Diphenhydramine

Brand names  Reversal agents Warnings 
Description  Special circumstances Alternative medications 
Dosing  Side effects and risks Contraindications 
Overdose  Common issues   


Brand Names

 Benadryl Injection

Description

Diphenhydramine hydrochloride is an anti-histamine H1-receptor drug with anticholinergic and sedative properties.  It is usally given as a premedication prior to endoscopic procedures to achieve a synergistic effect with the combination of a narcotic and benzodiazepine which allows for lower doses of these drugs.

Dosing

 Diphenhydramine Dosing for Endoscopic Sedation

Adult  

  • One time dose:  25-50 mg up to100mg if required
  • Onset of action:  2-3 minutes
  • Peak effect:  60-90 minutes
  • Duration of effect:  More than 240 minutes 

Pediatric (children other than premature infants and neonates)

  • One time dose: 1.25 mg/kg

Note: 

  • Administer intravenously at a rate generally not exceeding 25 mg/minute, or deep intramuscularly.

Overdose

  • Antihistamine overdosage reactions may vary from central nervous system depression to stimulation. Stimulation is particularly likely in pediatric patients. Atropine-like signs and symptoms, dry mouth; fixed, dilated pupils; flushing, and gastrointestinal symptoms may also occur.
  • Stimulants should not be used.
  • Vasopressors may be used to treat hypotension.

Reversal Agents

  • None

Special Circumstances

  • Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals to determine mutagenic and carcinogenic potential have not been performed.
  • Use in Pregnancy: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 5 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to diphenhydramine hydrochloride. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
  • Use in Pediatric Patients:
    • Diphenhydramine should not be used in neonates and premature infants.
    • Diphenhydramine may diminish mental alertness, or in the young pediatric patient, cause excitation.
    • Overdosage may cause hallucinations, convulsions or death.

Side Effects and Risks

  • Diphenhydramine may cause drowsiness and has an additive effect with alcohol. Patients should be warned about engaging in activities requiring mental alertness, such as driving a car or operating appliances, machinery, etc. Patients receiving diphenhydramine should not drive themselves home following discharge.
  • Drug Interactions:
    • Alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc): Additive effects with diphenhydramine.
    • MAO inhibitors:  Prolong and intensify the anticholinergic (drying) effects of antihistamines.
  • General: Urticaria drug rash; anaphylactic shock; photosensitivity; excessive perspiration; chills; dryness of mouth, nose and throat
  • Cardiovascular system: Hypotension, headache, palpitations, tachycardia, premature cardiac contractions.
  • Hematologic system: Hemolytic anemia, thrombocytopenia, agranulocytosis
  • Nervous system: Sedation, sleepiness, dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, neuritis, convulsions
  • Gastrointestinal system: Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation
  • Genitourinary system: Urinary frequency, difficult urination, urinary retention, early menses
  • Respiratory system: Thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness

Common Issues

The side effects most commonly encountered with diphenhydramine are:
  • Sedation
  • Sleepiness
  • Dizziness
  • Disturbed coordination
  • Epigastric distress
  • Thickening of bronchial secretions 

Warnings

  • Antihistamines should be used with considerable caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy or bladder-neck obstruction.
  • Local necrosis has been associated with the use of subcutaneous or intradermal use of intravenous diphenhydramine.
  • In pediatric patients, especially, antihistamines in overdosage may cause hallucinations, convulsions or death.
  • Antihistamines may diminish mental alertness in pediatric patients. In the young pediatric patient, particularly, they may produce excitation.
  • Antihistamines are more likely to cause dizziness, sedation and hypotension in elderly patients (approximately 60 years or older). 

Alternative Medications

Although in a different pharmaceutical class, droperidol is sometimes used in for premedication in a similar manner as diphenhydramine. 

Contraindications

  • This drug should not be used in neonates or premature infants.
  • Because of the higher risk of antihistamines for infants generally, and for neonates and premature infants in particular, antihistamine therapy is contraindicated in nursing mothers.
  • Because of the risk of local necrosis, this drug should not be used as a local anesthetic.
  • Diphenhydramine is contraindicated in patients with a hypersensitivity to diphenhydramine and other antihistamines of similar chemical structure.
Sources

Cohen LB, DeLegge MH, Aisenberg J, Brill JV, Inadomi JM, et al. AGA Institute review of endoscopic sedation. Gastroenterology. 2007 Aug;133(2):675-701.

Diphenhydramine. Official FDA Information. Drugs.com. February, 2006.
http://www.drugs.com/pro/diphenhydramine-injection-usp.html

Tu RH, Grewall P, Leung JW et al. Diphenhydramine as an adjunct to sedation for colonoscopy: a double-blind randomized, placebo-controlled study, Gastrointestinal Endoscopy. 2006; 63(1): 95-6.

 

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Last Updated November 11, 2008