Label: promethazine hcl- Promethazine hydrochloride injection

Sulfite Sensitivity

Promethazine HCl Injection 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 Patients”).

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 CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl INJECTION 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 NOT FIRMLY WEIGHT-RELATED, WHICH MIGHT OTHERWISE PERMIT SAFE ADMINISTRATION OF INDIVIDUALIZED DOSING. 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 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 intravenous 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 intravenous 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 per mL and at a rate not to exceed 25 mg per minute. When administering any irritant drug intravenously, it is usually preferable to inject it through the tubing of an intravenous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intended intravenous 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 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 HCl Injection should be used cautiously in persons with cardiovascular disease or impairment of liver function.

Information for Patients

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.

Drug Interactions

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.

Laboratory Tests Interactions

The following laboratory tests may be affected in patients who are receiving therapy with Promethazine HCl Injection:

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 glucose tolerance has been reported in patients receiving promethazine HCl.

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

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 “Pregnancy: 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 Effects:

Drowsiness is the most prominent CNS effect of this 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 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.

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 intravenous fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to intravenous 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.