CONTRAINDICATIONS Pediatric Use: Diphenhydramine should not Diphenhydramine Use in Neonates or Premature Infants: This drug be used in neonates and premature infants Hydrochloride should not be used in neonates or premature infants. (see CONTRAINDICATIONS). Use in Nursing Mothers: Because of the higher risk of Diphenhydramine may diminish mental alertness, or Injection, USP antihistamines for infants generally, and for neonates in the young pediatric patient, cause excitation. and prematures in particular, antihistamine therapy is Overdosage may cause hallucinations, convulsions, or contraindicated in nursing mothers. Rx Only death (see WARNINGS and OVERDOSAGE). Use as a Local Anesthetic: Because of the risk of local See also DOSAGE AND ADMINISTRATION section. necrosis, this drug should not be used as a local anes- DESCRIPTION thetic. Diphenhydramine hydrochloride is an antihistamine ADVERSE REACTIONS drug having the chemical name 2-(Diphenylmethoxy)- Antihistamines are also contraindicated in the fol- The most frequent adverse reactions are under- N,N-dimethylethylamine hydrochloride. It occurs as a lowing conditions: Hypersensitivity to diphenhydra- scored: white, crystalline powder, is freely soluble in water mine hydrochloride and other antihistamines of simi- 1. General: Urticaria, drug rash, anaphylactic shock, and alcohol and has a molecular weight of 291.82. lar chemical structure. photosensitivity, excessive perspiration, chills, dry- The molecular formula is C H NO·HCl and the struc-

17 21 ness of mouth, nose, and throat. tural formula is as follows: 1212 P0104 WARNINGS 2. Cardiovascular System: Hypotension, headache, + Antihistamines should be used with considerable cau- HH tion in patients with narrow-angle glaucoma, stenos- palpitations, tachycardia, extrasystoles. COCH2CH2N(CH3)2 ing peptic ulcer, pyloroduodenal obstruction, symp- 3. Hematologic System: Hemolytic anemia, thrombo- Cl- tomatic prostatic hypertrophy, or bladder-neck cytopenia, agranulocytosis.

obstruction.

4. Nervous System: Sedation, sleepiness, dizziness, USP Injection,

Local necrosis has been associated with the use of disturbed coordination, fatigue, confusion, rest- Hydrochloride Diphenhydramine subcutaneous or intradermal use of intravenous lessness, excitation, nervousness, tremor, irritabil- diphenhydramine. ity, insomnia, euphoria, paresthesia, blurred vision, Diphenhydramine hydrochloride in the parenteral Use in Pediatric Patients: In pediatric patients, espe- diplopia, vertigo, tinnitus, acute labyrinthitis, form is a sterile, pyrogen-free solution. Each mL con- cially, antihistamines in overdosage may cause hallu- neuritis, convulsions. Diphenhydramine Hydrochloride tains a concentration of 50 mg of diphenhydramine cinations, convulsions, or death. hydrochloride and water for injection, for intra- 5. GI System: Epigastric distress, anorexia, nausea, Injection, USP muscular or intravenous use. The solution for paren- As in adults, antihistamines may diminish mental vomiting, diarrhea, constipation. teral use has been adjusted to a pH between 4 and alertness in pediatric patients. In the young pediatric 6. GU System: Urinary frequency, difficult urination, 6.5 with either sodium hydroxide or hydrochloric patient, particularly, they may produce excitation. urinary retention, early menses. acid. Use in the Elderly (approximately 60 years or older): Antihistamines are more likely to cause dizziness, 7. Respiratory System: Thickening of bronchial secre- P0104 1212 CLINICAL PHARMACOLOGY sedation, and hypotension in elderly patients. tions, tightness of chest or throat and wheezing, Diphenhydramine hydrochloride is an antihistamine nasal stuffiness. with anticholinergic (drying) and sedative side effects. PRECAUTIONS Antihistamines appear to compete with histamine for General: Diphenhydramine hydrochloride has an OVERDOSAGE cell receptor sites on effector cells. atropine-like action and, therefore should be used Antihistamine overdosage reactions may vary from Diphenhydramine hydrochloride in the injectable with caution in patients with a history of bronchial central nervous system depression to stimulation. form has a rapid onset of action. Diphenhydramine asthma, increased intraocular pressure, hyperthyroid- Stimulation is particularly likely in pediatric patients. ism, cardiovascular disease or hypertension. Use with hydrochloride is widely distributed throughout the Atropine-like signs and symptoms; dry mouth; fixed, body, including the CNS. A portion of the drug is caution in patients with lower respiratory disease including asthma. dilated pupils; flushing; and gastrointestinal symp- excreted unchanged in the urine, while the rest toms may also occur. is metabolized via the liver. Detailed information Information for Patients: Patients taking diphen- Stimulants should not be used. on the pharmacokinetics of Diphenhydramine hydramine hydrochloride should be advised that this Hydrochloride Injection is not available. drug may cause drowsiness and has an additive effect Vasopressors may be used to treat hypotension. with alcohol. INDICATIONS AND USAGE Patients should be warned about engaging in activ- DOSAGE AND ADMINISTRATION Diphenhydramine hydrochloride in the injectable ities requiring mental alertness such as driving a car THIS PRODUCT IS FOR INTRAVENOUS OR INTRA- form is effective in adults and pediatric patients, or operating appliances, machinery, etc. MUSCULAR ADMINISTRATION ONLY. other than premature infants and neonates, for the following conditions when diphenhydramine hydro- Drug Interactions: Diphenhydramine hydrochloride Diphenhydramine hydrochloride in the injectable chloride in the oral form is impractical. has additive effects with alcohol and other CNS form is indicated when the oral form is impractical. depressants (hypnotics, sedatives, tranquilizers, etc). Antihistaminic: For amelioration of allergic reactions Parenteral drug products should be inspected visually MAO inhibitors prolong and intensify the anticholin- to blood or plasma, in anaphylaxis as an adjunct to for particulate matter and discoloration prior to admin- ergic (drying) effects of antihistamines. epinephrine and other standard measures after the istration, whenever solution and container permit. acute symptoms have been controlled, and for other Carcinogenesis, Mutagenesis, Impairment of Fertility: DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING uncomplicated allergic conditions of the immediate Long-term studies in animals to determine mutagenic TO THE NEEDS AND THE RESPONSE OF THE PATIENT. type when oral therapy is impossible or contraindi- and carcinogenic potential have not been performed. cated. Pregnancy: Pregnancy Category B: Reproduction Pediatric Patients, other than premature infants and Motion Sickness: For active treatment of motion sick- 2 studies have been performed in rats and rabbits at neonates: 5 mg/kg/24 hr or 150 mg/m /24 hr. Maximum ness. doses up to 5 times the human dose and have daily dosage is 300 mg. Divide into four doses, admin- Antiparkinsonism: For use in parkinsonism, when oral revealed no evidence of impaired fertility or harm to istered intravenously at a rate generally not exceed- therapy is impossible or contraindicated, as follows: the fetus due to diphenhydramine hydrochloride. ing 25 mg/min, or deep intramuscularly. parkinsonism in the elderly who are unable to toler- There are, however, no adequate and well-controlled ate more potent agents; mild cases of parkinsonism studies in pregnant women. Because animal repro- Adults: 10 mg to 50 mg intravenously at a rate gener- in other age groups, and in other cases of parkinson- duction studies are not always predictive of human ally not exceeding 25 mg/min, or deep intramuscu- ism in combination with centrally acting anticholin- response, this drug should be used during pregnancy larly, 100 mg if required; maximum daily dosage is ergic agents. only if clearly needed. 400 mg.

Reference ID: 3243048 P0104 1212.indd 1 2013/01/04 8:42 AM HOW SUPPLIED 5. Do not remove plastic wrap around the external Diphenhydramine Hydrochloride Injection, USP is a collar. Push plunger rod slightly to break the stop- clear and colorless solution available as: per loose while tip cap is still on. 50 mg/mL in a 1 mL prefilled single-use syringe. 6. Do not remove plastic wrap around the external Available in a carton of twenty-four (24) syringes. collar. Remove tip cap by twisting it off. 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. 7. Discard the tip cap. Instructions for use: 8. Expel air bubble. CAUTION: Certain glass syringes may malfunction, 9. Adjust dose into sterile material (if applicable). break or clog when connected to some Needleless 10. Connect the syringe to appropriate injection con- Luer Access Devices (NLADs) and needles. This syringe nection depending on route of administration. has a larger internal syringe tip and an external collar Before injection, ensure that the syringe is secure- (luer adapter). The external collar must remain ly attached to the needle or NLAD. attached to the syringe. Data show that the syringe achieves acceptable connections with the BD Eclipse™ 11. Depress plunger rod to deliver medication. Needle and the Terumo SurGuard2™Safety Needle 12. Remove syringe from IV connector (if applicable) and with the following non-center post NLADs: Alaris and discard into appropriate receptacle. If deliv- SMARTSITE™, B-Braun ULTRASITE™, BD-Q SYTE™, ering medication via intramuscular route, do not Maximum MAX PLUS™, and B-Braun SAFSITE™. The recap needle. data also show acceptable connections are achieved to the center post ICU Medical CLAVE™. However, spontaneous disconnection of this glass syringe from NOTES: needles and NLADs with leakage of drug product – All steps must be done sequentially. may occur. Assure that the needle or NLAD is securely – Do not autoclave syringe. attached before beginning the injection. Visually – Do not use this product on a sterile field. inspect the glass syringe-needle or glass syringe- – Do not introduce any other fluid into the NLAD connection before and during drug administra- syringe at any time. tion. Do not remove the clear plastic wrap around the – This product is for single dose only. external collar. For more information concerning this drug or to Plastic Wrap report an adverse event please call BD Rx Inc. at (Do Not Remove) 1-866-943-8534.

Syringe Tip Cap Simplist™ (Remove)  External Collar (Do Not Remove) 1. Inspect the outer packaging (blister pack) for: Verify: – blister integrity – expiry date Rev 12/12 – drug name, drug strength P0104 – dose volume – route of administration – sterile field applicability BD Rx Inc. 2. Peel open the paper (top web) of the outer pack- Franklin Lakes, NJ 07417 aging that displays the product information to access the syringe. Do not pop syringe through. 3. Bend the plastic part of the outer packaging (thermoform) so as to present the plunger rod for syringe removal.

4. Perform visual inspection on the syringe Verify: – absence of external particles – absence of internal particles – solution is clear and colorless – expiration date – drug name, drug strength – dose volume – route of administration – sterile field applicability – Integrity of the plastic wrap around the exter- nal collar

Reference ID: 3243048 P0104 1212.indd 2 2013/01/04 8:42 AM