DIPHENHYDRAMINE HYDROCHLORIDE

ADVERSE REACTIONS The most frequent adverse reactions are underscored. General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of the 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. To report SUSPECTED ADVERSE REACTIONS, contact Pharmaceutical Associates, Inc. at 1-800-845-8210 of FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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. 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 and has the molecular formula C 17 H 21 NO•HCI (molecular weight 291.82). It occurs as a white odorless, crystalline powder and is freely soluble in water and alcohol. The structural formula is as follows: Each 5 mL contains 12.5 mg of diphenhydramine hydrochloride and alcohol 14% for oral administration. Inactive Ingredients: Citric acid, D&C Red No. 33, FD&C Red No. 40, flavoring, purified water, sodium citrate, and sucrose. Diphenhydramine chemical structure

DOSAGE AND ADMINISTRATION DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT. A single oral dose of diphenhydramine hydrochloride is quickly absorbed with maximum activity occurring in approximately one hour. The duration of activity following an average dose of diphenhydramine hydrochloride is from four to six hours. Adults 25 to 50 mg three to four times daily. The nightime sleep aid dosage is 50 mg at bedtime. Pediatric Patients (over 20 lbs.) 12.5 to 25 mg three or four 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 hydrochloride 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

INDICATIONS AND USAGE Diphenhydramine hydrochloride 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.

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 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 most 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. 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. Precaution 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 beforehand. 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. 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 effects. Antihistamines appear to compete with histamine for cell receptor sites on effector cells. A single oral dose of diphenhydramine hydrochloride is quickly absorbed with maximum activity occurring in approximately one hour. The duration of activity following an average dose of diphenhydramine hydrochloride is from four to six hours. Diphenhydramine is 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.

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DIPHENHYDRAMINE HYDROCHLORIDE DIPHENHYDRAMINE HYDROCHLORIDE ALCOHOL CITRIC ACID MONOHYDRATE D&C RED NO. 33 FD&C RED NO. 40 WATER SODIUM CITRATE SUCROSE DIPHENHYDRAMINE HYDROCHLORIDE DIPHENHYDRAMINE

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

ANDA087513

DIPHENHYDRAMINE HYDROCHLORIDE

DIPHENHYDRAMINE HYDROCHLORIDE

71872-7242

HUMAN PRESCRIPTION DRUG

ORAL

PRINCIPAL DISPLAY PANEL - CUP LABEL Delivers 10 mL DIPHENHYDRAMINE HCl ORAL SOLUTION USP 25 mg/10 mL Alcohol 14% FOR INSTITUTIONAL USE ONLY Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Rx ONLY 10 mL Unit Dose Cup Label

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.

Use in the Elderly (approximately 60 years or older) Antihistamines are most likely to cause dizziness, sedation, and hypotension in elderly patients.

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

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 Each 5 mL of Diphenhydramine Hydrochloride Oral Solution USP (clear purple/red liquid, cinnamon/anise flavor) contains 12.5 mg diphenhydramine hydrochloride with 14% alcohol and is supplied in the following oral dosage forms: NDC: 0121-0489-04: 118 mL (4 oz) bottle NDC 0121-0489-05: 5 mL unit dose cup NDC 0121-0489-00: Case contains 100 unit dose cups of 5 mL (0121-0489-05) packaged in 10 trays of 10 unit dose cups each. NDC 0121-0978-10: 10 mL unit dose cup NDC 0121-0978-00: Case contains 100 unit dose cups of 10 mL (0121-0978-10) packaged in 10 trays of 10 unit dose cups each.

STORAGE Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Protect from freezing and light.

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