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Each tablet of Phenergan contains 12.5 mg, 25 mg, or 50 mg promethazine hydrochloride. The inactive ingredients present are lactose, magnesium stearate, and methylcellulose. Each dosage strength also contains the following:
12.5 mg--FD&C Yellow 6 and saccharin sodium;
50 mg--FD&C Red 40.
Each rectal suppository of Phenergan contains 12.5 mg, 25 mg, or 50 mg promethazine hydrochloride with ascorbyl palmitate, silicon dioxide, white wax, and cocoa butter. Phenergan Suppositories are for rectal administration only.
Promethazine hydrochloride is a racemic compound; the empirical formula is C 17 H 20 N 2 S·HCl and its molecular weight is 320.88.
Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10 H -Phenothiazine-10-ethanamine, N,N, (alpha)-trimethyl-, monohydrochloride, (±)- with the following structural formula:
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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.
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 dopaminergic (CNS) action.
Promethazine is an H 1 receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects. In therapeutic dosage, promethazine produces no significant effects on the cardiovascular system.
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.
Phenergan, either orally or by suppository, is 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.
Dermographism.
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 is 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 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 hydrochloride (see PRECAUTIONS -- Information for Patients and Drug Interactions ).
Phenergan Tablets and Suppositories may lead to potentially fatal respiratory depression.
Use of Phenergen Tablets and Suppositories in patients with compromised respiratory function (e.g. COPD, sleep apnea) should be avoided.
Promethazine 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 threshold.
Phenergan Tablets and Suppositories should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when Phenergan has been used in association with other bone marrow-toxic agents.
PHENERGAN TABLETS AND SUPPOSITORIES ARE NOT RECOMMENDED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PHENERGAN TABLETS AND SUPPOSITORIES TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. 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 PHENERGAN TABLETS AND SUPPOSITORIES ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE'S SYNDROME. THE USE OF PHENERGAN TABLETS AND 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 in pediatric patients may cause hallucinations, convulsions, and sudden death. In pediatric patients who are actually 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 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 obstruction.
Promethazine should be used cautiously in persons with cardiovascular disease or with impairment of liver function.
Phenergan 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. Ambulatory patients should be told to avoid engaging in such activities until it is known that they do not become drowsy or dizzy from Phenergan therapy. Children should be supervised to avoid potential harm in bike riding or in 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 or unusual sensitivity to sunlight.
CNS Depressants --Phenergan Tablets and Suppositories may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine. When given concomitantly with Phenergan Tablets and Suppositories, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics 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 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 Phenergan to reverse epinephrine' vasopressor effect, epinephrine should NOT be used to treat hypotension associated withPhenergan overdose.
Anticholinergics --Concomitant use of other agents with anticholinergic properties should be undertaken with caution.
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 Phenergan Tablets and Suppositories.
The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride:
Pregnancy Tests
Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.
An increase in blood glucose has been reported in patients receiving promethazine.
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. 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. 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, including promethazine, 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 in pregnant women. Phenergan® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects
Promethazine taken within two weeks of delivery may inhibit platelet aggregation in the newborn.
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 Phenergan Tablets 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 is excreted in human milk. Caution should be exercised when promethazine is administered to a nursing woman.
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Phenergan Tablets and Suppositories, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in children under 2 years of age have not been established.
Phenergan Tablets and Suppositories should be used with caution in pediatric patients 2 years of age and older (see WARNINGS -- Use in Pediatric Patients ).
Nervous System --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.
Dermatolgic --Dermatitis, photosensitivity, urticaria.
Hematologic --Rarely leukopenia, thrombocytopenia; agranulocytosis (1 case).
Gastrointestinal --Dry mouth, nausea, vomiting, jaundice.
Respiratory --Astham, nasal stuffness, respiratory depression (potentially fatal) and apnea (potentially fatal).
(See WARNINGS -- Respiratory Depression ).
Other --Angioneurotic edema.
Hyperexcitability and abnormal movements, which have been reported in pediatric patients following a single administration of promethazine, may be manifestations of relative overdosage, in which case, consideration should be given to the discontinuation of the promethazine and to the use of other drugs. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.
Signs and symptoms of overdosage with promethazine range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, and unconsciousness.
Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical 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 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 anti-parkinson agents, diphenhydramine, or barbiturates. Oxygen may also be administered.
Limited experience with dialysis indicates that it is not helpful.
Phenergan Tablets and Phenergan Rectal Suppositories are not recommended for children under 2 years of age (see WARNINGS -- Use in Pediatric Patients ).
Phenergan Suppositories are for rectal administration only.
The average oral dose is 25 mg taken before retiring; however, 12.5 mg may be taken before meals and on retiring, if necessary. Children tolerate this product well. 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, Phenergan Tablets, Syrup, or Rectal Suppositories, 12.5 to 25 mg, twice daily, may be administered.
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 Phenergan 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. Phenergan 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 Phenergan 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.
Phenergan 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 Phenergan 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.
Phenergan Tablets and Phenergan Rectal Suppositories are not recommended for children under 2 years of age.
Phenergan® (promethazine HCl) Tablets are available as follows:
12.5 mg, orange tablet with "WYETH" on one side and "19" on the scored reverse side.
NDC 0008-0019-01, bottle of 100 tablets.
25 mg, white tablet with "WYETH" and "27" on one side and scored on the reverse side.
NDC 0008-0027-02, bottle of 100 tablets.
NDC 0008-0027-07, Redipak® carton of 100 tablets (10 blister strips of 10).
50 mg, pink tablet with "WYETH" on one side and "227" on the other side.
NDC 0008-0227-01, bottle of 100 tablets.
Keep tightly closed.
Store at room temperature, between 15°C and 25°C (59°F and 77°F).
Protect from light.
Dispense in light-resistant, tight container.
Use carton to protect contents from light.
Phenergan® (promethazine HCl) Rectal Suppositories are available in boxes of 12 as follows:
12.5 mg, ivory, torpedo-shaped suppository wrapped in copper-colored foil, NDC 0008-0498-01.
25 mg, ivory, torpedo-shaped suppository wrapped in light-green foil, NDC 0008-0212-01.
50 mg, ivory, torpedo-shaped suppository wrapped in blue foil, NDC 0008-0229-01.
Store refrigerated between 2°-8°C (36°-46°F).
Dispense in well-closed container.
Manufactured by:
Wyeth Laboratories
A Wyeth-Ayerst Company
Philadelphia, PA 19101
CI 5184-1 Issued March 29, 1999
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