Diphenhydramine Hydrochloride
Anti-histamine
View Brand Names (2)Dose and dosage
As an antihistamine:
a) 2–4 mg/kg q8–12h PO; 1 mg/kg q8–12h IM, SC, IV (do not exceed 40 mg total dose) (Papich 2000)
b) 2.2 mg/kg PO twice daily–three times daily (Peikes 2003)
c) For severe urticaria and angioedema: 2 mg/kg IM twice daily as needed (with steroids: prednisone 2 mg/kg IM twice daily and epinephrine 1:10,000: 0.5–2 mL SC) (Giger & Werner 1989)(
d) For canine atopic dermatitis: 25–50 mg (total dose) PO three times daily. (Hill 2007)
e) For treatment of anaphylaxis (associated with doxorubicin chemotherapy): 3–4 mg/kg IM with dexamethasone sodium phosphate (0.5–1 mg/kg IV) wait for reaction to subside before restarting infusion at slower rate. (Vail 2006)
f) For preoperative therapy for splenic mast cell tumors: 2 mg/kg PO three times daily with famotidine (0.5 mg/kg PO once daily) are used to prevent anaphylaxis. (Garrett 2006)
g) For adjunctive tx of pruritus: 2–4 mg/kg PO two to three times a day. (Marsella 2008)
Prevention of motion sickness/antiemetic:
a) 2–4 mg/kg PO, IM q8h (Washabau & Elie 1995), (Richter 2009) For preoperative therapy for splenic mast cell tumors:
a) 2 mg/kg PO three times daily with famotidine (0.5 mg/kg PO once daily) are used to prevent anaphylaxis. (Garrett 2006)
For treatment of the reverse sneeze syndrome:
a) 25 mg PO three to four times a day, dosage is usually decreased to once or twice a week for maintenance (Prueter 1989)
As an antihistamine:
a) 0.5 mg/kg PO q12h; liquid formulation is distasteful (Messinger 2000)
b) 2–4 mg (total dose) q12–24h (Hnilica 2003)
c) 2–4 mg/kg PO q8h (Scherk 2006)
d) For severe urticaria and angioedema: 2 mg/kg IM twice daily as needed (with steroids: prednisone 2 mg/kg IM twice daily and epinephrine 1:10,000 (0.5–2 mL SC) (Giger & Werner 1989)
For adjunctive treatment of pancreatitis:
a) 2–4 mg/kg PO q8h (Scherk 2005)
a) Prevaccination: 2 mg/kg PO, IM or IV 10 minutes prior to vaccination (Williams 2000)
b) Pretreatment before doxorubicin: 5 mg (total dose) IM (Johnson 2006)
1–2 mg/kg PO twice daily as an antihistamine (Morrisey & Antinoff 2003), (Antinoff 2008)
7.5 mg/kg PO (Adamcak & Otten 2000)
For adjunctive treatment of pruritus causing feather picking in Psittacines:
a) 2 mg/kg PO q12h (Siebert 2003)
As an antihistamine:
a) For adjunctive therapy of anaphylaxis: 0.25–1 mg/kg IV or IM (Evans 1996)
b) For allergic skin diseases (atopy): 1–2 mg/kg twice daily (route not specified) (Miller 2005)
c) For allergic skin diseases (atopy): 0.75–1 mg/kg PO q12h (Rees 2004)
d) For adjunctive tx of pruritus: 1–2 mg/kg PO two to three times a day. (Marsella 2008)
a) For adjunctive therapy of anaphylaxis: 0.5–1 mg/kg IM or IV (used with epinephrine and steroids) (Clark 1986)
b) For adjunctive therapy of aseptic laminitis: During the acute phase (with corticosteroids): 55–110 mg/100 kg body weight (0.55–1.1 mg/kg) IV or IM (Berg 1986)
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Antihistamines used as antiemetics are administered for motion sickness, vomiting induced by chemotherapy, and GI disease that stimulates vomiting. Antihistamines are not effective antiemetics for cats. They may be effective in some dogs; however, there are other antiemetics available for dogs and cats that are consistently more effective.
Antimuscarinic effects (atropine-like effects) are common. Do not use in conditions for which anticholinergic drugs may be contraindicated, such as glaucoma, ileus, or cardiac arrhythmias. Do not administer to patients in which theophylline products are contraindicated.
Antihistamine (H1-blocker). Diphenhydramine is the active moiety of dimenhydrinate. The pharmacologic properties are the same as diphenhydramine. Dimenhydrinate contains diphenhydramine and chlortheophylline. Dimenhydrinate is a salt consisting of 53.0%–55.5% diphenhydramine and 44.0%–46.5% 8-chlorotheophylline. In people, it is used for treatment of nausea, dizziness, and vomiting associated with motion sickness. Diphenhydramine produces the antinausea effects, and chlorotheophylline, a methylxanthine derivative related to caffeine, is added to reduce drowsiness. Similar to other antihistamines, diphenhydramine acts by blocking the H1 receptor and suppresses inflammatory reactions caused by histamine. The H1 blockers have been used to control pruritus and skin inflammation in dogs and cats; however, success rates in dogs have not been high. Commonly used antihistamines include clemastine, chlorpheniramine, diphenhydramine, and hydroxyzine. Diphenhydramine also has central-acting antiemetic properties, possibly by acting on the vomiting center or via the chemoreceptor-trigger zone (CRTZ).
Pharmacokinetics: The oral bioavailability of diphenhydramine is much higher when administered as the dimenhydrinate salt—as much as 50–70 times in some studies. Diphenhydramine oral bioavailability is 22% in dogs when administered as dimenhydrinate but only 8% when administered alone. The terminal half-life of diphenhydramine from this formulation in dogs is 12 hours. The theophylline component in this formulation is also absorbed and attains levels that can be considered to have therapeutic effects.
ANTICHOLINERGIC DRUGS (including tricyclic antidepressants): Diphenhydramine may potentiate anticholinergic effects
CNS DEPRESSANT DRUGS: Increased sedation can occur
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. Diphenhydramine may cause paradoxical excitement in cats. The liquid formulation is very distasteful.
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 after oral ingestion 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 clinical signs 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.
Meat: 7 days
Milk: 2 days