Each teaspoon (5 mL) of Phenergan with dextromethorphan contains 6.25 mg promethazine hydrochloride and 15 mg dextromethorphan hydrobromide 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 Yellow 10, FD&C Yellow 6, glycerin, saccharin sodium, sodium benzoate, sodium citrate, sodium propionate, water, and other ingredients.
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:
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.
Dextromethorphan hydrobromide is a salt of the methyl ether of the dextrorotatory isomer of levorphanol, a narcotic analgesic. It is chemically named as 3-methoxy-17-methyl-9(alpha), 13(alpha), 14(alpha)-morphinan hydrobromide monohydrate with the following structural formula:
Dextromethorphan hydrobromide monohydrate occurs as white crystals, is sparingly soluble in water, and is freely soluble in alcohol. The empirical formula is C 18 H 25 NO·HBr·H 2 O, and the molecular weight of the monohydrate is 370.33. Dextromethorphan HBr monohydrate is dextrorotatory with a specific rotation of +27.6 degrees in water (20 degrees C, sodium D-line).
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 dosages, 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.
Dextromethorphan is an antitussive agent and, unlike the isomeric levorphanol, it has no analgesic or addictive properties.
The drug acts centrally and elevates the threshold for coughing. It is about equal to codeine in depressing the cough reflex. In therapeutic dosage dextromethorphan does not inhibit ciliary activity.
Dextromethorphan is rapidly absorbed from the gastrointestinal tract and exerts its effect in 15 to 30 minutes. The duration of action after oral administration is approximately three to six hours. Dextromethorphan is metabolized primarily by liver enzymes undergoing O-demethylation, N-demethylation, and partial conjugation with glucuronic acid and sulfate. In humans, (+)-3-hydroxy-N-methylmorphinan, (+)-3-hydroxymorphinan, and traces of unmetabolized drug were found in urine after oral administration.
Phenergan with dextromethorphan is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold.
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.
Dextromethorphan should not be used in patients receiving a monoamine oxidase inhibitor (MAOI) (see " PRECAUTIONS --DRUG INTERACTIONS").
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 hydrochloride 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 hydrochloride. When given concomitantly with promethazine hydrochloride, 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.
Administration of dextromethorphan may be accompanied by histamine release and should be used with caution in atopic children.
Animal reproduction studies have not been conducted with the drug combination--promethazine and dextromethorphan. It is not known whether this drug combination can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Phenergan with dextromethorphan should be given to a pregnant woman only if clearly needed.
Promethazine should be used cautiously in persons with cardiovascular disease or with impairment of liver function.
Dextromethorphan should be used with caution in sedated patients, in the debilitated, and in patients confined to the supine position.
INFORMATION FOR PATIENTS
Phenergan with dextromethorphan 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 with dextromethorphan 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.
Hyperpyrexia, hypotension, and death have been reported coincident with the coadministration of monoamine oxidase (MAO) inhibitors and products containing dextromethorphan. Thus, concomitant administration of Phenergan with dextromethorphan and MAO inhibitors should be avoided (see " Contraindications ").
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.
DRUG/LABORATORY TEST INTERACTIONS
The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride:
Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.
Glucose Tolerance Test
An increase in blood glucose has been reported in patients receiving promethazine.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine or of dextromethorphan. There are no animal or human data concerning the carcinogenicity, mutagenicity, or impairment of fertility with these drugs. 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 8.3 and 16.7 times the maximum recommended total daily dose for a 50-kg subject. 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 with dextromethorphan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Promethazine taken within two weeks of delivery may inhibit platelet aggregation in the newborn.
LABOR AND DELIVERY
See " Nonteratogenic Effects ."
It is not known whether promethazine or dextromethorphan is excreted in human milk. Caution should be exercised when Phenergan with dextromethorphan is administered to a nursing woman.
This product should not be used in children under 2 years of age because safety for that use has not been established.
Nervous System --Sedation, sleepiness, occasional blurred vision, dryness of mouth, dizziness; rarely confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion (usually in association with parenteral injection or excessive dosage).
Cardiovascular --Increased or decreased blood pressure.
Dermatologic --Rash, rarely photosensitivity.
Hematologic --Rarely leukopenia, thrombocytopenia; agranulocytosis (1 case).
Gastrointestinal --Nausea and vomiting.
Dextromethorphan hydrobromide occasionally causes slight drowsiness, dizziness, and gastrointestinal disturbances.
According to the WHO Expert Committee on Drug Dependence, dextromethorphan could produce very slight psychic dependence but no physical dependence.
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.
Dextromethorphan may produce central excitement and mental confusion. Very high doses may produce respiratory depression. One case of toxic psychosis (hyperactivity, marked visual and auditory hallucinations) after ingestion of a single dose of 20 tablets (300 mg) of dextromethorphan has been reported.
Treatment of overdosage with Phenergan with dextromethorphan 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. The antidotal efficacy of narcotic antagonists to dextromethorphan has not been established; note that any of the 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 a patient with partial adrenergic blockade may further lower the blood pressure.
Limited experience with dialysis indicates that it is not helpful.
The average effective dose for adults is one teaspoon (5 mL) every 4 to 6 hours, not to exceed 30.0 mL in 24 hours. For children 6 years to under 12 years of age, the dose is one-half to one teaspoon (2.5 to 5.0 mL) every 4 to 6 hours, not to exceed 20.0 mL in 24 hours. For children 2 years to under 6 years of age, the dose is one-quarter to one-half teaspoon (1.25 to 2.5 mL) every 4 to 6 hours, not to exceed 10.0 mL in 24 hours.
Phenergan with dextromethorphan is not recommended for children under 2 years of age.
Phenergan® with dextromethorphan (Promethazine Hydrochloride and Dextromethorphan Hydrobromide) Syrup is a clear, yellow solution supplied as follows:
NDC 0008-0548-02, case of 24 bottles of 4 fl. oz. (118 mL).
NDC 0008-0548-03, bottle of 1 pint (473 mL).
Protect from light.
Dispense in light-resistant, glass, tight containers.
A Wyeth-Ayerst Company
Philadelphia, PA 19101
CI 4872-1 Issued September 6, 1996