Diphenhydramine (Benadryl) is a first-generation antihistamine. It is primarily used to treat symptoms of allergies such as itching, sneezing, urticaria, and redness.

Diphenhydramine Uses:

• To reduce allergic reactions caused by histamine release, such as allergic dermatoses and nasal allergies
• Treatment of anaphylaxis as an adjunct to epinephrine;
• Insomnia
• Prevention or treatment of motion sickness.
• As an antitussive
• It is also used, either alone or in combination with centrally acting anticholinergic medications, to treat Parkinsonian syndrome and drug-induced extrapyramidal symptoms, such as dystonic responses.

• Guideline recommendations:

  • Anaphylaxis:
    • Antihistamines are only used as an additional, second-line therapy for anaphylaxis following epinephrine injection.
  • Insomnia:
    • The American Academy of Sleep Medicine does not recommend its use for insomnia.
    • According to recommendations, diphenhydramine should not be used to induce or maintain sleep in people who have chronic insomnia.
    • There is no strong evidence for clinically significant improvement.

Diphenhydramine (Benadryl) Dose in Adults

Diphenhydramine (Benadryl) Dose in the treatment of Allergic reactions:

• Oral: maximum of 25–50 mg per 4–8 hours: 300 mg per day IM
• IV: 10–50 mg per dosage
• a single dose of up to 100 mg may be administered if necessary
• not more than 400 mg each day

Diphenhydramine (Benadryl) Dose in the treatment of severe anaphylaxis as an adjunct to epinephrine; second-line agent) (off-label dose):

• IV: over 10 to 15 minutes, 25 to 50 mg.

Diphenhydramine (Benadryl) Dose in the treatment of Antitussive:

• Oral: 150 mg per day at a maximum of 25 mg every 4 hours.

Diphenhydramine (Benadryl) Dose in the treatment of Occasional Insomnia:

• Oral: 50 mg before bed; note: Adults should not take this medication to cure insomnia.

Diphenhydramine (Benadryl) Dose in the treatment of Motion sickness:

Note: Give the medication prophylactically 30 minutes before the move.

• Oral (treatment or prophylaxis): 25 to 50 mg each six to eight hours
• 10 to 50 mg/dose (treatment) for IM and IV
• maximum: 400 mg/day

Diphenhydramine (Benadryl) Dose in the treatment of Parkinsonism:

• Oral: 25 - 50 mg 3 or 4 times daily
• IM, IV: 10 - 50 mg/dose;
• maximum: 400 mg/day

Diphenhydramine (Benadryl) Dose in the treatment of Rhinitis and sneezing due to common cold:

• Oral: 25 - 50 mg every 4 to 6 hours;
• maximum: 300 mg/day

Diphenhydramine (Benadryl) Dose in Children

Note:

• There are different concentration of oral solutions: for example 12.5 mg/5 mL and 50 mg/30 mL.
• This may create confusion between the different concentrations, precaution advised avoiding such mistakes in dose calculation and administration.
• The dosage must be stated explicitly as "mg"; the 50 mg/30 mL oral solution is occasionally used to treat insomnia.

Diphenhydramine (Benadryl) Dose in the treatment of Allergies and Hay Fever:

• Infants, Children, and Adolescents: Oral:

  • Weight-directed dosing:
    • 5 mg/kg/day in 3-4 divided doses;
    • maximum daily dose: 300 mg per day;
  • Age-related maximum daily doses may also be considered:
    • <6 years: 37.5 mg per day
    • 6-11 years: 150 mg per day
    • ≥12 years: 300 mg per day

• Fixed dosing:

  • Children 2 to <6 years: Limited data available:
    • 6.25 mg every 4-6 hours;
    • maximum dose: 37.5 mg per day
  • Children 6 to <12 years:
    • 5-25 mg every 4-6 hours;
    • maximum dose: 150 mg per day
  • Children ≥12 years and Adolescents:
    • 25-50 mg every 4-6 hours;
    • maximum dose: 300 mg per day

Diphenhydramine (Benadryl) Dose in the treatment of severe allergic reaction/ anaphylaxis (as an adjunct to epinephrine):

• Infants, Children, and Adolescents:

  • Manufacturer's labeling: IV, IM, Oral:
    • 1.25 mg/kg/dose given every 6 hours;
    • The maximum dose is 300 mg per day
  • Alternate dosing: IV, IM, Oral:
    • 1-2 mg/kg/dose;
    • The maximum single dose is 50 mg/dose

Diphenhydramine (Benadryl) Dose in the treatment of Rhinitis and sneezing due to common cold: Oral:

• Children 6 to <12 years:

  • 25 mg every 4-6 hours;
  • The maximum dose is 150 mg per day.

• Children ≥12 years and Adolescents:

  • 25-50 mg every 4-6 hours;
  • The maximum dose is 300 mg per day.

Diphenhydramine (Benadryl) Dose in the treatment of Dystonic reactions:

• Infants, Children, and Adolescents:

  • IV, IM: 1-2 mg/kg/dose;
  • The maximum single dose is 50 mg

Diphenhydramine (Benadryl) Dose in the treatment of Motion sickness:

• Infants, Children, and Adolescents:

  • Prophylaxis: Oral:

    • Manufacturer's labeling:
      • 30 minutes before travel, administer the first dose
    • Weight-directed dosing:
      • 5 mg/kg/day in 3-4 divided doses;
      • The maximum dose is 300 mg per day
    • Fixed dosing:
      • 5-25 mg 3-4 times daily
    • Alternate dosing: Children 2-12 years: Limited data available:
      • 0.5-1 mg/kg/dose every 6 hours;
      • The maximum single dose is 25 mg.
      • Administered the first dose 1 hour before travel.

  • Treatment:

    • IV, IM:
      • 1.25 mg/kg/dose every 6 hours;
      • maximum dose: 300 mg per day
    • Oral:
      • Weight-directed dosing:
        • 5 mg/kg/day divided into 3-4 doses;
        • maximum dose: 300 mg per day
      • Fixed dosing:
        • 5-25 mg 3-4 times a day

Diphenhydramine (Benadryl) Dose in the treatment of occasional insomnia: Oral:

• Children 2-12 years, weighing 10-50 kg: Limited data available:

  • 1 mg/kg 30 minutes before bedtime;
  • The maximum single dose is 50 mg

• Children ≥12 years and Adolescents:

  • 50 mg 30 minutes before bedtime

Diphenhydramine (Benadryl) Dose in the treatment of Pruritus (opioid-induced): Limited data available:

• Infants, Children, and Adolescents:

  • IM, IV, Oral:
    • 0.5-1 mg/kg/dose every 6 hours;
    • The maximum dose: 100 mg per day

Diphenhydramine (Benadryl) Dose in the treatment of Urticaria:

• Infants, Children, and Adolescents: Oral:

  • Weight-directed dosing:
    • 5 mg/kg/day in 3-4 divided doses;
    • The maximum dose: 300 mg per day
  • Fixed dosing:
    • 5-25 mg 3-4 times a day

Pregnancy Risk Factor B

• If given right before parturition, diphenhydramine can cross the placenta. This could cause respiratory depression in newborns.
• Diphenhydramine can be used to treat allergic conditions when an antihistamine of first-generation is prescribed for a pregnant woman
• Diphenhydramine may also be used in conjunction with preferred agents if there is no relief from nausea or vomiting.
• Antihistamines should not be used if pruritus is caused by intrahepatic cholesterol during pregnancy

Use of diphenhydramine during breastfeeding

• Breast milk contains diphenhydramine. It is not recommended for breastfeeding.
• The possibility of drowsiness may be caused by infant exposure.
• The first-generation antihistamine administered via breast milk can cause irritability or drowsiness.
• This should be checked for. When necessary, 2nd-generation antihistamines should be used in lactating mothers
• Infants who are not yet born are more likely to be sensitive to anti-histamines
• If given prior to the establishment of lactation, it may reduce the production of maternal Prolactin.

Dose in Kidney Disease:

No dose adjustments listed in the manufacturer’s labeling.

Dose in Liver disease:

No dose adjustments listed in the manufacturer’s labeling.

Side effects of Diphenhydramine (Benadryl):

• Cardiovascular:

  • Chest Tightness
  • Extrasystoles
  • Hypotension
  • Palpitations
  • Tachycardia

• Central Nervous System:

  • Ataxia
  • Chills
  • Confusion
  • Dizziness
  • Drowsiness
  • Euphoria
  • Excitement
  • Fatigue
  • Headache
  • Irritability
  • Nervousness
  • Neuritis
  • Paradoxical Excitation
  • Paresthesia
  • Restlessness
  • Sedation
  • Seizure
  • Vertigo

• Dermatologic:

  • Diaphoresis
  • Skin Photosensitivity
  • Skin Rash
  • Urticaria

• Gastrointestinal:

  • Anorexia
  • Constipation
  • Diarrhea
  • Dry Mucous Membranes
  • Epigastric Distress
  • Nausea
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Difficulty In Micturition
  • Urinary Frequency
  • Urinary Retention

• Hematologic & Oncologic:

  • Agranulocytosis
  • Hemolytic Anemia
  • Thrombocytopenia

• Hypersensitivity:

  • Anaphylactic Shock

• Neuromuscular & Skeletal:

  • Tremor

• Ophthalmic:

  • Blurred Vision
  • Diplopia

• Respiratory:

  • Nasal Congestion
  • Pharyngeal Edema
  • Thickening Of Bronchial Secretions
  • Wheezing

Contraindications to Diphenhydramine (Benadryl):

• Hypersensitivity to any component diphenhydramine
• Premature infants or neonates
• Breastfeeding
• Local anesthesia using parenteral injections

Labeling of over-the-counter (OTC), products:

• If used as self-medication, it is not recommended for children under 6 years of age.
• Other diphenhydramine-containing products including topical products should also be given with caution below 6 years as self-medication

Warnings and precautions

• CNS depression:

  • CNS depression may be caused by diphenhydramine, which can impair mental or physical abilities. 
  • Driving or performing other tasks that call on mental clarity can be risky. Patients should be aware of these effects.

• Asthma

  • Asthmatic patients should be cautious

• Cardiovascular disease

  • Patients with cardiovascular diseases such as hypertension or ischemic heart disease (IHD), should be cautious.

• Glaucoma/increased intraocular pressure

  • Patients with angle-closure or other conditions that increase intraocular pressure should be cautious

• Prostatic hyperplasia/urinary block:

  • Patients with genitourinary and prostatic obstruction (BPH), bladder neck obstruction, or genitourinary hyperplasia (GPH) should be cautious

• Occlusion of the pyloroduodenum:

  • Caution is advised for stenotic peptic and pyloroduodenal blockages

• Thyroid dysfunction:

  • Thyroid dysfunction: Be cautious

Diphenhydramine (systemic): Drug Interaction

Monitoring parameters:

• Relief of symptoms
• mental alertness

How to administer Diphenhydramine (Benadryl)?

Oral:

• Give 30 minutes before exposure as prophylaxis for motion sickness.
• Given 30 minutes before bedtime for occasional insomnia

IM, IV: IV or deep IM administration only. Not for the subcutaneous or intradermal route

• IV: Inject at a rate of 25 mg or less per minute. There may be Local necrosis with subcutaneous or intradermal use.

Mechanism of action of Diphenhydramine (Benadryl):

• There are many sites where H1 receptors can be found, including the gastrointestinal smooth muscle, blood vessels, respiratory tract, and respiratory system. 
• Diphenhydramine counteracts the effects of histamine by competing with it for H1-receptor sites in the effector cells of these organs.
• You can also see anticholinergic, sedative and other effects.

Duration:

• Histamine-induced wheal suppression: ≤10 hours
• Histamine-induced flare suppression: ≤12 hours

Protein binding:

• 98.5%

Metabolism:

• Mainly hepatic n-demethylation via CYP2D6; minor demethylation via CYP1A2, 2C9, and 2C19
• smaller degrees in pulmonary and renal systems
• There is a significant first-pass effect

Bioavailability:

• 42% to 62%

Half-life elimination:

• Children: 5 hours (range: 4 to 7 hours)
• Adults: 9 hours (range: 7 to 12 hours)
• Elderly: 13.5 hours (range: 9 to 18 hours)

Time to peak, serum:

• About 2 hours

Excretion:

• Through Urine as metabolites and unchanged drug.

International Brand Names of Diphenhydramine:

• Aler-Dryl
• Allergy Relief Childrens
• Allergy Relief
• Altaryl
• Anti-Hist Allergy
• Banophen
• Benadryl Allergy Childrens
• Benadryl Allergy
• Benadryl Dye-Free Allergy
• Complete Allergy Medication
• Complete Allergy Relief
• Diphen
• Diphenhist
• Genahist
• Geri-Dryl
• GoodSense Allergy Relief
• GoodSense Sleep Aid
• Naramin
• Nighttime Sleep Aid
• Nytol Maximum Strength
• Nytol
• Ormir
• PediaCare Childrens Allergy
• Pharbedryl
• Q-Dryl
• QlearQuil Nighttime Allergy
• Quenalin
• ScotTussin Allergy Relief
• Siladryl Allergy
• Silphen Cough
• Simply Sleep
• Sleep Tabs
• Sominex Maximum Strength
• Sominex
• TetraFormula Nighttime Sleep
• Total Allergy Medicine
• Total Allergy
• Triaminic Cough/Runny Nose
• ZzzQuil
• Diphenist
• PMS-DiphenhydrAMINE
• Aliserin
• Allermin
• Amydramine
• Amydramine-II
• Amydramkine-II
• Azaron
• Beanamine
• Belarmin
• Belarmin Expectorant
• Bena
• Benadrex
• Benadryl
• Benadryl A
• Benadryl Allergy
• Benadryl for the Family Original
• Benamine
• Bendol
• Benocten
• Benylan
• Bexil
• Butix
• Calm U
• Calmaben
• Cerylana
• Daedalon
• Danzamin
• Desentol
• DiBendryl
• Dibrondrin
• Didra
• Didryl
• Difenidrin
• Dormital
• Dormutil
• Dramylin
• Exylin
• Fenilar
• Histergan
• Hydramine
• Hydrazol
• Hyphen
• Menna
• Nardyl
• Otede
• Pediphen
• Phenadryl
• Phenycof
• Psilo Balsam
• R Calm
• Rabaphen
• Recodryl
• Resmin
• Rivedramine
• Rosmylin Expectorant
• Sleepeze-PM
• Snuzaid
• Somol
• Soniphen
• Sonodor
• Stopkof P
• Sultan
• Unisom Sleepgels
• Valdres
• Vena
• Venapas Oint
• Venasmin
• Vertirosan
• Vivinox

Diphenhydramine Brand Names in Pakistan: