United States - English - NLM (National Library of Medicine)
PROMETHAZINE HYDROCHLORIDE- promethazine hydrochloride suppository
A-S Medication Solutions
Each rectal suppository contains 12.5 mg or 25 mg promethazine HCl with ascorbyl
palmitate, colloidal silicon dioxide, glyceryl monostearate, hard fat, and white wax.
Promethazine HCl Suppositories, USP are for rectal administration only.
Promethazine HCl is a racemic compound; the empirical formula is C
N S∙HCl and
its molecular weight is 320.88.
Promethazine HCl, a phenothiazine derivative, is designated chemically as 10H-
Phenothiazine, 10-ethanamine, N,N, α-trimethyl-, monohydrochloride, (±)- with the
following structural formula:
Promethazine HCl 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.
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 properties.
Promethazine is an H receptor blocking agent. In addition to its antihistaminic action, it
provides clinically useful sedative and antiemetic effects.
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 HCl Suppositories, USP 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 postoperative 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 HCl Suppositories are contraindicated for use in pediatric patients less
than two years of age.
Promethazine HCl Suppositories 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 asthma.
PROMETHAZINE HCL SUPPOSITORIES 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 HCL
SUPPOSITORIES IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A
WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HCL
SUPPOSITORIES HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE
HCL TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER.
IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF
PROMETHAZINE HCL BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE
AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS
WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED.
Promethazine HCl Suppositories 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 HCl Suppositories may lead to potentially fatal respiratory depression.
Use of Promethazine HCl Suppositories in patients with compromised respiratory
function (e.g., COPD, sleep apnea) should be avoided.
Lower Seizure Threshold
Promethazine HCl Suppositories may lower seizure threshold. It 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
Promethazine HCl Suppositories 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 cardiac dysrhythmias).
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 illnesses (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
Since recurrences of NMS have been reported with phenothiazines, the reintroduction of
promethazine HCl should be carefully considered.
Use in Pediatric Patients
PROMETHAZINE HCL SUPPOSITORIES ARE CONTRAINDICATED FOR THE USE IN
PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCL
SUPPOSITORIES 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 PEDIATRIC PATIENTS.
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 HCL
SUPPOSITORIES ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS
OF UNDIAGNOSED PRIMARY DISEASE, E.G., ENCEPHALOPATHY OR REYE'S
SYNDROME. THE USE OF PROMETHAZINE HCL SUPPOSITORIES 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 HCl Suppositories,
in pediatric patients may cause sudden death (see OVERDOSAGE). Hallucinations and
convulsions have occurred with therapeutic doses and overdoses of promethazine HCl
in pediatric patients. In pediatric patients who are acutely ill associated with dehydration,
there is an increased susceptibility to dystonias with the use of promethazine HCl.
Administration of promethazine HCl has been associated with reported cholestatic
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 obstruction.
Promethazine HCl Suppositories should be used cautiously in persons with
cardiovascular disease or with impairment of liver function.
Information for Patients
Promethazine HCl Suppositories 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 other hazardous activities.
The concomitant use of alcohol or other central nervous system depressants, including
narcotic analgesics, sedatives, hypnotics, and tranquilizers, may have an additive effect
and should be avoided or their dosage reduced.
Patients should be advised to report any involuntary muscle movements.
Avoid prolonged exposure to the sun.
Promethazine HCl Suppositories 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 HCl Suppositories, 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.
Because of the potential for promethazine HCl to reverse epinephrine's vasopressor
effect, epinephrine should NOT be used to treat hypotension associated with
Promethazine HCl Suppositories overdose.
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 HCl Suppositories.
Drug/Laboratory Test Interactions
The following laboratory tests may be affected in patients who are receiving therapy with
Diagnostic pregnancy tests based on immunological reactions between HCG and anti-
HCG may result in false-negative or false-positive 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.
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. 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 rats.
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
HCl Suppositories in pregnant women.
Promethazine HCl Suppositories should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
Promethazine HCl Suppositories 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 and delivery. (See "DOSAGE AND ADMINISTRATION"). Limited data suggest
that use of promethazine HCl 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 HCl Suppositories, 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 HCL SUPPOSITORIES ARE CONTRAINDICATED FOR USE IN
PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (see WARNINGS-Black
Box Warning and Use in Pediatric Patients).
Promethazine HCl Suppositories 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 HCl suppositories and
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,
Dermatologic – Dermatitis, photosensitivity, urticaria.
Hematologic – Leukopenia, thrombocytopenia, thrombocytopenic purpura,
Gastrointestinal – Dry mouth, nausea, vomiting, jaundice.
Respiratory – Asthma, nasal stuffiness, respiratory depression (potentially fatal) and
apnea (potentially fatal). (See WARNINGS–Respiratory 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.
To report SUSPECTED ADVERSE REACTIONS, contact G&W Laboratories, Inc.
at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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, and 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 that 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 HCl Rectal Suppositories are contraindicated for children under
2 years of age (see WARNINGS–Black Box Warning and Use in Pediatric
Promethazine HCl Suppositories are for rectal administration only.
The average 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 hydrochloride 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 HCl Rectal
Suppositories, 12.5 to 25 mg, twice daily, may be administered.
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 HCl for the active therapy of nausea and
vomiting in children or adults is 25 mg. 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 HCl 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 Postopertive Use
Promethazine HCl 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 HCl Rectal Suppositories are not recommended for children under 2 years
NDC: 50090-5362-1 1 SUPPOSITORY in a BLISTER PACK / 4 in a CARTON
NDC: 50090-5362-2 1 SUPPOSITORY in a BLISTER PACK / 12 in a CARTON
Mfd. by: Cosette Pharmaceuticals, Inc.
111 Coolidge Street, South Plainfield, NJ 07080
Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532