TDM Fundamentals - The "Just Right" Dose
- Goal: Maintain drug plasma concentration within the therapeutic window to maximize efficacy and minimize toxicity.
- Indicated for: Drugs with a Narrow Therapeutic Index (NTI) where effect is related to concentration.
- Key Metrics:
- Trough ($C_{min}$): Lowest level, drawn just before the next dose. Monitors for toxicity.
- Peak ($C_{max}$): Highest level, drawn after administration. Assesses efficacy.
⭐ For most NTI drugs like Vancomycin and Aminoglycosides, trough concentration is the primary monitoring parameter to prevent dose-dependent toxicity.
The Usual Suspects - Rogues' Gallery of Drugs
*A quick reference for high-risk medication monitoring.
| Drug Class / Agent | Key Monitoring Parameter(s) & Critical Thresholds |
|---|---|
| Anticoagulants | |
| - Warfarin | INR (Target: 2.0-3.0 for most indications) |
| - UFH | aPTT (Target: 1.5-2.5x baseline) |
| Antiarrhythmics | |
| - Amiodarone | TFTs, LFTs, PFTs (Baseline, then q6 months) |
| - Digoxin | Serum Level (Therapeutic: 0.5-0.9 ng/mL), Serum K+, Renal function |
| Psychotropics | |
| - Lithium | Serum Level (Therapeutic: 0.6-1.2 mEq/L), TFTs, RFTs |
| - Clozapine | ⚠️ ANC weekly for 6 months, bi-weekly for 6 months, then monthly. |
| Other High-Risk | |
| - Methotrexate | CBC, LFTs, Creatinine (Baseline & periodic) |
| - Statins | LFTs (Baseline), CK (only if myalgia develops) |
Warfarin & Digoxin - Heart-Watch Protocols
-
Warfarin (Oral Anticoagulant)
- Monitor: Prothrombin Time (PT) / International Normalized Ratio (INR).
- Target INR: 2.0-3.0 (standard); 2.5-3.5 (mechanical valves).
- Antidote: Vitamin K, Fresh Frozen Plasma (FFP), Prothrombin Complex Concentrate (PCC).
- 📌 Mnemonic: WEPT → Warfarin, Extrinsic pathway, PT.
-
Digoxin (Cardiac Glycoside)
- Monitor: Serum digoxin levels (trough levels).
- Therapeutic Range: 0.8-2.0 ng/mL.
- Toxicity Risk: ↑ with hypokalemia, renal failure.
- Antidote: Digoxin Immune Fab (DigiFab).
⭐ Amiodarone significantly increases levels of both Warfarin (↑INR) and Digoxin; dose reduction is crucial.
Lithium & Antiepileptics - Brain-Balancer Surveillance
-
Lithium:
- Baseline: TFT, RFT, ECG.
- Therapeutic Level: 0.6-1.2 mEq/L. Check 12h post-dose, 5 days after start, then every 3-6 months.
- Toxicity >1.5 mEq/L. Monitor TFT/RFT annually.
- 📌 Mnemonic "LITH": Leukocytosis, Insipidus, Tremor, Hypothyroidism.
-
Key Antiepileptics:
- Valproate: Monitor LFTs (hepatotoxicity) & CBC.
- Carbamazepine: Monitor CBC (agranulocytosis). Screen Asians for HLA-B*1502 (SJS risk).
- Phenytoin: Watch for nystagmus & ataxia (toxicity).
⭐ In Asian populations, screening for the HLA-B*1502 allele is crucial before starting Carbamazepine to prevent Stevens-Johnson syndrome (SJS).
High‑Yield Points - ⚡ Biggest Takeaways
- Lithium requires regular monitoring of thyroid (TSH) and renal function tests (RFTs).
- Clozapine mandates strict Absolute Neutrophil Count (ANC) monitoring due to high agranulocytosis risk.
- For Valproate, periodically check liver function tests (LFTs) and complete blood count (CBC).
- Amiodarone necessitates baseline and periodic TFTs, LFTs, and chest X-rays/PFTs.
- Warfarin/Acenocoumarol therapy is closely guided by PT/INR to prevent bleeding or thrombosis.
- Methotrexate requires routine checks of CBC, LFTs, and RFTs.
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