Taking a Dozen Pills a Day? The Real Risks of Polypharmacy, the "Brown Bag" Review, Which Drugs Must Be Adjusted as Kidney Function Falls, and How to Deprescribe Safely

Why polypharmacy is a problem

Polypharmacy is usually defined as taking ≥5 medicines at the same time. About 40% of people over 65 qualify; CKD patients take 10–12 on average, dialysis patients more [1][2]. More is not better:

• Each additional drug raises the risk of an adverse drug reaction by about 7–10%; at ≥5 drugs, interactions are almost inevitable [1].
• Adverse drug reactions account for 10–15% of emergency visits and 5–10% of admissions in older adults, about half of them preventable [1][2].
• Prescribing cascades: a side effect of drug A is mistaken for a new illness and treated with drug B — e.g. a calcium-channel blocker causes ankle swelling → a diuretic is added → the diuretic triggers gout → a urate-lowering drug is added.
• More drugs mean more missed, wrong or duplicated doses; adherence falls to about 50% at ≥5 medicines [2].

WHO's 2017 global challenge "Medication Without Harm" aims to halve severe avoidable medication harm, focusing on three areas: polypharmacy, high-risk situations (such as kidney impairment) and transitions of care [1].

Once a year: the "brown bag" review

Put everything you take into a bag and bring it to your appointment: prescriptions, over-the-counter drugs, supplements, herbal products, creams, eye drops, patches. Your doctor or pharmacist goes through each item [2]:

1. Why am I taking this? Does the original indication still exist? (e.g. a PPI started for an ulcer 10 years ago)
2. Is it working? Is there a measurable goal (BP, glucose, symptoms)?
3. Is it causing side effects? Could a "new symptom" actually be a drug effect?
4. Is the dose right? Especially since kidney function changed (see below).
5. Any duplicates? Same-class drugs from different prescribers (two NSAIDs, two sleeping pills, two cold remedies containing paracetamol).
6. Any dangerous combinations?
7. Is it still needed? When life expectancy or goals change, the time-to-benefit of preventive drugs (statins, osteoporosis drugs) may no longer fit.

Shared medication records (Taiwan's NHI MediCloud, Japan's "okusuri techō" medication notebook, or your pharmacy's record) help consolidate prescriptions from different clinics — ask your doctor to check them.

Drugs that must be adjusted as kidney function falls

The kidney eliminates most drugs or their metabolites. Every time eGFR drops a stage, every drug's dose should be reviewed [3]. The classes most often needing adjustment or avoidance:

Two key reminders:

• Most drug labels use Cockcroft-Gault creatinine clearance (CrCl), not CKD-EPI eGFR; they differ substantially at extremes of body weight [3].
• During acute illness (fever, diarrhoea, vomiting, dehydration), KDIGO advises temporarily holding "SADMANS" drugs to prevent acute kidney injury: Sulfonylureas, ACE inhibitors, Diuretics, Metformin, ARBs, NSAIDs, SGLT2 inhibitors — restart once eating and drinking normally [3]. These are the "sick day rules".

The most common dangerous combinations for kidney and transplant patients

• NSAID + ACEi/ARB + diuretic (the "triple whammy"): about 30% higher risk of acute kidney injury [6].
• ACEi/ARB + spironolactone/finerenone + potassium supplements or high-potassium diet: hyperkalaemia.
• Azathioprine + allopurinol/febuxostat: fatal marrow suppression (transplant).
• Tacrolimus/ciclosporin + clarithromycin/diltiazem/verapamil/azole antifungals/grapefruit: immunosuppressant levels soar.
• Tacrolimus/ciclosporin + rifampicin/carbamazepine/St John's wort: levels collapse → rejection.
• Statin + ciclosporin/clarithromycin/gemfibrozil: rhabdomyolysis.
• Colchicine + clarithromycin/ciclosporin: colchicine toxicity.
• Two or more anticholinergic drugs (some antihistamines, tricyclics, bladder antispasmodics, some antipsychotics): cognitive decline, constipation, urinary retention and falls in older adults — "avoid" in Beers 2023 [4].
• Benzodiazepines/Z-drugs: falls, fractures and cognitive decline in older adults; slower clearance in CKD [4][5].

This site's anti-rejection interaction lookup covers the transplant combinations above; for general medicines, ask a pharmacist.

How to deprescribe safely

Deprescribing is not "stopping treatment"; it is re-weighing each drug's benefits and harms for who you are now [2][5]:

1. Never stop abruptly on your own — beta-blockers, steroids, anti-epileptics, antidepressants, PPIs and benzodiazepines all carry rebound or withdrawal risk; anti-rejection drugs must never be self-adjusted.
2. Change one drug at a time and observe for 2–4 weeks so you know what caused any change.
3. Candidates to stop: drugs without a clear indication, downstream drugs in a prescribing cascade, preventive drugs whose time-to-benefit exceeds life expectancy, high-risk drugs on the Beers/STOPP lists [4][5].
4. Candidates to start (START): CKD with albuminuria without an ACEi/ARB, heart failure without the four pillars, a fracture history without osteoporosis treatment — under-prescribing is as much a problem as over-prescribing [5].
5. Carry a written medication list (name, dose, timing, reason, prescriber) — this site's Medical Travel Passport tool can generate one.

Everyday medication-safety habits

• Use a pill organiser or phone reminders; refill it once a week.
• Use one pharmacy so the pharmacist sees the whole picture.
• Before taking anything new (including OTC drugs, supplements and herbal remedies), ask the pharmacist: "Does this clash with my kidney function or my anti-rejection drugs?"
• Know your eGFR stage and tell every clinician you see: "I have kidney disease, my eGFR is about X."
• "Natural" does not mean safe: high-dose vitamin C (oxalate stones), potassium-based salt substitutes, certain herbs (aristolochic acid), creatine and protein powders all carry risk in CKD.

When to seek care

Urgently: widespread rash, swollen lips/eyes or breathing difficulty after a new drug (allergy); severe drowsiness, confusion or a fall; black stools or vomiting blood (anticoagulants); severe muscle pain with dark urine (rhabdomyolysis); very slow or very fast heartbeat.

Same day: fever, diarrhoea or vomiting with inability to eat or drink (confirm sick-day rules); new dizziness or blackouts on standing; clearly reduced urine output.

Questions to ask your doctor or pharmacist

1. Can I bring all my medicines for a full review?
2. With my current eGFR, which doses need adjusting?
3. Which drugs should I pause when I am ill and cannot eat or drink?
4. Can any of these be stopped or swapped for something safer?
5. Are any of my supplements or herbal products a concern?

References

1. World Health Organization. Medication Without Harm — WHO Global Patient Safety Challenge. 2017; Medication Safety in Polypharmacy: Technical Report. 2019. https://www.who.int/publications/i/item/WHO-UHC-SDS-2019.11
2. Masnoon N, et al. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230. https://doi.org/10.1186/s12877-017-0621-2 ; Scott IA, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med. 2015;175(5):827–834. https://doi.org/10.1001/jamainternmed.2015.0324
3. KDIGO 2024 Clinical Practice Guideline for CKD (Chapter 4: medication management and drug stewardship). Kidney Int. 2024;105(4S):S117–S314. https://doi.org/10.1016/j.kint.2023.10.018
4. 2023 AGS Beers Criteria® Update Expert Panel. J Am Geriatr Soc. 2023;71(7):2052–2081. https://doi.org/10.1111/jgs.18372
5. O'Mahony D, et al. STOPP/START criteria, version 3. Eur Geriatr Med. 2023;14(4):625–632. https://doi.org/10.1007/s41999-023-00777-y
6. Lapi F, et al. Concurrent use of diuretics, ACE inhibitors and ARBs with NSAIDs and risk of acute kidney injury. BMJ. 2013;346:e8525. https://doi.org/10.1136/bmj.e8525

This article compiles publicly available medical information for educational purposes only. It is not medical advice and has not been reviewed by a practising physician. For any health or medication question, consult a qualified professional. For chest pain, sudden breathlessness, one-sided weakness or slurred speech, call your local emergency number or go to the emergency department immediately.