Elephant Formulary

© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International

Disclaimer: the information on this page is used entirely at the reader's discretion, and is made available on the express condition that no liability, expressed or implied, is accepted by the authors or publisher for the accuracy, content, or use thereof.


Diphenhydramine HCl

Elephant specific information, if available, is in blue.


Chemistry – An ethanolamine-derivative antihistamine, diphenhydramine HCl occurs as an odorless, white, crystalline powder which will slowly darken upon exposure to light. It has a melting range of 167 – 172° C. One gram is soluble in about 1 ml of water or 2 ml of alcohol. Diphenhydramine HCl has a pKa of about 9, and the commercially available injection has its pH adjusted to 5-6.


Storage/Stability/Compatibility – Preparations containing diphenhydramine should be stored at room temperature (15-30°C) and solutions should be protected from freezing. Tablets and oral solutions should be kept in well-closed containers. Capsules and the elixir should be stored in tight containers.


Diphenhydramine for injection is reportedly compatible with all commonly used IV solutions and the following drugs: amikacin sulfate, aminophylline, ascorbic acid injection, atropine sulfate, bleomycin sulfate, butorphanol tartrate, cephapirin sodium, chlorpro­mazine HCl, colistimethate sodium, diatrizoate meglumine/sodium, dimenhydrinate, droperidol, erythromycin lactobionate, fentanyl citrate, glycopyrrolate, hydromorphone HCl, hydroxyzine HCl, iothalamate meglumine/sodium, lidocaine HCl, meperidine HCl, methicillin sodium, metoclopramide, methyldopate HCl, morphine sulfate, nafcillin sodium, netilmicin sulfate, penicillin G potassium/sodium, pentazocine lactate, perphenazine, polymyxin B sulfate, prochlorperazine edisylate, promazine HCl, promethazine HCl, scopolamine HBr, tetracycline HCl and vitamin B complex w/C. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.


Diphenhydramine is reportedly incompatible with the following drugs: amobarbital sodium, amphotericin B, cephalothin sodium, hydrocortisone sodium succinate, iodipamide meglumine, pentobarbital sodium, secobarbital sodium, and thiopental sodium.


Pharmacology – Like other antihistamines, diphenhydramine competitively inhibits histamine at H1 receptors. In addition; it also has substantial sedative, anticholinergic, antitussive, and antiemetic effects.


Uses/Indications – In veterinary medicine, diphenhydramine is used principally for its antihistaminic effects, but also for its other pharmacologic actions as well. Its sedative effects can be of benefit in treating the agitation (pruritis, etc.) associated with allergic responses. It has also been used for treatment and prevention of motion sickness and as an antiemetic in small animals. It has also been suggested for use as adjunctive treatment of aseptic laminitis in cattle. For other suggested uses, refer to the Dosage section below.


Pharmacokinetics – The pharmacokinetics of this agent have apparently not been studied in domestic animals. In humans, diphenhydramine is well absorbed after oral administration, but because of a relatively high first-pass effect, only about 40-60% reaches the systemic circulation.


Following IV administration in rats, diphenhydramine reaches its highest levels in the spleen, lungs and brain. The drug is distributed into milk, but has not been measured quantitatively. In humans, diphenhydramine crosses the placenta and is approximately 80% bound to plasma proteins.


Diphenhydramine is metabolized in the liver and the majority of the drug is excreted as metabolites into the urine. The terminal elimination half-life in adult humans ranges from 2.4-9.3 hours.


Contraindications/Precautions – Diphenhydramine is contraindicated in patients who are hypersensitive to it or other antihistamines in its class. Because of their anticholinergic activity, antihistamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, pyloroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Additionally, they should be used with caution in patients with hyperthyroidism, cardiovascular disease or hypertension.


Adverse Effects/Warnings – The most commonly seen adverse effects are CNS depression (lethargy, somnolence), and anticholinergic effects (dry mouth, urinary retention). The sedative effects of antihistamines may diminish with time. GI effects (diarrhea, vomit­ing, anorexia), are a possibility. The sedative effects of antihistamines may adversely affect the performance of working dogs.


Overdosage – Overdosage can cause CNS stimulation (excitement to seizures) or depression (lethargy to coma), anticholinergic effects, respiratory depression and death. Treatment consists of emptying the gut if the ingestion was oral using standard protocols. Induce emesis if the patient is alert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may be given after emesis or gastric lavage. Treatment of other symptoms should be performed using symptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine over­dose in humans; barbiturates and diazepam should be avoided.


Drug Interactions – Increased sedation can occur if diphenhydramine is combined with other CNS depressant drugs.

Antihistamines may partially counteract the anticoagulation effects of heparin or war­farin.

Diphenhydramine may enhance the effects of epinephrine.


Laboratory Interactions – Antihistamines can decrease the wheal and flare response to antigen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing.


Doses –


For adjunctive therapy of anaphylaxis:

a)   0.25 – 1 mg/kg IV or IM (Evans 1996)


Monitoring Parameters –

1)   Clinical efficacy and adverse effects


Client Information/FDA Approval Status – Diphenhydramine is approved for use in humans. The oral dosage forms are either prescription or non-prescription agents, depending on the product’s labeling. The injectable products are prescription only.


Dosage Forms/Preparations –


Veterinary-Approved Products: None


Human-Approved Products:

Diphenhydramine HCl Capsules 25 mg, 50 mg; 12.5 mg chewable) & 50 mg Tablets


Diphenhydramine HCl Oral Elixir or Syrup 12.5 mg/5 ml (2.5 mg/ml) in 4 oz, pint and gallon bottles


Diphenhydramine Injection 10 mg/ml in 10 ml or 30 ml vials; 50 mg/ml in 1 ml amps and 10 ml vials


Diphenhydramine is available under several trade names; a commonly known product is Benadryl®  (Parke-Davis).