B. TDM EXEMPLARS Flashcards
example of bronchodilators monitored
Theophylline
- Drug toxic effects difficult to distinguish from clinical symptoms
- Liver metabolism decreases due to heart failure, cirrhosis, viral infection and age (so increases drug conc) and increases in smokers, chronic alcoholics and other drug-drug interactions
- narrow therapeutic window
example of antibiotics monitored
Gentamicin, Amikacin
- Narrow therapeutic window and nephrotoxicity at high concentrations
examples of anti-cancer drugs monitored
Methotrexate
- High dosage methotrexate requires different levels of leucovrin rescue depending upon variation in excretion
examples of immunosupressants monitored
Cyclosporine (to prevent rejection in organ transplants)
- Narrow therapeutic window and can cause nephrotoxicity
- Large variability in pharmacokinetics in single patient and patient-to-patient
examples of psychoactive drugs monitored
Lithium, tricyclic antidepressants
- Narrow therapeutic window and many drug-drug interactions
- Lithium has inter and intra variability in PKs
examples of cardiac drugs monitored
Digoxin, Procainamide, Lidocain
examples of antiepileptics monitored
Phenobarbitone, Phenytoin, Carbamazepine
when are TDM measurements only of value
if the plasma level reflects the therapeutic effect of the drug ie: a higher plasma level results in an increased therapeutic effect
what is an important consideration in the use of TDM for digoxin and phenytoin
impaired renal function
what may phenytoin (anti epileptic) toxicity cause
fits
what may digoxin (heart drug) toxicity cause
cardiac dysrhythmias
scenarios where monitoring phenytoin levels may be clinically useful
- establishing an individual therapeutic concentration
- aiding in diagnosis of clinical toxicity
- assessing patient compliance
- guiding dosage adjustments in patients likely to have greater pharmacokinetic variability
- TDM of phenytoin is often considered essential
why is TDM of phenytoin needed
- narrow therapeutic range: 10–20 mg/L (µg/mL)
- dose dependent adverse effects: nystagmus (involuntary eye movement), vertigo, diplopia (double vision), ataxia, drowsiness, and speech disturbances
- highly protein bound (approximately 90% to serum albumin so only 10% active) and free phenytoin is what is producing the pharmacological effect
- unbound phenytoin increases in renal failure
important factors for phenytoin TDM
- phenytoin metabolism is non-linear, zero order pharmacokinetics
- Css reached 2-4 weeks after initiating dose so won’t know for 2-4 weeks
- dose increments must not be >25-50 mg/day
- phenytoin sodium formulations are not bioequivalent to those containing phenytoin base, i.e. 100 mg of phenytoin sodium is approximately equivalent in therapeutic effect to 92 mg phenytoin base
- CEDIA (cloned enzyme donor immunoassay) method commonly used to measure phenytoin concentrations
- need to consider bound and unbound forms
target sample conc and toxic range of digoxin
- 0.5-2microgram/l which is very narrow (depends what it’s being used for)
- > 2.4 µg/L
when should you sample digoxin levels
in the trough
when should you measure serum digoxin levels
at least 4 hours after an IV dose or 6 hours after oral dose
why is there a risk of sampling at wrong time or too frequently with digoxin
- Half-life: 33-51 hours
- Steady state Css: 7- 10 days (possibly longer)
*if an adjustment is made you will need to wait another 7 days before you can check whether the desired steady state concentration has been reached
why is TDM very important for digoxin
combination of narrow therapeutic range, low concentration for toxicity and long half life
methods used to to monitor serum digoxin concentrations
- radioimmunoassay
- fluorescence polarisation immunoassay
- enzyme immunoassay
criteria for TDM of digoxin
- borderline renal function
- possible drug accumulation
- hypokalemia or hypomagnesesmia can increase digoxin induced arrythmia
- aged subjects
- renal elimination reduces with age
- patients with rapid atrial fibrillation who require higher doses for heart rate control
- target concentration close to toxic level
- heart failure patients
*require a lower dose (0.5-1 ug/L): exert a beneficial effect via neuro-hormonal modulation - susceptible to inotropic stimulation by digoxin at higher concentration
which drugs don’t need TDM
- most drugs don’t
- it’s expensive
- drugs used for treating diseases with clear clinical end points e.g., BP, HR, cardiac rhythm, blood sugar, blood cholesterol and triglycerides, urine volume, body temperature, inflammation, pain, headache (use obs instead)
- drugs whose serum concentrations do not correlate with therapeutic or toxic effects
- drugs with straightforward pharmacokinetics
- drugs used to treat diseases that are not life threatening
role of pharmacist in TDM
hospital pharmacists may:
- advise other health care professionals about correct use of TDM-sampling time, sampling technique and interpretation of results
- select initial drug dosage regimen-dose, dosing interval, route of administration, dosage form
- revise and re-calculate dosage regimen depending upon TDM results and patient’s response
- assess various reasons for unexpected results (ie progression) such as non-compliance,
medication or laboratory errors
- evaluate and adjust dosage for patients on renal or haemodialysis
- advise and manage acute drug interactions
how does TDM help to achieve optimal drug therapy
- maximises the desired pharmacological effect of the drug
- reaches this maximal effect in the shortest possible time
- decreases the risks of adverse effects and toxicity
what type of kinetics does digoxin have
linear
what type of kinetics does phenytoin have
non-linear
