PATIENTS AND THERAPEUTIC DRUG MONITORING

Written by Timothy Okooboh

There are drugs that should not be prescribed without regularly monitoring the patient or drug concentration in the plasma or serum. In this era of pharmaceutical care, these are medications a pharmacist should dispense after ensuring that the patient is under regular monitoring at the health facility the drug was prescribed.

Some drugs have narrow therapeutic index, meaning that small differences in dosage or blood concentration may lead to treatment failure or adverse drug reactions. Some drugs without  a narrow therapeutic index are even potentially toxic hence, patients on these drugs need to be monitored through out therapy. Some patients may already have liver or kidney problems before starting a medication. These patients belong to a high risk group and need to be monitored while on some medications because most drugs are metabolized and cleared by the liver or kidneys and for patients who already have problems with these organs, drug toxicity may occur while on medications.

The diagram above represents the patient centered care process. This emphasizes the fact that the patient is at the center of physician care, pharmaceutical care, nursing care and the service of every health care giver. Therefore, patient safety should be a priority for health care providers.

The Golden Rule:

Decide to prescribe? Check!

Before you dispense, Check!

Details about medications to be prescribed and past medical history of the patients should be properly checked before prescribing or dispensing.

For patients on some medications, monitoring may involve tests such as Complete Blood Count, Liver Function Tests, Kidney Function Tests, etc. before, during or after therapy, while some may require Therapeutic Drug Monitoring which is the process of measuring drug concentrations in plasma or serum in order to individualize dosage and maintain drug concentration within therapeutic range as well as preventing toxicity.

Drugs that require regular patient or therapeutic drug monitoring include but not limited to :

Digoxin, statins, Disease-modifying antirheumatic drugs (DMARDs), vancomycin, gentamicin, tobramycin,  lithium, carbamazepine, sodium valproate,  phenytoin and metformin.

STATINS

Statins also known as HMG-CoA reductase inhibitors belong to a class of drugs that lower cholesterol levels and prevent atherosclerosis, stroke, heart attack and death in heart diseases.

Examples of statins are atorvastatin, simvastatin, rosuvastatin and pravastatin. Serious adverse effects of statins including rhabdomyolysis ( damage of muscles that release proteins into blood which collects in the kidneys), myositis (inflammation of the muscles) and elevated levels of creatinine kinase leading to muscle pain and weakness.

Baseline liver enzymes should be measured before starting a statin. Liver function should be measured within 3 months of starting treatment and at 12 months, but not again unless clinically indicated. Treatment should be discontinued if creatinine kinase concentration rise to and persist three times the normal range.

Reference values for CK

Males :

< or equal to 3 months = not established

> 3 months = 39 - 308 u/l

Females :

< or equal to 3 months = not established

> 3 months =26 - 192 u/l

DMARDs

Disease-modifying antirheumatic drugs act on the immune system to slow the progression of rheumatoid arthritis.

They include methotrexate, hydroxychloroquine, sulfasalazine, azathioprine cyclosporine and mycophenolate. Due to their potential toxicity, treatment with these drugs is only initiated by specialist rheumatologist. GPs must receive a clear protocol for any dosage adjustment and requirement for routine testing from the specialist clinic.

Tests for patients on DMARDs include:

Complete Blood Count for patients on methotrexate, azathioprine, cyclosporine, sulfasalazine and mycophenolate. Pancytopenia, a condition in which blood cell count is reduced is a serious side effect of DMARDs.

Liver function tests for patients on methotrexate, azathioprine, cyclosporin or sulfasalazine.

Kidney function tests for patients on methotrexate or cyclosporine.

Eye examination for patients on hydroxychloroquine in order to check for blurred vision and visual acuity.

All DMARDS have the potential to cause myelosuppression. Patients should be warned to report symptoms such as sore throat, mouth ulcers, cough or breathlessness, purpura and rashes, fever, and unexpected bleeding or bruising.

Digoxin

Digoxin is a cardiac glycoside used in the treatment of heart failure and atrial fibrillation. Digoxin therapy requires close monitoring and proper handling because of its narrow therapeutic index and the wide variety of factors that affect its serum levels.

Therapeutic index of digoxin is 1-2.5 nmol/l. Toxicity increases significantly with concentration > 2.5 nmol/l. However, routine monitoring of serum digoxin concentration is not recommended. Serum digoxin concentration should be measured at least 8hrs following the last oral dose when the drug has reached steady state, Sidwell et al., 2003. This can help to confirm a clinical impression of toxicity or non adherence.

Common adverse drug reactions of digoxin toxicity are ventricular tachycardia, ventricular ectopic beats, SA node arrest, 2nd and 3rd degree heart block. Non cardiac ADR include diarrhea, fatigue, anorexia, confusion and abnormal colour vision.

It is not enough for drugs to be prescribed based on correct indication and dosage only. Certain drugs require monitoring because of their narrow therapeutic index and potential toxicity and certain patients require monitoring because of their liver or kidney impairment. It is therefore important for physicians and pharmacists to regularly update their knowledge of drugs and diseases and work together in order to help the patient get the best benefits from their medications.