Promethazine Hydrochloride and Phenylephrine Hydrochloride

INDICATIONS AND USAGE 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. Phenylephrine: Because phenylephrine is an adrenergic agent, it should be given with caution to patients with thyroid diseases, diabetes mellitus, and heart disease or those receiving tricyclic antidepressants. Men with symptomatic, benign prostatic hypertrophy can experience urinary retention when given oral nasal decongestants. Phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug parenterally or orally to patients with arteriosclerosis, to elderly individuals, and/or to patients with initially poor cerebral or coronary circulation. Phenylephrine should be used with caution in patients taking diet preparations, such as amphetamines or phenylpropanolamine, because synergistic adrenergic effects could result in serious hypertensive response and possible stroke.

ADVERSE REACTIONS 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.