How Liver and Kidney Changes in Older Adults Affect Drug Metabolism

When you’re over 65, your body doesn’t process medications the same way it did when you were 40. It’s not about being weak or slow-it’s about biology. Your liver and kidneys, the two main organs that clear drugs from your system, change as you age. And those changes can turn a safe dose into a dangerous one.

What Happens to Your Liver as You Age?

Your liver shrinks. By the time you reach 70, it’s about 30% smaller than it was in your 30s. Blood flow to the liver drops by nearly 40%. That means drugs don’t get processed as quickly. Some medications rely on the liver to break them down before they enter your bloodstream. When that process slows, those drugs build up. You might feel dizzy, confused, or overly sleepy-not because the drug is too strong, but because your body can’t clear it fast enough.

Not all drugs are affected the same. Some, like propranolol, lidocaine, and morphine, are called flow-limited. Their clearance depends almost entirely on how much blood reaches the liver. When blood flow drops, these drugs stick around longer. For someone over 75, their blood levels could be 40% higher than a younger person taking the same dose.

Other drugs, like diazepam, phenytoin, and theophylline, are capacity-limited. Their breakdown depends more on enzyme activity than blood flow. Here, the news is better: enzyme levels stay fairly stable with age. These drugs may only see a 10-15% drop in clearance. That doesn’t mean they’re safe without adjustment-but the risk is lower.

Then there’s the tricky case of prodrugs. These are inactive until the liver turns them into their active form. Perindopril, a blood pressure drug, is one example. In older adults, that conversion happens slower. You might think the medicine isn’t working-but it’s not that it’s ineffective. It’s just taking longer to kick in.

How Kidney Changes Impact Medication Clearance

Your kidneys filter waste-and drugs-from your blood. As you age, your glomerular filtration rate (GFR) drops by 30-50% between ages 30 and 80. That’s a huge change. Many drugs, like metformin, digoxin, and vancomycin, are cleared almost entirely by the kidneys. If your kidneys aren’t filtering well, these drugs accumulate. That’s why kidney function, not just age, determines dosing.

Here’s the catch: your blood test for creatinine might look normal. That’s because muscle mass decreases with age, and creatinine comes from muscle. So even if your kidneys are failing, your creatinine level can stay in the “normal” range. That’s why doctors need to calculate your estimated GFR using the CKD-EPI equation-not just rely on creatinine alone.

Doctors use the Cockcroft-Gault or CKD-EPI formulas to estimate kidney function. These numbers tell them how much to reduce your dose. For example, a standard dose of metformin can cause lactic acidosis in someone with reduced kidney function. But cut the dose by half based on GFR, and it’s safe.

Why Drug Interactions Get Riskier After 65

Most older adults take five or more medications. The 2017-2018 NHANES survey found that 41% of adults over 65 were taking five or more prescription drugs. That’s a recipe for trouble.

Take acetaminophen. It’s in hundreds of over-the-counter cold and pain meds. Most people think it’s harmless. But in older adults with reduced liver function, even 3,000 mg a day-a common daily dose-can cause liver damage. The Acetaminophen Hepatotoxicity Registry shows it’s responsible for half of all acute liver failure cases in seniors.

Or consider amitriptyline, an old antidepressant still prescribed for nerve pain. It’s metabolized by the liver and cleared slowly in older adults. One Reddit user, “CaregiverInMA,” shared how their 82-year-old mother started on a standard 25 mg dose. Within days, she was stumbling, confused, and nearly falling. Her doctor later realized: her liver couldn’t break it down. The dose was cut to 10 mg-and her symptoms vanished.

Drug interactions don’t just happen between prescriptions. They happen between pills, supplements, and even grapefruit juice. Grapefruit blocks liver enzymes that break down over 85 drugs, including statins and blood pressure meds. In an older adult, that blockage can spike drug levels dangerously.

What Doctors Should Do-And Often Don’t

The Beers Criteria®, updated in 2019, recommends reducing initial doses by 20-40% for liver-metabolized drugs in people over 65. For those over 75, even more reduction may be needed. But many doctors still prescribe based on age alone-not actual liver or kidney function.

Some still rely on serum creatinine without calculating GFR. Others don’t check for over-the-counter meds or herbal supplements. A 2020 meta-analysis in Age and Ageing showed that using the STOPP/START criteria-evidence-based tools for safe prescribing-reduced adverse drug events by 22% in nursing homes.

The FDA says 10% of hospital admissions in older adults are due to bad drug reactions. That’s 300,000 people a year in the U.S. alone. And it’s preventable. The $30 billion spent annually on these avoidable hospitalizations isn’t just money-it’s lost independence, broken hips, and confusion that turns into dementia-like symptoms.

What You Can Do Right Now

If you or someone you care for is over 65 and taking multiple medications:

• Ask your doctor: “Is this dose right for my kidney and liver function?”
• Request a GFR test-not just a creatinine level.
• Make a full list of everything you take: pills, patches, vitamins, herbal teas, even cough syrup.
• Ask if any drugs can be stopped or replaced with safer ones.
• Watch for new symptoms: dizziness, confusion, fatigue, falls. These aren’t just “getting older.” They could be drug side effects.

There’s no magic pill. But there is better science. The FDA approved GeroDose v2.1 in 2023-a software tool that simulates how a drug will behave in your body based on your age, weight, liver enzymes, and kidney function. It’s not in every clinic yet, but it’s coming.

Research is also uncovering why some older adults process drugs differently than others. A 2023 study found 17 gene methylation sites linked to liver enzyme activity that change with age. That means two 78-year-olds might need completely different doses of the same drug-not because of weight or diet, but because of their unique biology.

The Bottom Line

Aging isn’t just about wrinkles and gray hair. It’s about your body’s ability to handle chemicals-including medicines. Your liver and kidneys aren’t broken. They’re just different. And that difference changes everything about how drugs work.

Safe prescribing for older adults isn’t about giving less. It’s about giving the right amount-based on real function, not just a number on a calendar. If your doctor hasn’t checked your kidney or liver function in the last year, ask. Your next dose could be the difference between feeling well-and ending up in the hospital.