Pharmacotherapy in Frailty

Frailty is a state of reduced physiological reserve in which small stressors, including a new medicine, cause disproportionate loss of function. It is graded on a nine-point clinical frailty scale, and scores of 5 to 9 identify people in whom prescribing priorities move from prevention towards symptom control, function and safety. Frailty is not defined by age alone, and chronological age should not decide treatment.

Assessment. Score function over the previous 2 weeks rather than the best day. Record activities of daily living, mobility, weight loss, continence, cognition, mood, swallowing and any admission in the past 6 months.

Altered handling. Low lean mass, low albumin, dehydration and reduced hepatic and renal reserve raise free drug levels, and creatinine falsely reassures.

Time to benefit. Preventive benefit takes time: roughly 1 year for bisphosphonates to reduce fractures and more than 2 years for statins in primary prevention. Where expected survival is shorter than this, the drug adds burden without benefit.

Order of priority. First symptom relief, then treatments with short time to benefit (anticoagulation in atrial fibrillation, secondary prevention after stroke or myocardial infarction, heart failure therapy), then long-term preventive drugs.

Anticoagulation. Frailty and falls alone are not reasons to withhold it. Apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when two of the following apply: age 80 years or over, weight 60 kg or under, creatinine 133 micromol/L or over. Continue long term; check renal function, haemoglobin and weight at least every 6 months.

Analgesia. Paracetamol 500 mg orally every 6 hours, maximum 2 g daily in frail or low-weight people, is the first choice for persistent pain. Avoid oral NSAIDs.

Targets. Accept clinic systolic pressure of 140 to 150 mmHg and avoid standing systolic under 110 mmHg. Accept HbA1c of 8.0% to 8.5% (64 to 69 mmol/mol) and prioritise avoiding hypoglycaemia.

Simplify. Prefer once-daily regimens, one dosing time, a blister pack or labelled organiser, and no more than one new drug at a time.

Special groups. In advanced dementia or the last months of life, stop statins, aspirin for primary prevention and bisphosphonates, and keep symptom drugs. Where family members manage medicines, teach them the purpose of each drug and which are not to be stopped suddenly.

Dose. Start renally cleared or sedating drugs at 25% to 50% of the usual adult dose and increase every 2 to 4 weeks. Review the dose after any weight loss, dehydration or hospital stay.

Renal and hepatic. Estimate creatinine clearance with Cockcroft-Gault and use the lower of that and eGFR. Reduce hepatically cleared drugs in moderate impairment.

Monitoring. Record weight monthly, lying and standing blood pressure with each titration, falls, cognition and appetite at each review, and sodium, potassium and creatinine after any diuretic, ACE inhibitor or SSRI change. For anticoagulants the interval in months between renal checks is roughly the creatinine clearance divided by 10.

Stopping. Stop preventive drugs first when the clinical frailty scale is 7 or over or when function is declining. Stop one drug at a time and review after 2 to 4 weeks.

Switching. Replace glibenclamide with a lower-risk agent, amitriptyline with sertraline 25 mg once daily, and chronic NSAIDs with paracetamol and topical agents.

Referral and escalation. Refer to a geriatrician when frailty is new or worsening without a clear cause, when more than 10 regular medicines remain after review, or when treatment aims conflict between conditions.