Diphenhydramine is an antihistamine that antagonizes the histamine H1 receptor to suppress uncomfortable histamine-induced allergic symptoms. As it is a first-generation antihistamine that crosses the blood-brain barrier, it has sedative and antinausea properties. By a different mechanism, it also causes local anesthetic effects.¹
Diphenhydramine is US Food and Drug Administration (FDA)-approved for several indications.²
The drug is primarily used to suppress unpleasant allergic symptoms like runny nose, itchy skin, hives, rashes, wheezing, coughing, and itchy, red, and teary eyes.³
Doctors prescribe diphenhydramine to prevent and alleviate vomiting, dizziness, and nausea caused by motion sickness.
The medication also treats involuntary movements called extrapyramidal symptoms that can occur as a side effect of some medicines. It also can be used for tremors and other movement symptoms that develop in Parkinson disease.
Diphenhydramine has been used off-label as a treatment for oral mucositis and as a local anesthetic alternative for patients who are allergic to others, but these are not approved uses.⁴
Diphenhydramine is available in several forms. Most forms are available over the counter (OTC) without a prescription, and some OTC medications combine diphenhydramine with one or more other drugs.
Diphenhydramine-only products are available in the following forms and strengths:
Tablet: 25mg, 50mg
Chewable tablet: 12.5mg
Orally disintegrating tablet (ODT): 35mg
Capsule: 25mg, 50mg
Oral solution: 12.5mg/5mL
Injection solution (IM or IV): 50mg/mL
Topical cream, gel, and solution: 1%, 2%
The dosage for this medication depends on the condition being treated, the patient's age, and the severity of the symptoms. Most people will take a dose and form available without a prescription.
If symptoms are severe, higher doses may be given orally, IM, or IV, and the dosing for younger children is based on their weight and age.⁵ ⁶
When taking OTC forms, follow the instructions on the package. If your medication is prescribed or you’re taking an OTC form under your doctor’s guidance, take it precisely as instructed by your prescriber.
Swallow the regular tablets and capsules whole instead of chewing. Chewing a non-chewable tablet releases the drug at once, increasing the likelihood of severe side effects. Chewable tablets, on the other hand, are uniquely formulated to be chewed before swallowing. The ODT form is placed directly onto the tongue, where it dissolves before swallowing. The oral solution is measured using a specialized syringe or dosing spoon provided in the package. Topical forms are applied directly to the skin. Finally, injectable types are administered by a qualified healthcare provider in a medical setting.
People who take diphenhydramine to prevent motion sickness usually take it 30 minutes before the activity. Similarly, those using it as a sleep aid take it 30 minutes before bedtime.⁷
The body absorbs diphenhydramine rapidly in less than one hour. Thus, if you are treating allergy symptoms like coughing, hives, teary eyes, itchy throat, sneezing, and runny nose, you should begin to experience some relief within an hour of taking your dose. The same will apply to its other uses.⁸
Diphenhydramine is contraindicated for patients with the following:⁹
History of a previous allergic reaction to the drug or one of its ingredients
Age under two years
Patients with the following should take the medication cautiously:
Although safe, diphenhydramine can trigger side effects in some individuals, especially for those who are above 60 years of age, drink alcohol, or have certain underlying medical conditions.¹⁰
The most common side effects reported by patients using the drug include the following:¹¹ ¹²
Dry mouth, nose, and throat
Loss of appetite
Nausea or vomiting
Blurred or double vision
Dizziness or vertigo
Palpitations or rapid heart rate
Urinary retention or difficulty urinating
Agitation (especially in children)
While uncommon, some patients experience severe reactions, such as the following:¹³
It’s possible to overdose on diphenhydramine. Occasionally, people accidentally overdose when taking diphenhydramine alongside combination medications that also contain the drug.
Signs and symptoms of an overdose include:¹⁴
Irritability, agitation, or confusion
Inability to urinate
Ringing in the ears
Abnormal heart rhythms
Loss of consciousness or coma
If you or someone in your care has taken too much diphenhydramine, call 911 or go to your nearest emergency department. A delay could lead to life-threatening complications, which may be fatal.
Some people are allergic to diphenhydramine. Monitor for the following symptoms of a drug allergy while taking this medication:
Rash, hives, or itching
Swelling of the face, lips, or tongue
Wheezing or difficulty breathing
Rapid heart rate
Loss of consciousness
If you experience any signs of a drug allergy while taking diphenhydramine, stop taking the medication and seek urgent medical care.
Health practitioners prescribe diphenhydramine for the short-term management of allergy symptoms, insomnia, and motion sickness. Long-term use is discouraged since studies have shown an increased risk of dementia.¹⁵
The US FDA has designated diphenhydramine as a pregnancy category B drug. While the medication demonstrated no risk to the mother or fetus in animal studies, there’s a lack of research involving humans. Your doctor may recommend using this medication during pregnancy if there’s a critical clinical need. Animal studies have shown that the drug does not cause congenital disorders in developing fetuses.¹⁶
It’s worth noting that diphenhydramine use is associated with weakness, drowsiness, and dizziness. These side effects increase the risk of falling, which could lead to pregnancy complications.
Diphenhydramine is considered safe for the mother and baby when used occasionally in small doses while breastfeeding. Nevertheless, high doses and prolonged use could reduce milk production or make the infant feel drowsy — an issue that was shown in one study to affect one in 12 infants whose mothers were taking the medication while breastfeeding.¹⁷ ¹⁸
Most people take diphenhydramine as needed. However, you may take scheduled doses if you're using the drug under your doctor's guidance. If that’s the case and you miss a dose, take it as soon as you remember unless it’s nearly time for your next dose. If it’s closer in time to your next scheduled dose, skip the missed one and continue as scheduled. Don’t double your dose to make up for a missed one.¹⁹
Diphenhydramine can interact with some prescription and OTC medications as well as supplements to trigger unwanted side effects.
Medicines that are known to interact with diphenhydramine include the following:²⁰
Monoamine oxidase inhibitors (MAOIs), such as isocarboxazid (Marplan), tranylcypromine (Parnate), and phenelzine (Nardil)
Serotonin and norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (Effexor)
Antinausea medicines like trimethobenzamide (Tigan) and promethazine (Phenergan)
Antipsychotics, such as thioridazine (Mellaril) and clozapine (Clozaril, Zaponex)
Medications for abnormal heart rhythms, such as propafenone (Rythmol)
Diabetic treatments, such as pramlintide (Symlin) and glucagon
Pain medications, including codeine, hydrocodone (Vicodin, Lortab), and tramadol (Ultram)
Benzodiazepines like midazolam (Versed) and alprazolam (Xanax)
Sleep aids, such as doxylamine (Unisom)
Supplements containing potassium
Alcohol and recreational drugs like kratom, kava, and opium
Like diphenhydramine, alcohol causes drowsiness. Drinking alcohol while taking this medication increases the risk of intense drowsiness, confusion, and dizziness, which could be dangerous.
While diphenhydramine is available without a prescription, it’s a good idea to meet with your doctor before taking a new medication, especially if you have a known health condition or take other medicines. At your appointment, you should discuss the following:
Known drug allergies or past reactions to medicines
All medications you take regularly or occasionally, including prescription and OTC drugs, herbs, vitamins, and supplements
Your medical history, including any health conditions such as asthma, high blood pressure, heart disease, lung disease, seizures, and glaucoma
If you are pregnant, breastfeeding, or have plans to conceive
Any upcoming surgeries or dental procedures
If you’ve been taking high doses of diphenhydramine or taken it long-term, you may experience withdrawal symptoms like irritability, difficulty sleeping, restlessness, cold symptoms, and nausea when you stop.
Therefore, when planning to stop taking the drug after regular use for an extended period, seek support from your doctor to discontinue it safely.
1946: Benadryl (diphenhydramine) entered the US market²¹
1981: Benylin became the first diphenhydramine-based medication available without a prescription (OTC)²²
Take your medication as directed on the package or by your doctor.
Avoid alcohol and other recreational drugs when taking diphenhydramine.
Speak with your doctor before taking this medication to ensure it’s safe for you.
Store the medicine in a tightly closed container in a dry place at room temperature.
Keep this and all medications out of the reach of children.
Diphenhydramine helps alleviate the unpleasant symptoms associated with hay fever, allergic reactions, movement disorders, and motion sickness.
Diphenhydramine can cause coma, severe heart problems, or death when taken in high doses. It is a sedative, so extra caution is needed in people who plan to drive or engage in tasks demanding alertness while taking the medication. Taking it long-term may increase the risk of dementia.
The most common side effects are mild and include dizziness, drowsiness, dry mouth, blurry vision, instability, and constipation.
Here at HealthMatch, we’ve done our best to ensure that the information provided in this article is helpful, up to date, and, most importantly, accurate.
However, we can’t replace the one-to-one advice of a qualified medical practitioner or outline all of the possible risks associated with this particular drug and your circumstances.
It is therefore important for you to note that the information contained in this article does not constitute professional medical or healthcare advice, diagnosis or recommendation of treatment and is not intended to, nor should be used to, replace professional medical advice. This article may not always be up to date and is not exhaustive of all of the risks and considerations relevant to this particular drug. In no circumstances should this article be relied upon without independent consideration and confirmation by a qualified medical practitioner.
Your doctor will be able to explain all possible uses, dosages, precautions, interactions with other drugs, and other potential adverse effects, and you should always talk to them about any kind of medication you are taking, thinking about taking or wanting to stop taking.
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