displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Each tablet of promethazine hydrochloride contains 12.5 mg. 25 mg. or 50 mg promethazine hydrochloride. The Inactive Ingredients present are hydroxypropyl cellulose, lactose monohydrate, low-substituted hydroxypropyl cellulose and magnesium stearate. Promethazine hydrochloride is a racemic compound; the molecular formula Is C17H20N2S.HCI and its molecular weight is 320.88.
Promethazine hydrochloride, a phenothiazine derivative, Is designated chemically as 10H-Phenothiazine-10-ethanamine. N,N, a-trimethyl-, monohydrochloride, (±)- with the following structural formula:
Promethazine hydrOChloride, USP occurs as a white to faint yellow, practically oderless, crystalline powder whlch slowly oxidizes and turns blue on prolonged exposure to air. It Is freely soluble In water, In hot dehydrated alcohol, and In chloroform; practically insoluble in ether, In acetone andlnethylacelate.
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothlazines by the presence of abranched 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 H₁ receptor blocking agent. In addition to its antlhlstamlnlc action, it provides clinically useful sedabve and anllemetic effects.
Promethazine is well absorbed from the gastrointeslinal 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-demethylpromethazlne are the predominant metabolites appearing in the urine.
INDICATIONS AND USAGE
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Promethazine Hydrochloride, is useful orally for:
Perennial and seasonal allergic rhinitis.
Allergic conjunctiritis 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 associaated with certain types of anesthesia and surgery.
Therapy adjunctive to meperidine or other analgesics for control of post-operallve 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.
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Promethazine hydrochloride tablets, USP are contraindicated for use in pediatric patients less than two years of age.
Promethazine hydrochloride tablets, USP are contraindicated in comatose states, and in Individuals known to be hypersensltlve or to have had an ldIosyncratic reaction to promethazine or to other phenothiazines.
Antihlstamlnes are contralndicated for use In the treatment of lower respiratory tract symptoms including asthma.
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
PROMETHAZJNE HYDROCHLORIDE TABLETS, USP SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OFAGE B£CAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION.
POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITlES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HYDROCHLORIDE TABl.ETS,. USP IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HYDROCHLORIDE TABLETS, USP HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS.
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERlNG PROMETHAZINE HYDROCHLORIDE TABLETS, USP TO PEDIATRIC PATIENTS 2 YEARS OFAGE AND OLDER. IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HYDROCHlORIDE BE USED IN PEDIATRIC PATIENTS 2 YEARS OFAGE AND OLDER ANO CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED.
Promethazine hydrochloride tablets, USP 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, sedatlve/hlypnotlcs (including barbiturates), narcolics, 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 PRECAUTtONS Information for Patlents and Drug Interactions).
Promethazine hydrochloride tablets, USP may lead to potentially fatal respiratory depression. Use of promethazine hydrochloride tablets, USP in patlents with compromised respiratory function (a.g., COPD, sleep apnea) should be avoided.
Lower Seizure Threshold
Promethazine hydrochloride tablets, USP may lower seizure threshold. It should be used with caution in persons with seizure dissorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, whlch may also affect seizure threshold.
Promethazine hydrochloride tablets, USP should be used wilh caution in patients with bonemarrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine hydrochloride has been used in association with other known marrow-toxic agents.
Neuroleptic Malignant Syndrome
A potentlally fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazlne hydrochloride 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 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 hydrochloride, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) Intensive symptomatic treatment and medical monitoring, and 3) treatmenl of any concomitant serious medical problems for which specefic 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 hydrochloride should be carefully considered.
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
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.
Dermatologlc- 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 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 hydrochloride. Consideration should be given to the discontinuation of promethazine hydrochloride 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.
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
Signs and symptoms of overdosage with promethazine hydrochloride range from mild depression of the central nervous system and ardiovascular 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 paradoxicel-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 to 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 hydrochloride 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
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
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 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 hydrochloride tablets, USP, 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 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 (ct. Promethazine hydrochloride Injection). 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 hydrochloride 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, USP are contraindicated for children under 2 years of age.
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Promethazine hydrochloride tablets USP, 12.5 mg are, white to off-white, round shape, biconvex, uncoated tablets debossed with the logo of “ZC”, “01” and bisect on one side and plain on the other side and are supplied as follows:
NDC 0615-1539-39 In blistercards of 30 tablets
NDC 0615-1539-05 in blistercards of 15 tablets
NDC 0615-1539-31 in blistercards of 31 tablets
Promethazine hydrochloride tablets USP, 25 mg are, white to off-white, round shape, biconvex, uncoated tablets debossed with the quadrisect and the logo of “Z”, “C”, “O”, and “2” on one side and plain on the other side.
Promethazine hydrochloride tablets USP, 50 mg are, white to off-white, round shape, biconvex, uncoated tablets debossed with the logo of “ZC03” on one side and plain on the other side.
Store at 20· – 25·C (68· – 77°F) [See USP Controlled Room Temperature].
Protect from light.
Dispense In light-resistant, tight container.
PATIENT INFORMATION LEAFLET
displayName: PATIENT MEDICATION INFORMATION SECTION
FDA Article Code: 68498-5
Promethazine Hydrochloride Tablets, USP
This is a summary of the most important information about promethazine. For details, talk to your healthcare professional.
What Is Promethazine?
Promethazine is an antihistamine which can be taken by mouth as a tablet or syrup, rectally as a suppository, or by injection. It can be used for:
• “hay fever” or, a stuffy runny nose from allergy
• watery, itchy eyes due to inhaled allergies and foods
• mild allergic skin reactions with itching and swelling
• allergic reactions to blood or plasma
• dermographism, a form of hives known as “skin writing”
• serious allergic reactions along with epinephrine and other treatments
• sedation before or after surgery, or during childbirth
• prevention and control of nausea and vomiting after surgery
• along with meperidine (demerol) or other pain medicines
• sedation, relief of anxiety, and production of light sleep
• from which the patient can be easily aroused
• treatment and prevention of motion sickness
Who Should Not Use Promethazine?
Promethazine should not be given to:
• children under two years of age
• patients who are unconscious
• patients who are allergic to promethazine, any of the ingredients in promethazine, or to other phenothiazines
• patients with lung symptoms including asthma
• children who are vomiting unless the vomiting is prolonged and there is a known cause
What Are The R!sks?
The following are the major potential risks and side effects of promethazine therapy. However, this list is not complete.
• Severe drowsiness and reduced mental alertness. Promethazine may cause drowsiness which may impair your ability to ride a bike, drive a car, or operate machinery. This may be worsened if taken with alcohol or other drugs that also cause central nervous system (CNS) slowing such as sedatives, pain medicines, tranquilizers or certain drugs for depression.
Serious breathing problems. Promethazine should not be used in patients with poor lung function such as chronic obstructive lung disease or breathing problems while sleeping (sleep apnea).
• Increased risk of seizures. Promethazine should be used with caution in patients with seizures or who are on other medicines which may also increase the risk of seizures.
• Bone-marrow problems and blood cell production. Promethazine should not be used in patients with bone-marrow problems or used with other drugs that affect the bone marrow”s production of blood cells.
• Neuroleptic malignant syndrome. This potentially deadly syndrome includes symptoms such as fever, muscle rigidity, mental changes, changes in pulse or blood pressure, fast heartbeat, increased sweating or irregular heart rhythm.
• The most common side effects are drowsiness, changes In blood pressure, skin reactions, blood cell changes and breathing problems. Increased excitability or abnormal movemehts may occur after one dose of promethazine. If they do, consult your doctor about using another medicine.
What Should I Tell My Healthcare Professional?
Before you start taking promethazine, tell your healthcare professional if you:
• have narrow-angle glaucoma
• have an enlarged prostate
• have a stomach ulcer
• have an intestinal blockage
• have a bladder blockage
• have heart problems
• have liver problems
• have breathing or lung problems
• have sleep apnea (breathing problems when sleeping)
• have seizures
• drink alcohol
• are trying to become pregnant, are already pregnant, or are breast-feeding
Can Other Medicines Or Food Affect Promethazine?
Promethazine and certain other medicines can interact with each other. Tell your healthcare professional about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how promethazine works or promethazine may affect how your other medicines work. Know the medicines you take. Keep a list of them with you to show your healthcare professional.
Especially tell your healthcare professional if you take:
• medicines that affect your brain such as anti-anxiety medicine, sleeping pills, pain medicines, sedatives, narcotics, antidepressants or tranquilizers
• a monoamine oxidase inhibitor (MAOI) which is used to treat depression or other mental disorders
• medicines called anticholinergics
Call your doetorfor medical advice about side effects.You may report side effects to FDA at 1-800-FDA-1088.
Cadila Healthcare Ltd.
Zydus Pharmaceuticals USA Inc.
Pennington, NJ 08534
PRINCIPAL DISPLAY PANEL
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4