Diphenhydramine Hydrochloride

ADVERSE REACTIONS The most frequent adverse reactions are underscored: General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of mouth, nose, and throat. Cardiovascular System: Hypotension, headache, palpitations, tachycardia, extrasystoles. 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. GI System: Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation. GU System: Urinary frequency, difficult urination, urinary retention, early menses. Respiratory System: Thickening of bronchial secretions , tightness of chest or throat and wheezing, nasal stuffiness.

CONTRAINDICATIONS 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.

DESCRIPTION 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 and has a molecular weight of 291.82. The molecular formula is C 17 H 21 NO·HCl and the structural formula is as follows: Diphenhydramine hydrochloride in the parenteral form is a sterile, pyrogen-free solution. Each mL contains a concentration of 50 mg of diphenhydramine hydrochloride and water for injection, for intramuscular or intravenous use. The solution for parenteral use has been adjusted to a pH between 4 and 6.5 with either sodium hydroxide or hydrochloric acid. Structural Formula

DOSAGE AND ADMINISTRATION 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/m 2 /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 mg 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.

INDICATIONS AND USAGE 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.

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. Use in Pediatric Patients: In pediatric patients, especially, antihistamines in overdosage may cause hallucinations, convulsions, 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.

OVERDOSAGE 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.

Drug Interactions: Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc). MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines.

CLINICAL PHARMACOLOGY Diphenhydramine hydrochloride is an antihistamine 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 distributed throughout the body, including the CNS. A portion of the drug is excreted unchanged in the urine, while the rest is metabolized via the liver. Detailed information on the pharmacokinetics of Diphenhydramine Hydrochloride Injection is not available.

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Diphenhydramine Hydrochloride Diphenhydramine Hydrochloride SODIUM HYDROXIDE HYDROCHLORIC ACID WATER DIPHENHYDRAMINE HYDROCHLORIDE DIPHENHYDRAMINE

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals to determine mutagenic and carcinogenic potential have not been performed.

ANDA091526

Diphenhydramine Hydrochloride

Diphenhydramine Hydrochloride

76045-102

HUMAN PRESCRIPTION DRUG

INTRAMUSCULAR,INTRAVENOUS

PACKAGE LABEL - PRINCIPAL DISPLAY – Diphenhydramine 1 mL Carton Rx only NDC 76045-102-10 DiphenhydrAMINE HCl Injection, USP HIGH POTENCY 50 mg/mL For Intravenous or Intramuscular Use. Do NOT place syringe on a Sterile Field. 24 x 1mL Prefilled Single-use Syringes Discard unused portion. PACKAGE LABEL - PRINCIPAL DISPLAY – Diphenhydramine 1 mL Carton Panel

Rx Only

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 activities requiring mental alertness such as driving a car or operating appliances, machinery, etc.

Pediatric Use: Diphenhydramine should not be used in neonates and premature infants (see CONTRAINDICATIONS ). Diphenhydramine may diminish 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.

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.

HOW SUPPLIED Diphenhydramine Hydrochloride Injection, USP is a clear and colorless solution available as: 50 mg/mL in a 1 mL prefilled single-use syringe. Available in a carton of twenty-four (24) syringes. NDC 76045-102-10 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature.] Protect from freezing and light. Retain in carton until time of use. Do not place syringe on a sterile field.

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 pressure, hyperthyroidism, cardiovascular disease or hypertension. Use with caution in patients with lower respiratory disease including asthma.

PRECAUTIONS 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 pressure, 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 activities 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 depressants (hypnotics, sedatives, tranquilizers, etc). MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines. 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 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. Pediatric Use: Diphenhydramine should not be used in neonates and premature infants (see CONTRAINDICATIONS ). Diphenhydramine may diminish 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.