Narcan, Flumazenil, Protamine, and More: 10 Common Medication Reversal Agents

It can be frightening if you or a loved one takes too much medication. This may happen accidentally or deliberately. Another scenario could be experiencing side effects, such as bleeding, from your prescription.

Whatever the reason, acting quickly is key to remedy the situation. Sometimes you need medication to help reverse the effects.

We’ve got you covered with some of the most common medication reversal agents.

What are medication reversal agents?

Medication reversal agents work by counteracting the effects of other medications. Some are designed for at-home use; others are administered only in a hospital setting. Some are available over the counter (OTC), but many need a prescription.

Below, we break down 10 common options that fall within the list of reversal agents.

1. Narcan (and other naloxone products)

When you hear about overdoses, Narcan (naloxone) likely comes to mind. It’s a lifesaving medication that can reverse opioid overdoses.

Narcan is a needle-free medication that’s available OTC. It comes as a 4 mg nasal spray. You can find it online and at a variety of pharmacies. The nasal spray is a convenient reversal option to have on hand, especially if you or a loved one takes an opioid medication like oxycodone (Roxicodone, OxyContin).

The typical Narcan nasal spray dosage for adults and kids is one spray in one nostril at the first signs of an opioid overdose. If it doesn’t work within 2 to 3 minutes, you can administer another spray in the other nostril. You can keep giving one spray in alternating nostrils every 2 to 3 minutes until the person responds.

To make naloxone widely available, there are also a variety of similar products to choose from. RiVive is a 3 mg naloxone nasal spray that is available OTC. Naloxone also comes in a higher-dose prescription nasal spray, such as Kloxxado. Prescription injection naloxone products, such as Zimhi, are on the market too.

Good to know: It’s important for your family and friends to know how to administer Narcan. If you’re unconscious, you won’t be able to administer it yourself.

2. Flumazenil

Benzodiazepines are popular medications for managing conditions like anxiety. Alprazolam (Xanax) and diazepam (Valium) are two examples. But if you take too much, they can be dangerous. Common signs and symptoms of a benzodiazepine overdose include drowsiness, confusion, and shallow breathing.

EXPERT PICKS: WHAT TO READ NEXT

• Opioid overdose 101: Learn from experts about the signs and symptoms of an opioid overdose and how to treat them.

• Benzodiazepine trouble: Experts review how to spot benzodiazepine (benzo) overdose symptoms and what your next steps should entail.

• Vitamin K and warfarin: Learn how vitamin K can treat an elevated warfarin (Coumadin, Jantoven) blood test.

Flumazenil is an IV injection administered in the hospital for benzodiazepine overdoses. It’s not generally administered at home. It takes about 6 to 10 minutes to reach peak effects once it’s given.

3. Protamine

Protamine is FDA approved to reverse the effects of a blood thinner called heparin. You may need protamine if you experience heavy or significant bleeding while receiving heparin.

Protamine is an IV injection that’s administered over 10 minutes in the hospital. It works quickly as a reversal agent, typically within a few minutes.

4. Vitamin K

Warfarin (Coumadin, Jantoven) is an oral blood thinner that requires frequent monitoring. This is done with a blood test known as an international normalized ratio (INR). If your INR is too high, you have a higher risk of bleeding.

That’s where vitamin K comes in. It also goes by the generic name phytonadione. Oral and IV vitamin K can help reverse the effects of warfarin.

Oral vitamin K is available OTC and by prescription. The prescription form is a better option for warfarin reversal since the pill strengths are higher than the OTC products. A typical initial dosage for oral vitamin K is 2.5 mg by mouth. Oral vitamin K can lower your INR within about 24 hours.

The IV form of vitamin K is administered in the hospital for more severe bleeding. It can lower your INR quickly, within about 4 to 6 hours.

5. Andexxa

Andexxa (andexanet alfa) is the first approved antidote for reversing the effects of apixaban (Eliquis) and rivaroxaban (Xarelto), two common blood thinners.

Andexxa is administered as a quick IV injection to get the medication into your system. This is followed by an IV infusion given over 2 hours. Andexxa starts working in about 2 minutes.

6. N-acetylcysteine

Acetaminophen (Tylenol) is generally safe to take. But it’s important to not take too much (more than 4,000 mg per day). With over 600 medications on the market containing acetaminophen, it can be easy to double up on it accidentally.

Acetaminophen overdoses can cause potentially serious side effects, including liver failure. N-acetylcysteine (Acetadote) is a first-choice medication for treating liver harm related to an acetaminophen overdose. It’s given through an IV in the hospital. Healthcare professionals determine the dose based on body weight.

IV N-acetylcysteine is typically given as 3 doses over a 21-hour time frame. But research shows people may need N-acetylcysteine longer depending on blood test results. Your healthcare team will determine how many doses you need.

7. Glucagon

Hypoglycemia (low blood sugar) can be life-threatening. It happens when your blood glucose (blood sugar) drops below 70 mg/dL. It’s a possible side effect of certain medications — such as insulin — that lower your blood sugar levels by design.

Most experts recommend keeping glucagon on hand if you’re prescribed insulin. You’ll need a prescription from a healthcare professional. It works by sending a message to your liver to release more glucose.

Glucagon traditionally comes in an injection kit that you put together. But it’s ideal to have a ready-to-use glucagon product in an emergency. These include a nasal spray called Baqsimi and a subcutaneous (under-the-skin) injection called Gvoke. Both versions are approved to treat severe hypoglycemia in adults and kids. They should start working within about 10 minutes after administering it. But it could take up to 30 minutes to see their full benefits.

8. Insulin regular

When you think of insulin regular (Humulin R), treating diabetes likely comes to mind. But it can also reverse the effects of calcium channel blocker (CCB) and beta blocker overdoses. Amlodipine (Norvasc) is an example of a CCB, while metoprolol (Lopressor, Toprol XL) is a common beta blocker.

CCBs and beta blockers are effective treatment options for managing hypertension (high blood pressure) and other heart-related health conditions. But they can be dangerous in an overdose. Insulin regular can help treat shock, which in turn prevents organ failure.

If an insulin injection is needed, a healthcare professional will administer it, followed by an infusion.

9. Atropine

Atropine injections can treat organophosphate poisoning, a type of insecticide and nerve agent poisoning. This is typically done in a hospital.

Atropine is an anticholinergic medication that works by blocking the neurotransmitter (chemical messenger) acetylcholine. This helps improve heart rate and breathing. IV atropine is typically given every 3 to 5 minutes until your symptoms improve.

10. Folic acid and leucovorin

Methotrexate (Trexall, Rasuvo) treats several cancers and autoimmune conditions. It can also cause side effects and toxicity.

If you’re taking methotrexate for an autoimmune condition like rheumatoid arthritis, a healthcare professional may recommend supplementing with folic acid. That’s because methotrexate can lower folic acid levels, which may cause side effects like mouth sores and nausea.

The typical folic acid dosage is 1 mg by mouth once daily. You can also take 5 mg once weekly. It’s available as a prescription (in higher strengths) and OTC medication.

Methotrexate toxicity, by comparison, is typically treated with a rescue medication called leucovorin (folinic acid). It prevents serious side effects, such as nerve cell damage, from high-dose methotrexate for cancer. It comes as a prescription oral tablet. Leucovorin is also available as an IV or intramuscular (into the muscle) injection.

Why trust our experts?

Written by:

Jennifer Gershman, PharmD, CPh, PACS

Jennifer Gershman, PharmD, is a licensed pharmacist in Florida. She has worked in the pharmacy industry for more than 15 years and is currently a medical writer.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

Our editorial standards

Meet our experts