PHENERGAN 12.5 MG Rectal Suppository

DRUG INTERACTIONS

Drug Interactions CNS Depressants – Phenergan (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 Phenergan (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.

Epinephrine – 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.

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 (Promethazine HCl) Suppositories.

OVERDOSAGE

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 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.

DESCRIPTION

Each rectal suppository contains 12.5 mg or 25 mg promethazine HCl with ascorbyl palmitate, colloidal silicon dioxide, white wax, hard fat, and glyceryl monostearate.

Phenergan (Promethazine HCl) Suppositories, USP are for rectal administration only.

Promethazine HCl is a racemic compound; the empirical formula is C 17 H 20 N 2 S•HCl and its molecular weight is 320.88.

Promethazine HCl, a phenothiazine derivative, is designated chemically as 10 H -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.

Structural formula

HOW SUPPLIED

Phenergan (Promethazine HCl) Rectal Suppositories, USP are available in boxes of 12 as follows: 12.5 mg, white, bullet-shaped suppository wrapped in silver foil.

Box of 12 NDC 40076-318-12 25 mg, white, bullet-shaped suppository wrapped in silver foil.

Box of 12 NDC 40076-319-12 Store refrigerated between 2°-8°C (36°-46°F).

Dispense in well-closed container.

Manufactured for: Prestium Pharma, Inc.

Newtown, PA 18940 By: G&W Laboratories, Inc.

South Plainfield, NJ 07080

GERIATRIC USE

Geriatric Use 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 Phenergan (Promethazine HCl) Suppositories and observed closely.

INDICATIONS AND USAGE

Phenergan (Promethazine HCl) Suppositories, USP are useful for: Perennial and seasonal allergic rhinitis.

Vasomotor 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.

PEDIATRIC USE

Pediatric Use PHENERGAN (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).

Phenergan (Promethazine HCl) Suppositories should be used with caution in pediatric patients 2 years of age and older (see WARNINGS – Use in Pediatric Patients ).

PREGNANCY

Pregnancy 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.

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 Phenergan (Promethazine HCl) Suppositories in pregnant women.

Phenergan (Promethazine HCl) Suppositories should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects Phenergan (Promethazine HCl) Suppositories administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.

NUSRING MOTHERS

Nursing Mothers 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 Phenergan (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.

BOXED WARNING

WARNINGS WARNING: PHENERGAN (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 PATIENTS.

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.

INFORMATION FOR PATIENTS

PRECAUTIONS General 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.

Phenergan (Promethazine HCl) Suppositories should be used cautiously in persons with cardiovascular disease or with impairment of liver function.

Information for Patients Phenergan (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.

DOSAGE AND ADMINISTRATION

Phenergan (Promethazine HCl) Suppositories are contraindicated for children under 2 years of age ( see WARNINGS–Black Box Warning and Use in Pediatric Patients).

Phenergan (Promethazine HCl) Suppositories are for rectal administration only.

Allergy 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.

Motion Sickness 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 (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.

Sedation 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 Postoperative 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.

Phenergan (Promethazine HCl) Rectal Suppositories are not recommended for children under 2 years of age.