Promethazine Hydrochloride and Phenylephrine Hydrochloride

Promethazine and Phenylephrine · Solution · Oral

Prescription (Rx) Phenothiazine alpha-1 Adrenergic Agonist

Uses

Promethazine hydrochloride and phenylephrine hydrochloride oral solution, USP is indicated for the temporary relief of upper respiratory symptoms, including nasal congestion, associated with allergy or the common cold.

Dosage and administration

It is important that promethazine hydrochloride and phenylephrine hydrochloride oral solution, USP is measured with an accurate measuring device (see Precautions-Information for Patients ). A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when half a teaspoon is to be measured. It is strongly recommended that an accurate measuring device be used. A pharmacist can provide instructions for measuring the correct dose. Promethazine hydrochloride and phenylephrine hydrochloride oral solution, USP is contraindicated for children under 2 years of age (see WARNINGS –Black Box Warning and Use in Pediatric Patients ). The recommended doses are given in the following table: Adults and Children 12 Years and Over 1 teaspoonful (5 mL) every 4 to 6 hours, not to exceed 6 teaspoonfuls (30 mL) in 24 hours. Children 6 to Under 12 Years of Age ½ to 1 teaspoonful (2.5 to 5 mL) every 4 to 6 hours, not to exceed 6 teaspoonfuls (30 mL) in 24 hours. Children 2 to Under 6 Years of Age ¼ to ½ teaspoonful (1.25 to 2.5 mL) every 4 to 6 hours.

Contraindications

Promethazine is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma. Phenylephrine is contraindicated in patients with hypertension or with peripheral vascular insufficiency (ischemia may result with risk of gangrene or thrombosis of compromised vascular beds). Phenylephrine should not be used in patients known to be hypersensitive to the drug or in those receiving a monoamine oxidase inhibitor (MAOI).

Warnings

Promethazine hydrochloride 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 hydrochloride in pediatric patients less than 2 years of age. A wide range of weight-based doses of promethazine hydrochloride have results in respiratory depression in these patients. Caution should be exercised when administering promethazine hydrochloride to pediatric patients 2 years of age and older. It is recommended that the lowest effective dose of promethazine hydrochloride be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided. Sulfite Sensitivity: Promethazine Hydrochloride and Phenylephrine Hydrochloride Oral Solution contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic 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. Promethazine: CNS Depression- Promethazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine HCl (see PRECAUTIONS-Information for Patients and Drug Interactions ). Respiratory Depression - Promethazine may lead to potentially fatal respiratory depression. Use of Promethazine in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided. Lower Seizure Threshold - Promethazine may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold. Bone-Marrow Depression - Promethazine 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 products are contraindicated for use in pediatric patients less than two years of age. Caution should be exercised when administering promethazine products to pediatric patients 2 years of age and older because of the potential for fatal respiratory depression. Respiratory depression and apnea, sometime associated with death, are strongly associated with promethazine products and are not directly related to individualized weight-based dosing, which might otherwise permit safe administration. Concomitant administration of promethazine products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients. 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 hydrochloride administration may be confused with the CNS signs of undiagnosed primary disease, e.g., encephalopathy or Reye’s syndrome. The use of promethazine products 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 hydrochloride, in pediatric patients may cause sudden death (see OVERDOSAGE ). Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride 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 has been associated with reported cholestatic jaundice.

Precautions

Animal reproduction studies have not been conducted with the drug combination - promethazine and phenylephrine. It is not known whether this drug combination can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Promethazine and phenylephrine should be given to a pregnant woman only if clearly needed. 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. Promethazine should be used cautiously in persons with cardiovascular disease or impairment of liver function. Phenylephrine should be used with caution in patients with cardiovascular disease, particularly hypertension. Information For Patients: Patients should be advised to measure promethazine hydrochloride and phenylephrine hydrochloride oral solution with accurate measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when a half teaspoon is measured. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose. Promethazine and phenylephrine may cause marked drowsiness or may 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 and phenylephrine 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. Avoid prolonged exposure to the sun. Drug Interactions: Promethazine CNS Depressants - Promethazine 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, tricylic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine HCl. When given concomitantly with promethazine, 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 to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine 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. Phenylephrine Drug Phenylephrine with prior administration of monoamine oxidase inhibitors (MAOI). Effect Cardiac pressor response potentiated. May cause acute hypertensive crisis. Drug Phenylephrine with tricyclic antidepressants. Effect Pressor response increased. Drug Phenylephrine with ergot alkaloids. Effect Excessive rise in blood pressure. Drug Phenylephrine with bronchodilator sympathomimetic agents and with epinephrine or other sympathomimetics. Effect Tachycardia or other arrhythmias may occur. Drug Phenylephrine with atropine sulfate Effect Reflex bradycardia blocked; pressor response enhanced. Drug Phenylephrine with prior administration of propranolol or other β -adrenergic blockers. Effect Cardiostimulating effects blocked. Drug Phenylephrine with prior administration of phentolamine or other α-adrenergic blockers. Effect Pressor response decreased. Drug Phenylephrine with diet preparations, such as amphetamines or phenylpropanolamine. Effect Synergistic adrenergic response. Drug/Laboratory Test Interactions: The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride. Pregnancy Tests: Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations. Glucose Tolerance Test: An increase in blood glucose has been reported in patients receiving promethazine. Carcinogenesis, Mutagenesis, Impairment of Fertility: Promethazine: Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility with this drug. Promethazine was nonmutagenic in the Salmonella test system of Ames. Phenylephrine: A study which followed the development of cancer in 143,574 patients over a four-year period indicated that in 11,981 patients who received phenylephrine (systemic or topical), there was no statistically significant association between the drug and cancer at any or all sites. Long-term animal studies have not been performed to assess the carcinogenic potential of phenylephrine, nor are there other animal or human data concerning mutagenicity. A study of the effects of adrenergic drugs on ovum transport in rabbits indicated that treatment with phenylephrine did not alter incidence of pregnancy; the number of implantations was significantly reduced when high doses of the drug were used.

Side effects

Promethazine: 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. Dermatologic - 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-Promethazine; Respiratory Depression .) Other - Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. (See WARNINGS - Promethazine; Neuroleptic Malignant Syndrome .) 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. Phenylephrine: Nervous System - Restlessness, anxiety, nervousness and dizziness. Cardiovascular - Hypertension (see " WARNINGS "). Other - Precordial pain, respiratory distress, tremor, and weakness.

Overdosage

Promethazine: 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 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. Phenylephrine: Signs and symptoms of overdosage with phenylephrine include hypertension, headache, convulsions, cerebral hemorrhage, and vomiting. Ventricular premature beats and short-paroxysms of ventricular tachycardia may also occur. Headache may be a symptom of hypertension. Bradycardia may also be seen early in phenylephrine overdosage through stimulation of baroreceptors. Treatment: The treatment of overdosage with promethazine and phenylephrine 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 a patient with partial adrenergic blockade may further lower the blood pressure. Limited experience with dialysis indicates that it is not helpful.

Description

Each 5 mL (one teaspoonful), for oral administration contains: Promethazine hydrochloride, USP 6.25 mg; phenylephrine hydrochloride, USP 5 mg. Alcohol 7%. Inactive Ingredients: alcohol, ascorbic acid, caramel color, citric acid, edetate disodium, glycerin, methylparaben, natural & artificial citrus flavor, purified water, saccharin sodium, sodium benzoate, sodium citrate, sodium metabisulfite and sucrose. Promethazine hydrochloride, USP, a phenothiazine derivative, is chemically designated as (±)-10-[2-(Dimethylamino)propyl] phenothiazine monohydrochloride. Promethazine hydrochloride, USP 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. It has a molecular weight of 320.88, a molecular formula of C 17 H 20 N 2 S
• HCl and the following structural formula: Phenylephrine hydrochloride, USP is a sympathomimetic amine salt which is chemically designated as (-)- m -Hydroxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride. It occurs as white or nearly white crystals, having a bitter taste. It is freely soluble in water and alcohol. Phenylephrine hydrochloride, USP is subject to oxidation and must be protected from light and air. It has a molecular weight of 203.67, a molecular formula of C 9 H 13 NO 2
• HCl, and the following structural formula: ee90bcbe-figure-01 ee90bcbe-figure-02

How supplied

Promethazine Hydrochloride and Phenylephrine Hydrochloride Oral Solution, USP is a clear, pale yellow to yellow colored, citrus-flavored solution containing 6.25 mg Promethazine Hydrochloride, USP, 5 mg Phenylephrine Hydrochloride, USP and 7 percent alcohol in each teaspoonful (5 mL) Available as: 4 fl. oz (118 mL) NDC 65162-679-86 16 fl. oz (473 mL) NDC 65162-679-90 Dispense in a tight, light-resistant container as defined in the USP. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. Rx Only Manufactured by: Amneal Pharmaceuticals Branchburg, NJ 08876 Distributed by: Amneal Pharmaceuticals Glasgow, KY 42141 Rev. 05-2015-01

Label text from the FDA structured product label by Amneal Pharmaceuticals LLC (revised Oct 30, 2024). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Promethazine Hydrochloride in 2 products
Phenylephrine Hydrochloride in 2 products

Promethazine Hydrochloride and Phenylephrine Hydrochloride NDC products (2)

NDC	Strength & form	Labeler	Type
65162-679	Promethazine Hydrochloride 6.25 mg/5mL; Phenylephrine Hydrochloride 5 mg/5mL Solution	Amneal Pharmaceuticals LLC	ANDA
64950-345	Promethazine Hydrochloride 6.25 mg/5mL; Phenylephrine Hydrochloride 5 mg/5mL Solution	Genus Lifesciences Inc.	ANDA

Frequently asked questions

What is Promethazine Hydrochloride and Phenylephrine Hydrochloride used for?

What are the side effects of Promethazine Hydrochloride and Phenylephrine Hydrochloride?

Who makes Promethazine Hydrochloride and Phenylephrine Hydrochloride?

Promethazine Hydrochloride and Phenylephrine Hydrochloride is listed by 2 labelers in the FDA NDC directory, including Amneal Pharmaceuticals LLC, Genus Lifesciences Inc..