Promethazine Hydrochloride (Injection)

Promethazine hydrochloride injection is indicated for the following conditions:

• Amelioration of allergic reactions to blood or plasma.
• In anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled.
• For other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.
• For sedation and relief of apprehension and to produce light sleep from which the patient can be easily aroused.
• Active treatment of motion sickness.
• Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery.
• As an adjunct to analgesics for the control of postoperative pain.
• Preoperative, postoperative, and obstetric (during labor) sedation.
• 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.

Promethazine is a phenothiazine derivative which blocks postsynaptic mesolimbic dopaminergic receptors in the brain. It exhibits strong α-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones. It competes with histamine for the H1-receptor; muscarinic blocking effect may be responsible for antiemetic activity. It also reduces stimuli to the brainstem reticular 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 hydrochloride injection 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.

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 Promethazine Hydrochloride 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 Promethazine Hydrochloride 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.

CNS Depressants: Promethazine hydrochloride (promethazine hydrochloride 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 promethazine hydrochloride (promethazine hydrochloride 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 hydrochloride (promethazine hydrochloride 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 hydrochloride (promethazine hydrochloride injection), it is recommended that epinephrine NOT be used in the case of promethazine hydrochloride (promethazine hydrochloride injection) overdose.

Promethazine hydrochloride 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 Promethazine hydrochloride injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene.

Promethazine hydrochloride 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 intramuscularinjection.

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 Promethazine hydrochloride injection. Venous thrombosis at the injection site has been reported.

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 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. 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.

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 Promethazine hydrochloride 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 Promethazine hydrochloride injection in pregnant women. Because animal reproduction studies are not always predictive of human response, Promethazine hydrochloride injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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. Promethazine hydrochloride (promethazine hydrochloride injection) should be used cautiously in persons with cardiovascular disease or impairment of liver function.

Carcinogenesis, Mutagenesis and Impairment of Fertility: Long term animal studies have not been performed to assess the carcinogenic potential of promethazine hydrochloride (promethazine hydrochloride injection), nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility. Promethazine hydrochloride was nonmutagenic in the Ames Salmonella test system.

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 promethazine hydrochloride (promethazine hydrochloride 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.

Anti-emetic drugs, Miscellaneous sedatives & hypnotics, Sedating Anti-histamine.

Pediatric Patients: Promethazine hydrochloride are contraindicated for children under 2 years 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 

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.

Store between 15-30° C. Protect from light..