CONTRAINDICATIONS SECTION

CONTRAINDICATIONS

Children Less Than 2 Years of Age

Promethazine hydrochloride injection is contraindicated for use in pediatric patients less than two years of age due to the risk of respiratory depression (see WARNINGS - Respiratory Depression).

Comatose State

Promethazine hydrochloride injection is contraindicated in comatose states.

Intra-Arterial Injection

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 (see WARNINGS - Severe Tissue Injury, Including Gangrene).

Subcutaneous Injection

Promethazine hydrochloride injection should not be given by the subcutaneous route because evidence of chemical irritation has been noted, and necrotic lesions have resulted following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection.

Idiosyncratic Reaction or Hypersensitivity

Promethazine hydrochloride injection is contraindicated in patients who have demonstrated an idiosyncratic reaction or hypersensitivity to promethazine or other phenothiazines.

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ADVERSE REACTIONS SECTION

ADVERSE REACTIONS

Respiratory Depression

Promethazine hydrochloride injection is contraindicated in pediatric patients less than 2 years of age, because of the potential for fatal respiratory depression. Promethazine hydrochloride injection should be used with caution in pediatric patients 2 years of age and older (see WARNINGS - Respiratory Depression).

Severe Tissue Injury, Including Gangrene

Promethazine hydrochloride injection can cause severe chemical irritation and damage to tissues regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra- arterial injection and intraneuronal or perineuronal infiltration. Adverse reactions include burning, pain, erythema, swelling, sensory loss, palsies, paralysis, severe spasm of distal vessels, thrombophlebitis, venous thrombosis, phlebitis, abscesses, tissue necrosis, and gangrene. In some cases, surgical intervention, including fasciotomy, skin graft, and/or amputation have been required (see WARNINGS - Severe Tissue Injury, Including Gangrene; and DOSAGE AND ADMINISTRATION).

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 injection. Consideration should be given to the discontinuation of promethazine hydrochloride injection 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.

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OVERDOSAGE SECTION

OVERDOSAGE

Signs and symptoms of overdosage range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex).

Stimulation may be evident, especially in pediatric patients and geriatric patients. Convulsions may rarely occur. A paradoxical-type reaction has been reported in pediatric patients receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares.

Atropine-like signs 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 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 norepinephrine 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.

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