Diphenhydramine Hydrochloride (Benadryl®)- Oral / IV / IM / Topical

Author: OncoLink Team
Last Reviewed: June 23, 2020

Pronounced: DYE-fen-HYE-dra-meen

Classification: H1-antihistamine; anticholinergic

About: Diphenhydramine Hydrochloride (Benadryl®)- Oral / IV / IM / Topical

Diphenhydramine hydrochloride is an antihistamine. Antihistamines are used for many reasons, such as for treating and preventing allergic reactions (including anaphylaxis), motion sickness, and some movement disorders.

Diphenhydramine hydrochloride works by blocking histamine in the body. Histamine occurs naturally in the body and is part of our immune system. Histamine is released when foreign allergens (like pollen, cat dander, certain medications) enter our body. Histamine tries to rid our body of the allergen, through things like sneezing, itching, or tearing up. 

This medication sheet will focus on diphenhydramine hydrochloride used during cancer treatment.

How this Medication Comes

This medication comes as tablets, capsules, an oral solution (liquid), intramuscular (IM, into a muscle) and intravenous (IV, into a vein) formulations. It can also come as a spray or mist, and as a topical ointment or cream. This medication sheet will focus on the oral, IM, and IV formulations of diphenhydramine hydrochloride. 

How to Take Diphenhydramine Hydrochloride (Benadryl®)

How you take diphenhydramine hydrochloride depends on why you were prescribed the medication. It can be given on as needed or scheduled basis and should be taken as prescribed by your provider. 

Diphenhydramine hydrochloride is sometimes given before certain cancer treatments to prevent an allergic reaction. You may hear it, and other medications, referred to as “pre-medications” or “pre-meds.” These are given, either by mouth or IV, about 30 minutes to 1 hour before your cancer treatment. Some cancer treatments have a higher chance of causing an allergic reaction. Your provider may prescribe diphenhydramine hydrochloride to lessen the chances you will have an allergic reaction. It can also be given along with other medications if you do have an allergic reaction. 

Diphenhydramine hydrochloride may be prescribed for other reasons. You may be told to buy it over the counter (without a prescription). Do not take diphenhydramine hydrochloride without first checking with your provider. Talk with your provider about why diphenhydramine hydrochloride may be used in your treatment. 

You should not drink alcohol while taking this medication. You should not drive a car or operate heavy machinery while taking diphenhydramine hydrochloride. If this medication is part of your cancer treatment, you may need someone to drive you home from your appointment.

Be sure to tell your healthcare provider about all medications and supplements you take. This medication can affect how other medications work in your body, including CNS depressants (hypnotics, sedatives, tranquilizers) and MAO inhibitors.

Tell your provider if you have a history of asthma, increased pressure in your eyes, thyroid issues, peptic ulcer, prostate hypertrophy, urinary obstruction, heart disease, or high blood pressure before taking diphenhydramine hydrochloride.

Taking too much of this medication can result in overdose. Be sure you take the right amount of medication that has been prescribed. When using over-the-counter medications, make sure that you are not using more than one product containing diphenhydramine. Signs of overdose with diphenhydramine hydrochloride include being unable to stay awake, having trouble breathing or having shallow breaths, extreme dry mouth, fixed and dilated pupils of the eyes, flushing, and stomach upset. Call 911 right away if you take too much diphenhydramine hydrochloride at one time.

Storage and Handling

If your provider prescribes or suggests you get the tablet, capsule, or liquid formulation of diphenhydramine hydrochloride, store this medication in the original container at room temperature. Keep this medication out of reach of children and pets. 

Where do I get this medication?

This medication is available at retail pharmacies. You can buy diphenhydramine hydrochloride over the counter, without a prescription. The intravenous or intramuscular form would be provided to you in a healthcare setting as ordered by your medical team.

Insurance information

Diphenhydramine hydrochloride is available without a prescription. Depending on your prescription plan, this medication may be covered by your insurance. Talk with your pharmacist about the most cost-effective options for getting this medication. 

Possible Side Effects of Diphenhydramine Hydrochloride (Benadryl®)

This medication is given to manage and/or prevent side effects of your cancer treatment. If you are having side effects from this medication you should talk to your team about if this medication is necessary to your treatment or if there are other options to help manage the side effect this medication is treating. These are some of the most common side effects:

Anticholinergic Effects

Because of how this medication works, diphenhydramine hydrochloride may cause constipation, dry mouth, blurred vision, or urinary retention (not being able to or peeing less). These side effects may be worse if you are elderly and/or are on other medications with similar effects. If these effects make it hard to carry out daily life, talk with your provider.

Central Nervous System (CNS) Effects

Because of how this medication works and its effects on neurotransmitters in the brain, diphenhydramine hydrochloride may cause drowsiness, fatigue, sedation, trouble with coordination, feeling nervous, double vision, flushed skin, dizziness, and weakness. If these effects make it hard to carry out daily life, talk with your provider. If you or a caretaker notice you are having a hard time staying awake, or have shallow breathing, call 911 right away.

Cardiovascular (Heart) Effects

This medication can cause low blood pressure, palpitations or fast heart rate, and headache. Tell your provider right away if you have any of these side effects. In high doses and in rare cases, this medication can cause slow or abnormal heartbeats or an abnormal heart rhythm called QT prolongation. Notify your oncology care team right away if you feel abnormal heartbeats or if you feel dizzy or faint.

Reproductive Concerns 

You should consult with your healthcare team prior to becoming pregnant, fathering a child or breastfeeding while receiving this medication.  

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