6 TPOXX Side Effects You Should Know About

Few diseases have been as prolific and devastating as the smallpox virus has throughout history. It persisted around the world for centuries and about 3 in 10 people who contracted the disease also died from it. Many others had permanent scars, often on their faces, or blindness.

Thankfully, smallpox is not an infection people get anymore. That’s because it was wiped out in 1980, a few decades after the development of the smallpox vaccine. And yet, although the natural spread of smallpox is no longer a worry, a new threat looms in the modern era. 

It’s believed that the smallpox virus could be used as a bioterrorism weapon to purposely infect people. And since we aren’t routinely vaccinated against smallpox anymore — that stopped in the 1970s — it leaves a lot of people vulnerable. In the case of an attack that weaponizes smallpox, the FDA has approved medications like TPOXX (tecovirimat) to treat it. More recently, the CDC expanded the use of TPOXX as an off-label treatment for certain people infected with mpox (formerly known as monkeypox).

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So if you’re prescribed TPOXX, what should you expect? The medication comes as an oral capsule and an intravenous (IV) infusion. Side effects are usually mild and can often be easily managed. And since TPOXX is usually only taken for a short time, side effects are usually temporary, as well. Below, we’ll discuss the TPOXX side effects you should be aware of.

1. Headache

In safety trials of oral TPOXX in healthy volunteers, 12% experienced headaches while taking the medication. But 8% of people taking placebo (a capsule with no medicine in it) also reported headache. In people who received the IV version, 15% reported headaches, compared to zero headaches reported with placebo.

If you have a headache after taking TPOXX, there are several things that may help. You can try drinking plenty of water, getting enough sleep, and avoiding alcohol. Taking over-the-counter (OTC) pain relievers, like Tylenol (acetaminophen), may also help.

If your headache is severe or won’t go away, check with your healthcare provider. They’ll be able to tell if something else is causing your symptoms.

2. Nausea and vomiting

Nausea and vomiting are also common side effects of TPOXX. They usually happen with the oral capsules, not as much with the IV form. In trials, 5% of participants reported nausea with TPOXX, compared to 4% with placebo. And 2% reported vomiting, while no vomiting was reported with placebo.

You should take TPOXX capsules within 30 minutes of a meal that contains moderate or high amounts of fat. This helps your body absorb TPOXX. But it may also help prevent nausea and vomiting.

If you experience severe or persistent nausea or vomiting, let your healthcare provider know. If it’s from TPOXX, they may want to make sure you’re taking it correctly. They can also help you manage this side effect if it becomes bothersome.

3. Stomach pain

Stomach pain is another possible side effect of TPOXX capsules. About 2% of people reported stomach pain in trials, compared to 1% with placebo.

Taking TPOXX with food may also help prevent this side effect. Stomach pain may go away on its own. But if your stomach pain doesn’t go away, gets worse, or becomes severe, you should let your healthcare provider know. You may need medical attention.

4. Dry mouth

It’s rare, but sometimes TPOXX can cause dry mouth and chapped lips. Only people taking the oral capsule had this side effect.

There are some simple things you can try at home to help treat and prevent dry mouth. These include sucking on ice chips, chewing sugar-free gum, and using OTC saliva substitutes like Biotene. Good oral hygiene can also help prevent dry mouth.

If this side effect gets worse, or you notice mouth sores or you’re having trouble swallowing, seek medical care right away. There could be something more serious going on.

5. Muscle pain

Pain in the muscles and joints was a rare side effect of both oral and IV TPOXX in trials. Some people reported that they had arthritis-like symptoms when taking the medication.

Treating mild muscle and joint pain may involve using OTC pain relievers. Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen (Advil, Motrin), tend to be more effective for muscle and joint pain. They help relieve both pain and inflammation. But talk to your pharmacist or healthcare provider first to make sure they’re OK for you to take.

Your healthcare provider can help determine how to manage any muscle pain side effects you’re having. If the pain is severe, be sure to let them know — you may need to stop taking TPOXX or get emergency care.

6. Infusion site reactions

Infusion site reactions only happen with the IV version of TPOXX. This side effect is possible with most IV medications, and it can be severe. But almost as many people receiving a placebo infusion had these reactions as people receiving TPOXX in trials. They happened in 73% of people given TPOXX compared to 67% of people given placebo.

Symptoms of infusion site reactions include swelling, redness, and pain. These reactions usually happen in the area where the medication is being given.

But there are more serious risks that can happen, like if the medication starts leaking outside of the blood vessel (extravasation). If this happens, it could damage muscle tissue or lead to an infection.

If you’re getting the IV form of TPOXX, your care team will keep an eye out for any signs of an infusion site reaction. If this side effect happens, they may recommend using a warm compress, ice packs, or OTC medications to manage it. If you notice any new redness or swelling after you’ve received IV TPOXX, be sure to let your care team know right away.

When should I contact my healthcare provider about TPOXX side effects?

If you have any concerns about TPOXX side effects, talk to your pharmacist or healthcare provider. It’s best to be on the safe side and double-check.

If you have any severe stomach pain, headaches, or infusion-site reactions, let your healthcare provider know right away. They can determine whether you need to seek medical care. Never stop TPOXX without talking to your healthcare provider or pharmacist first. It’s very important to finish the full course of treatment for it to work properly.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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