Therapeutic Drug Monitoring

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 y

Drugs

Treatment Use

Digoxin, digitoxin, quinidine, procainamide, NCardiac Congestive heart failure, angina, acetyl-procainamide (a metabolite of drugs arrhythmias procainamide) Antibioti Aminoglycosides (gentamicin, tobramycin, cs amikacin), Vancomycin, Chloramphenicol

Infections with bacteria that are resistant to less toxic antibiotics

Antiepil Phenobarbital, phenytoin, valproic acid, eptics carbamazepine, ethosuximide, sometimes

Epilepsy, prevention of seizures, sometimes to stabilize moods

gabapentin, lamotrigine Broncho Theophylline, caffeine dilators

Asthma, Chronic obstructive pulmonary disorder (COPD), neonatal apnea

Immuno Cyclosporine, tacrolimus, sirolimus, suppress mycophenolate mofetil, azathioprine ants

Prevent rejection of transplanted organs, autoimmune disorders

Anticancer drugs

Psoriasis, rheumatoid arthritis, various cancers, non-hodgkin's lymphomas, osteosarcoma

Methotrexate

Lithium, valproic acid, some antidepressants Psychiat (imipramine, amitriptyline, nortriptyline, ric drugs doxepin, desipramine)

Bipolar disorder (manic depression), depression

Protease Indinavir, ritonavir, lopinavir, saquinavir, inhibitor atazanavir, nelfinavir s

HIV/AIDS

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