Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold.

It is important that promethazine hydrochloride and dextromethorphan hydrobromide oral solution 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 an appropriate device and can provide instructions for measuring the correct dose. 
Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is CONTRAINDICATED for children under 2 years of age (see WARNINGS – Boxed Warning and Use in Pediatric Patients). 
The average effective dose for adults is 5 mL (one teaspoon) every 4 to 6 hours, not to exceed 30 mL in 24 hours. For children 6 years to under 12 years of age, the dose is 2.5 to 5 mL (one-half to one teaspoon) every 4 to 6 hours, not to exceed 20 mL in 24 hours. For children 2 years to under 6 years of age, the dose is 1.25 to 2.5 mL (one-quarter to one-half teaspoon) every 4 to 6 hours, not to exceed 10 mL in 24 hours.

Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is contraindicated for use in pediatric patients less than two years of age.
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.
Dextromethorphan should not be used in patients receiving a monoamine oxidase inhibitor (MAOI) (see PRECAUTIONS – Drug Interactions).

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 hydrochloride (see PRECAUTIONS - Information for Patients and Drug Interactions).
Respiratory Depression
Promethazine may lead to potentially fatal respiratory depression.
Use of promethazine hydrochloride and dextromethorphan hydrobromide oral solution in patients with compromised respiratory function (e.g. COPD, sleep apnea syndrome) 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 hydrochloride and dextromethorphan hydrobromide oral solution should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine hydrochloride has been used in association with other known marrow-toxic agents.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine hydrochloride alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g. pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of promethazine hydrochloride, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) 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 hydrochloride should be carefully considered.
Use in Pediatric Patients
Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is contraindicated for use in pediatric patients less than two years of age.
Caution should be exercised when administering promethazine hydrochloride and dextromethorphan hydrobromide oral solution to pediatric patients 2 years of age and older because of the potential for fatal respiratory depression. Respiratory depression and apnea, sometimes 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 and dextromethorphan hydrobromide administration may be confused with the CNS signs of undiagnosed primary disease, e.g., encephalopathy or Reye's syndrome. The use of promethazine hydrochloride and dextromethorphan hydrobromide 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 hydrochloride.
Other Considerations
Administration of promethazine has been associated with reported cholestatic jaundice.
DEXTROMETHORPHAN
Administration of dextromethorphan may be accompanied by histamine release and should be used with caution in atopic children.

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 hydrochloride and dextromethorphan hydrobromide oral solution 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.

Patients should be advised to measure promethazine hydrochloride and dextromethorphan hydrobromide oral solution with an accurate measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when a half a teaspoon is measured. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.
Promethazine hydrochloride and dextromethorphan hydrobromide oral solution 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 and dextromethorphan therapy. Pediatric patients 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, such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers, may enhance impairment (see WARNINGS – CNS Depression and PRECAUTIONS – Drug Interactions).
Patients should be advised to report any involuntary muscle movements.
Avoid prolonged exposure to the sun.

Monoamine Oxidase (MAO) Inhibitors – Hyperpyrexia, hypotension, and death have been reported coincident with the co-administration of monoamine oxidase (MAO) inhibitors and products containing dextromethorphan. Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAO inhibitors and phenothiazines are used concomitantly. Thus, concomitant administration of promethazine hydrochloride and dextromethorphan hydrobromide oral solution and MAO inhibitors should be avoided (see CONTRAINDICATIONS).
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, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine. When given concomitantly with promethazine hydrochloride and dextromethorphan hydrobromide oral solution, 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 hydrochloride 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 hydrochloride and dextromethorphan hydrobromide overdose.
Anticholinergics – Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

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.

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 carcinogenicity, mutagenicity, or impairment of fertility with these drugs. Promethazine was nonmutagenic in the Salmonellatest system of Ames.

Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine hydrochloride. These doses are 8.3 and 16.7 times the maximum recommended total daily dose for a 50 kg subject. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.
Specific studies to test the action of promethazine 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.
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. Promethazine hydrochloride and dextromethorphan hydrobromide oral solution should be given to a pregnant woman only if clearly needed. Promethazine hydrochloride and dextromethorphan hydrobromide oral solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Promethazine administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.

Limited data suggest that use of promethazine hydrochloride 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 Nonteratogenic Effects.

It is not known whether promethazine or dextromethorphan 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 hydrochloride and dextromethorphan hydrobromide oral solution, 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.

Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is contraindicated for use in pediatric patients less than two years of age (see WARNINGS – Boxed Warning and Use in Pediatric Patients).
Promethazine hydrochloride and dextromethorphan hydrobromide oral solution should be used with caution in pediatric patients 2 years of age and older (see WARNINGS – Use in Pediatric Patients).

Clinical studies of promethazine hydrochloride 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 hydrochloride and dextromethorphan hydrobromide and observed closely.

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 –Respiratory Depression.)
Other – Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported (see WARNINGS –Neuroleptic Malignant Syndrome.)
Paradoxical Reactions 
Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine hydrochloride and dextromethorphan hydrobromide oral solution. Consideration should be given to the discontinuation of promethazine hydrochloride and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.
DEXTROMETHORPHAN
Dextromethorphan hydrobromide occasionally causes slight drowsiness, dizziness, and gastrointestinal disturbances.
To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 hydrochloride and dextromethorphan hydrobromide oral solution 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.

Patients should be advised to measure promethazine hydrochloride and dextromethorphan hydrobromide oral solution with an accurate measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when a half a teaspoon is measured. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.
Promethazine hydrochloride and dextromethorphan hydrobromide oral solution 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 and dextromethorphan therapy. Pediatric patients 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, such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers, may enhance impairment (see WARNINGS – CNS Depression and PRECAUTIONS – Drug Interactions).
Patients should be advised to report any involuntary muscle movements.
Avoid prolonged exposure to the sun.

Monoamine Oxidase (MAO) Inhibitors – Hyperpyrexia, hypotension, and death have been reported coincident with the co-administration of monoamine oxidase (MAO) inhibitors and products containing dextromethorphan. Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAO inhibitors and phenothiazines are used concomitantly. Thus, concomitant administration of promethazine hydrochloride and dextromethorphan hydrobromide oral solution and MAO inhibitors should be avoided (see CONTRAINDICATIONS).
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, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine. When given concomitantly with promethazine hydrochloride and dextromethorphan hydrobromide oral solution, 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 hydrochloride 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 hydrochloride and dextromethorphan hydrobromide overdose.
Anticholinergics – Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

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.

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 carcinogenicity, mutagenicity, or impairment of fertility with these drugs. Promethazine was nonmutagenic in the Salmonellatest system of Ames.

Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine hydrochloride. These doses are 8.3 and 16.7 times the maximum recommended total daily dose for a 50 kg subject. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.
Specific studies to test the action of promethazine 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.
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. Promethazine hydrochloride and dextromethorphan hydrobromide oral solution should be given to a pregnant woman only if clearly needed. Promethazine hydrochloride and dextromethorphan hydrobromide oral solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Promethazine administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.

Limited data suggest that use of promethazine hydrochloride 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 Nonteratogenic Effects.

It is not known whether promethazine or dextromethorphan 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 hydrochloride and dextromethorphan hydrobromide oral solution, 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.

Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is contraindicated for use in pediatric patients less than two years of age (see WARNINGS – Boxed Warning and Use in Pediatric Patients).
Promethazine hydrochloride and dextromethorphan hydrobromide oral solution should be used with caution in pediatric patients 2 years of age and older (see WARNINGS – Use in Pediatric Patients).

Clinical studies of promethazine hydrochloride 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 hydrochloride and dextromethorphan hydrobromide and observed closely.