TDM of Phenytoin Study Guide: Pharmacokinetics, Dosage, and Monitoring

This in-depth study guide on Phenytoin Therapeutic Drug Monitoring (TDM) covers essential pharmacokinetic principles, dosage adjustments, and adverse drug reactions. It’s an essential resource for healthcare professionals, medical students, or anyone studying the use of Phenytoin in the management of seizures, providing critical information for safe and effective use.
 
Key Features:
What is Phenytoin? Learn about Phenytoin, a first-generation anticonvulsant used primarily to prevent tonic-clonic and focal seizures. Understand why it’s no longer first-line treatment and how it compares to alternatives like sodium valproate and carbamazepine.
 
Mechanism of Action: Phenytoin works by blocking voltage-gated sodium channels in neurons, reducing neuronal excitability and preventing seizure activity.
 
Adverse Drug Reactions (ADRs):
Dose-Related ADRs: Ataxia, nystagmus, slurred speech, diplopia, drowsiness.
Chronic ADRs: Gingival hyperplasia, hirsutism, coarsening of facial features, megaloblastic anemia, peripheral neuropathy, and vitamin D metabolism issues leading to fractures.
 
Idiosyncratic ADRs: Severe skin reactions like Stevens-Johnson syndrome (SJS), drug-induced lupus, and hepatitis.
Teratogenicity: Risks during pregnancy include cleft palate and congenital heart defects.
Phenytoin Overdose: Understand the symptoms of overdose, including nystagmus, ataxia, dysarthria, and severe effects like coma and respiratory depression.
 
Therapeutic Range and TDM:
Therapeutic Range: 10–20 mg/L (40–80 µmol/L).
TDM Necessity: Due to the narrow therapeutic window, high protein binding, and non-linear pharmacokinetics, TDM is essential for safe use.
Drug Interactions:
Increase levels: Amiodarone, antifungals like fluconazole, omeprazole.
Decrease levels: Rifampicin, St. John’s wort, chronic alcohol use.
Phenytoin also reduces the effectiveness of oral contraceptives, warfarin, and ciclosporin.
 
Protein Binding & Adjustments: Learn how Phenytoin’s ~90% protein binding affects drug levels, especially in patients with low albumin, leading to higher free drug concentrations and potential toxicity.
Non-Linear Pharmacokinetics: Understand how small dose changes lead to large plasma concentration changes, and why dose adjustments must be gradual, with monitoring after 14 days.
 
Pharmacogenomics: Learn how genetic variants (e.g., CYP2C9) affect Phenytoin metabolism and toxicity, and the importance of genetic screening for high-risk groups (e.g., HLA-B*15:02) to prevent severe skin reactions like SJS/TEN.\
 
Whether you are studying for exams, managing Phenytoin therapy in clinical practice, or seeking a deeper understanding of TDM, this guide offers a structured and detailed approach to safe Phenytoin use and monitoring.