Phenergan Injection :: Wyeth-Ayerst

DESCRIPTION

Phenergan (promethazine HCl) Injection, is a sterile, pyrogen-free solution for deep intramuscular or intravenous administration. Promethazine HCl (10 H -phenothiazine-10-ethanamine, N,N, (alpha)-trimethyl-, monohydrochloride, (±)-) is a racemic compound and has the following structural formula:

data/images/19/04052001.jpg

    C 17 H 21 ClN 2 S                                                         MW=320.89    

Each mL of ampul contains either 25 mg or 50 mg promethazine HCl with 0.1 mg edetate disodium, 0.04 mg calcium chloride, 0.25 mg sodium metabisulfite, and 5 mg phenol in Water for Injection. The pH range is 4.0 to 5.5, buffered with acetic acid-sodium acetate, and it is sealed under nitrogen.

Each mL of the TUBEX® and TUBEX® BLUNT POINTE™ Sterile Cartridge Units contains either 25 mg or 50 mg promethazine HCl with 0.1 mg edetate disodium, 0.04 mg calcium chloride, not more than 5 mg monothioglycerol; and 5 mg phenol in Water for Injection. The pH range is 4.0 to 5.5, buffered with sodium acetate-acetic acid, and it is sealed under nitrogen.

Phenergan (promethazine HCl) Injection is a clear, colorless solution. The product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.

CLINICAL PHARMACOLOGY

Promethazine HCl is a phenothiazine derivative which possesses antihistaminic, sedative, antimotion-sickness, antiemetic, and anticholinergic effects. Promethazine is a competitive H 1 receptor antagonist, but does not block the release of histamine. Structural differences from the neuroleptic phenothiazines results in its relative lack (1/10) of dopamine antagonist properties. In therapeutic doses, promethazine HCl produces no significant effects on the cardiovascular system. Clinical effects are generally apparent within 5 minutes of an intravenous injection and within 20 minutes of an intramuscular injection. Duration of action is four to six hours, although effects may persist up to 12 hours. Promethazine HCl is metabolized in the liver, with the sulfoxides of promethazine and N-desmethylpromethazine being the predominant metabolites appearing in the urine. Following intravenous administration in healthy volunteers, the plasma half-life for promethazine has been reported to range from 9 to 16 hours. The mean plasma half-life for promethazine after intramuscular administration in healthy volunteers has been reported to be 9.8±3.4 hours.

INDICATIONS AND USAGE

Phenergan Injection is indicated for the following conditions:

  1. Amelioration of allergic reactions to blood or plasma.
  2. In anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled.
  3. For other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.
  4. For sedation and relief of apprehension and to produce light sleep from which the patient can be easily aroused.
  5. Active treatment of motion sickness.
  6. Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery.
  7. As an adjunct to analgesics for the control of postoperative pain.
  8. Preoperative, postoperative, and obstetric (during labor) sedation.
  9. Intravenously in special surgical situations, such as repeated bronchoscopy, ophthalmic surgery, and poor-risk patients, with reduced amounts of meperidine or other narcotic analgesic as an adjunct to anesthesia and analgesia.

CONTRAINDICATIONS

Phenergan Injection is contraindicated in comatose states and in patients who have demonstrated an idiosyncrasy or hypersensitivity to promethazine or other phenothiazines.

Under no circumstances should Phenergan Injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see " WARNINGS -- Inadvertent Intra-arterial Injection ").

Phenergan Injection should not be given by the subcutaneous route; evidence of chemical irritation has been noted, and necrotic lesions have resulted on rare occasions following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection.

WARNINGS

Sulfite Sensitivity

Phenergan Injection (ampuls only) 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

Phenergan 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

Phenergan 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

Phenergan Injection should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when Phenergan has been used in association with other known marrow-toxic agents.

Use in Pediatric Patients

PHENERGAN INJECTION IS NOT RECOMMENDED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PHENERGAN INJECTION TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. 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 PHENERGAN INJECTION ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE'S SYNDROME. THE USE OF PHENERGAN 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 Phenergan 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 Phenergan 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 Phenergan 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 Phenergan 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, Phenergan 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 intraveous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intended intravenous injection of Phenergan 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.

PRECAUTIONS

General

Drugs having anticholingeric properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction.

Phenergan Injection should be used cautiously in persons with cardiovascular disease or impairment of liver function.

Information for Patients

Phenergan 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 Phenergan 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 -- Phenergan 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 concomitanty with Phenergan 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 Phenergan 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 Phenergan Injection, it is recommended that epinephrine NOT be used in the case of Phenergan 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 conomitantly. Although such a reaction has not been reported with Phenergan Injection, the possibility should be considered.

Laboratory Test Interactions

The following laboratory tests may be affected in patients who are receiving therapy with Phenergan 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 Phenergan Injection, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility. Phenergan Injection was nonmutagenic in the Ames Salmonella test system.

Pregnancy

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 (approximately 2.1 and 4.2 times the maximum recommended human daily dose) of Phenergan Injection. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.

There are no adequate and well-controlled studies of Phenergan Injection in pregnant women. Because animal reproduction studies are not always predictive of human response, Phenergan Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Adequate studies to determine the action of the drug on parturition, lactation and development of the animal neonate have not been conducted.

Nonteratogenic Effects

Phenergan Injection received within two weeks of delivery may inhibit platelet aggregation in the newborn.

Labor and Delivery

Phenergan Injection may be used alone or as an adjunct to narcotic analgesics during labor (see " DOSAGE AND ADMINISTRATION " ). Limited data suggest that use of Phenergan 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 " Nonteratogenic Effects .")

Nursing Mothers

It is not known whether Phenergan Injection is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Phenergan Injection is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients under 2 years of age have not been established.

Phenergan 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.

ADVERSE REACTIONS

CNS Effects

Drowsiness is the most prominent CNS effect of the 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 Phenergan 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 Phenergan 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 Phenergan. 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 Phenergan Injection, may be manifestations of relative overdosage, in which case, consideration should be given to the discontinuation of Phenergan Injection and to the use of other drugs. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.

OVERDOSAGE

Signs and symptoms of overdosage 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 pediatric patients and geriatric patients. Convulsions may rarely occur. A paradoxical reaction has been reported in pediatric patients receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares.

Atropine-like and symptoms--dry mouth, fixed, dilated pupils, flushing, etc., as well as gastrointestinal symptoms, may occur.

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 Phenergan 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.

DOSAGE AND ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use Phenergan Injection if solution has developed color or contains precipitate.

To avoid the possibility of physical and/or chemical incompatibility, consult specialized literature before diluting with any injectable solution or combining with any other medication. Do not use if there is a precipitate or any sign of incompatibility.

Important Notes on Administration

The preferred parenteral route of administration for Phenergan Injection is by deep intramuscular injection. The proper intravenous administration of this product is well-tolerated, but use of this route is not without some hazard. Not for subcutaneous administration.

INADVERTENT INTRA-ARTERIAL INJECTION CAN RESULT IN GANGRENE OF THE AFFECTED EXTREMITY (see "WARNINGS --Inadvertent Intra-arterial Injection"). SUBCUTANEOUS INJECTION IS CONTRAINDICATED, AS IT MAY RESULT IN TISSUE NECROSIS (see "CONTRAINDICATIONS ").

Injection into or near a nerve may result in permanent tissue damage.

When used intravenously, Phenergan Injection should be given in concentration no greater than 25 mg/mL as at rate not to exceed 25 mg per minute; it is preferable to inject through the tubing of an intravenous infusion set that is known to be functioning satisfactorily.

The TUBEX® BLUNT POINTE™ Sterile Cartridge Unit is suitable for substances to be administered intravenously. It is intended for use with injection sets specifically manufactured as "needle-less" injection systems. As of the date of this circular, the TUBEX BLUNT POINTE is compatible with LifeShield® Prepierced Reseal injection site, Inter-Link® Injection Site, Safe Line® Injection Site, User-Gard® Intermittent Injection Cap, and SafSite® reflux valve.

The TUBEX® Sterile Cartridge Needle Unit is suitable for substances to be administered intravenously or intramuscularly.

Allergic Conditions

The average adult dose is 25 mg. This dose may be repeated within two hours if necessary, but continued therapy, if indicated, should be via the oral route as soon as existing circumstances permit. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The average adult dose for amelioration of allergic reactions to blood or plasma is 25 mg.

Sedation

In hospitalized adult patients, nighttime sedation may be achieved by a dose of 25 to 50 mg of Phenergan Injection.

Nausea and Vomiting

For control of nausea and vomiting, the usual adult dose is 12.5 to 25 mg, not to be repeated more frequently than every four hours. When used for control of postoperative nausea and vomiting, the medication may be administered either intramuscularly or intravenously and dosage of analgesics and barbiturates reduced accordingly.

Preoperative and Postoperative Use

As an adjunct to preoperative or postoperative medication, 25 to 50 mg Phenergan Injection in adults may be combined with appropriately reduced doses of analgesics and atropine-like drugs as desired. Dosage of concomitant analgesic or hypnotic medication should be reduced accordingly.

Obstetrics

Phenergan Injection in doses of 50 mg will provide sedation and relieve apprehension in the early stages of labor. When labor is definitely established, 25 to 75 mg (average dose, 50 mg) Phenergan Injection may be given intramuscularly or intravenously with an appropriately reduced dose of any desired narcotic. If necessary. Phenergan Injection with a reduced dose of analgesic may be repeated once or twice at four-hour intervals in the course of a normal labor. A maximum total dose of 100 mg of Phenergan Injection may be administered during a 24-hour period to patients in labor.

Pediatric Patients

Phenergan Injection is not recommended for use in pediatric patients less than two year of age.

In pediatric patients 2 years of age and older, the dosage should not exceed half that of the suggested adult dose. As an adjunct to premedication, the suggested dose is 0.5 mg per lb. of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug. Antiemetics should not be used in vomiting of unknown etiology in pediatric patients (see " WARNINGS -- Use in Pediatric Patients ).

HOW SUPPLIED

Phenergan® (promethazine HCl) Injection is available in 1 mL ampuls, in packages of 25 ampuls, as follows:

25 mg per mL, NDC 0008-0630-01

50 mg per mL, NDC 0008-0746-01

Store at controlled room temperature 15°-30°C (59°-86°F).

Protect from light. Keep covered in carton until time of use.

Do not use if solution has developed color or contains a precipitate.

Also Available:

Phenergan Injection is also available in the following dosage strengths in TUBEX® BLUNT POINTE™ Sterile Cartridge Units and Sterile Cartridge-Needle Units, packaged in boxes of 10 TUBEX® as follows:

25 mg per mL, NDC 0008-0416-50, 1 mL size BLUNT POINTE™ .

25 mg per mL, NDC 0008-0416-01, 1 mL size (22 gauge × 1-1/4 inch needle).

50 mg per mL, NDC 0008-0417-01, 1 mL size (22 gauge × 1-1/4 inch needle).

TUBEX is a registered trademark of Wyeth-Ayerst Laboratories. BLUNT POINTE is a trademark of Wyeth-Ayerst Laboratories.

InterLink is a registered trademark of Baxter International, Inc.

LifeShield is a registered trademark of Abbott Laboratories.

SafeLine is a registered trademark of McGaw, Inc.

SafSite is a registered trademark of B. Braun Medical, Inc.

User-Gard is a registered trademark of Arrow International, Inc.

Manufactured by:

Wyeth Laboratories Inc.

A Wyeth-Ayerst Company

Philadelphia PA 19101

CI 3727-7                                Revised January 10, 2000



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