diphenhydramine

What is diphenhydramine

Diphenhydramine is an antihistamine [histamine-1 (H1) receptor blocker or antagonist] medicine that relieves allergy by blocking the action of histamine in your body. Histamine is a chemical that’s released by Mast cells in your body when an allergen is encountered that can produce symptoms of sneezing, hives, itching, watery eyes, and runny nose, also known as hypersensitivity reactions. Diphenhydramine is used to relieve red, irritated, itchy, watery eyes; sneezing; and runny nose caused by hay fever, allergies, or the common cold. Diphenhydramine is also used to relieve cough caused by minor throat or airway irritation. Diphenhydramine is also used to prevent and treat motion sickness, and to treat insomnia (difficulty falling asleep or staying asleep). Diphenhydramine is also used to control abnormal movements in people who have early stage parkinsonian syndrome (a disorder of the nervous system that causes difficulties with movement, muscle control, and balance) or who are experiencing movement problems as a side effect of a medication.

Diphenhydramine will relieve the symptoms of these conditions but will not treat the cause of the symptoms or speed recovery. Diphenhydramine should not be used to cause sleepiness in children.

Like other antihistamines, diphenhydramine should be used with caution in infants and young children and should NOT be used in premature or full-term neonates 1. Children younger than 6 years of age should receive diphenhydramine only under the direction of a physician 1. Safety and efficacy of diphenhydramine as a nighttime sleep aid in children younger than 12 years of age have not been established 1. In addition, children may be more prone than adults to paradoxically experience CNS stimulation rather than sedation when antihistamines are used as nighttime sleep aids 1. Because diphenhydramine may cause marked drowsiness that may be potentiated by other CNS depressants (e.g., sedatives, tranquilizers), diphenhydramine should be used in children only under the direction of a physician 1.

Because diphenhydramine has an atropine-like action, it should be used with caution in patients who have asthma 2. Patients should be cautioned about taking diphenhydramine with other depressant substances, because of the additive effect. Persons should also be advised not to operate a motor vehicle, fly an airplane, or operate hazardous machinery while on this drug. The incidence of side effects is approximately 30-60% 2.

The most frequent side effect of diphenhydramine the first-generation H1 antagonists is sedation. Although sedation may be a desirable adjunct in the treatment of some patients, it may interfere with the patient’s daytime activities 3. Concurrent ingestion of alcohol or other CNS depressants produces an additive effect that impairs motor skills. Other untoward reactions referable to central actions include dizziness, tinnitus, lassitude, incoordination, fatigue, blurred vision, diplopia, euphoria, nervousness, insomnia, and tremors.

What does diphenhydramine do

Diphenhydramine is a first generation antihistamine with sedative and anti-allergic properties. Diphenhydramine competitively inhibits the histamine-1 (H1) receptor, thereby alleviating the symptoms caused by endogenous histamine on bronchial, capillary and gastrointestinal smooth muscles. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and gastrointestinal smooth muscle spasms.

Diphenhydramineis used to treat sneezing, runny nose, watery eyes, hives, skin rash, itching (pruritus), and other cold or allergy symptoms.

Diphenhydramine is also used to treat motion sickness as an antiemetic, antitussive, to induce sleep, and to treat certain symptoms (e.g. tremors) of Parkinson’s disease (off-label use).

Before taking diphenhydramine – Precautions

  • tell your doctor and pharmacist if you are allergic to diphenhydramine or any other medications.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: other diphenhydramine products (even those that are used on the skin); other medications for colds, hay fever, or allergies; medications for anxiety, depression, or seizures; muscle relaxants; narcotic medications for pain; sedatives; sleeping pills; and tranquilizers.
  • tell your doctor if you have or have ever had asthma, emphysema, chronic bronchitis, or other types of lung disease; glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision); ulcers; difficulty urinating (due to an enlarged prostate gland); heart disease; high blood pressure; seizures; or an overactive thyroid gland.If you will be using the liquid, tell your doctor if you have been told to follow a low-sodium diet.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking diphenhydramine, call your doctor.
  • talk to your doctor about the risks and benefits of taking diphenhydramine if you are 65 years of age or older. Older adults should not usually take diphenhydramine because it is not as safe as other medications that can be used to treat the same conditions.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking diphenhydramine.
  • you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
  • remember that alcohol can add to the drowsiness caused by this medication. Avoid alcoholic beverages while you are taking this medication.
  • if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that some brands of chewable tablets and rapidly disintegrating tablets that contain diphenhydramine may be sweetened with aspartame, a source of phenylalanine.
  • Like other antihistamines, diphenhydramine should be used with caution in infants and young children and should not be used in premature or full-term neonates. Children younger than 6 years of age should receive diphenhydramine only under the direction of a physician. Safety and efficacy of diphenhydramine as a nighttime sleep aid in children younger than 12 years of age have not been established. In addition, children may be more prone than adults to paradoxically experience CNS stimulation rather than sedation when antihistamines are used as nighttime sleep aids. Because diphenhydramine may cause marked drowsiness that may be potentiated by other CNS depressants (e.g., sedatives, tranquilizers), the antihistamine should be used in children receiving one of these drugs only under the direction of a physician.

Diphenhydramine and alcohol

Ask your doctor before using diphenhydramine together with ethanol. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking diphenhydramine. Using diphenhydramine together with alcohol increases your risk for overdose. You should be warned not to exceed recommended dosages and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Diphenhydramine Pregnancy Warnings

Animal models have failed to reveal evidence of impaired fertility or fetal harm at doses up to 5 times the human dose. There are no controlled data in human pregnancy.

  • US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Use is recommended only if clearly needed and the benefit outweighs the risk.

I just found out I am pregnant. Should I stop taking diphenhydramine?

You should always talk with your health care provider before making any changes in your medication. It is important to consider the benefits of treating allergy symptoms and other conditions during pregnancy. Treating allergy symptoms may reduce asthma symptoms and the need for more asthma medicine. Allergy treatment can also result in better sleep and emotional well-being.

Can use of diphenhydramine during pregnancy cause birth defects?

It is unlikely that diphenhydramine would cause an increased chance for birth defects. Most studies show no increased chance of birth defects with the use of diphenhydramine in early pregnancy. While one study suggested an increased chance of several types of birth defects, the study does not prove causation and these findings have not been confirmed.

Can use of diphenhydramine cause other pregnancy complications?

At recommended doses, diphenhydramine has not been shown to cause problems in pregnancy. There are rare reports of problems with the use of diphenhydramine in the third trimester. These reports usually involve using more of the medication than is recommended or using it for long-term (chronic) use. High levels of diphenhydramine could cause uterine hyperstimulation (contractions that are too long or too often). Uterine hyperstimulation can affect the developing baby such as increasing the baby’s heart rate. Uterine contractions can also lead to serious complications, including uterine rupture (a tear in the uterus) or placental abruption (when the placenta pulls away from the wall of the uterus before the baby is born).

Also, there are a few reports of withdrawal symptoms in infants whose mothers took diphenhydramine daily throughout pregnancy.

Is there anyone who should avoid taking diphenhydramine during pregnancy?

A single human report and animal data have suggested that the combination of two medications: temazepam (a benzodiazepine) and diphenhydramine may increase the chance for stillbirth or infant death shortly after birth 4. It is unknown if this interaction will occur with all medications in the benzodiazepine class. Women taking benzodiazepines should talk with their health care provider before taking diphenhydramine during their pregnancy 4.

Diphenhydramine and Breastfeeding

Diphenhydramine has been detected in milk 1. Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or diphenhydramine, taking into account the importance of the drug to the woman.

Because diphenhydramine can cause sleepiness in adults, it may do the same for the baby 5. If you need to take an antihistamine regularly, ask your health care provider if a non-sedating one would work for your symptoms.

Antihistamines, as a group, might lower the amount of milk a woman makes, especially when using long acting antihistamines 6 and when used with decongestants like pseudoephedrine or phenylephrine. This is less likely to be of concern in a woman with established milk supply (has been breastfeeding for a while).

Two studies 7 with women who used an antihistamine (not just diphenhydramine) while breastfeeding reported their babies were irritable, sleepier, and/or slept less.

Be sure to discuss any medications you are taking and your options for breastfeeding with your health care provider as well as the baby’s pediatrician.

What is diphenhydramine used for

Diphenhydramine uses

  • Temporarily relieves these symptoms due to hay fever or other upper respiratory allergies:
    • Runny nose
    • Sneezing
    • Itchy, watery eyes
    • Itching of the nose or throat
  • Temporarily relieves these symptoms due to the common cold:
    • Runny nose
    • Sneezing
diphenhydramine

Diphenhydramine dosage

Applies to the following strengths diphenhydramine: 50 mg/mL; 12.5 mg; 25 mg; 12.5 mg/5 mL; 50 mg; 10 mg/mL; 19 mg; 6.25 mg/5 mL; 25 mg/5 mL; 50 mg/30 mL; 6.25 mg/mL

Usual Adult Dose for Insomnia

  • Diphenhydramine Citrate: 76 mg orally once a day at bedtime
  • Diphenhydramine Hydrochloride (diphenhydramine HCL): 50 mg orally once a day at bedtime

Comment:

Patients should contact their healthcare provider if symptoms of insomnia persist for more than 2 weeks while receiving treatment.

Uses:

  • As a nighttime sleep aid
  • To reduce difficulty falling asleep
  • Relief of occasional sleeplessness

Usual Adult Dose for Motion Sickness

Oral:

  • Prescription formulations: 25 to 50 mg orally 3 to 4 times a day, with the first dose given 30 minutes before exposure to motion and repeated before meals and upon retiring throughout the duration of the journey.
  • Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
    • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Use:

Active and prophylactic treatment of motion sickness

Usual Adult Dose for Allergic Rhinitis

Oral:

  • Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
    • Maximum dose: 456 mg/day
  • Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
    • Maximum dose: 300 mg/day
  • Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
    • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Allergic conjunctivitis due to foods
  • Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
  • Amelioration of allergic reactions to blood or plasma
  • Dermatographism
  • Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Cold Symptoms

Oral:

  • Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
    • Maximum dose: 456 mg/day
  • Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
    • Maximum dose: 300 mg/day
  • Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
    • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Allergic conjunctivitis due to foods
  • Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
  • Amelioration of allergic reactions to blood or plasma
  • Dermatographism
  • Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Pruritus

Oral:

  • Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
    • Maximum dose: 456 mg/day
  • Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
    • Maximum dose: 300 mg/day
  • Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
    • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Allergic conjunctivitis due to foods
  • Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
  • Amelioration of allergic reactions to blood or plasma
  • Dermatographism
  • Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Urticaria

Oral:

  • Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
    • Maximum dose: 456 mg/day
  • Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
    • Maximum dose: 300 mg/day
  • Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
    • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Allergic conjunctivitis due to foods
  • Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
  • Amelioration of allergic reactions to blood or plasma
  • Dermatographism
  • Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Extrapyramidal Reaction

  • Oral: 25 to 50 mg orally 3 to 4 times a day
  • Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
    • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Parkinsonism of the elderly who are unable to tolerate more potent agents
  • Mild cases of parkinsonism in other age groups
  • Other cases of parkinsonism in combination with centrally acting anticholinergic agents

Usual Pediatric Dose for Allergic Rhinitis

Prescription formulations:

1 month and older:

Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used

-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Oral Over-the-Counter (OTC) formulations:

Diphenhydramine Citrate:

6 to 12 years: 19 to 38 mg orally every 4 to 6 hours as needed

  • Maximum dose: 228 mg/day

12 years and older: 38 to 76 mg orally every 4 to 6 hours as needed

  • Maximum dose: 456 mg/day

Diphenhydramine Hydrochloride (diphenhydramine HCL):

2 to 6 years: 6.25 mg orally every 4 to 6 hours as needed

  • Maximum dose: 37.5 mg/day

6 to 12 years: 12.5 to 25 mg orally every 4 to 6 hours as needed

  • Maximum dose: 150 mg/day

12 years and older: 25 to 50 mg orally every 4 to 6 hours as needed

  • Maximum dose: 300 mg/day

Comments:

  • IV injection rates should not exceed 25 mg/min.
  • To prevent motion sickness, the first dose should be given 30 minutes before exposure to motion and should be repeated before meals and upon retiring throughout the duration of the journey.

Uses:

  • Active and prophylactic treatment of motion sickness
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Pediatric Dose for Cold Symptoms

Prescription formulations:

1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Oral Over-the-Counter (OTC) formulations:

Diphenhydramine Citrate:

6 to 12 years: 19 to 38 mg orally every 4 to 6 hours as needed
-Maximum dose: 228 mg/day

12 years and older: 38 to 76 mg orally every 4 to 6 hours as needed
-Maximum dose: 456 mg/day

Diphenhydramine Hydrochloride (diphenhydramine HCL):

2 to 6 years: 6.25 mg orally every 4 to 6 hours as needed

  • Maximum dose: 37.5 mg/day

6 to 12 years: 12.5 to 25 mg orally every 4 to 6 hours as needed

  • Maximum dose: 150 mg/day

12 years and older: 25 to 50 mg orally every 4 to 6 hours as needed

  • Maximum dose: 300 mg/day

Comments:

  • IV injection rates should not exceed 25 mg/min.
  • To prevent motion sickness, the first dose should be given 30 minutes before exposure to motion and should be repeated before meals and upon retiring
  • Throughout the duration of the journey.

Uses:

  • Active and prophylactic treatment of motion sickness
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Pediatric Dose for Motion Sickness

Prescription formulations:
1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Oral Over-the-Counter (OTC) formulations:

Diphenhydramine Citrate:
6 to 12 years: 19 to 38 mg orally every 4 to 6 hours as needed
-Maximum dose: 228 mg/day

12 years and older: 38 to 76 mg orally every 4 to 6 hours as needed
-Maximum dose: 456 mg/day

Diphenhydramine Hydrochloride (diphenhydramine HCL):

2 to 6 years: 6.25 mg orally every 4 to 6 hours as needed

  • Maximum dose: 37.5 mg/day

6 to 12 years: 12.5 to 25 mg orally every 4 to 6 hours as needed

  • Maximum dose: 150 mg/day

12 years and older: 25 to 50 mg orally every 4 to 6 hours as needed

  • Maximum dose: 300 mg/day

Comments:

  • IV injection rates should not exceed 25 mg/min.
  • To prevent motion sickness, the first dose should be given 30 minutes before exposure to motion and should be repeated before meals and upon retiring
  • hroughout the duration of the journey.

Uses:

  • Active and prophylactic treatment of motion sickness
  • Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
  • Temporarily relieves runny nose and sneezing due to the common cold

Usual Pediatric Dose for Insomnia

12 years and older:

  • Diphenhydramine citrate: 76 mg orally once a day at bedtime
  • Diphenhydramine hydrochloride (diphenhydramine HCL): 50 mg orally once a day at bedtime

Comment:

Patients should contact their healthcare provider if symptoms of insomnia persist for more than 2 weeks while receiving treatment.

Uses:

  • As a nighttime sleep aid
  • To reduce difficulty falling asleep
  • Relief of occasional sleeplessness

Usual Pediatric Dose for Extrapyramidal Reaction

Prescription formulations

1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Mild cases of parkinsonism
  • Other cases of parkinsonism, including drug-induced, in combination with centrally acting anticholinergic agents

Usual Pediatric Dose for Allergic Reaction

Prescription formulations

1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

  • Allergic conjunctivitis due to foods
  • Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
  • Amelioration of allergic reactions to blood or plasma
  • Dermatographism
  • Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dialysis

Data not available

How should diphenhydramine be used?

Diphenhydramine comes as a tablet, a rapidly disintegrating (dissolving) tablet, a capsule, a liquid-filled capsule, a dissolving strip, powder, and a liquid to take by mouth. When diphenhydramine is used for the relief of allergies, cold, and cough symptoms, it is usually taken every 4 to 6 hours. When diphenhydramine is used to treat motion sickness, it is usually taken 30 minutes before departure and, if needed, before meals and at bedtime. When diphenhydramine is used to treat insomnia it is taken at bedtime (30 minutes before planned sleep). When diphenhydramine is used to treat abnormal movements, it is usually taken three times a day at first and then taken 4 times a day. Follow the directions on the package or on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take diphenhydramine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor or directed on the label.

Diphenhydramine comes alone and in combination with pain relievers, fever reducers, and decongestants. Ask your doctor or pharmacist for advice on which product is best for your symptoms. Check nonprescription cough and cold product labels carefully before using two or more products at the same time. These products may contain the same active ingredient(s) and taking them together could cause you to receive an overdose. This is especially important if you will be giving cough and cold medications to a child.

Nonprescription cough and cold combination products, including products that contain diphenhydramine, can cause serious side effects or death in young children. Do not give these products to children younger than 4 years of age. If you give these products to children 4 to 11 years of age, use caution and follow the package directions carefully.

If you are giving diphenhydramine or a combination product that contains diphenhydramine to a child, read the package label carefully to be sure that it is the right product for a child of that age. Do not give diphenhydramine products that are made for adults to children.

Before you give a diphenhydramine product to a child, check the package label to find out how much medication the child should receive. Give the dose that matches the child’s age on the chart. Ask the child’s doctor if you don’t know how much medication to give the child.

If you are taking the liquid, do not use a household spoon to measure your dose. Use the measuring spoon or cup that came with the medication or use a spoon made especially for measuring medication.

If you are taking the dissolving strips, place the strips on your tongue one at a time and swallow after they melt.

If you are taking the rapidly dissolving tablets, place a tablet on your tongue and close your mouth. The tablet will quickly dissolve and can be swallowed with or without water.

If you are taking the capsules, swallow them whole. Do not try to break the capsules.

What should I do if I forget a dose?

Diphenhydramine is usually taken as needed. If your doctor has told you to take diphenhydramine regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Diphenhydramine side effects

The most commonly reported side effects included somnolence, dizziness, and incoordination.

Diphenhydramine may cause side effects. Numerous side effects including drowsiness, confusion, restlessness, nausea, vomiting, diarrhea, blurring of vision, diplopia, difficulty in urination, constipation, nasal stuffiness, vertigo, palpitation, headache, and insomnia 2. Other side effects observed were urticaria, drug rash, photosensitivity, hemolytic anemia, hypotension, epigastric distress, anaphylactic shock, tightness of the chest and wheezing, thickening of bronchial secretions, dryness of the mouth, nose and throat and tingling, and heaviness and weakness of the hands 2.

Prolonged use of antihistamines … may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort 8.

Tell your doctor if any of these symptoms are severe or do not go away:

  • dry mouth, nose, and throat
  • drowsiness
  • dizziness
  • nausea
  • vomiting
  • loss of appetite
  • constipation
  • increased chest congestion
  • headache
  • muscle weakness
  • excitement (especially in children)
  • nervousness

Some side effects may be serious. If you experience any of the following symptoms, call your doctor immediately:

  • vision problems
  • difficulty urinating or painful urination

Diphenhydramine may cause other side effects. Call your doctor if you experience any unusual problems while you are taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch/default.htm)

Common side effects

The most common side effect of diphenhydramine is feeling sleepy and tired. This happens in more than 1 in 10 people. Talk to your doctor or pharmacist if this side effect bothers you or won’t go away.

Other common side effects of diphenhydramine happen in more than 1 in 100 people. Talk to your doctor or pharmacist if these side effects bother you or won’t go away:

  • dry mouth
  • feeling dizzy

Common side effects of diphenhydramine mixed with pseudoephedrine happen in more than 1 in 100 people. They include:

  • difficulty sleeping
  • hallucinations
  • rashes
  • difficulty peeing in men – especially men with an enlarged prostate

Nervous system

  • Common (1% to 10%): Sedation/somnolence/sleepiness, drowsiness, unsteadiness, dizziness, headache, attention disturbance
  • Rare (0.01% to 0.1%): Extrapyramidal effects, tremor, convulsions
  • Frequency not reported: Paresthesia, dyskinesia/muscle dyskinesia, vertigo, neuritis, incoordination, psychomotor impairment, activation of epileptogenic foci.

Drowsiness usually diminishes after a few days.

Gastrointestinal

  • Common (1% to 10%): Dry mouth
  • Frequency not reported: Gastrointestinal disturbance, nausea, vomiting, constipation, diarrhea, dyspepsia, epigastric distress

Other

  • Common (1% to 10%): Fatigue
  • Frequency not reported: Lassitude, tinnitus, acute labyrinthitis, asthenia, chills, impaired performance (including impaired driving, work, and/or information processing)

Psychiatric

  • Rare (0.01% to 0.1%): Confusion, depression, sleep disturbances
  • Frequency not reported: Paradoxical excitation/excitation, agitation, increased energy, restlessness, nervousness, euphoria, anxiety, hallucinations, insomnia, irritability

Cardiovascular

  • Rare (0.01% to 0.1%): Palpitations, hypotension, arrhythmia
  • Frequency not reported: Tachycardia, chest tightness, extrasystoles

Hematologic

  • Rare (0.01% to 0.1%): Blood disorders
  • Frequency not reported: Hemolytic anemia, thrombocytopenia, agranulocytosis

Hypersensitivity

  • Rare (0.01% to 0.1%): Hypersensitivity reactions
  • Frequency not reported: Angioedema, anaphylactic shock

Hepatic

  • Rare (0.01% to 0.1%): Liver dysfunction

Dermatologic

  • Frequency not reported: Rash, urticaria, skin rashes, erythema, photosensitivity, pruritus, drug rash, excessive perspiration

Respiratory

  • Frequency not reported: Dyspnea, thickening of bronchial secretions, throat tightening, wheezing, nasal stuffiness, dry nose or throat

Genitourinary

  • Frequency not reported: Urinary hesitancy/difficulty/retention, dysuria, early menses

Ocular

  • Frequency not reported: Blurred vision, dry eyes, diplopia

Metabolic

  • Frequency not reported: Increased appetite, anorexia

Musculoskeletal

  • Frequency not reported: Muscle twitching/weakness

Serious side effects

In rare cases, it’s possible to have a serious allergic reaction to diphenhydramine.

The warning signs of serious allergic reaction are:

  • getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
  • wheezing
  • tightness in the chest or throat
  • having trouble breathing or talking
  • swelling of the mouth, face, lips, tongue, or throat

These are not all the side effects of diphenhydramine. For a full list see the leaflet inside your medicines packet.

How to cope with side effects

What to do about:

  • feeling sleepy – try a different non-drowsy antihistamine. If this doesn’t help, talk to your doctor.
  • dry mouth chew sugar-free gum or suck sugar-free sweets.
  • feeling dizzy – lie down until the dizziness passes, then get up slowly. Move slowly and carefully. Avoid coffee, cigarettes, alcohol and recreational drugs. If the dizziness doesn’t get better within a couple of days, speak to your pharmacist or doctor.

Diphenhydramine overdose

Diphenhydramine overdose occurs when someone takes more than the normal or recommended amount of this medicine. This can be by accident or on purpose.

In case of diphenhydramine overdose, get medical help or contact a Poison Control Center helpline at 1-800-222-1222 right away!

Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your local emergency services number.

Excessive diphenhydramine doses may cause flushing, tachycardia, blurred vision, delirium, toxic psychosis, urinary retention, and respiratory depression 9.

Overdosage of diphenhydramine may result in the development of anticholinergic symptoms, seizures, and coma 10. A fatal outcome following a diphenhydramine overdose does not commonly occur. This report describes an overdosage of diphenhydramine (7.5 g) which resulted in the death of a 14-year-old girl 10. The patient initially developed seizures following by cardiac conduction and hemodynamic compromise resulting in death despite life support measures.

Symptoms of diphenhydramine overdose

Below are symptoms of a diphenhydramine overdose in different parts of the body 11.

Bladder and Kidneys

  • Inability to urinate

Eyes, ears, nose, mouth and throat

  • Blurred vision
  • Dry mouth
  • Enlarged pupils
  • Very dry eyes
  • Ringing in the ears

Heart and blood vessels

  • Low blood pressure
  • Rapid heartbeat

Nervous system

  • Agitation
  • Confusion
  • Seizures
  • Delirium
  • Depression
  • Drowsiness
  • Hallucinations (seeing or hearing things that aren’t there)
  • Increased sleepiness
  • Nervousness
  • Tremor
  • Unsteadiness

Skin

  • Dry, red skin

Stomach and intestines

  • Nausea
  • Vomiting

What to Expect at the Emergency Room

Take the container to the hospital with you, if possible.

The health care provider will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure.

Tests that may done include 12:

  • Blood and urine tests
  • Chest x-ray
  • ECG (electrocardiogram or heart tracing)

Treatment may include 12:

  • Fluids through a vein (by IV)
  • Medicines to treat symptoms
  • Activated charcoal
  • Laxative
  • Breathing support, including a tube through the mouth into the lungs and connected to a breathing machine (ventilator)

Outlook (Prognosis)

Recovery is likely if the person survives the first 24 hours. Complications such as pneumonia, muscle damage from lying on a hard surface for a long period of time, or brain damage from lack of oxygen may result in permanent disability.

Few people actually die from an antihistamine overdose. However, serious heart rhythm disturbances may occur, which can cause death.

Keep all medicines in child-proof bottles and out of reach of children.

Case reports

A 13-month-old male who ingested 20 diphenhydramine (25 mg) tablets presented with seizures and ultimately progressed to status epilepticus and wide-complex tachycardia 13. Due to worsening clinical course, hemodialysis was performed with temporal resolution of his symptoms. Hemodialysis may be considered in critically ill diphenhydramine overdoses not responsive to conventional supportive care.

Case report

Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive 14. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine (octanol/water partition coefficient of 3.3), successful use of intravenous fat emulsion after a confirmed sole ingestion of diphenhydramine is not previously reported. This case study 14 present the case of a 30-year-old woman presenting with seizures, a wide complex tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine refractory to other therapies with rapid improvement after intravenous fat emulsion administration.

Case report

Overdosage of diphenhydramine may result in the development of anticholinergic symptoms, seizures, and coma 15. A fatal outcome following a diphenhydramine overdose does not commonly occur. This report describes /an/ overdosage of diphenhydramine (7.5 g) which resulted in the death of a 14-year-old girl. The patient initially developed seizures following by cardiac conduction and hemodynamic compromise resulting in death despite life support measures 15.

Case report

Overdosage and toxicity (including death) have been reported in children younger than 2 years of age receiving nonprescription (over-the-counter, OTC) preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection 1. There is limited evidence of efficacy for these preparations in this age group, and appropriate dosages (i.e., approved by the US Food and Drug Administration [FDA]) for the symptomatic treatment of cold and cough have not been established 1. Therefore, FDA stated that nonprescription cough and cold preparations should not be used in children younger than 2 years of age; the agency continues to assess safety and efficacy of these preparations in older children. Meanwhile, because children 2-3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations recently have agreed to voluntarily revise the product labeling to state that such preparations should not be used in children younger than 4 years of age. Because FDA does not typically request removal of products with previous labeling from pharmacy shelves during a voluntary label change, some preparations will have the new recommendation (“do not use in children younger than 4 years of age”), while others will have the previous recommendation (“do not use in children younger than 2 years of age”). FDA recommends that parents and caregivers adhere to the dosage instructions and warnings on the product labeling that accompanies the preparation if administering to children and consult with their clinician about any concerns.

Case report

Two cases of diphenhydramine-containing hypnotics overdose, exhibiting delirium and involuntary choreic movement were identified 16. In case 1, a 32-year-old man ingested 24 tablets of Drewell, each containing 25 mg diphenhydramine, in a suicidal attempt. About four hours after ingestion, he showed generalized convulsion, delirium, and involuntary choreic movements 16. Intravenous diazepam was ineffective and he was sedated with continuous infusion of propofol. About 15 hours after ingestion and on discontinuing the sedation, he became alert and did not show any neurological abnormality. The blood concentration of diphenhydramine, measured by liquid chromatography/electrospray mass spectrometry, was 1.26 ug/ mL. In case 2, a 24-year-old woman ingested 114 tablets of Drewell and was admitted to a hospital 16. Her consciousness was impaired and she was treated with intravenous fluids. About four hours after ingestion, she became restless and showed confusion, agitation, and involuntary choreic movements 16. Sedation with continuous propofol infusion was required. She awoke the next day on discontinuing the sedation, and she did not show any neurological abnormalities. The blood concentration of diphenhydramine was 2.37 ug/mL. It is suggested that physicians should be aware of psychotic-like symptoms and choreic involuntary movement in patients with diphenhydramine-containing hypnotics overdose 16.

Case report

A 13-month-old infant girl was brought in by the emergency medical service for a witnessed tonic-clonic seizure 17. Two hours previously, the child had been found with an open bottle of 25-mg diphenhydramine tablets, 24 of which were missing. Midazolam was administered with seizure resolution 17. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry, flushed skin; and altered mental status. Initial electrocardiograms revealed sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130 milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave in aVR, which later resolved after sodium bicarbonate treatment. The patient was discharged home the following day with no sequelae 17.

Case report

A 36-year-old woman with a medical history of hypothyroidism on levothyroxine was brought to the emergency department with active seizures by emergency medical services after what was later determined to be a diphenhydramine overdose 18. One hour after an argument with her husband he found her lethargic in a locked room. Initial vital signs were: blood pressure, 90/55 mmHg; heart rate, 160 beats/min; respiratory rate 18 breaths/min; room air oxygen saturation, 99%; temperature, 99.8 deg F; rapid point-of-care glucose, 130 mg/dL. The generalized seizures continued for duration of 30 min, despite the intravenous administration of 8 mg of lorazepam. The patient underwent endotracheal intubation and a propofol infusion terminated her seizures. An electrocardiogram after the status was terminated which revealed a wide-complex tachycardia with QRS duration of 127 ms. The QRS narrowed after 200 mEq of intravenous sodium bicarbonate was administrated. The patient was neurologically intact upon extubation on hospital day 2. The serum diphenhydramine concentration drawn on arrival to the ED was 1200 ng/mL (9-120 ng/mL); a tricyclic screen was negative. While seizures and sodium channel blockade are recognized complications of diphenhydramine toxicity, reported cases of status epilepticus from diphenhydramine overdose are rare. Elements of the patient’s presentation were similar to a tricyclic overdose and management required aggressive control of her seizures, sodium bicarbonate therapy, and recognizing that physostigmine was contraindicated due to wide complex tachycardia. Diphenhydramine overdose may cause status epilepticus and wide-complex tachycardia. Management should focus on antidotal therapy with sodium bicarbonate and supportive neurological management with appropriate anticonvulsants and airway protection if clinically indicated 18.

Case report

Drug- and toxin-induced rhabdomyolysis is a nonspecific clinical syndrome resulting from the release of skeletal muscle cell contents into the plasma and urine. Antihistamine drugs are the active ingredients in a number of over-the-counter preparations and are frequently ingested in suicide attempts. The authors report rhabdomyolysis as a rare adverse effect of diphenhydramine toxicity in a 29-year-old man who ingested an unknown quantity of an over-the-counter sleep preparation in a suicide attempt 19. The patient had documented toxic concentration of diphenhydramine in his cerebrospinal fluid and no history of seizures, coma, or hypothermia. A high index of suspicion and an evaluation for rhabdomyolysis is warranted in antihistamine toxicity.

Case report

A case of electrocardiographic signature of the Brugada syndrome: a genetic condition that causes disruption of the heart’s normal rhythm in a 39-year-old patient with an overdose of diphenhydramine is reported 20. He was found unconscious and hypotensive. His serum potassium concentration was 8.3 mEq/L and the ECG revealed a coved-type ST-segment elevation in leads V2-V3. These repolarization abnormalities neither normalize with the correction of the hyperkalemia nor with an intravenous infusion of isoproterenol. When he regained consciousness, he was admitted the toxic ingestion of diphenhydramine and progressively the ECG normalized. A negative flecainide test confirmed that the transient ECG abnormalities were the consequence of the drug overdose and ruled out the Brugada syndrome 20.

Case report

Diphenhydramine it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death 21. Reports of fatal intoxications in young children are rare. The authors present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old 21. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child’s father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle 21. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities 21.

Case report

Diphenhydramine toxicity (e.g., dilated pupils, facial flushing, hallucinations, ataxic gait, urinary retention) has been reported in pediatric patients (19 months to 9 years of age) following topical application of diphenhydramine to large areas of the body (often areas with broken skin) or following concomitant use of topical and oral preparations containing the drug for self-medication in the symptomatic management of pain and pruritus associated with varicella (chickenpox), poison ivy, or sunburn 1. Manifestations typically resolved within 48 hours following discontinuance of the drug, and no deaths have been reported following topical use of diphenhydramine alone.

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