DRUG THERAPY MONITORING

(MEDICATION CHART REVIEW, CLINICAL REVIEW,

PHARMACIST INTERVENTION)
INTODUCTION:
Drug therapy monitoring is a significant role of clinical pharmacist in health care that ensures a SAFE
and EFFECTIVE therapy.

Many times, same doses of a drug may produce satisfactory therapeutic actions in some patient,
whereas, it causes toxicity in others, and has a little effect on some people.

Hence to improve the situation clinical pharmacokinetics and laboratory technology were integrated
with clinical medicines, giving birth to “THERAPEUTIC DRUG MONITORING”.

It is defined as:

“A practice to individualize, the dosage regimen and the therapy such that it maximize the benefits of
the prescribing drug minimum toxicity.”

Or

“The measurement and interpretation of principally blood or plasma drug concentration measurements
with the purpose of optimising a patient’s drug therapy and clinical outcome while minimising the risk
of drug-induced toxicity.”

Thus, it aims to maximize benefits of the prescribed drug simultaneously minimizing its toxicity.

It benefits the patient medically as well as financially.

OBJECTIVES OF DRUG THERAPY MONITORING:

 To achieve optimal drug therapy.
 To achieve desired pharmacological effect of a drug within shortest possible time with no
toxicity.
 To monitor serum concentration with clinical response, so as to modulate the therapy.
 To benefit the patient, medically and economically by reducing the hospital stay and drug’s
toxicity.
 To monitor individual complication factors of patient like habits, disease susceptibility and
drug sensitivity.

STAGE IN DRUG THERAPY MONITORING:

 Development and validation of a suitable analytical technique.
 Selection of appropriate samples for analysis and their preservation.
 To establish the blood drug con centration correlation with therapeutic efficacy or/ and toxicity
of the drug.

For TDM to be considered for routine clinical use, the following criteria should generally
apply:
  The drug should have a narrow therapeutic index. For these agents, small changes in dose
may result in loss of efficacy (if the dose is lowered) or toxicity (if the dose is increased).
Examples of drugs with a narrow therapeutic index include digoxin, theophylline, lithium and
phenytoin. The usefulness of TDM is reinforced if the drug has a narrow therapeutic index and
also displays non-linear pharmacokinetics (for example, phenytoin), has potentially clinically
important interactions, or is associated with large pharmacokinetic variations between
individuals (for example, perhexiline).
 There should be a beneficial concentration–response relationship between the blood drug
concentration and the pharmacological effects, preferably with respect to both clinical
efficacy and toxicity. The therapeutic range represents drug concentrations that are effective for
a particular indication in most patients, with a minimal risk of toxicity.
 There should be no other easily measurable physiological parameter. As mentioned
previously for drugs such as anti-hypertensive and hypoglycaemic agents, it is much more
convenient, cheaper and clinically appropriate to use measures such as blood pressure and
glucose level rather than plasma drug concentrations.

When Should TDM be requested?

Drug assays are expensive, so your reason for performing TDM should always be clear. Routine
monitoring of many drugs is not required in a clinically stable patient.

TDM is most commonly used to assist the optimisation of drug therapy.

The decision if, and when, to perform TDM typically depends on a variety of considerations.
Appropriate indications for TDM include:
 A patient with an inadequate clinical response. For some drugs, a minimum serum
concentration is needed to ensure efficacy. TDM can be used to assess whether the dosing
regimen is achieving this minimum concentration. For example, TDM may be useful in a
transplant patient to ensure cyclosporine concentrations are adequate.
 A patient with signs or symptoms which may indicate drug toxicity. For example, a patient
who complains of persistent nausea while on theophylline.
 To minimise the risk of drug toxicity. Ensuring that the concentration of a drug remains within
a targeted range can help minimise the risk of toxicity. The most common example here is the
use of TDM to minimise the risk of nephrotoxicity and ototoxicity associated with
aminoglycoside therapy.
 To individualise dosing for some drugs with an unpredictable dose– response curve. For
example, phenytoin has non-linear kinetics, and an increase in dose may lead to a
disproportionate increase in serum drug concentration.
 To help predict a patient’s dose requirements. TDM combined with an understanding of a
drug’s pharmacokinetic profile can allow individualised rapid dose titration to be undertaken
while minimising the risk of toxicity.
 To assess medication compliance. For example, TDM for anticonvulsants in patients with poor
seizure control.
 To identify poisons and to assess the severity of poisoning in a poisoning emergency (for
example, paracetamol poisoning). The effectiveness of antidotes and the excretion of poisons
can be monitored by measuring the concentration of the poison in body fluids.
The TDM commonly performed in drug like carbamazepine, cyclosporine, valproate,
amiodarone, gentamicin, phenytoin, lithium, theophylline, digoxin, and vancomycin. Other drugs
where TDM may be used less commonly include other immunosupressants, analgesics (paracetamol,
methadone), anti-depressants, anti-psychotics, anti-retrovirals, anti-fungal agents and anti-neoplastic
agents.

Relevant data for drugs for which TDM is used commonly used is given in below table:
Interpreting TDM Results:
Many factors need to be considered when interpreting TDM results. The minimum information needed is the
indication for therapy, dosing regimen, duration of therapy, time of the last dose, time of the sample and the
reason why TDM has been requested. An algorithm for the interpretation of TDM results for drugs used as
prophylactic therapy is presented below:
Major components of drug therapy monitoring involve MEDICATION CHART REVIEW, CLINICAL
REVIEW and PHARMACIST INTERVENTION.

MEDICATION CHART REVIEW

Medication chart review (MCR) is one of the fundamental responsibilities of clinical pharmacy practice as it
is the basis for other clinical pharmacy activities such as medication counselling, therapeutic drug
monitoring (TDM) and detection and management of ADRs.

MOR is a systematic review of a patient’s drug therapy to ensure that the prescribed medication is
appropriate for the patient. It involves the assessment of all current and recent medication orders, including
routine medication and over-the-counter (OTC) drugs and the use of other systems of medicine (Unani,
Ayurvedic, Siddha).

Goal of MCR:

The goal of MOR is to optimise the patients’ drug therapy by ensuring that patients receive the right drug,
dose and dosage form for the right duration.

Steps:

In reviewing a patient’s drug therapy, any condition or drug-related problem that requires change in drug
therapy or the management plan should be identified as an issue and discussed with the relevant medical
practitioners.

A medication order should be reviewed for appropriateness by considering all relevant information including
presenting complaints, clinical assessment, previous allergy status, laboratory investigation, treatment plans
and the daily progress of the patient. The pharmacist should consider available data from sources such as the
treatment chart, case notes, laboratory results and medication history obtained during patient interview.

The steps involved in MOR include:

 Collection and interpretation of patient-specific information, including medication history interview

 Assessment of therapeutic goals
 Identification of drug-related problems
 Individualising medication regimens
 Monitoring of treatment outcomes
 Medication chart endorsement
 Documentation

Collection and Interpretation of Patient-specific Information

Collection of patient-specific information is the first step in setting the therapeutic goal for a patient.
Pharmacists need to collect information that will assist them to determine the appropriateness of drug
therapy. This includes the patient’s demographic details such as age, sex and body weight, social
history, presenting complaints, past medical history, allergy and sensitivity status, current and recent
medication, and results of relevant laboratory tests and other investigations.

This enables the pharmacist to understand the patient’s disease condition, the reason why certain drugs
are being administered and the patient’s daily clinical progress. This understanding is the foundation
for medication review. Relevant information can be obtained from a variety of sources including the
patient, case notes, the medication chart, nursing notes, observational charts, laboratory results and
through discussions with medical and nursing staff.
When a patient is admitted to hospital, medical staff document relevant information regarding the
admission in the patient’s case notes. This usually includes a list of medications which the patient is
currently taking. This list may be inaccurate or incomplete, particularly in situations where medical
staff are over-burdened with a high patient load. By speaking personally to patients about their
medications, pharmacists can obtain further information which may be of importance to the ongoing
medical management of the patient. This process is sometimes referred to as a medication history
interview (MHI)

The medication history interview provides an ideal opportunity for pharmacists to apply their expertise
as ‘medication managers’.

It enables the pharmacist to:

 Establish a rapport with the patient

 Explain their role in patient management
 Conduct preliminary medication counselling
 Plan ongoing patient management/ pharmaceutical care

Aspects of medication use which may be obtained from a medication history interview
o History of previous allergies and/or ADRs
o Indication/Purpose of each medication
o Dosing regimen including dose, route, frequency and duration of therapy
o Perceived efficacy of each medication
o Perceived side-effects
o Adherence to medication regimen
o Medication administration techniques
o Use of medication aids
o Treatment with other systems of medicine (Ayurveda, Siddha and Unani)
o Use of prescription and/or non-prescription medications
o Specific problems relating to medication
o use Immunisation status (if relevant)
o Possibility of pregnancy in women of childbearing age
o Social drug use (alcohol, tobacco, pan masala, etc.)
o Evidence of drug abuse
o General attitudes towards illness and medication use
Assessment of Therapeutic Goals

In order to determine the appropriateness of drug therapy, it is essential to understand the therapeutic
goals for the individual patient.

These may include one or more of the following:

 Cure of the disease

 Reduction/elimination of signs and symptoms

 Arresting or slowing disease progression

 Preventing disease/symptoms

These goals should be tailored to the patient’s individual circumstances, and may differ from patient to
patient based on their age, co-morbidities and the nature and severity of their illness. For example, for
a 40-year-old patient with diabetes and hypertension, the goal may be to reduce blood pressure below
130/85 mmHg. However, in a 75-yearold patient with diabetes, hypertension and a history of postural
hypotension, the goal may be to reduce blood pressure to no lower than 150/90 mmHg in order to
minimise the risk of symptomatic hypotension.

Identification of Drug-related Problems

When reviewing a patient’s drug therapy, one of the main objectives is to identify and resolve any
drug-related problems. A drug related problem is any event or circumstance involving drug treatment
that interferes or potentially interferes with the patient achieving an optimum outcome of medical care.
Eight categories of drug-related problems (DRPs) were outlined by Charles Hepler and Linda Strand in
their landmark paper in 1990 (Am J Hosp Pharm 1990; 47:533–43), and are summarised below
Drug-related problems:
o Subtherapeutic dose

o Untreated indication

o Improper drug selection

o Overdosage

o Adverse drug reactions

o Failure to receive drugs

o Drug interactions

o Drug use without indication

Individualising Medication Regimens

Once drug-related problems relating to individual drugs on the medication chart have been resolved,
the next step is to consider the patient’s overall medication regimen. This is particularly important for
patients with chronic diseases who are on many drugs on a long-term basis. In individualising the
medication regimen, the pharmacist should consider patient data including past medical history, co-
morbid conditions, allergic history and concurrent disease. The aim should be to simplify the regimen
as much as possible and to adjust the regimen to maximise longterm medication adherence.

Monitoring of Treatment Outcome

Monitoring of treatment outcome is the key to assessing whether the therapeutic goals of drug
treatment have been achieved. It is an ongoing process and involves a review of the patient’s clinical
status, laboratory data and other markers of drug therapy response. In hospitals, monitoring of
treatment outcome is usually carried out on a daily basis by the attending doctors as part of their
overall clinical review of the patient’s progress and clinical status.

Medication Chart Endorsement

Chart endorsement (annotations to the treatment chart) is one of the primary responsibilities of the
pharmacist in ensuring that medication orders are unambiguous, legible and complete. It is now routine
practice for pharmacists to document on the medication chart the relevant aspects of medication
administration. It is essential to avoid medication errors, including those that might occur at the level
of prescribing and/ or administration due to incompleteness of the order, lack of adequate instructions
and illegibility.

Documentation

The pharmaceutical care provided to a patient should be an integral part of the patient’s medical
record. The documentation of pharmaceutical care provided can be made either in the medication chart
or in case notes with a clear title (for example, clinical pharmacy) with the pharmacist’s signature.
Documentation of services in the patient’s medical record is then accessible to all other healthcare
professionals. Computerisation of relevant information relating to pharmaceutical problems may be
useful in hospitals where patients’ data is accessible to healthcare providers through a networking
system.

Clinical/Daily Progress Review

Clinical review is one of the integral components of medication review and should preferably be
performed on a daily basis. It is the review of the patient’s progress for the purpose of assessing the
therapeutic outcome. The therapeutic goal for the specific disease should be clearly identified before
the review as described earlier under the section on assessment of therapeutic goals.

Goals

The primary aims of the clinical review are to:

 Assess the response to drug treatment Evaluate the safety of the treatment regimen
 Assess the progress of the disease and the need for any change in therapy
 Assess the need for monitoring, if any
 Assess the convenience of therapy (to improve compliance)

Procedure:

Ideally, clinical review should be done routinely for all patients. It is usually carried out every day by
the attending doctors, while evaluating their patients, to monitor the patient outcome to drug therapy.
In evaluating a patient’s response to drug therapy, the pharmacist may need to review biochemical,
haematological, microbiological and other investigations, as appropriate (Table 13.4). Other essential
information required may be obtained from other healthcare professionals and patients.

Collection of all clinically relevant data involves the use of the following sources:

 Case notes
 Observation charts (fluid balance, blood/urine sugar, temperature and pulse)
 Medication history
 interview record
 Discussion with the patient and other healthcare professionals

The data should be interpreted to assess whether or not progress is being made towards the targeted
objectives. These objectives should be specific to the patient’s condition as mentioned earlier and
could be cure of the disease, reduction in the patient’s signs and symptoms, arresting/slowing the
disease process, prevention of disease and improving the quality of life.

Monitoring parameters to assess the patient’s response to medication

1) Clinical parameters:

 Signs
 Symptoms

2) Clinical charts:

 Diabetic chart
 Fluid balance chart
 Observation chart
 Pain management chart
 Bowel chart
 Alcohol withdrawal chart

3) Laboratory parameters (if clinically indicated):

 Biochemistry: electrolytes, renal function and liver function tests

 Hematological: Total WBC, RBC indices, platelets, DC, ESR, Hb% etc.
 Microbiology: Culture results, antibiotic sensitivities
 Other tests: Echocardiogram, ECG, CT scan, MRI etc.

The information obtained must be interpreted and evaluated with reference to:

 The clinical features of the disease being treated

 The need for an investigation
 Aspects related to drug effects (onset and duration)
 Medication history of the patient
 The desired therapeutic outcome(s)

If the therapeutic objectives are not being achieved, the clinical pharmacist should reevaluate the
appropriateness of treatment and discuss any relevant issues with the clinicians. The intervention could
be of any type (change of drug, dose adjustment, cessation of drug, etc.), but the recommendations
should be specific and directed towards achieving the therapeutic goals for the problem identified.
 PHARMACIST INTERVENTION
Clinical pharmacists can audit their impact on patient care by intervention monitoring. Some hospitals
undertake these audits at regular intervals and present the result internally or to the multidisciplinary
team.

Data collection forms or electronic hand held are used to collect the relevant data on a pharmacist’s
interventions to improve patient care.

Examples of data collected for this purpose include the following:

 Patient details and demographics

 Area of work/ specialization
 Written details of the intervention
 Date of intervention
 Other healthcare professionals contacted
 Evidence used to support the intervention- e.g. pharmacist, doctor, nurse, or patient
 Possible effect the intervention would have on patient care
 Outcome of the intervention
 Actual outcome on patient care that the intervention had
 Significance of intervention
 Category of intervention

Aims

 Reduce ADR and medication error

 Ensure patient achieve the best possible result from medication
 Ensure patient follow their medication regimen correctly
 Minimize unnecessary health care cost by optimizing drug therapy
 Increase patient knowledge about their medication and current healthcare
 Promote vaccination and life style modification for better health outcomes.

Procedure

 Medication review comprehensive, medication therapy management

 Patient assessment ( medication history, profile )
 Identify problems ( ADR, doses of medication, duplicate therapy )
 Develop a care plan
 Monitor and follow up
 Documentation