10 Most Common Drug Combinations

Did you know that nearly 7 in 10 Americans take a prescription drug, and about 50% of Americans take at least two? In many cases, taking more than one drug is necessary to cure an ailment, treat symptoms, or control a chronic disease. But in others, multiple drugs may not mix well in your body, and in your pocketbook.

We’ve compiled a list of drugs commonly taken together. We’ll tell you more about why these drugs are taken together, and which ones work. But are all of these combinations safe?

What’s going on in this table?

We compiled a representative sample of nationwide U.S. prescription drug claims to see common drug combinations. Here are some patterns we found interesting.

• Heart disease medications dominate the list. In many cases, certain heart medications may be taken together to increase effectiveness, or treat different symptoms. Most people with a heart condition will likely take any combination of an ace inhibitor (lisinopril), a beta blocker (metoprolol) a diuretic (furosemide) or a statin (atorvastatin). Heart disease is currently the leading cause of death for men and women in the US, so it makes sense that these medications overtake the list.

• Heart medications and diabetes medications are a common combination. Over time, high blood sugar from diabetes can damage the blood vessels and heart, increasing your chances for heart disease. In many cases, people with diabetes will be prescribed metformin along with a heart medication like lisinopril or atorvastatin to reduce the risk for heart complications.

• Anxiety medication alprazolam. After heart and diabetes medications, alprazolam for anxiety also makes the list. Alprazolam is a popular benzodiazepine used to treat anxiety and panic attacks and is commonly prescribed with amphetamine salt combo for ADHD and hydrocodone/acetaminophen for pain. But are these combinations safe? Read on.

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Dangerous combinations

It’s hard to imagine that people would be prescribed drugs that have dangerous interactions. Unfortunately, it’s more common than you think. Most dangerous combinations happen when two different doctors prescribe two different medications and are unaware of the other prescription. In order to avoid taking drugs that may interact, make sure you discuss any medication you are on with every doctor you see.

• Hydrocodone/acetaminophen & alprazolam. Opioids (hydrocodone/acetaminophen) should not be taken with benzodiazepines (alprazolam)—they are the two most common drug classes associated with emergency department visits and prescription drug overdose deaths. The combination can result in severe breathing difficulties. Not good.

• Alprazolam & amphetamine salt combo. This is a common combination as alprazolam, a common anxiety medication, can help combat the restlessness and insomnia that people typically feel after taking an amphetamine. While the combination isn’t necessarily dangerous, alprazolam should not be taken on a regular basis. One way to combat the restlessness and insomnia? Try taking a long-acting stimulant, like amphetamine salt combo XR, instead. Longer-acting amphetamines tend to have more constant delivery and can have negative side effects.

• Lisinopril & metformin. Most people with diabetes are treated with metformin, and an ace inhibitor, like lisinopril. In most cases, there are few interactions between the two. However, lisinopril can increase the effects of metformin, and cause blood sugar to dip too low. If you are taking both of these medications and consistently experience signs of low blood sugar, be sure to speak with your doctor—this combo could be the culprit.

What’s the good news?

Although some drug combinations can be dangerous, there are some combinations that work very well together, with few side effects or interactions.

• Atorvastatin & lisinopril. The American Association of Clinical Endocrinologists and American Diabetes Association recommend that all diabetics with a blood pressure greater than 140/90 be on a statin (atorvastatin, simvastatin, rosuvastatin, etc) and an ace inhibitor (lisinopril, benazepril, etc).

• Amphetamine salt combo & amphetamine salt combo XR. It might seem odd that people fill for both the short (amphetamine salt combo) and long (amphetamine salt combo XR) version. However, it’s quite common. Most people who fill for this combination use the short-acting amphetamine like a booster—taken only if they feel the long-acting amphetamine is wearing off. If taken responsibly, there are no interactions between the two.

• Most heart medications. There are many types of heart medications on this list—ace inhibitors, statins, diuretics, and beta blockers—all treating some component or symptom of heart disease. But do they work well together, and can you take them long term? If taken appropriately, yes.

Are there ways to save?

Believe it or not, in some cases, you can save by taking fewer drugs, or switching to a less expensive alternative. These common combinations have less expensive alternatives you might want to discuss with your doctor.

• Lisinopril & hydrochlorothiazide. This combination is good for high blood pressure/hypertension, and are both first-line therapies. However, there they come in a combination pill–Zestoretic (lisinopril/hctz)–that is more affordable, and more convenient, than taking two separate medications.

• Amlodipine & lisinopril. Both of these medications tend to work well together to control blood pressure. However, if you currently take these together, you have another option that can help save you time and money! Lotrel (amlodipine/benazepril) is a combination calcium channel blocker/ace inhibitor that works just like amlodipine and lisinopril, in just one pill!

Information on drug interactions and savings tips come from Dr. Sharon Orrange, MD MPH, a contributor on the GoodRx Medical Team. Data comes from several sources, including pharmacy data and insurer data, and provides a representative sample of nationwide US prescription drug claims.

Why trust our experts?

Written by:

Tori Marsh, MPH

Tori Marsh is GoodRx’s resident expert on prescription drug pricing, prescribing trends, and drug savings. She oversees the GoodRx drug database, ensuring that all drug information is accurate and up to date.

Analysis by:

Jeroen van Meijgaard, PhD

Dr. van Meijgaard is a health economist with over 20 years of experience in healthcare informatics and has a knack for distilling meaningful insights from data. With extensive expertise in population research and the social, economic, and environmental determinants of health, Dr. van Meijgaard has published in leading academic journals.

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