DIPHENHYDRAMINE HYDROCHLORIDE INJECTION, USP

Diphenhydramine hydrochloride is an anti­histamine drug having the chemical name 2-(Diphenylmethoxy)-N,N-dimethylethylamine hydrochloride. It occurs as a white, crystalline powder, is freely soluble in water and alcohol.

The structural formula is as follows:

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Diphenhydramine hydrochloride  in  the  par­ enteral  form is a sterile,  pyrogen-free solution available in a concentration of 50 mg of diphen­ hydramine hydrochloride per  ml. pH 4.0 to 6.5; sodium hydroxide and/or hydrochloric acid added, if needed, for pH adjustment.

Diphenhydramine hydrochloride is an anti­-histamine with anticholinergic (drying) and sedative side effects. Antihistamines appear to compete with histamine for cell receptor sites on effector cells. Diphenhydramine hydrochloride in the  injectable form  has  a rapid onset of action.  Diphenhydramine hydrochloride is widely dis­ tributed throughout the  body, including the  CNS. A portion of  the drug is excreted  unchanged in the urine, while the rest is metab­ olized via the liver. Detailed information on the  pharmacokinetics  of diphenhydramine hydrochloride injection is not available.

Diphenhydramine hydrochloride in the injectable form is effective in adults and pedi­atric patients, other than premature infants and neonates, for the following conditions when diphenhydramine hydrochloride in the oral form is impractical.

Antihistaminic

For amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled, and for  other  uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.

Motion Sickness

For active treatment of motion sickness.

Antiparkinsonism

For use in parkinsonism, when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents; mild  cases of  parkinsonism in other age groups, and in other  cases of parkinsonism in combination with  centrally acting anticholinergic agents.

Use in Neonates or Premature Infants

This drug should not be used  in neonates or premature infants.

Use in Nursing Mothers

Because of the  higher risk  of antihistamines for  infants generally, and  for  neonates and prematures in particular, antihistamine therapy is contraindicated in nursing mothers.

Use as a Local Anesthetic

Because of the risk of local necrosis, this drug should not be used as a local  anesthetic. Antihistamines are  also contraindicated in the following conditions: Hypersensitivity  to diphenhydramine hydrochloride and other antihistamines of similar chemical structure.

Antihistamines should be used  with consider­able caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduo­ denal obstruction, symptomatic prostatic hyper­ trophy, or bladder-neck obstruction.

Local necrosis has been associated with the use  of  subcutaneous or  intradermal use  of intravenous diphenhydramine hydrochloride.

Use in Pediatric Patients

In pediatric patients, especially, antihistamines in overdosage may cause hallucinations, con­ vulsions, or death.

As in adults, antihistamines may diminish mental alertness in pediatric patients.  In the young pediatric patient, particularly, they may produce excitation.

Use in the  Elderly (approximately 60 years or older)

Antihistamines are more likely to cause  dizzi­ness, sedation, and  hypotension in elderly patients.

General

Diphenhydramine hydrochloride has  an atropine-like action and,  therefore, should be used  with caution in patients with a history  of bronchial asthma, increased intraocular pres­ sure, hyperthyroidism, cardiovascular disease or hypertension. Use with caution in patients with lower respiratory disease including asthma.

Information for  Patients

Patients taking diphenhydramine hydrochloride should be advised that this drug may cause drowsiness and has an additive effect with alcohol.  Patients should be warned about engaging in activites requiring mental alertness such as  driving a car  or operating appliances, machinery. etc.

Drug Interactions

Diphenhydramine hydrochloride has additive effects  with  alcohol and  other  CNS  depres­ sants (hypnotics, sedatives, tranquilizers, etc.). MAO inhibitors prolong and intensify the  anticholinergic (drying)  effects of  antihista­ mines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in  animals to determine mutagenic and carcinogenic potential have  not been performed.

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 ade­ quate and well-controlled studies in pregnant  women. Because animal reproduction studies are not always predictive of human response, t his drug should be used during pregnancy only if clearly  needed.

Pediatric Use

Diphenhydramine hydrochloride should not be used  in neonates and premature infants  (see CONTRAINDICATIONS).

Diphenhydramine hydrochloride may dimimish mental alertness, or, in the young pediatric patient, cause  excitation. Overdosage may cause hallucinations, convulsions, or death  (see WARNINGS and OVERDOSAGE) .

See also DOSAGE AND ADMINISTRATION section.

The most frequent adverse reactions are  underscored.

1. General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspira­ tion, chills, dryness of  mouth, nose and  throat.

2. Cardiovascular  System:  Hypotension, headache,  palpitations,  tachycardia,  extrasystoles.

3. Hematologic System : Hemolytic anemia, thrombocytopenia, agranulocytosis.

4. Nervous System : Sedation, sleepiness, dizzi­ness, disturbed coordination , fatigue, con­ fusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, pares­ thesia,  blurred vision, diplopia, vertigo, tin­ nitus, acute labyrinthitis, neuritis, convulsions.

5. Gl  System: Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation.

6. GU System:  Urinary frequency, difficult uri­nation, urinary retention, early menses.

7. Respiratory System :   Thickening of bronchial secretions, tightness of chest or throat and  wheezing, nasal stuffiness.

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

Vasopressors may be used to treat hypoten­sion.

THIS PRODUCT IS FOR INTRAVENOUS OR INTRAMUSCULAR ADMINISTRATION ONLY.

Diphenhydramine hydrochloride in the injectable form is indicated when the oral form is impractical.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND  THE RESPONSE OF THE PATIENT.

Pediatric Patients, other than premature infants and neonates: 5  mg/kg/24 hr or 150 mg/m2/24 hr.  Maximum daily dosage is  300 mg.  Divide into four doses, administered  intravenously at a rate generally not exceeding  25 mg/min, or deep intramuscularly.

Adults: 10 to 50 mg  intravenously at a rate generally not exceeding 25 mg/min, or deep intramuscularly, 100 mg if required; maximum daily dosage is 400 mg.

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It is supplied as a sterile, pyrogen-free solution containing 50 mg diphenhydramine hydrochlo­ ride in each milliliter of solution, and available in packages of 25.

Vial stoppers do  not  contain natural rubber latex.

Store  at 20° to  25°C  (68°  to  7rF) [see  USP Controlled Room Temperature] .

Protect  from freezing and light.

APP Pharmaceuticals, LLC

Schaumburg, IL 60173

45954C

Revised: April 2008

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