Diphenhydramine

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. 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.

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, other than premature infants and neonates 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

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 hydrochloride. 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. 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.

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. 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.

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.

ADVERSE REACTIONS: To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 or throat and wheezing, nasal stuffiness.

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.