Diphenhydramine

What is diphenhydramine?

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

What is diphenhydramine used to treat?

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

Dosage forms and strengths

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

How do you take diphenhydramine?

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

Seeing results

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

Who should not take diphenhydramine?

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:

• Asthma

• Angle-closure glaucoma

• Hyperthyroidism

• High blood pressure

• Increased intracranial pressure

• Age under six years or over 65

• Prostatic hypertrophy or bladder obstruction

• Gastrointestinal obstruction

• Cardiovascular disease

Potential side effects of diphenhydramine

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

Common side effects

The most common side effects reported by patients using the drug include the following:¹¹ ¹²

• Drowsiness

• Headache

• Dry mouth, nose, and throat

• Sweating

• Sun sensitivity

• Loss of appetite

• Difficulty concentrating

• Muscle weakness

• Impaired coordination

• Nausea or vomiting

• Constipation

• Blurred or double vision

• Dizziness or vertigo

• Erectile dysfunction

• Palpitations or rapid heart rate

• Low blood pressure

• Epigastric discomfort

• Urinary retention or difficulty urinating

• Agitation (especially in children)

Severe side effects

While uncommon, some patients experience severe reactions, such as the following:¹³

• Anaphylaxis

• Low white blood cell or platelet counts

• Hemolytic anemia

• Heat stroke

• Seizures

• Toxic psychosis

• Arrhythmias

• Confusion

Overdose

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

• Blurry vision

• Flushed skin

• Psychosis

• Seizures

• Hallucinations

• Irritability, agitation, or confusion

• Delirium

• Inability to urinate

• Ringing in the ears

• Delirium

• Tremor

• Vomiting

• Respiratory depression

• 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.

Allergy information

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

• Vomiting

• 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.

Long-term use of diphenhydramine

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

Pregnancy category

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.

Breastfeeding

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

Missed doses

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

Drug interactions

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

• Antidepressants:

  • 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)

• Sedatives:

  • 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

Can I drink alcohol while taking diphenhydramine?

Like diphenhydramine, alcohol causes drowsiness. Drinking alcohol while taking this medication increases the risk of intense drowsiness, confusion, and dizziness, which could be dangerous.

What to discuss with your doctor before starting diphenhydramine

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

Stopping diphenhydramine

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.

Drug approval history

1946: Benadryl (diphenhydramine) entered the US market²¹

1981: Benylin became the first diphenhydramine-based medication available without a prescription (OTC)²²

Tips for taking diphenhydramine

• 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.

Frequently asked questions

What is diphenhydramine used to treat?

Diphenhydramine helps alleviate the unpleasant symptoms associated with hay fever, allergic reactions, movement disorders, and motion sickness.

What are the risks of taking diphenhydramine?

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.

What are the most common diphenhydramine side effects?

The most common side effects are mild and include dizziness, drowsiness, dry mouth, blurry vision, instability, and constipation.