DIPHENHYDRAMINE- diphenhydramine hydrochloride injection, solution

DIPHENHYDRAMINE by

Drug Labeling and Warnings

DIPHENHYDRAMINE by is a Prescription medication manufactured, distributed, or labeled by Micro Labs Limited. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

DESCRIPTION

Diphenhydramine hydrochloride USP 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 17H 21NO HCI. The structural formula is as follows:

Diphenhydramine hydrochloride USP in the parenteral form is a sterile, pyrogen-free solution available in a concentration of 50 mg of diphenhydramine hydrochloride USP per mL. The solutions for parenteral use have been adjusted to a pH between 4 and 6.5 with either sodium hydroxide or hydrochloric acid.

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.

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.

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.

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 injection.

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.

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 injection 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.

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 or throat and wheezing, nasal stuffiness.

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.

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 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.

HOW SUPPLIED

Diphenhydramine Hydrochloride Injection, USPin parenteral form is supplied as:

Sterile, pyrogen-free solution containing 50 mg diphenhydramine hydrochloride USP in a 1 mL amber color glass ampule with yellow bands and white OPC mark, and available in packages of ten packed in a PVC rondo tray in a single carton.

1 mL fill in 1 mL Ampule                               NDC: 42571-169-54

Carton of 10 x 1 mL Ampule                         NDC: 42571-169-55

Clear, colorless solution, free from any visible particles, no visible leaks or damage to the container closure system filled in tubular USP Type I glass vials.

1 mL fill in 2 mLVial                                       NDC: 42571-337-95

Carton of 25 x 1 mL Vial                              NDC: 42571-337-87

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.

Rx only

Manufactured by:      

Micro Labs Limited

Bangalore-560 099, India.

Manufactured for:

Micro Labs USA Inc.

Basking Ridge, NJ 07920

Revised: September 2018

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-1 mL Ampule Label

NDC: 42571-169-54
DiphenhydrAMINE
HCl Injection, USP
50 mg/mL
Rx Only
HIGH POTENCY
IV or DEEP IM
1 mL
MICRO LABS

NDC: 42571-337-95
DiphenhydrAMINE
HCl Injection, USP
50 mg/mL
Rx Only
HIGH POTENCY
IV or DEEP IM
1 mL Single-Dose Vial
MICRO LABS

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-Carton of 10x1 mL Ampule

NDC: 42571-169-55
Rx Only
DiphenhydrAMINE Hydrochloride
Injection, USP
50 mg/mL
HIGH POTENCY
Sterile, Pyrogen-free
For Intravenous or Deep Intramuscular Use
10 Single-Dose Ampules (1 mL each)
MICRO LABS

NDC: 42571-337-87
Rx Only
DiphenhydrAMINE Hydrochloride
Injection, USP
50 mg/mL
HIGH POTENCY
Sterile, Pyrogen-free
For Intravenous or Deep Intramuscular Use
25 x 1 mL Single-Dose Vial
MICRO LABS

INGREDIENTS AND APPEARANCE

DIPHENHYDRAMINE  
diphenhydramine hydrochloride injection, solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 42571-169
Route of Administration	INTRAMUSCULAR, INTRAVENOUS

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
DIPHENHYDRAMINE HYDROCHLORIDE (UNII: TC2D6JAD40) (DIPHENHYDRAMINE - UNII:8GTS82S83M)	DIPHENHYDRAMINE HYDROCHLORIDE	50 mg  in 1 mL

Inactive Ingredients
Ingredient Name	Strength
SODIUM HYDROXIDE (UNII: 55X04QC32I)
HYDROCHLORIC ACID (UNII: QTT17582CB)
WATER (UNII: 059QF0KO0R)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 42571-169-55	10 in 1 CARTON	12/04/2018
1	NDC: 42571-169-54	1 mL in 1 AMPULE; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA205723	12/04/2018

DIPHENHYDRAMINE  
diphenhydramine hydrochloride injection, solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 42571-337
Route of Administration	INTRAVENOUS, INTRAMUSCULAR

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
DIPHENHYDRAMINE HYDROCHLORIDE (UNII: TC2D6JAD40) (DIPHENHYDRAMINE - UNII:8GTS82S83M)	DIPHENHYDRAMINE HYDROCHLORIDE	50 mg  in 1 mL

Inactive Ingredients
Ingredient Name	Strength
SODIUM HYDROXIDE (UNII: 55X04QC32I)
HYDROCHLORIC ACID (UNII: QTT17582CB)
WATER (UNII: 059QF0KO0R)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 42571-337-87	25 in 1 CARTON	12/10/2019
1	NDC: 42571-337-95	1 mL in 1 VIAL; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA205723	12/10/2019

Labeler - Micro Labs Limited (862174955)

Establishment
Name	Address	ID/FEI	Business Operations
Micro Labs Limited		677600482	analysis(42571-169, 42571-337) , label(42571-169, 42571-337) , manufacture(42571-169, 42571-337) , pack(42571-169, 42571-337)