• Diphenhydramine — sold under many brand names, including 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 they may not be a good option for preinfusion treatment in some people.

Some people with multiple sclerosis may be given diphenhydramine before undergoing certain treatments aimed at slowing disease progression and disability progression. Preventive use of this antihistamine can help people with relapsing-remitting MS (RRMS) or other types of MS 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,” said 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 give diphenhydramine with treatments and how you can prepare for possible side effects.

Diphenhydramine With MS Treatments

MS providers sometimes administer diphenhydramine or another antihistamine as a precaution so that an infusion-related reaction with MS treatment may be less likely to occur or less severe. 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 directly through a vein via intravenous (IV) injection. Oral diphenhydramine is available over the counter (OTC), and injected diphenhydramine requires a prescription or order with administration and supervised monitoring by a health care provider.

Doctors sometimes give diphenhydramine or another antihistamine 30 minutes before an infusion to reduce the likelihood or severity of an allergic reaction.

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 or methylprednisolone (Medrol)
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Motrin)
• 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-related 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

Some MS infusion treatments can cause mild or severe allergic responses such as itchy skin, hives, headaches, breathing trouble, or fainting.

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)
• Ublituximab-xiiy (Briumvi)

IV or subcutaneous (under the skin) immunoglobulin is a supportive treatment sometimes used to reduce symptoms of an MS flare. This therapy is also sometimes given with diphenhydramine.

MS treatment options 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’s impossible to predict which of these two effects a person will experience until they take the medication for the first time.

Diphenhydramine can cause mild side effects, such as drowsiness and dry mouth, as well as more serious ones, such as breathing difficulties and confusion.

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

• Difficulty breathing
• Swelling of the mouth or throat
• Pounding heartbeat
• Trouble 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 your options for switching treatments. They may be able to suggest how to avoid negative effects on your quality of life while still having a positive treatment experience. You may also want to talk to your doctor about switching treatments if your MS symptoms are getting worse due to disease activity and damage to myelin, the protective sheath of nerve fibers in the central nervous system (CNS).

New Research on Antihistamines and Multiple Sclerosis

Although not related to the use of diphenhydramine with MS treatments, recent neurology research has pointed to other promising benefits of antihistamines that could ultimately lead to new ways of treating MS. In a clinical trial (a study that tests a drug’s safety and effectiveness) with 50 participants, medical scientists discovered that clemastine, an OTC antihistamine, may bring on myelin repair in people with MS. This effect could potentially help heal lesions that cause nerve damage, according to the authors of the study.

However, this is not a treatment approach that has been approved by the U.S. Food and Drug Administration (FDA). The authors emphasized that clemastine acts as a sedative, which is highly problematic for people with MS, and research is still in the early stages.

If you have questions about the latest research on MS treatments, talk with your doctor.

Find Your Team

MyMSTeam is the social network for people with multiple sclerosis and their loved ones. On MyMSTeam, more than 217,000 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? How did this strategy affect you? Share your story in the comments below, or start a conversation by posting on your Activities page.