What is therapeutic drug monitoring?

Therapeutic drug monitoring is the measurement of specific drugs at intervals in order to

maintain a relatively constant concentration of the medication in the bloodstream. Drugs
that are monitored tend to have a narrow “therapeutic range” – the quantity required to be
effective is not far removed from the quantity that causes significant side effects and/or
signs of toxicity. Maintaining this steady state is not as simple as giving a standard dose
of medication. Each person will absorb, metabolize, utilize, and eliminate drugs at a
different rate based upon their age, general state of health, genetic makeup, and the
interference of other medications that they are taking. This rate may change over time
and vary from day to day.
Not all medications require therapeutic monitoring. Most drugs have a larger therapeutic
range and can be prescribed based upon pre-established dosing schedules. The
effectiveness of these treatments is evaluated, but it is not usually necessary to determine
the concentration of the drug in the bloodstream. Examples of this include high blood
pressure medications and many of the antibiotics given to treat bacterial infections. If the
infection resolves and the blood pressure is lowered, then the treatments have been
effective.

Why is it important?
Many of the drugs that are monitored therapeutically are taken for a lifetime. They must
be maintained at steady concentrations year after year while the patient ages and goes
through life events such as pregnancies, temporary illnesses, infections, emotional and
physical stresses, accidents, and surgeries. Over time, patients may acquire other chronic
conditions that also require lifetime medication and that may affect the processing of
their monitored drugs. Examples of these conditions include cardiovascular disease,
kidney disease, thyroid disease, liver disease, and HIV/AIDS.
Therapeutic drug monitoring follows these changes and accommodates them. It identifies
patient noncompliance (when the patient does not take the medication regularly as
prescribed), identifies the effect of drug interactions (may cause drug concentrations that
are higher or lower than expected at a given dosage), and helps to tailor dosages to fit the
current needs of the specific patient. Along with tests such as BUN, creatinine, and liver
panel to check kidney and liver function, monitoring can help identify decreases in the
efficiency of and dysfunctions in the body in metabolizing and eliminating therapeutic
drugs.

How does TDM work?

Through years of testing, the optimum therapeutic blood level range for each drug has
been determined. In this range, most people will be effectively treated without excessive
side effects or symptoms of toxicity. The drug dosage to reach this level must be
individually determined. When a patient starts on a monitored drug (or returns to it after
an absence), the doctor adjusts the dose upwards and tests blood concentrations
frequently until the appropriate steady state level is achieved. If a patient’s levels are too
high, the doctor will adjust them lower. Often, each different dosage level will take a
short period of time to stabilize so these corrections up and down may take place over a
few days or weeks (although if they are causing symptoms associated with toxicity, they
will be decreased relatively rapidly to relieve these symptoms). It is important that
patients work closely with their doctors during this process and not make their own
adjustments or stop taking their medication. Abrupt changes can sometimes worsen
conditions and cause acute symptoms.
Once the patient’s results are in the therapeutic range and their clinical signs indicate that
the treatment is appropriate, then the doctor may monitor the drug at regular intervals and
as needed to accommodate changes in patient status to ensure that the drug stays in the
therapeutic range. The frequency of testing required will depend on the drug and on the
needs of the patient. If treatment does not appear to be fully effective or if the patient has
either excessive side effects or signs of toxicity, then testing will be done to see if blood
concentrations have become too low or high. If they have, then the dosage will be
adjusted; if they have not, then the patient and doctor may need to re-evaluate the use of
that specific medication and consider switching to another type of drug if it is available.
The timing of blood collection is an important part of therapeutic drug monitoring. When
a person takes a dose of a drug, the amount in the blood rises for a time period, peaks,
and then begins to fall, usually reaching its lowest level (trough) just before the next
dose. To be effective, peak levels should be below toxic concentrations and trough levels
should remain in the therapeutic range. Through experience and studies, doctors know
when to expect peaks and troughs to occur and will request blood sample collections as
either trough levels (usually drawn just before the next dose), peak levels (timing varies
depending on the drug), or sometimes will request a random level. Consistent and
accurate interpretation of the results depends on the timing of sample collection. If a
patient is unable to take their medication and have their blood drawn at the appropriate
time interval, then they should talk to their doctor before the sample is collected.

Monitored Drugs by Category

There are several categories of drugs that require monitoring, as
summarized here.
Drug
Categor Drugs Treatment Use
y
Digoxin, digitoxin, quinidine, procainamide, N-
Cardiac Congestive heart failure, angina,
acetyl-procainamide (a metabolite of
drugs arrhythmias
procainamide)
Antibioti Aminoglycosides (gentamicin, tobramycin, Infections with bacteria that are
cs amikacin), Vancomycin, Chloramphenicol resistant to less toxic antibiotics
Antiepil Phenobarbital, phenytoin, valproic acid, Epilepsy, prevention of seizures,
eptics carbamazepine, ethosuximide, sometimes sometimes to stabilize moods
 gabapentin, lamotrigine
Asthma, Chronic obstructive
Broncho
Theophylline, caffeine pulmonary disorder (COPD), neonatal
dilators
apnea
Immuno
Cyclosporine, tacrolimus, sirolimus, Prevent rejection of transplanted
suppress
mycophenolate mofetil, azathioprine organs, autoimmune disorders
ants
Anti- Psoriasis, rheumatoid arthritis, various
cancer Methotrexate cancers, non-hodgkin's lymphomas,
drugs osteosarcoma
Lithium, valproic acid, some antidepressants
Psychiat Bipolar disorder (manic depression),
(imipramine, amitriptyline, nortriptyline,
ric drugs depression
doxepin, desipramine)
Protease
Indinavir, ritonavir, lopinavir, saquinavir,
inhibitor HIV/AIDS
atazanavir, nelfinavir
s
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