Medications That Are High-Risk for Seniors: What to Review

Every year, tens of thousands of seniors end up in the hospital-not because of a fall, heart attack, or infection, but because of a medication they were told was safe. For people over 65, some of the most common prescriptions can be more dangerous than helpful. The problem isn’t always the doctor’s mistake. It’s that many drugs were designed for younger bodies, and aging changes how the body handles them. Kidneys slow down. Liver metabolism drops. Brain sensitivity to sedatives goes up. What worked at 50 can become a risk at 75.

What Makes a Medication High-Risk for Seniors?

It’s not just about side effects. It’s about how much worse those side effects become with age. A drug that causes mild drowsiness in a 30-year-old might cause a fall, fracture, or confusion in someone over 70. The American Geriatrics Society (AGS) keeps a living list called the Beers Criteria, updated every two years. The 2023 version identifies 30 classes of drugs and 14 individual medications that should generally be avoided in older adults. These aren’t banned drugs-they’re flagged because the risks outweigh the benefits for most seniors.

Three big red flags show up again and again:

• Anticholinergic burden: Drugs that block acetylcholine-a brain chemical vital for memory and muscle control. These include old-school antihistamines like diphenhydramine (Benadryl) and antidepressants like amitriptyline. Cumulative use over a year increases dementia risk by 54%.
• Hypoglycemia risk: Some diabetes meds, especially glyburide, can drop blood sugar dangerously low in seniors. One study found nearly 30% of elderly patients on glyburide had at least one severe low-blood-sugar episode.
• Fall and fracture risk: Sedatives, sleep aids, and blood pressure drugs that cause dizziness or low blood pressure when standing up can turn a simple walk to the bathroom into a broken hip.

Top 5 High-Risk Medications Seniors Should Review

Here are five of the most common high-risk medications still being prescribed-and what to ask your doctor instead.

1. Zolpidem (Ambien®) and Other Sleep Aids

Zolpidem is one of the most prescribed sleep medications for seniors. But it doesn’t just help you sleep-it leaves you groggy, confused, and unsteady the next day. Studies show it increases fall risk by 82% compared to safer alternatives. Some seniors report sleepwalking, confusion, or even driving while half-asleep. The effects can last up to 11 hours, long after the intended sleep window.

Better options: Trazodone (a low-dose antidepressant), cognitive behavioral therapy for insomnia (CBT-I), or simple sleep hygiene changes like reducing screen time before bed and keeping a consistent schedule.

2. Glyburide (Diabeta®)

Glyburide is an older type of diabetes pill that stays in the body too long. It forces the pancreas to keep releasing insulin, even when blood sugar is already low. In seniors, this leads to severe hypoglycemia-sometimes so bad they need emergency treatment. One study showed glyburide caused 2.1 times more low-blood-sugar episodes than glipizide, a similar but safer drug.

Better options: Glipizide, metformin, or newer drugs like semaglutide (Ozempic®). These have lower hypoglycemia risk and better safety profiles for aging kidneys and livers.

3. Diphenhydramine (Benadryl®) and Other First-Gen Antihistamines

Many seniors take Benadryl for allergies, colds, or even as a sleep aid because it’s cheap and available over the counter. But it’s one of the strongest anticholinergic drugs on the market. A score of 3 on the Anticholinergic Cognitive Burden (ACB) scale means it’s high-risk. Long-term use (over 1,095 doses total) is linked to a 54% higher chance of developing dementia.

Better options: Loratadine (Claritin®), cetirizine (Zyrtec®), or fexofenadine (Allegra®). These are non-sedating and don’t cross into the brain the same way.

4. Nitrofurantoin (Macrobid®)

This antibiotic is often used for urinary tract infections (UTIs), which are common in older adults. But if kidney function is even slightly reduced-common after 65-it can cause serious lung damage. The risk of pulmonary toxicity is over 12 times higher in patients with an eGFR below 60. Mortality from this reaction can reach 18%.

Better options: Nitrofurantoin should be avoided if kidney function is impaired. Alternatives like fosfomycin or cephalexin are safer for seniors with reduced kidney function.

5. Alpha-1 Blockers (Doxazosin, Terazosin, Prazosin)

These drugs were once popular for high blood pressure and prostate issues. But they cause a sudden drop in blood pressure when standing up-a condition called orthostatic hypotension. In seniors over 75, this leads to dizziness, fainting, and falls at 3.2 times the rate of safer blood pressure meds.

Better options: Chlorthalidone, ACE inhibitors like lisinopril, or ARBs like losartan. These lower blood pressure without the same risk of sudden drops.

What You Can Do Right Now

You don’t need to wait for your annual checkup to review your meds. Here’s how to take action today:

1. Do a brown bag review: Empty all your pills-prescription, over-the-counter, vitamins, supplements-into a bag. Take them to your doctor or pharmacist. Don’t just say, “I take what’s on the list.” Show them what you actually use.
2. Ask about anticholinergic burden: Ask your pharmacist to calculate your ACB score. If it’s 3 or higher, you’re in the danger zone. Ask if any meds can be switched.
3. Check for duplicates: Many seniors get the same drug from different doctors. For example, someone might be prescribed both diphenhydramine and an antidepressant with anticholinergic effects. Together, the risk multiplies.
4. Ask about tapering: Never stop a sedative, antidepressant, or blood pressure med cold turkey. Ask how to safely reduce or replace it. Tapering over 4-6 weeks with support cuts withdrawal risks and improves success rates.
5. Use tech tools: Many pharmacies now use systems like Surescripts that flag Beers Criteria drugs at the counter. Ask your pharmacist: “Is this on the Beers list for seniors?”

Who Should Be Involved in the Review?

Medication safety isn’t just your doctor’s job. It’s a team effort.

• Your pharmacist: They see all your prescriptions. They can spot interactions you don’t know about.
• A clinical pharmacist: These are pharmacists trained in geriatrics. They work with doctors to adjust meds and reduce risk. Ask if your clinic has one.
• Your family: A daughter or son can help track symptoms. Did Mom start stumbling after starting a new sleep pill? Did Dad get confused after switching to a new antidepressant? These are clues.
• Medicare Advantage plans: Most now use the Beers Criteria to limit coverage of high-risk drugs. If your plan denies a prescription, ask why. It might be because it’s flagged as unsafe.

What’s Changing in 2025?

The rules are catching up to the science. In 2023, the AGS added five new drugs to the high-risk list, including baclofen (a muscle relaxant) and benzodiazepines for insomnia. They also removed three older drugs that were found to be safer than previously thought.

Medicare is now tying 5% of bonus payments to health plans that reduce high-risk prescribing. Electronic health records like Epic and Cerner now auto-flag Beers Criteria drugs when a doctor tries to prescribe them to someone over 65. If you’re seeing a new doctor, they’re likely getting a warning before they hit “send.”

And the FDA recently strengthened warnings on glyburide, requiring a boxed warning about hypoglycemia risk in seniors. That’s a big deal-it means the government now officially says: “Don’t use this in older adults unless absolutely necessary.”

Real Stories, Real Results

One 78-year-old woman in Cape Town was taking amitriptyline for nerve pain. She developed severe constipation, then vomiting, and ended up in the ER. Her doctor switched her to duloxetine. Within two weeks, her symptoms vanished. No hospital visits since.

A 72-year-old man on glyburide had three low-blood-sugar episodes in six months. He passed out once at the grocery store. His doctor switched him to glipizide. He hasn’t had another episode in over a year.

On Reddit, hundreds of families share stories about relatives who became “a different person” after starting diphenhydramine-confused, withdrawn, forgetful. After stopping it, they returned to themselves.

These aren’t rare cases. They’re predictable outcomes of outdated prescribing.

Final Thought: It’s Not About Cutting Meds-It’s About Choosing Better Ones

This isn’t about stopping all your pills. It’s about making sure each one still serves you. Some seniors need blood pressure meds, insulin, or heart drugs. But many don’t need the old, risky versions. Safer alternatives exist. They’re just not always offered.

If you’re over 65 and taking five or more medications, it’s time for a full review. Don’t wait for a crisis. Ask your doctor: “Which of my meds are on the Beers Criteria list? What’s safer?” Bring your pills. Ask about side effects. Ask about alternatives. You’re not being difficult-you’re being smart.

Medication safety isn’t a luxury. It’s a necessity for living well into your 70s, 80s, and beyond.