CATEGORIES: Rhinitis, allergic; Rhinitis, vasomotor; Conjunctivitis, allergic; Transfusion reaction; Anaphylaxis, adjunct; Motion sickness; Pain, adjunct; Sedation; Dermographism; Urticaria; Nausea; Vomiting; Allergic reactions; Pregnancy Category C; WHO Formulary; FDA Approved June 1955
Drug Classes: Antiemetics/antivertigo; Antihistamines, H1; Phenothiazines
BRAND NAMES: Adgan; Anergan 50; Antinaus 50; Pentazine; Phenergan; Phenoject-50; Promacot; Promethegan
FOREIGN BRAND AVAILABILITY:
Allerfen (Italy);
Atosil (Germany);
Bonnox (Germany);
Farganesse (Italy);
Fenazine (Israel);
Fenergan (Argentina, Peru);
Goodnight (New Zealand);
Hibechin (Japan);
Hiberna (Japan);
Insomn-Eze (Australia);
Lergigan (Sweden);
Prome (Indonesia);
Proneurin (Germany);
Prothiazine (Israel);
Pyrethia (Japan)
COST OF THERAPY:
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Phenergan (promethazine hydrochloride) injection is a sterile, pyrogen-free solution for deep IM or IV administration. Promethazine hydrochloride (10H-phenothiazine-10-ethanamine, N,N,α-trimethyl-, monohydrochloride, (±)-) is a racemic compound.
Each ml of ampul contains either 25 or 50 mg promethazine hydrochloride with 0.1 mg edetate disodium, 0.04 mg calcium chloride, 0.25 mg sodium metabisulfite, and 5 mg phenol in water for injection. The pH range is 4.0-5.5, buffered with acetic acid-sodium acetate, and it is sealed under nitrogen.
Each ml of the Tubex and Tubex Blunt Pointe Sterile Cartridge Units contains either 25 or 50 mg promethazine hydrochloride with 0.1 mg edetate disodium, 0.04 mg calcium chloride, not more than 5 mg monothioglycerol; and 5 mg phenol in water for injection. The pH range is 4.0-5.5, buffered with sodium acetate-acetic acid, and it is sealed under nitrogen.
Phenergan (promethazine hydrochloride) injection is a clear, colorless solution. The product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.
Promethazine HCl is a phenothiazine derivative which possesses antihistaminic, sedative, antimotion-sickness, antiemetic, and anticholinergic effects. Promethazine is a competitive H1 receptor antagonist, but does not block the release of histamine. Structural differences from the neuroleptic phenothiazines results in its relative lack (1/10) of dopamine antagonist properties. In therapeutic doses, promethazine HCl produces no significant effects on the cardiovascular system. Clinical effects are generally apparent within 5 minutes of an IV injection and within 20 minutes of an IM injection. Duration of action is 4-6 hours, although effects may persist up to 12 hours. Promethazine HCl is metabolized in the liver, with the sulfoxides of promethazine and N-desmethylpromethazine being the predominant metabolites appearing in the urine. Following IV administration in healthy volunteers, the plasma half-life for promethazine has been reported to range from 9-16 hours. The mean plasma half-life for promethazine after IM administration in healthy volunteers has been reported to be 9.8 ± 3.4 hours.
Promethazine HCl injection is indicated for the following conditions:
Non-FDA Approved Indications
Promethazine has been used for prenatal treatment of erythroblastosis fetalis, although this use is not FDA approved.
Promethazine HCl injection is contraindicated in comatose states and in patients who have demonstrated an idiosyncrasy or hypersensitivity to promethazine or other phenothiazines.
Under no circumstances should promethazine HCl injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGS, Inadvertent Intra-Arterial Injection).
Promethazine HCl injection should not be given by the SC route; evidence of chemical irritation has been noted, and necrotic lesions have resulted on rare occasions following SC injection. The preferred parenteral route of administration is by deep IM injection.
Sulfite Sensitivity
Promethazine HCl injection (ampuls only) contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthma episodes, in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
CNS Depression
Promethazine HCl injection may impair the mental and 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, sedative-hypnotics (including barbiturates), general anesthetics, narcotics, narcotic analgesics, tranquilizers, etc. (see PRECAUTIONS, Information for the Patient).
Lower Seizure Threshold
Promethazine HCl injection may lower seizure threshold and 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.
Bone-Marrow Depression
Promethazine HCl injection 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.
Use in Pediatric Patients
PROMETHAZINE HCl INJECTION IS NOT RECOMMENDED FOR USE IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE.
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl INJECTION TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. 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 INJECTION ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE'S SYNDROME. THE USE OF PROMETHAZINE HCl INJECTION 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 injection, in pediatric patients may cause hallucinations, convulsions, and sudden death. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine HCl injection.
Inadvertent Intra-Arterial Injection
Due to the close proximity of arteries and veins in the areas most commonly used for IV injection, extreme care should be exercised to avoid perivascular extravasation or inadvertent intra-arterial injection. Reports compatible with inadvertent intra-arterial injection of promethazine HCl injection, usually in conjunction with other drugs intended for IV use, suggest that pain, severe chemical irritation, severe spasm of distal vessels, and resultant gangrene requiring amputation are likely under such circumstances. Intravenous injection was intended in all the cases reported, but perivascular extravasation or arterial placement of the needle is now suspect. There is no proven successful management of this condition after it occurs, although sympathetic block and heparinization are commonly employed during the acute management because of the results of animal experiments with other known arteriolar irritants. Aspiration of dark blood does not preclude intra-arterial needle placement, because blood is discolored upon contact with promethazine HCl injection. Use of syringes with rigid plungers or of small bore needles might obscure typical arterial backflow if this is relied upon alone.
When used intravenously, promethazine HCl injection should be given in a concentration no greater than 25 mg/ml and at a rate not to exceed 25 mg/min. When administering any irritant drug intravenously, it is usually preferable to inject it through the tubing of an IV infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intended IV injection of promethazine HCl injection, the injection should be stopped immediately to provide for evaluation of possible arterial placement or perivascular extravasation.
Visual Inspection
This product is light sensitive and should be inspected before use and discarded if either color or particulate is observed.
Other Considerations
Sedative drugs or CNS depressants should be avoided in patients with a history of sleep apnea.
Administration of promethazine has been associated with reported cholestatic jaundice.
General
Drugs having anticholingeric 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 injection should be used cautiously in persons with cardiovascular disease or impairment of liver function.
Information for the Patient
Promethazine HCl injection may cause marked drowsiness or impair the mental or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The use of alcohol, sedative-hypnotics (including barbiturates), general anesthetics, narcotics, narcotic analgesics, tranquilizers, etc., with promethazine HCl injection may enhance impairment. 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.
Persistent or worsening pain or burning at the injection site should be reported immediately.
Avoid prolonged exposure to the sun.
Laboratory Test Interactions
The following laboratory tests may be affected in patients who are receiving therapy with promethazine HCl injection:
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine HCl injection, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility. Promethazine HCl injection was nonmutagenic in the Ames Salmonella test system.
Pregnancy Category C
Teratogenic Effects
Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg (approximately 2.1 and 4.2 times the maximum recommended human daily dose) of promethazine HCl injection. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.
There are no adequate and well-controlled studies of promethazine HCl injection in pregnant women. Because animal reproduction studies are not always predictive of human response, promethazine HCl injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Adequate studies to determine the action of the drug on parturition, lactation and development of the animal neonate have not been conducted.
Nonteratogenic Effects
Promethazine HCl injection received within 2 weeks of delivery may inhibit platelet aggregation in the newborn.
Labor and Delivery
Promethazine HCl injection may be used alone or as an adjunct to narcotic analgesics during labor (see DOSAGE AND ADMINISTRATION). Limited data suggest that use of promethazine HCl injection 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 PRECAUTIONS, Nonteratogenic Effects.)
Nursing Mothers
It is not known whether promethazine HCl injection is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when promethazine HCl injection is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients under 2 years of age have not been established.
Promethazine HCl injection should be used with caution in pediatric patients 2 years of age and older (see WARNINGS, Use in Pediatric Patients).
Use in Geriatric Patients (approximately 60 years or older)
Since therapeutic requirements for sedative drugs tend to be less in geriatric patients, the dosage should be reduced for these patients.
CNS Depressants
Promethazine HCl injection may increase, prolong, or intensify the sedative action of central nervous system depressants, such as alcohol, sedative-hypnotics (including barbiturates), general anesthetics, narcotics, narcotic analgesics, tranquilizers, etc. When given concomitantly with promethazine HCl injection, 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 injection 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
Although reversal of the vasopressor effect of epinephrine has not been reported with promethazine HCl injection, it is recommended that epinephrine NOT be used in the case of promethazine HCl injection 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. Although such a reaction has not been reported with promethazine HCl injection, the possibility should be considered.
CNS Effects
Drowsiness is the most prominent CNS effect of the drug. Extrapyramidal reactions may occur with high doses; this is almost always responsive to a reduction in dosage. Other reported reactions include dizziness, lassitude, tinnitus, incoordination, fatigue, blurred vision, euphoria, diplopia, nervousness, insomnia, tremors, convulsive seizures, oculogyric crises, excitation, catatonic-like states, hysteria, and hallucinations.
Cardiovascular Effects
Tachycardia, bradycardia, faintness, dizziness, and increases and decreases in blood pressure have been reported following the use of promethazine HCl injection. Venous thrombosis at the injection site has been reported. INTRA-ARTERIAL INJECTION MAY RESULT IN GANGRENE OF THE AFFECTED EXTREMITY (see WARNINGS, Inadvertent Intra-Arterial Injection).
Gastrointestinal Effects
Nausea and vomiting have been reported, usually in association with surgical procedures and combination drug therapy.
Allergic Reactions
These include urticaria, dermatitis, asthma, and photosensitivity. Angioneurotic edema has been reported.
Other Reported Reactions
Leukopenia and agranulocytosis, usually when promethazine HCl has been used in association with other known marrow-toxic agents, have been reported. Thrombocytopenic purpura and jaundice of the obstructive type have been associated with the use of promethazine HCl. The jaundice is usually reversible on discontinuation of the drug. Subcutaneous injection has resulted in tissue necrosis. Nasal stuffiness may occur. Dry mouth has been reported.
Paradoxical Reactions (overdosage)
Hyperexcitability and abnormal movements, which have been reported in pediatric patients following a single administration of promethazine HCl injection, may be manifestations of relative overdosage, in which case, consideration should be given to the discontinuation of the promethazine HCl injection 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 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 pediatric patients and geriatric patients. Convulsions may rarely occur. A paradoxical reaction has been reported in pediatric patients receiving single doses of 75-125 mg orally, characterized by hyperexcitability and nightmares.
Atropine-like signs and symptoms — dry mouth, fixed, dilated pupils, flushing, etc., 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. 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 injection are not reversed by naloxone.
Avoid analeptics, which may cause convulsions. The treatment of choice for resulting hypotension is administration of IV fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to IV fluids and repositioning, the administration of levarterenol or phenylephrine should be considered. EPINEPHRINE SHOULD NOT BE USED, since its use in a patient with partial adrenergic blockade may further lower the blood pressure. Extrapyramidal reactions may be treated with anticholinergic antiparkinson agents, diphenhydramine, or barbiturates. Oxygen may also be administered. Limited experience with dialysis indicates that it is not helpful.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Do not use promethazine HCl injection if solution has developed color or contains precipitate.
To avoid the possibility of physical and/or chemical incompatibility, consult specialized literature before diluting with any injectable solution or combining with any other medication. Do not use if there is a precipitate or any sign of incompatibility.
Important Notes on Administration
The preferred parenteral route of administration for promethazine HCl injection is by deep IM injection. The proper IV administration of this product is well-tolerated, but use of this route is not without some hazard. Not for subcutaneous administration.
INADVERTENT INTRA-ARTERIAL INJECTION CAN RESULT IN GANGRENE OF THE AFFECTED EXTREMITY (SEE WARNINGS, Inadvertent Intra-Arterial Injection ). SUBCUTANEOUS INJECTION IS CONTRAINDICATED, AS IT MAY RESULT IN TISSUE NECROSIS (SEE CONTRAINDICATIONS ).
Injection into or near a nerve may result in permanent tissue damage.
When used intravenously, promethazine HCl injection should be given in concentration no greater than 25 mg/ml at a rate not to exceed 25 mg/min; it is preferable to inject through the tubing of an IV infusion set that is known to be functioning satisfactorily.
The Tubex Blunt Pointe Sterile Cartridge Unit is suitable for substances to be administered intravenously. It is intended for use with injection sets specifically manufactured as "needle-less" injection systems. Tubex Blunt Pointe is compatible with Abbott's LifeShield Prepierced Reseal injection site, Baxter's Inter-Link injection site, McGaw, Inc's Safe Line injection site, Arrow International, Inc's User-Gard Intermittent Injection Cap, and B. Braun Medical's SafSite reflux valve.
The Tubex Sterile Cartridge Needle Unit is suitable for substances to be administered intravenously or intramuscularly.
Allergic Conditions
The average adult dose is 25 mg. This dose may be repeated within 2 hours if necessary, but continued therapy, if indicated, should be via the oral route as soon as existing circumstances permit. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The average adult dose for amelioration of allergic reactions to blood or plasma is 25 mg.
Sedation
In hospitalized adult patients, nighttime sedation may be achieved by a dose of 25-50 mg of promethazine HCl injection.
Nausea and Vomiting
For control of nausea and vomiting, the usual adult dose is 12.5-25 mg, not to be repeated more frequently than every 4 hours. When used for control of postoperative nausea and vomiting, the medication may be administered either intramuscularly or intravenously and dosage of analgesics and barbiturates reduced accordingly.
Preoperative and Postoperative Use
As an adjunct to preoperative or postoperative medication, 25-50 mg of promethazine HCl injection in adults may be combined with appropriately reduced doses of analgesics and atropine-like drugs as desired. Dosage of concomitant analgesic or hypnotic medication should be reduced accordingly.
Obstetrics
Promethazine HCl injection in doses of 50 mg will provide sedation and relieve apprehension in the early stages of labor. When labor is definitely established, 25-75 mg (average dose, 50 mg) promethazine HCl injection may be given intramuscularly or intravenously with an appropriately reduced dose of any desired narcotic. If necessary, promethazine HCl injection with a reduced dose of analgesic may be repeated once or twice at 4 hour intervals in the course of a normal labor. A maximum total dose of 100 mg of promethazine HCl injection may be administered during a 24 hour period to patients in labor.
Pediatric Patients
Promethazine HCl injection is not recommended for use in pediatric patients less than 2 years of age.
In pediatric patients 2 years of age and older, the dosage should not exceed half that of the suggested adult dose. As an adjunct to premedication, the suggested dose is 0.5 mg/lb of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug. Antiemetics should not be used in vomiting of unknown etiology in pediatric patients (see WARNINGS, Use in Pediatric Patients).
Ampuls
Phenergan (promethazine HCl) injection is available in 1 ml ampuls as follows:
Storage: Store at controlled room temperature 15-30°C (59-86°F). Protect from light. Keep covered in carton until time of use. Do not use if solution has developed color or contains a precipitate.
Also Available
Phenergan injection is also available in the following dosage strengths in Tubex Blunt Pointe Sterile Cartridge Units and Sterile Cartridge-Needle Units as follows:
NOTE: Prescribing information for suppositories is included in this section.
Promethazine hydrochloride is a racemic compound; the empirical formula is C17H20N2S·HCl and its molecular weight is 320.88.
Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10H-phenothiazine-10-ethanamine, N,N,α-trimethyl-, monohydrochloride, (±)-.
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.
Syrup
Each teaspoon (5 ml) of Phenergan Syrup Plain contains 6.25 mg promethazine hydrochloride in a flavored syrup base with a pH between 4.7 and 5.2. Alcohol 7%. The inactive ingredients present are artificial and natural flavors, citric acid, D&C red 33, D&C yellow 10, FD&C blue 1, FD&C yellow 6, glycerin, saccharin sodium, sodium benzoate, sodium citrate, sodium propionate, water, and other ingredients.
Each teaspoon (5 ml) of Phenergan Syrup Fortis contains 25 mg promethazine hydrochloride in a flavored syrup base with a pH between 5.0 and 5.5. Alcohol 1.5%. The inactive ingredients present are artificial and natural flavors, citric acid, saccharin sodium, sodium benzoate, sodium propionate, water, and other ingredients.
Tablets and Suppositories
Each tablet of Phenergan contains 12.5, 25, 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; 25 mg: Saccharin sodium; 50 mg: FD&C red 40.
Each rectal suppository of Phenergan contains 12.5, 25, or 50 mg promethazine hydrochloride with ascorbyl palmitate, silicon dioxide, white wax, and cocoa butter. Phenergan suppositories are for rectal administration only.
Syrup
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 H1 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 4-6 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.
Tablets and Suppositories
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 H1 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 4-6 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.
Syrup, Tablets, and Suppositories
Promethazine HCl is useful for:
Non-FDA Approved Indications
Promethazine has been used for prenatal treatment of erythroblastosis fetalis, although this use is not FDA approved.
Syrup
Promethazine is contraindicated 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.
Tablets and Suppositories
Promethazine HCl tablets and 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.
Syrup
Promethazine may cause marked drowsiness. Ambulatory patients should be cautioned against such activities as driving or operating dangerous machinery until it is known that they do not become drowsy or dizzy from promethazine therapy.
The sedative action of promethazine HCl is additive to the sedative effects of central nervous system depressants; therefore, agents such as alcohol, narcotic analgesics, sedatives, hypnotics, and tranquilizers should either be eliminated or given in reduced dosage in the presence of promethazine HCl. When given concomitantly with promethazine HCl, the dose of barbiturates should be reduced by at least one-half, and the dose of analgesic depressants, such as morphine or meperidine, should be reduced by one-quarter to one-half.
Promethazine may lower seizure threshold. This should be taken into consideration when administering to persons with known seizure disorders or when giving in combination with narcotics or local anesthetics which may also affect seizure threshold.
Sedative drugs or CNS depressants should be avoided in patients with a history of sleep apnea.
Antihistamines should be used with caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, and urinary bladder obstruction due to symptomatic prostatic hypertrophy and narrowing of the bladder neck.
Administration of promethazine has been associated with reported cholestatic jaundice.
Tablets and Suppositories
CNS Depression
Promethazine HCl tablets and 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, Tablets and Suppositories, Information for the Patient and DRUG INTERACTIONS, Tablets and Suppositories).
Respiratory Depression
Promethazine HCl tablets and suppositories may lead to potentially fatal respiratory depression.
Use of promethazine HCl tablets and suppositories in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided.
Lower Seizure Threshold
Promethazine HCl tablets and 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 threshold.
Bone-Marrow Depression
Promethazine HCl tablets and 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 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 HCl TABLETS AND SUPPOSITORIES ARE NOT RECOMMENDED FOR USE IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE.
CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl 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 PROMETHAZINE HCl 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 PROMETHAZINE HCl 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 HCl tablets and suppositories, in pediatric patients may cause sudden death (see OVERDOSAGE, Tablets and Suppositories). 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.
Other Considerations
Administration of promethazine HCl has been associated with reported cholestatic jaundice.
Syrup
General
Promethazine should be used cautiously in persons with cardiovascular disease or with impairment of liver function.
Information for the Patient
Promethazine HCl 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 promethazine HCl 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.
Drug/Laboratory Test Interactions
The following laboratory tests may be affected in patients who are receiving therapy with promethazine HCl:
Carcinogenesis, Mutagenesis, and 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
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 2.1-4.2 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. Promethazine HCl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects
Promethazine taken within 2 weeks of delivery may inhibit platelet aggregation in the newborn.
Labor and Delivery
Promethazine HCl, in appropriate dosage form, may be used alone or as an adjunct to narcotic analgesics during labor and delivery. (See INDICATIONS AND USAGE, Syrup, Tablets, and Suppositories and DOSAGE AND ADMINISTRATION, Syrup.)
See also Syrup, Nonteratogenic Effects.
Nursing Mothers
It is not known whether promethazine is excreted in human milk. Caution should be exercised when promethazine is administered to a nursing woman.
Pediatric Use
This product should not be used in children under 2 years of age because safety for such use has not been established.
Tablets and Suppositories
General
Drugs having anticholingeric 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 tablets and suppositories should be used cautiously in persons with cardiovascular disease or impairment of liver function.
Information for the Patient
Promethazine HCl tablets and 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, Tablets and Suppositories, CNS Depression and DRUG INTERACTIONS, Tablets and Suppositories). 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.
Drug/Laboratory Test Interactions
The following laboratory tests may be affected in patients who are receiving therapy with promethazine HCl:
Carcinogenesis, Mutagenesis, and 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
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 2.1-4.2 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 tablets and suppositories in pregnant women.
Promethazine HCl tablets and suppositories should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects
Promethazine HCl tablets and suppositories administered to a pregnant woman within 2 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, Tablets and Suppositories). 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 Tablets and Suppositories, Nonteratogenic Effects.)
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 promethazine HCl tablets and 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.
Pediatric Use
Safety and effectiveness in children under 2 years of age have not been established.
Promethazine HCl tablets and suppositories should be used with caution in pediatric patients 2 years of age and older (see WARNINGS, Tablets and Suppositories, Use in Pediatric Patients).
Geriatric Use
Clinical studies of promethazine HCl 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 tablets and suppositories and observed closely.
Syrup
The sedative action of promethazine is additive to the sedative effects of other central nervous system depressants, including alcohol, narcotic analgesics, sedatives, hypnotics, tricyclic antidepressants, and tranquilizers; therefore, these agents should be avoided or administered in reduced dosage to patients receiving promethazine.
Tablets and Suppositories
CNS Depressants
Promethazine HCl tablets and 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 tablets and 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 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 tablets and 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 promethazine HCl tablets and suppositories.
Syrup
Tablets and Suppositories
Paradoxical Reactions
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.
Syrup
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 75-125 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 are not reversed by naloxone. Avoid analeptics, which may cause convulsions.
Severe hypotension usually responds to the administration of norepinephrine or phenylephrine. EPINEPHRINE SHOULD NOT BE USED, since its use in patients with partial adrenergic blockage may further lower the blood pressure.
Limited experience with dialysis indicates that it is not helpful.
Tablets and Suppositories
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 75-125 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 IV fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to IV 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 antiparkinson agents, diphenhydramine, or barbiturates. Oxygen may also be administered.
Limited experience with dialysis indicates that it is not helpful.
Syrup
Allergy
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 6.25-12.5 mg taken 3 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.
Promethazine HCl rectal suppositories may be used if the oral route is not feasible, but oral therapy should be resumed as soon as possible if continued therapy is indicated.
The administration of promethazine HCl 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 ½ to 1 hour before anticipated travel and be repeated 8-12 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 tablets, syrup, or rectal suppositories, 12.5-25 mg, twice daily, may be administered.
Nausea and Vomiting
The average effective dose of promethazine HCl 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 HCl injection) or by rectal suppository. 12.5-25 mg doses may be repeated, as necessary, at 4-6 hour intervals.
For nausea and vomiting in children, the usual dose is 0.5 mg/lb 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 4-6 hour intervals, as necessary.
Sedation
This product relieves apprehension and induces a quiet sleep from which the patient can be easily aroused. Administration of 12.5-25 mg promethazine HCl by the oral route or by rectal suppository at bedtime will provide sedation in children. Adults usually require 25-50 mg for nighttime, presurgical, or obstetrical sedation.
Pre- and Postoperative Use
Promethazine HCl in 12.5-25 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/lb of body weight in combination with an equal dose of meperidine and the appropriate dose of an atropine-like drug.
Usual adult dosage is 50 mg promethazine HCl with an equal amount of meperidine and the required amount of a belladonna alkaloid.
Postoperative sedation and adjunctive use with analgesics may be obtained by the administration of 12.5-25 mg in children and 25-50 mg doses in adults.
Promethazine HCl syrup plain and syrup fortis are not recommended for children under 2 years of age.
Tablets and Suppositories
Promethazine HCl tablets and rectal suppositories are not recommended for children under 2 years of age (see WARNINGS, Tablets and Suppositories, Use in Pediatric Patients).
Promethazine HCl suppositories are for rectal administration only.
Allergy
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 6.25-12.5 mg taken 3 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.
Motion Sickness
The average adult dose is 25 mg taken twice daily. The initial dose should be taken ½ to 1 hour before anticipated travel and be repeated 8-12 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 tablets, syrup, or rectal suppositories, 12.5-25 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, Tablets and Suppositories, 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. When oral medication cannot be tolerated, the dose should be given parenterally (cf. promethazine HCl injection) or by rectal suppository. 12.5-25 mg doses may be repeated, as necessary, at 4-6 hour intervals.
For nausea and vomiting in children, the usual dose is 0.5 mg/lb 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 4-6 hour intervals, as necessary.
Sedation
This product relieves apprehension and induces a quiet sleep from which the patient can be easily aroused. Administration of 12.5-25 mg promethazine HCl by the oral route or by rectal suppository at bedtime will provide sedation in children. Adults usually require 25-50 mg for nighttime, presurgical, or obstetrical sedation.
Pre- and Postoperative Use
Promethazine HCl in 12.5-25 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/lb 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 12.5-25 mg in children and 25-50 mg doses in adults.
Promethazine HCl tablets and rectal suppositories are not recommended for children under 2 years of age.
Syrup
Phenergan (promethazine HCl) Syrup Plain is a clear, green solution supplied as follows:
Phenergan Syrup Fortis is a clear, light straw-colored solution supplied as follows:
Storage
Keep bottles tightly closed.
Store at room temperature, between 15-25°C (59-77°F).
Protect from light.
Dispense in light-resistant, glass, tight containers.
Tablets and Suppositories
Phenergan Tablets
Phenergan tablets are available as follows:
Storage
Keep tightly closed.
Store at controlled room temperature between 20-25°C (68-77°F).
Protect from light.
Dispense in a light-resistant, tight container.
Use carton to protect contents from light.
Phenergan Suppositories
Phenergan rectal suppositories are available as follows:
Storage: Store refrigerated between 2-8°C (36-46°F).
Dispense in well-closed container.
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