Diphenhydramine Hydrochloride
Indications: Anaphylaxis, adjunct; Angioedema; Conjunctivitis, allergic; Dermatographism; Motion sickness; Parkinson's disease; Transfusion reaction; Urticaria
DESCRIPTION:
Diphenhydramine HCl, is an antihistamine drug having the chemical name 2-(Diphenylmethoxy)-N,N-dimethylethylamine hydrochloride and has the empirical formula C17H21NOΒ·HCl. It occurs as a white, crystalline powder and is freely soluble in water and alcohol and has a molecular weight of 291.82.
Each diphenhydramine HCl capsule contains 25 mg or 50 mg diphenhydramine HCl for oral administration.
Each Benadryl 25-mg capsule also contains lactose and magnesium stearate. The capsule shell and/or band contains D&C red no. 28; FD&C blue no. 1; FD&C red no. 3; FD&C red no. 40; gelatin; colloidal silicon dioxide; and sodium lauryl sulfate.
Each Benadryl 50-mg capsule also contains confectioner's sugar and talc. The capsule shell and/or band contains FD&C blue no. 1; FD&C red no. 3; gelatin; glyceryl monooleate; colloidal silicon dioxide; sodium lauryl sulfate; and titanium dioxide.
Each 5 ml of diphenhydramine HCl elixir contains 12.5 mg diphenhydramine HCl with 14% alcohol for oral administration.
Diphenhydramine HCl in the parenteral form is a sterile, pyrogen-free solution available in two concentrations: 10 mg and 50 mg of diphenhydramine HCl per ml. The solutions for parenteral use have been adjusted to a pH between 5.0 and 6.0 either with sodium hydroxide or hydrochloric acid. The multidose Steri-Vials contain 0.1 mg/ml benzethonium chloride as a germicidal agent.
CLINICAL PHARMACOLOGY:
Diphenhydramine HCl is an antihistamine with anticholinergic (drying) and sedative effects. Antihistamines appear to compete with histamine for cell receptor sites on effector cells.
Diphenhydramine is widely distributed throughout the body, including the CNS.
Capsules and Elixer
A single oral dose of diphenhydramine HCl is quickly absorbed with maximum activity occurring in approximately 1 hour. The duration of activity following an average dose of diphenhydramine HCl is from 4 to 6 hours. Diphenhydramine HCl capsules are widely distributed throughout the body, including the CNS. Little, if any, is excreted unchanged in the urine; most appears as the degradation products of metabolic transformation in the liver, which are almost completely excreted within 24 hours.
Injection
Diphenhydramine HCl in the injectable form has a rapid onset of action. Detailed information on the pharmacokinetics of diphenhydramine HCl injection is not available.
INDICATIONS AND USAGE:
Capsules and Elixer
Diphenhydramine HCl in the oral form is effective for the following indications:
Antihistaminic: For allergic conjunctivitis due to foods; mild, uncomplicated allergic skin manifestations of urticaria and angioedema; amelioration of allergic reactions to blood or plasma; dermatographism; as therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled.
Motion Sickness: For active and prophylactic treatment of motion sickness.
Antiparkinsonism: For parkinsonism (including drug-induced) in the elderly unable to tolerate more potent agents; mild cases of parkinsonism (including drug-induced) in other age groups; in other cases of parkinsonism (including drug-induced) in combination with centrally acting anticholinergic agents.
Nighttime sleep-aid.
Injection
Diphenhydramine HCl in the injectable form should only be used when the oral forms are impractical.
CONTRAINDICATIONS:
Use in Newborn or Premature Infants: This drug should not be used in newborn or premature infants.
Use in Nursing Mothers: Because of the higher risk of antihistamines for infants generally, and for newborns and prematures in particular, antihistamine therapy is contraindicated in nursing mothers.
Antihistamines are Also Contraindicated in the Following Conditions: Hypersensitivity to diphenhydramine HCl and other antihistamines of similar chemical structure.
Injection
Use as a Local Anesthetic: Because of the risk of local necrosis, this drug in the parenteral from should not be used as a local anesthetic.
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.
Use in Children: In infants and children, especially, antihistamines in overdosage may cause hallucinations, convulsions, or death.
As in adults, antihistamines may diminish mental alertness in children. In the young child, 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.
PRECAUTIONS:
General
Diphenhydramine HCl has an atropine-like action and therefore should be used with caution in patients with a history of lower respiratory disease including asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease or hypertension.
Information for the Patient
Patients taking diphenhydramine HCl should be advised that this drug 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.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term studies in animals to determine mutagenic and carcinogenic potential have not been performed.
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 HCl. 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.
Injection
Use with caution in patients with lower respiratory disease including asthma.
DRUG INTERACTIONS:
Diphenhydramine HCl has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc).
MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines.
ADVERSE REACTIONS:
The Most Frequent Adverse Reactions are Underscored:
1. General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, 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, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, neuritis, convulsions.
5. GI 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 and wheezing, nasal stuffiness.
OVERDOSAGE:
Antihistamine overdosage reactions may vary from central nervous system depression to stimulation. Stimulation is particularly likely in children. 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.
Capsules and Elixer
If vomiting has not occurred spontaneously the patient should be induced to vomit. This is best done by having him drink a glass of water or milk after which he should be made to gag. Precautions against aspiration must be taken, especially in infants and children.
If vomiting is unsuccessful gastric lavage is indicated within 3 hours after ingestion and even later if large amounts of milk or cream were given before hand. Isotonic or 1/2 isotonic saline is the lavage solution of choice.
Saline cathartics, as milk of magnesia, by osmosis draw water into the bowel and therefore are valuable for their action in rapid dilution of bowel content.
DOSAGE AND ADMINISTRATION:
DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT.
Capsules
A single oral dose of diphenhydramine HCl is quickly absorbed with maximum activity occurring in approximately 1 hour. The duration of activity following an average dose of diphenhydramine HCl is from 4 to 6 hours.
Adults: 25 to 50 mg 3 or 4 times daily. The nighttime sleep-aid dosage is 50 mg at bedtime.
Children (Over 20 lb): 12.5 to 25 mg 3 to 4 times daily. Maximum daily dosage not to exceed 300 mg. For physicians who wish to calculate the dose on the basis of body weight or surface area, the recommended dosage is 5 mg/kg/24 hours or 150 mg/m2/24 hours.
Data are not available on the use of diphenhydramine HCl as a nighttime sleep-aid in children under 12 years.
The basis for determining the most effective dosage regimen will be the response of the patient to medication and the condition under treatment.
In motion sickness, full dosage is recommended for prophylactic use, the first dose to be given 30 minutes before exposure to motion and similar doses before meals and upon retiring for the duration of exposure.
Elixer
A single oral dose of diphenhydramine HCl is quickly absorbed with maximum activity occurring in approximately 1 hour. The duration of activity following an average dose of diphenhydramine HCl is from 4 to 6 hours.
Children (Over 20 lb): One to two teaspoonfuls 3-4 times daily. Maximum daily dosage not to exceed 300 mg.
For physicians who wish to calculate the dose on the basis of body weight or surface area, the recommended dosage is 5 mg/kg/24 hours or 150 mg/m2/24 hours.
Adults: Two to four teaspoonfuls three to four times daily. The basis for determining the most effective dosage regimen will be the response of the patient to medication and the condition under treatment.
In motion sickness, full dosage is recommended for prophylactic use, the first dose to be given 30 minutes before exposure to motion and similar doses before meals and upon retiring for the duration of exposure.
Injection
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Children: 5 mg/kg/24 hr or 150 mg/m2/24 hr. Maximum daily dosage is 300 mg. Divide into four doses, administered intravenously or deeply intramuscularly.
Adults: 10 to 50 mg intravenously or deep intramuscularly, 100 mg if required; maximum daily dosage is 400 mg.