How Age Affects Medication Side Effects and Tolerability

By the time you hit 65, your body doesn’t process medications the same way it did at 35. It’s not just about taking fewer pills-it’s about how your body changes, and how those changes make even common drugs more dangerous. Older adults are more than twice as likely to suffer serious side effects from medications compared to younger people. And many of these reactions aren’t rare outliers-they’re predictable, preventable, and happening every day.

Why Your Body Handles Drugs Differently as You Age

Your liver, kidneys, fat, and water levels all shift as you get older. These aren’t minor tweaks-they change how drugs move through your body and how strongly they hit you.

For example, total body water drops by about 15% between ages 25 and 80. That means water-soluble drugs like lithium or certain antibiotics build up higher in your system because there’s less fluid to dilute them. At the same time, body fat increases-especially in women-so fat-soluble drugs like diazepam or amitriptyline stick around longer, lingering in fatty tissue and slowly leaking back into your bloodstream.

Your kidneys slow down too. After 40, your glomerular filtration rate (GFR)-the measure of how well your kidneys filter waste-drops by about 0.8 mL/min every year. That’s why drugs like digoxin or aminoglycosides can become toxic even at normal doses. Many doctors still prescribe these based on standard adult charts, not knowing the patient’s kidney function has slipped below safe levels.

Your liver isn’t working as hard either. Blood flow to the liver drops by 20-40% between ages 25 and 65. That means drugs like propranolol or verapamil, which rely on liver metabolism, stay in your system longer. The result? You get the same effect from half the dose-or worse, you get side effects because your body can’t clear the drug fast enough.

What Happens When Drugs Hit a Slower, More Sensitive Brain

It’s not just your organs changing. Your brain becomes more sensitive to certain drugs. That’s called pharmacodynamic change-your body’s response to the drug gets stronger, even if the drug level in your blood hasn’t changed.

Take benzodiazepines. A 5 mg dose of diazepam might help a 40-year-old sleep. In a 75-year-old, that same dose can cause severe dizziness, confusion, memory loss, and a 2-3 times higher risk of falling. One study found that older adults on zolpidem had 80% more next-day impairment than younger people. Falls aren’t just scary-they’re deadly. Hip fractures in older adults often lead to long-term disability or death.

Anticholinergic drugs-commonly found in allergy meds, sleep aids, and even some antidepressants like diphenhydramine-can trigger delirium in older adults. A 2023 University of Florida study showed people over 75 were 4.2 times more likely to experience sudden confusion or hallucinations from these drugs than those under 65. And once delirium hits, recovery can take weeks-or never happen.

The Polypharmacy Trap

Forty-eight percent of adults over 65 take five or more prescription drugs every month. That’s not just a number-it’s a ticking time bomb. Each new medication adds another layer of risk: interactions, overlapping side effects, and confusing instructions.

Take someone on warfarin (a blood thinner), lisinopril (for blood pressure), metformin (for diabetes), and amitriptyline (for nerve pain). All four can affect kidney function. All four can cause dizziness. All four can interact with each other or with over-the-counter painkillers like ibuprofen. One small change-a new supplement, a missed dose, a kidney infection-can tip the whole system into crisis.

Studies show that 35% of hospital admissions for people over 65 are caused by medication problems. Half of those could have been avoided. Yet, many doctors still prescribe based on guidelines written for 30-year-olds.

The Beers Criteria: What Drugs to Avoid After 65

In 1991, the American Geriatrics Society created the Beers Criteria-a list of medications that are risky for older adults. It’s updated every two years. The 2023 version lists 56 drugs that should generally be avoided in people over 65, and 19 drug classes that should be stopped entirely.

Here are a few that show up often:

• Diphenhydramine (Benadryl): Causes confusion, urinary retention, constipation. Often used for sleep or allergies.
• Benzodiazepines (Valium, Xanax, Ativan): High fall risk, memory loss, dependence.
• Nonsteroidal anti-inflammatories (ibuprofen, naproxen): Kidney damage, stomach bleeding, high blood pressure.
• Anticholinergic antidepressants (amitriptyline, doxepin): Can trigger urinary retention in men with enlarged prostates.
• Proton pump inhibitors (Prilosec, Nexium): Long-term use linked to bone loss, infections, and nutrient deficiencies.

These aren’t “bad” drugs. They work fine for younger people. But in older adults, the risks outweigh the benefits. The Beers Criteria isn’t a rulebook-it’s a warning system.

How Doctors Should Adjust Dosing-And Why They Often Don’t

The golden rule for prescribing to older adults is “start low, go slow.” That means beginning at 25-50% of the standard adult dose and increasing only if needed. But in practice, that doesn’t always happen.

One reason? Clinical trials rarely include people over 75. The FDA’s own data shows 90% of drug trials exclude older adults. So doctors are prescribing based on evidence from 25-year-olds. That’s like fitting a truck tire on a bicycle.

Another reason? Time. A 15-minute appointment doesn’t leave room for a full medication review. But when doctors do take the time, results improve. One study showed that using the STOPP/START criteria during hospital admissions cut adverse drug reactions by 22%.

“We need to ask: Is this drug still helping? Or is it just adding risk?” says Dr. Michael Steinman, lead author of the 2023 Beers Criteria update. “Sometimes, stopping a drug is the best treatment.”

Real Stories: When a Prescription Causes More Harm Than Good

A 78-year-old man started amitriptyline for nerve pain. Within three days, he couldn’t urinate. He ended up with a catheter. His doctor had prescribed the same dose used for a 40-year-old. He had benign prostatic hyperplasia-a common condition in older men. Amitriptyline worsened it. The side effect was preventable.

An 82-year-old woman was prescribed a standard dose of blood pressure medication. She developed severe orthostatic hypotension-her blood pressure dropped when she stood up. She fell, fractured her hip, and never walked without a cane again. Her doctor hadn’t checked her kidney function or adjusted the dose for her age.

These aren’t rare cases. A 2022 survey of over 1,200 older adults found that 68% had experienced dizziness or falls linked to medications. 54% reported memory problems. 41% had unintended weight loss or gain. And 45% admitted they’d stopped taking a drug because the side effects were worse than the condition it was treating.

What You Can Do: Protect Yourself and Your Loved Ones

You don’t have to accept side effects as normal. Here’s what works:

• Do a Brown Bag Review. Take all your medications-prescription, OTC, vitamins, supplements-to your doctor or pharmacist. They’ll spot duplicates, interactions, and unnecessary drugs.
• Ask about deprescribing. Say: “Is there a drug here I can stop?” or “Is this still necessary?” Many older adults are on drugs they started years ago for conditions that no longer exist.
• Know your kidney function. Ask for your eGFR number. If it’s below 60, your drug doses may need adjusting.
• Use the Beers Criteria app. It’s free, updated yearly, and used by over 125,000 clinicians. You can search any drug and see if it’s risky for older adults.
• Track side effects. Write down dizziness, confusion, constipation, falls, or mood changes. Bring the list to every appointment.

Medication isn’t a one-size-fits-all solution. As you age, your body’s needs change. What kept you healthy at 50 might hurt you at 75. The goal isn’t to take fewer drugs-it’s to take the right ones, at the right dose, for the right reason.

What’s Changing in Geriatric Medicine

The tide is turning. The FDA now encourages including older adults in clinical trials. The National Institute on Aging is spending $127 million on aging-specific drug research. Pharmacogenomic testing-checking your genes to see how you metabolize drugs-is becoming more common. One study showed it cut adverse reactions by 35% in older adults on antidepressants.

AI tools like MedAware are helping doctors catch dangerous interactions before they happen. Hospitals are being fined for medication-related readmissions. Medical schools are teaching geriatric pharmacology-72% now include it in their curriculum.

But the biggest change? The shift from “more is better” to “less is safer.”

Deprescribing is no longer a fringe idea. It’s becoming standard practice. And for older adults, that might be the most important medicine of all.