ABD - İngilizce - NLM (National Library of Medicine)
PROMETHAZINE HYDROCHLORIDE- promethazine hydrochloride tablet
STAT Rx USA LLC
Promethazine Hydrochloride Tablets USP
Revised: June 2009
Promethazine hydrochloride is a racemic compound.
Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10 H-
Phenothiazine-10-ethanamine, N, N,α-trimethyl-, monohydrochloride, (±)- with the following structural
H N SHCl M.W. 320.88
Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder
which slowly oxidizes and turns blue on prolonged exposure to air. It is soluble in water and freely
soluble in alcohol.
Each tablet, for oral administration, contains 25 mg or 50 mg of promethazine hydrochloride. In addition
each tablet contains the following inactive ingredients: dibasic calcium phosphate, magnesium stearate,
microcrystalline cellulose, sodium starch glycolate and stearic acid.
Promethazine Hydrochloride Tablets USP, 50 mg also contain anhydrous lactose.
Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic
phenothiazines by the presence of a branched side chain and no ring substitution. It is thought that this
configuration is responsible for its relative lack (1/10 that of chlorpromazine) of dopamine antagonist
Promethazine is an H receptor blocking agent. In addition to its antihistaminic action, it provides
clinically useful sedative and antiemetic effects.
Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20
minutes after oral administration and generally last four to six hours, although they may persist as long
as 12 hours. Promethazine is metabolized by the liver to a variety of compounds; the sulfoxides of
promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.
INDICATIONS AND USAGE
Promethazine hydrochloride tablets are useful for:
Perennial and seasonal allergic rhinitis.
Allergic conjunctivitis due to inhalant allergens and foods.
Mild, uncomplicated allergic skin manifestations of urticaria and angioedema.
Amelioration of allergic reactions to blood or plasma.
Anaphylactic reactions, as adjunctive therapy to epinephrine and other standard measures, after the acute
manifestations have been controlled.
Preoperative, postoperative, or obstetric sedation.
Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery.
Therapy adjunctive to meperidine or other analgesics for control of post-operative pain.
Sedation in both children and adults, as well as relief of apprehension and production of light sleep
from which the patient can be easily aroused.
Active and prophylactic treatment of motion sickness.
Antiemetic therapy in postoperative patients.
Promethazine hydrochloride tablets are contraindicated for use in pediatric patients less than two years
Promethazine hydrochloride tablets are contraindicated in comatose states, and in individuals known to
be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines.
Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including
PROMETHAZINE HYDROCHLORIDE TABLETS USP SHOULD NOT BE USED IN
PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL
FOR FATAL RESPIRATORY DEPRESSION.
POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITIES,
HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HYDROCHLORIDE IN
PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-
BASED DOSES OF PROMETHAZINE HYDROCHLORIDE HAVE RESULTED IN
RESPIRATORY DEPRESSION IN THESE PATIENTS. CAUTION SHOULD BE
EXERCISED WHEN ADMINISTERING PROMETHAZINE HYDROCHLORIDE TO
PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. IT IS RECOMMENDED THAT
THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HYDROCHLORIDE BE USED IN
PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT
ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS
Promethazine hydrochloride tablets may impair the mental and/or physical abilities required for the
performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The
impairment may be amplified by concomitant use of other central-nervous-system depressants such as
alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics,
tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in
reduced dosage in the presence of promethazine HCl (see PRECAUTIONS-Information for Patients
and Drug Interactions).
Promethazine hydrochloride tablets may lead to potentially fatal respiratory depression.
Use of promethazine hydrochloride tablets in patients with compromised respiratory function (e.g.,
COPD, sleep apnea) should be avoided.
Lower Seizure Threshold
Promethazine hydrochloride tablets may lower seizure threshold. They should be used with caution in
persons with seizure disorders or in persons who are using concomitant medications, such as narcotics
or local anesthetics, which may also affect seizure threshold.
Promethazine hydrochloride tablets should be used with caution in patients with bone-marrow
depression. Leukopenia and agranulocytosis have been reported, usually when promethazine HCl has
been used in association with other known marrow-toxic agents.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS)
has been reported in association with promethazine HCl alone or in combination with antipsychotic
drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and
evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is
important to identify cases where the clinical presentation includes both serious medical illness (e.g.
pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and
symptoms (EPS). Other important considerations in the differential diagnosis include central
anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of promethazine HCl,
antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic
treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for
which specific treatments are available. There is no general agreement about specific pharmacological
treatment regimens for uncomplicated NMS.
Since recurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine
HCl should be carefully considered.
Use in Pediatric Patients
PROMETHAZINE HYDROCHLORIDE TABLETS USP ARE CONTRAINDICATED FOR
USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE
HYDROCHLORIDE TABLETS TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER
BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION.
RESPIRATORY DEPRESSION AND APNEA, SOMETIMES ASSOCIATED WITH DEATH,
ARE STRONGLY ASSOCIATED WITH PROMETHAZINE PRODUCTS AND ARE NOT
DIRECTLY RELATED TO INDIVIDUALIZED WEIGHT-BASED DOSING, WHICH MIGHT
OTHERWISE PERMIT SAFE ADMINISTRATION. CONCOMITANT ADMINISTRATION
OF PROMETHAZINE PRODUCTS WITH OTHER RESPIRATORY DEPRESSANTS HAS AN
ASSOCIATION WITH RESPIRATORY DEPRESSION, AND SOMETIMES DEATH, IN
ANTIEMETICS ARE NOT RECOMMENDED FOR TREATMENT OF UNCOMPLICATED
VOMITING IN PEDIATRIC PATIENTS, AND THEIR USE SHOULD BE LIMITED TO
PROLONGED VOMITING OF KNOWN ETIOLOGY. THE EXTRAPYRAMIDAL
SYMPTOMS WHICH CAN OCCUR SECONDARY TO PROMETHAZINE
HYDROCHLORIDE TABLETS ADMINISTRATION MAY BE CONFUSED WITH THE CNS
SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE’S
SYNDROME. THE USE OF PROMETHAZINE HCL TABLETS SHOULD BE AVOIDED IN
PEDIATRIC PATIENTS WHOSE SIGNS AND SYMPTOMS MAY SUGGEST REYE’S
SYNDROME OR OTHER HEPATIC DISEASES.
Excessively large dosages of antihistamines, including promethazine hydrochloride tablets, in pediatric
patients may cause sudden death (see OVERDOSAGE). Hallucinations and convulsions have occurred
with therapeutic doses and overdoses of promethazine in pediatric patients. In pediatric patients who are
acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of
Administration of promethazine HCl has been associated with reported cholestatic jaundice.
Drugs having anticholinergic properties should be used with caution in patients with narrow-angle
glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck
Promethazine hydrochloride tablets should be used cautiously in persons with cardiovascular disease
or with impairment of liver function.
Information for Patients
Promethazine hydrochloride tablets may cause marked drowsiness or impair the mental and/or physical
abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or
operating machinery. The use of alcohol or other central-nervous-system depressants such as
sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics,
tricyclic antidepressants, and tranquilizers, may enhance impairment (see WARNINGS-CNS
Depression and PRECAUTIONS-Drug Interactions). Pediatric patients should be supervised to
avoid potential harm in bike riding or in other hazardous activities.
Patients should be advised to report any involuntary muscle movements.
Avoid prolonged exposure to the sun.
CNS Depressants - Promethazine hydrochloride tablets may increase, prolong, or intensify the sedative
action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including
barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and
tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients
receiving promethazine HCl. When given concomitantly with promethazine hydrochloride tablets, the
dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced
by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine HCl
relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these
symptoms usually disappear with adequate control of the pain.
Epinephrine - Because of the potential for promethazine to reverse epinephrine’s vasopressor effect,
epinephrine should NOT be used to treat hypotension associated with promethazine hydrochloride
Anticholinergics - Concomitant use of other agents with anticholinergic properties should be undertaken
Monoamine Oxidase Inhibitors (MAOI) - Drug interactions, including an increased incidence of
extrapyramidal effects, have been reported when some MAOI and phenothiazines are used
concomitantly. This possibility should be considered with promethazine hydrochloride tablets.
Drug/Laboratory Test Interactions
The following laboratory tests may be affected in patients who are receiving therapy with promethazine
Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in
false-negative or falsepositive interpretations.
Glucose Tolerance Test
An increase in blood glucose has been reported in patients receiving promethazine HCl.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine,
nor are there other animal or human data concerning carcinogenicity, mutagenicity or impairment of
fertility with this drug. Promethazine was nonmutagenic in the Salmonella test system of Ames.
Teratogenic Effects-Pregnancy Category C
Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg
of promethazine HCl. These doses are from approximately 2.1 to 4.2 times the maximum recommended
total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug
is prescribed. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in
Specific studies to test the action of the drug on parturition, lactation, and development of the animal
neonate were not done, but a general preliminary study in rats indicated no effect on these parameters.
Although antihistamines have been found to produce fetal mortality in rodents, the pharmacological
effects of histamine in the rodent do not parallel those in man. There are no adequate and well-
controlled studies of promethazine hydrochloride tablets in pregnant women.
Promethazine hydrochloride tablets should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Promethazine hydrochloride tablets administered to a pregnant woman within two weeks of delivery may
inhibit platelet aggregation in the newborn.
Labor and Delivery
Promethazine HCl may be used alone or as an adjunct to narcotic analgesics during labor (see DOSAGE
AND ADMINISTRATION). Limited data suggest that use of promethazine during labor and delivery
does not have an appreciable effect on the duration of labor or delivery and does not increase the risk
of need for intervention in the newborn. The effect on later growth and development of the newborn is
unknown. (See also Nonteratogenic Effects.)
It is not known whether promethazine HCl is excreted in human milk. Because many drugs are excreted
in human milk and because of the potential for serious adverse reactions in nursing infants from
promethazine hydrochloride tablets, a decision should be made whether to discontinue nursing or to
discontinue the drug, taking into account the importance of the drug to the mother.
PROMETHAZINE HYDROCHLORIDE TABLETS USP ARE CONTRAINDICATED FOR
USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (see WARNINGS-Black
Box Warning and Use in Pediatric Patients).
Promethazine hydrochloride tablets should be used with caution in pediatric patients 2 years of age and
older (see WARNINGS-Use in Pediatric Patients).
Clinical studies of promethazine formulations did not include sufficient numbers of subjects aged 65
and over to determine whether they respond differently from younger subjects. Other reported clinical
experience has not identified differences in responses between the elderly and younger patients. In
general, dose selection for an elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of
concomitant disease or other drug therapy.
Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should
be started on low doses of promethazine hydrochloride tablets and observed closely.
Central Nervous System
Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision,
dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis,
and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia,
insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have
also been reported.
Cardiovascular - Increased or decreased blood pressure, tachycardia, bradycardia, faintness.
Dermatologic - Dermatitis, photosensitivity, urticaria.
Hematologic - Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.
Gastrointestinal - Dry mouth, nausea, vomiting, jaundice.
Respiratory - Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially
fatal). (See WARNINGSRespiratory Depression.)
Other - Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been
reported. (See WARNINGS-Neuroleptic Malignant Syndrome.)
Hyperexcitability and abnormal movements have been reported in patients following a single
administration of promethazine HCl. Consideration should be given to the discontinuation of
promethazine HCl and to the use of other drugs if these reactions occur. Respiratory depression,
nightmares, delirium, and agitated behavior have also been reported in some of these patients.
Signs and symptoms of overdosage with promethazine HCl range from mild depression of the central
nervous system and cardiovascular system to profound hypotension, respiratory depression,
unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia,
athetosis, and extensor-plantar reflexes (Babinski reflex).
Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur.
A paradoxical-type reaction has been reported in children receiving single doses of 75 mg to 125 mg
orally, characterized by hyperexcitability and nightmares.
Atropine-like signs and symptoms — dry mouth, fixed, dilated pupils, flushing, as well as
gastrointestinal symptoms — may occur.
Treatment of overdosage is essentially symptomatic and supportive. Only in cases of extreme
overdosage or individual sensitivity do vital signs, including respiration, pulse, blood pressure,
temperature, and EKG, need to be monitored. Activated charcoal orally or by lavage may be given, or
sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of
adequate respiratory exchange through provision of a patent airway and institution of assisted or
controlled ventilation. Diazepam may be used to control convulsions. Acidosis and electrolyte losses
should be corrected. Note that any depressant effects of promethazine HCl are not reversed by
naloxone. Avoid analeptics which may cause convulsions.
The treatment of choice for resulting hypotension is administration of intravenous fluids, accompanied
by repositioning if indicated. In the event that vasopressors are considered for the management of
severe hypotension which does not respond to intravenous fluids and repositioning, the administration
of norepinephrine or phenylephrine should be considered. EPINEPHRINE SHOULD NOT BE USED,
since its use in patients with partial adrenergic blockade may further lower the blood pressure.
Extrapyramidal reactions may be treated with anticholinergic antiparkinsonian agents, diphenhydramine,
or barbiturates. Oxygen may also be administered.
Limited experience with dialysis indicates that it is not helpful.
DOSAGE AND ADMINISTRATION
Promethazine Hydrochloride Tablets USP are contraindicated for children under 2 years of age
(see WARNINGS-Black Box Warning and Use in Pediatric Patients).
The average oral dose is 25 mg taken before retiring; however, 12.5 mg may be taken before meals and
on retiring, if necessary. Single 25-mg doses at bedtime or 6.25 to 12.5 mg taken three times daily will
usually suffice. After initiation of treatment in children or adults, dosage should be adjusted to the
smallest amount adequate to relieve symptoms. The administration of promethazine HCl in 25-mg doses
will control minor transfusion reactions of an allergic nature.
The average adult dose is 25 mg taken twice daily. The initial dose should be taken one-half to one hour
before anticipated travel and be repeated 8 to 12 hours later, if necessary. On succeeding days of travel,
it is recommended that 25 mg be given on arising and again before the evening meal. For children,
promethazine hydrochloride tablets, syrup, or rectal suppositories, 12.5 to 25 mg twice daily, may be
Nausea and Vomiting
Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see
WARNINGS-Use in Pediatric Patients).
The average effective dose of promethazine hydrochloride for the active therapy of nausea and
vomiting in children or adults is 25 mg. When oral medication cannot be tolerated, the dose should be
given parenterally (cf. Promethazine Injection) or by rectal suppository. 12.5- to 25-mg doses may be
repeated, as necessary, at 4- to 6-hour intervals.
For nausea and vomiting in children, the usual dose is 0.5 mg per pound of body weight, and the dose
should be adjusted to the age and weight of the patient and the severity of the condition being treated.
For prophylaxis of nausea and vomiting, as during surgery and the postoperative period, the average
dose is 25 mg repeated at 4- to 6-hour intervals, as necessary.
This product relieves apprehension and induces a quiet sleep from which the patient can be easily
aroused. Administration of 12.5 to 25 mg promethazine hydrochloride by the oral route or by rectal
suppository at bedtime will provide sedation in children. Adults usually require 25 to 50 mg for
nighttime, presurgical, or obstetrical sedation.
Pre- and Postoperative Use
Promethazine hydrochloride in 12.5- to 25-mg doses for children and 50-mg doses for adults the night
before surgery relieves apprehension and produces a quiet sleep.
For preoperative medication, children require doses of 0.5 mg per pound of body weight in
combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of
an atropine-like drug. Usual adult dosage is 50 mg promethazine HCl with an appropriately reduced
dose of narcotic or barbiturate and the required amount of a belladonna alkaloid.
Postoperative sedation and adjunctive use with analgesics may be obtained by the administration of 12.5
to 25 mg in children and 25- to 50-mg doses in adults.
Promethazine hydrochloride tablets are contraindicated for children under 2 years of age.
Promethazine Hydrochloride Tablets USP, 25 mg are scored, round, white tablets imprinted DAN DAN
and 5307 supplied in:
Bottles of 10 NDC # 16590-191-10
Bottles of 15 NDC # 16590-191-15
Bottles of 20 NDC # 16590-191-20
Bottles of 28 NDC # 16590-191-28
Bottles of 30 NDC # 16590-191-30
Bottles of 45 NDC # 16590-191-45
Bottles of 56 NDC # 16590-191-56
Bottles of 60 NDC # 16590-191-60
Bottles of 120 NDC # 16590-191-72
Bottles of 112 NDC # 16590-191-73
Bottles of 75 NDC # 16590-191-75
Bottles of 90 NDC # 16590-191-90
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure.
Keep tightly closed.
Store at 20-25°C (68-77°F). [See USP controlled room temperature.]
Protect from light.
Watson Pharma Private Ltd.
Verna, Salcette Goa 403 722 INDIA
Watson Pharma, Inc.
Corona, CA 92880 USA
Revised: June 2009
Relabeling and Repackaging by:
STAT Rx USA LLC
Gainesville, GA. 30501
PACKAGE LABEL - PROMETHAZINE 25 MG TABLETS
promethazine hydrochloride tablet
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:16 59 0 -19 1(NDC:0 59 1-530 7)
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
PRO METHAZINE HYDRO CHLO RIDE (UNII: R6 1ZEH7I1I) (PROMETHAZINE -
UNII:FF28 EJQ 49 4)
Stre ng th
DIBASIC CALCIUM PHO SPHATE DIHYDRATE (UNII: O7TSZ9 7GEP)
MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )
CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)
SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)
STEARIC ACID (UNII: 4ELV7Z6 5AP)
S hap e
S iz e
Marketing Start Date
Marketing End Date
NDC:16 59 0 -19 1-10
10 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-15
15 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-20
20 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-28
28 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-30
30 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-45
45 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-56
56 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-6 0
6 0 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-72
120 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-73
112 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-75
75 in 1 BOTTLE, PLASTIC
NDC:16 59 0 -19 1-9 0
9 0 in 1 BOTTLE, PLASTIC
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 8 3426
0 9 /19 /19 73
ST AT Rx USA LLC (786036330)
STAT Rx USA LLC
PSS World Medical Inc. (101822682)
Ad d re s s
Busine ss Ope rations
STAT Rx USA LLC
78 6 0 36 330
relabel(16 59 0 -19 1) , repack(16 59 0 -19 1)