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Introduction

Prescribing for older patients with cancer is complex and challenging. They are a heterogeneous group, ranging from those who are medically well up until the time of cancer diagnosis to those who have multiple concurrent chronic diseases such as hypertension, coronary artery disease, heart failure, diabetes, chronic kidney disease, falls, stroke disease, depression and dementia. The majority of older patients presenting to oncology services are prescribed medications for treatment of coexisting conditions, in addition to primary and secondary prevention of illness.1 One British study of 100 older patients with metastatic cancer identified a median of seven prescribed medications (interquartile range 1-17 medications).1 A Canadian study of 112 older patients with newly diagnosed cancer identified a median of five medications before cancer treatments were initiated.2

A new diagnosis of cancer may: (1) change the therapeutic targets for existing conditions, e.g. strict lipid control for prevention of cardiovascular disease may no longer be a priority; (2) result in an altered physiological environment that can affect drug handling and drug response with a requirement for dose adjustment, particularly in the context of organ dysfunction; and (3) contribute to additional drug burden in the form of chemotherapy and supportive drugs to manage cancer symptoms, thus placing older patients at increased risk of additive toxicity, drug interactions and adverse drug events.3 These negative outcomes increase morbidity and healthcare resource use by requiring additional clinical consultations, laboratory testing and prescriptions to treat new symptoms.1

Optimizing drug therapy is an essential part of managing an older patient with cancer. All pharmacological treatments should be goal-directed with realistic regard for expected clinical outcome. Clinicians should be aware of age-related pharmacological changes which influence the appropriateness of drug selection in older patients, as well as the clinical implications of polypharmacy including drug-drug and drug-disease interactions, adverse drug events, prescribing cascades and difficulties with compliance.

Age-related pharmacological changes

Physiological changes associated with ageing can affect drug pharmacokinetics (absorption, distribution, metabolism and excretion) and pharmacodynamics (the effect of drugs on the body).4 Although normal ageing has little effect on drug absorption, gastric emptying can be increased by prokinetic drugs (e.g. domperidone and erythromycin). Anticholinergic drugs can reduce salivary secretion, thus impeding the rate but not the extent of buccal absorption of drugs such as midazolam or fentanyl.

Systemic bioavailability of most drugs is not affected by normal ageing, other than in those which undergo substantial first-pass hepatic metabolism, e.g. morphine, buprenorphine, midazolam and propranolol. With these drugs, age-related reductions in liver volume and blood flow (up to 30%) can result in significantly higher systemic bioavailability because of reduced first-pass hepatic extraction. Therefore, initial doses of these drugs should be reduced.

Ageing is associated with reduced lean body weight and muscle mass and a relative increase in total body fat, thus increasing the volume of distribution of lipid-soluble drugs, ...

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