for signs of toxicity at each visit: ataxia, nystagmus, tremor, somnolence, cognitive impairment 9
• Reduce infusion rate if heart rate decreases by 10 beats per minute 7

Drug Interaction Monitoring

• When phenytoin is co-administered with isoniazid, monitor phenytoin levels closely as isoniazid increases phenytoin concentrations through enzyme inhibition 7, 9
• Rifampin decreases phenytoin levels through enzyme induction 7
• Phenytoin levels can increase when given with carbamazepine 7

Common Pitfalls to Avoid

Carbamazepine-Specific

• Do not draw levels too soon after dosing (within 4-6 days of dose changes), as this leads to falsely elevated results and inappropriate dose adjustments 1
• Do not overlook drug interactions when adding medications—isoniazid can increase carbamazepine to toxic levels, while rifampin can render it subtherapeutic 7, 5
• Do not administer carbamazepine suspension simultaneously with other liquid medications, as precipitation can occur 5

Phenytoin-Specific

• Do not make dose adjustments before 7-10 days, as steady state has not been reached 2
• Be aware that switching between formulations requires careful monitoring and potential dose adjustment due to differences in bioavailability 2
• Do not ignore the 8% increase in drug content when switching from sodium salt to free acid form 2

Both Medications

• Recognize that therapeutic drug monitoring is particularly useful when seizure frequency dramatically increases, toxicity is suspected, or compliance is questionable 5, 10
• More intensive monitoring is needed when either drug is used with other medications that affect metabolism 7, 1