Therapeutic drug monitoring (TDM) measures the drug concentration in blood to keep it high enough to work and low enough to avoid toxicity. It is used for drugs with a narrow therapeutic index, large differences between people in how they are handled, and a known link between level and effect.

Principles

• Steady state is reached after about 4–5 half-lives of regular dosing. Levels drawn earlier underestimate the final level (unless a loading dose was given).
• Trough = lowest level, drawn just before the next dose (usually within 30 minutes). Reflects accumulation and many toxicities.
• Peak = highest level, drawn after absorption and distribution are complete (e.g., 30 minutes after the end of an IV aminoglycoside infusion). Reflects effectiveness for concentration-dependent drugs.
• Area under the curve (AUC) = total exposure over 24 hours; calculated from two levels or by software. Now preferred for vancomycin.
• Protein binding: only the unbound (free) drug is active. With low albumin (malnutrition, liver disease, kidney failure, pregnancy), a highly bound drug such as phenytoin can be toxic even when the total level looks normal.
• A level is a tool, not a goal: interpret it with the time of the last dose, the time of the draw, kidney and liver function, other drugs, and the client's condition.

Drug–laboratory interactions come in two kinds:

1. Physiologic (true) effects — the drug really changes the body (e.g., thiazides raise glucose; ACE inhibitors raise potassium).
2. Analytic interference — the drug disturbs the test method, so the result does not match the client (e.g., high-dose biotin gives falsely low troponin in some assays).

Common TDM drugs (typical adult ranges — always use the laboratory's reference range)

Boxed warnings for drugs in this table

• Lithium: toxicity is closely tied to serum level and can occur near the therapeutic range — level monitoring must be available before and during therapy
• Valproate: liver failure, pancreatitis, fetal harm (neural tube defects, lower IQ)
• Carbamazepine: SJS/TEN linked to HLA-B*15:02 — screen clients of Asian ancestry, including Filipino clients, before starting; aplastic anemia and agranulocytosis
• IV phenytoin: hypotension and dysrhythmias with rapid infusion — adults no faster than 50 mg/min
• Aminoglycosides: nephrotoxicity, ototoxicity, neuromuscular blockade (respiratory paralysis), fetal harm
• Tacrolimus, cyclosporine: serious infections and malignancy (lymphoma, skin cancer)

Anticoagulant monitoring (functional tests, not drug levels)

• Warfarin → PT/INR, target usually 2–3 (2.5–3.5 for some mechanical mitral valves)
• Unfractionated heparin → aPTT (about 1.5–2.5 × control) or anti-Xa per protocol; platelets for HIT
• DOACs → no routine monitoring; they can change PT, aPTT, and anti-Xa results

This topic's "adverse effects" are the drug effects on laboratory results.

Physiologic (true) changes to expect and monitor

Analytic interference (the result is misleading)

• Kidney impairment raises levels of renally cleared drugs (digoxin, lithium, aminoglycosides, vancomycin) — check creatinine and eGFR before and during therapy.
• Low albumin → interpret phenytoin and valproate with free levels or corrected values.
• Interacting drugs change levels: amiodarone, verapamil, and macrolides raise digoxin; thiazides, NSAIDs, ACE inhibitors, dehydration, and low sodium raise lithium; enzyme inducers (carbamazepine, phenytoin, rifampin) lower tacrolimus, cyclosporine, and many others; azoles and grapefruit raise tacrolimus; smoking cessation raises theophylline and clozapine levels.
• Nephrotoxin combinations (vancomycin + aminoglycoside, piperacillin–tazobactam, loop diuretics, NSAIDs, IV contrast) increase kidney injury — monitor creatinine and urine output closely.
• Pregnancy changes clearance (lithium, lamotrigine, phenytoin levels fall) — levels are checked more often, and again after delivery.
• Older adults: lower targets for lithium and digoxin are often used.

Listed in priority order.

1. Act on dangerous levels and symptoms first — for a toxic level or symptoms of toxicity, hold the next dose, assess the client (ECG for digoxin and lithium, neuro checks for phenytoin and lithium), and notify the prescriber; do not wait for the next routine level.
2. Time the sample correctly
   • Trough: just before the dose (within about 30 minutes); give the dose after the draw
   • Peak: at the ordered time after the dose or the end of infusion
   • Digoxin at least 6–8 hours after the last dose; lithium 12 hours after the last dose
3. Document exact times — dose given, infusion start and end, and specimen draw — on the requisition; a level without times cannot be interpreted.
4. Draw from the right place — from the arm opposite an IV infusion, never from the line infusing the drug; discard the correct volume from central lines; avoid heparin contamination for coagulation tests; send samples promptly to avoid hemolysis (falsely high potassium).
5. Check the whole picture — creatinine and eGFR, electrolytes (especially potassium and magnesium with digoxin), albumin, hearing and balance with aminoglycosides, urine output.
6. Reconcile drug–lab interactions — ask about biotin, supplements, and new drugs; tell the laboratory when an interfering drug was given; use a laboratory glucose method rather than a meter for clients on icodextrin; if a result does not fit the client, recheck before acting.
7. Trend, don't react to one number — compare with previous results and symptoms; report changes.

• Keep appointments for blood tests; on test days, do not take the dose until after the blood is drawn if a trough level is ordered
• Write down the time of your last dose and bring your medicine list
• Report symptoms of toxicity: nausea, vision changes, or irregular pulse (digoxin); tremor, vomiting, diarrhea, or unsteadiness (lithium); double vision or unsteady walking (antiseizure drugs); ringing in the ears or hearing change (aminoglycosides, vancomycin)
• Lithium: keep fluid and salt intake steady; avoid NSAIDs unless approved; seek care for vomiting, diarrhea, or heavy sweating
• Tell every provider about supplements, especially biotin, and stop high-dose biotin before tests as your provider or laboratory advises
• Do not start or stop other drugs, herbal products, or grapefruit without checking — they change blood levels
• Clients on SGLT2 inhibitors: glucose in the urine is expected; report nausea, vomiting, or abdominal pain even if blood glucose is normal

• TDM is for narrow therapeutic index drugs; interpret levels with dose and draw times
• Steady state = about 4–5 half-lives
• Trough just before the dose; peak after distribution
• Digoxin 0.5–2.0 ng/mL (lower, about 0.5–0.9, in HF); draw at least 6–8 hours after the dose; hypokalemia increases toxicity
• Lithium 0.6–1.2 mEq/L, drawn 12 hours after the last dose; toxic above 1.5
• Phenytoin 10–20 mcg/mL; low albumin → free drug is higher
• Vancomycin: AUC/MIC 400–600 (MIC 1) replaces trough-only monitoring; watch creatinine
• Aminoglycosides: nephrotoxicity and ototoxicity; trough must be low
• Never draw a level from the line infusing the drug
• Thiazides ↑glucose, uric acid, calcium; ACE inhibitors, spironolactone, trimethoprim, heparin ↑K⁺
• Biotin → falsely low troponin; icodextrin → falsely high meter glucose
• Trimethoprim raises creatinine without a true fall in GFR