*5.1.1 Examine the patient*

A systematic approach to the patient will reduce ADR. The patient has to be examined thoroughly in a comprehensive view, not just focusing on symptoms alone. As symptoms can be adverse reactions to the drugs or due to disease progression, patient's treatment need has to be identified and documented by the diagnosis.

#### *5.1.2 Maintain the record*

All drugs used by the patient including non-pharmacological agents such as herbal preparations, supplements, or over-the-counter (OTC) medications are recorded because alternatives or herbals may interact with the present regimen, increasing the risk of adverse reactions. The most commonly used herbals and dietary supplements are glucosamine, extract of gingko biloba, St. John's wort, and ginseng. A study in the United States found that out of 3072 ambulatory elderly patients, 82.5% used at least one supplement and 54.5% used three or more [31]. A record of all medications including herbals and other alternatives should be updated frequently with possible simplest regimens to reduce the duplication, unnecessary medication, and important drug interactions. It also reduces polypharmacy and the underuse of vital drugs.

### *5.1.3 Benefit-risk assessment*

The elderly patient is evaluated for benefits and risks while prescribing the medication. This reduces the use of unnecessary medication or duplication, and polypharmacy and further reduce the cost burden on the patient.

#### *5.1.4 Adjust the dose of the drug*

Aging decreases the filtration capacity of the glomerulus because of a decrease in renal size, perfusion, and nephron function [32]. Glomerular filtration rate must be calculated for drugs eliminated through the kidney. The dose of the drug has to be adjusted for renal impairment by using Cockroft and Gault Equation to minimize the risk of ADR.

#### *5.1.5 Inappropriate medications*

The use of inappropriate medications is most common in elderly patients. Approximately 50% of the elderly take one or more medications that are not necessary [33]. The Beers criteria are the most commonly used criteria to guide prescribers in preventing ADR [34, 35]. This was recently revised in 2019 by an expert panel sponsored by the American Geriatric Society. Screening Tool of Older Person's Prescriptions (STOPP) is another tool consisting of 65 STOPP criteria to represent common avoidable instances of inappropriate prescriptions [36]. "The Good Palliative–Geriatric Practice algorithm" for discontinuation of drug reduced polytherapy and improved morbidity and mortality in community-dwelling elders and nursing home inpatients [37]. These criteria consist of drugs to be avoided or used with caution in the elderly and reduce inappropriate prescribing and its related ADR. In the elderly, underuse of medicines is also prevalent. Prescribers may underuse the useful drug if the patient is not able to afford the medication. START (screening tool to alert doctors to the right treatment) is a tool designed specifically on the list of evidence-based useful medications but possibly omitted drugs in the elderly [38]. This can be reduced by documenting the patient's condition and prescribing the medication for the current condition.

#### *5.1.6 Start with a low dose*

Aging alters the pharmacodynamic responses. So, the elderly are more sensitive to the effects of drugs than young adults even with standard doses. Drugs such as morphine and neuroleptics cause more confusion and warfarin increases the anticoagulation effect with a regular therapeutic dose. This can be minimized by starting with the lowest possible dose and gradually titrating the dose depending on the response by carefully monitoring the patient.

#### *5.1.7 Drug frequency and dosing*

The time of drug administration also plays a role in the development of ADRs. Chronotherapy is the delivery of a drug following biorhythm that prevents an overdosing of any class of drug [39]. Patients with osteoarthritis have less pain in the morning and more at night. NSAIDs reduce pain when given at least 4–6 hrs before the pain reaches its peak. So, it is given around noon or midafternoon [40]. The incidence of ADR can be reduced by administering the right drug at the right time.

#### *5.1.8 Drug interactions (DI)*

Drug-drug, drug-disease, and drug-food interactions should be considered while prescribing to the elderly. Co-morbidities and polytherapy in the elderly increase the risk of DI. The prevalence rate of DI-induced ADR-related hospitalizations was 22.2% and 8.9% for hospital admission and hospital visits, respectively [41]. The most important DI occurs with drugs that have serious toxicity and a low therapeutic index. Bisphosphonates are often co-prescribed with calcium supplements in the treatment of osteoporosis. Calcium binds to the bisphosphonates and reduces its absorption with the possibility of therapeutic failure [42]. This may be avoided by allowing a sufficiently long dosage interval; the possible approach is to give bisphosphonates for 2 weeks and calcium supplements for 10 weeks [43].

The risk of potential drug interaction increases from 39% to 100% when patients are on more than six medications compared to when they are on 2–3 medications [44]. Most of the DI can be reduced by choosing alternative medications that are not associated with DI. For instance, pantoprazole is given to patients on clopidogrel in place of omeprazole to avoid interaction between omeprazole and clopidogrel.

The risk of drug-disease interaction is also important as the elderly population suffers from more than one condition. The most common interactions were aspirin and peptic ulcer disease; calcium channel blockers and heart failure and beta-blockers and diabetes [45].

These interactions are of utmost importance as they decrease the efficacy of the drug or may increase the toxicity of a drug. Hence, prescribers must have knowledge on the pharmacology of drugs and their interactions to reduce DI-related ADR.

#### *5.1.9 Economical alternative*

Strict adherence to the medication is very important to reduce the progression of the disease, treatment failure, and further adverse effects. An increase in the cost of medications reduces adherence to the treatment. The pill burden can be reduced by using medications that can control two or three conditions and by choosing economical alternative drugs [46].

### *5.1.10 Patient education*

Patients and their families should be educated about the effects of polytherapy and can stop the unnecessary medication if there is no benefit. Counseling is given on the probable adverse effects of the drugs, adherence to the therapy, and sudden stoppage of treatment. The plan of treatment, its effects, and follow-up visits should be clearly discussed with the patient and their families.
