• Diphenhydramine, sold as Benadryl, is a type of antihistamine that can help reduce the likelihood or severity of an allergic reaction to a multiple sclerosis (MS) infusion treatment.
• Antihistamines block histamines, chemicals made by white blood cells that cause allergy symptoms such as itchy skin, rash, and hives.
• Diphenhydramine and other antihistamines can cause their own set of undesirable side effects — both mild and serious — and are not a good pre-infusion treatment for some people.

Some people with multiple sclerosis may be given diphenhydramine (Benadryl) before undergoing certain treatments. Preventive use of this antihistamine can help you avoid adverse effects, such as allergic reactions to infusions.

MyMSTeam members have shared their experiences with diphenhydramine. “I had an infusion on Monday, and it went well, except the diphenhydramine makes me sooooo tired,” shared one member. Regarding infusion treatment sessions, another member said, “I tend to have a diphenhydramine hangover the rest of the day and the next day. Other than that, I’m good.”

Read on to understand more about why some providers administer diphenhydramine with treatments and how you can prepare for side effects.

Diphenhydramine With MS Treatments

MS providers sometimes administer diphenhydramine or another antihistamine as a precaution to help reduce the likelihood or severity of an infusion reaction with MS treatment. Antihistamines are drugs that block histamine — a chemical made by white blood cells. Histamine is responsible for allergy symptoms such as itchy skin, rash, and hives.

Diphenhydramine can be given orally or by intravenous injection. Oral diphenhydramine is available over the counter, and injected diphenhydramine requires a prescription.

Your health care team may give you other medications as pretreatment 30 minutes before your MS treatment. These medications may be administered in addition to or instead of diphenhydramine:

• Other antihistamines, such as cetirizine (Zyrtec)
• Steroids, such as prednisone (Deltasone) or methylprednisolone (Medrol)
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin
• Pain relievers, such as acetaminophen (Tylenol)

Infusion Reactions With MS Treatments

Infusion reactions are strong responses that can develop during or shortly after receiving an MS infusion treatment. The possibility of infusion reactions is one reason that some MS treatments are given in a clinic setting under medical supervision.

These responses can occur because the body may view the drug as an invader or a threat, and your immune system creates defenses to protect your health. Signs and symptoms of a reaction may include:

• Itchy skin
• Hives
• Reaction at the injection site, such as pain or swelling
• Fever
• Chills
• Headache
• Difficulty breathing

In rare cases, MS treatments can trigger a severe allergic reaction called anaphylaxis, which is a medical emergency. Signs and symptoms of anaphylaxis include:

• Rash or hives
• Constriction of the airways or throat
• Chest tightness
• Vomiting or diarrhea
• Dizziness or fainting

If you are taking one of the following disease-modifying therapies (DMTs), you may be given oral or IV diphenhydramine before your infusion:

• Alemtuzumab (Lemtrada)
• Ocrelizumab (Ocrevus)
• Natalizumab (Tysabri)
• IV or subcutaneous (under the skin) immunoglobulin

MS treatments that you take at home, including oral and injectable DMTs, may also cause allergic reactions. Your health care provider may recommend taking oral diphenhydramine at home 30 minutes before your MS treatment.

Side Effects of Diphenhydramine

As with any medication, you may experience some side effects when using diphenhydramine. Drowsiness is a common side effect of diphenhydramine. Other common side effects include:

• Dry mouth
• Dry eyes
• Dizziness
• Stomach upset

Less commonly, diphenhydramine has been known to cause hyperactivity rather than the expected drowsiness. It is impossible to predict which of these two effects a person will experience until they take the medication for the first time.

In rare cases, serious side effects or allergic reactions to diphenhydramine can occur that require emergency medical attention. Symptoms include:

• Difficulty breathing
• Swelling of the mouth or throat
• A pounding heartbeat
• Difficulty urinating
• Confusion

Some people with MS find that diphenhydramine helps prevent reactions, while others forgo it. “I take a Benadryl before my infusion and then halfway through, they have had to slow it down and give me another dose of Benadryl — my throat likes to itch and cough, but the extra Benadryl takes care of it all,” one MyMSTeam member wrote. Another said, “They don’t give me Benadryl anymore. The Benadryl made me worthless for the entire day.”

If you find that any of the pretreatment medications — diphenhydramine or otherwise — cause reactions that you find unpleasant, talk to your neurologist about potential alternative treatment options. They may be able to suggest how to avoid the negative effects on your quality of life while still giving you a positive treatment experience.

Talk With Others Who Understand

MyMSTeam is the social network for people with multiple sclerosis and their loved ones. On MyMSTeam, more than 195,000 members come together to ask questions, give advice, and share their stories with others who understand life with MS.

Are you living with multiple sclerosis? Have you taken diphenhydramine with your MS treatment? Share your story in the comments below, or start a conversation by posting on your Activities page.