How Liver and Kidney Changes in Older Adults Affect Medication Safety

When you’re over 65, your body doesn’t process medications the same way it did when you were 30. It’s not about being weak or slow-it’s about biology. Your liver and kidneys, the two main organs that clean drugs out of your system, change as you age. These changes can turn a safe dose into a dangerous one. Many older adults end up in the hospital because of side effects from medications they took exactly as prescribed. The problem isn’t the drugs-it’s that the rules for how much to take haven’t kept up with how the body has changed.

What Happens to Your Liver as You Age?

Your liver shrinks. By the time you’re 80, it’s about 30% smaller than it was at 30. Blood flow through it drops by nearly half. That means drugs don’t get processed as fast. For some medications, this isn’t a big deal. For others, it’s life-threatening.

Think of your liver like a factory. Some drugs are handled by machines that slow down with age-those are called flow-limited drugs. Propranolol, lidocaine, and morphine fall into this group. If your liver’s blood flow drops 40%, these drugs clear from your body 40% slower. That means they build up. A standard dose meant for a 40-year-old can turn into an overdose in a 75-year-old.

Other drugs, like diazepam or phenytoin, are handled by enzymes that don’t slow down as much. These are capacity-limited drugs. Their clearance drops only 10-15%. That’s why some medications are safer for older adults than others. But here’s the catch: even if the enzymes work fine, your liver’s structure changes. The tiny channels inside it, called sinusoids, get clogged. That slows down how drugs move through the organ, even if the machinery still runs.

Your Kidneys Don’t Work Like They Used To

Most people think their kidneys are fine because their blood tests look normal. That’s a trap. Your creatinine levels-what doctors use to check kidney function-can stay steady even as your kidneys weaken. Why? Because muscle mass drops with age. Less muscle means less creatinine, so the test doesn’t show the real problem.

Between ages 30 and 80, your kidney’s filtering rate (GFR) drops by 30-50%. That’s huge. Drugs like digoxin, metformin, and many antibiotics are cleared almost entirely by the kidneys. If your kidneys can’t filter them out, they pile up. A dose that was safe at 50 can cause confusion, falls, or heart rhythm problems at 75.

Doctors used to rely on the Cockcroft-Gault equation to estimate kidney function. Now, guidelines recommend the CKD-EPI equation because it doesn’t use race as a factor-and it’s more accurate for older adults. But even the best formula can’t replace real-world monitoring. If you’re on a drug that’s cleared by your kidneys, your doctor should check your function every 3-6 months, not just once a year.

Prodrugs and the Hidden Danger

Some drugs don’t work until your body turns them into something else. These are called prodrugs. Perindopril (used for high blood pressure) and codeine are examples. Your liver has to activate them. But with age, that activation slows down. You might take your pill, feel nothing, and then take another. That’s when things go wrong.

On the flip side, drugs with heavy first-pass metabolism-like verapamil or propranolol-get absorbed more fully in older adults because the liver doesn’t break them down as much before they enter your bloodstream. That means you get more of the drug than expected. A 25-50% increase in bioavailability isn’t theoretical. It’s why some older patients get dizzy or faint after starting a standard dose of these medications.

Why Some Drugs Are Riskier Than Others

Not all medications are created equal when it comes to aging. The Beers Criteria®, updated in 2019, lists drugs that are risky for older adults. It’s not a list of banned drugs-it’s a list of drugs that need extra caution.

For example:

• Amitriptyline (an antidepressant): High risk of confusion, dry mouth, falls. Liver metabolism slows, so levels build up. One Reddit user shared that their 82-year-old mother ended up in the ER after a standard dose caused severe dizziness.
• Benztropine (for Parkinson’s): Can cause delirium. Often prescribed unnecessarily.
• NSAIDs like ibuprofen: Harm kidneys and raise blood pressure. Over-the-counter doesn’t mean safe.
• Acetaminophen: Even though it’s common, it’s the #1 cause of acute liver failure in older adults. Why? Because the liver can’t handle even normal doses as well, and many people take it with other meds without realizing the risk.

On the other hand, drugs like lisinopril or atorvastatin are generally safer if dosed properly. The key isn’t avoiding all meds-it’s choosing the right ones and adjusting the dose.

Drug Interactions Multiply the Risk

Most older adults take five or more medications. The National Health and Nutrition Examination Survey found that 41% of people over 65 were on five or more prescription drugs in 2017-2018. That’s not rare-it’s normal.

But here’s the problem: when your liver and kidneys are slower, drugs interact more. A blood thinner like warfarin can become dangerous if you start taking an antibiotic like ciprofloxacin. The antibiotic slows down how fast your liver breaks down warfarin. Your blood thins too much. You bleed.

Even over-the-counter stuff matters. St. John’s wort, ginkgo biloba, and garlic supplements can interfere with how your body handles meds. Many seniors don’t tell their doctors about these because they think they’re “natural” and safe. They’re not.

What Doctors Should Do-And What They Often Miss

Good geriatric prescribing isn’t guesswork. It’s science. The START and STOPP criteria give clear guidance: which drugs to start, which to stop. Studies show that using these tools cuts adverse drug events by 22%.

But too often, doctors still prescribe by age, not function. They say, “You’re 78, so we’ll cut the dose in half.” That’s not enough. You need to know:

• Is this drug cleared by the liver or kidneys?
• What’s my actual GFR-not just my creatinine?
• Am I on any other drugs that might interfere?
• Do I have liver disease, heart failure, or diabetes? These change how drugs behave too.

And here’s the biggest oversight: many doctors still don’t check kidney function regularly. Or they rely on serum creatinine alone. That’s like judging a car’s fuel efficiency by how much gas is in the tank-not how far it’s actually going.

What You Can Do Right Now

You don’t need to wait for your doctor to fix this. Here’s what you can do today:

1. Make a complete list of every pill, patch, supplement, and OTC drug you take. Include vitamins, herbal teas, and pain relievers.
2. Ask your pharmacist to review it. Pharmacists are trained to spot interactions. Many offer free med reviews.
3. Request a GFR test if you’re on kidney-cleared drugs. Don’t accept “your creatinine is fine” as an answer.
4. Ask: “Is this drug on the Beers Criteria list?” If yes, ask if there’s a safer alternative.
5. Track side effects. Dizziness, confusion, falls, nausea, or sudden fatigue aren’t just “part of aging.” They could be drug reactions.

One 78-year-old patient in a 2022 study had his vancomycin dose adjusted based on his GFR. He avoided kidney damage. That’s not luck-it’s smart prescribing.

The Future Is Personalized

Right now, most drug dosing is based on age, weight, and maybe a lab number. But that’s changing. In 2023, the FDA approved GeroDose v2.1-the first software that simulates how a drug will behave in your body based on your liver enzymes, kidney function, age, and other factors.

Research from the National Institute on Aging is now focusing on epigenetics-how your genes turn on or off as you age. Scientists have found 17 methylation sites linked to liver enzyme activity that change with time. This could lead to blood tests that tell you exactly how your body will handle a drug-not just guess based on your birthday.

By 2030, experts predict that personalized dosing could cut adverse drug events by 35-50%. But that future won’t happen unless patients speak up. If you’re over 65 and on more than three medications, ask for a medication review. Don’t assume your doctor knows what’s happening in your liver and kidneys. They might not.

Bottom Line

Older adults aren’t just small adults. Their bodies handle drugs differently. A dose that’s safe for a 40-year-old can be toxic for a 75-year-old-even if they’re healthy. The problem isn’t that we’re taking too many drugs. It’s that we’re taking them the same way we did when we were younger.

The solution isn’t more pills. It’s smarter dosing. Better testing. And asking the right questions. Your liver and kidneys are working harder than ever to keep you safe. The least you can do is make sure they’re not being overworked by a pill that shouldn’t be there.