Promethazine

May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines).

May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, pyloroduodenal obstruction, urinary retention, bladder neck obstruction, BPH, xerostomia, or visual problems.

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia.

Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.

May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

May cause photosensitivity; avoid prolonged sun exposure.

Promethazine injection can cause severe tissue injury (including gangrene) regardless of the route of administration. Tissue irritation and damage may result from perivascular extravasation, unintentional intra-arterial administration, and intraneuronal or perineuronal infiltration. In addition to gangrene, adverse events reported include tissue necrosis, abscesses, burning, pain, erythema, edema, severe spasm of distal vessels, phlebitis, thrombophlebitis, venous thrombosis, sensory loss, paralysis, and palsies. Surgical intervention including fasciotomy, skin graft, and/or amputation have been necessary in some cases. The preferred route of administration is by deep intramuscular (IM) injection. Subcutaneous administration is contraindicated. Discontinue intravenous injection immediately with onset of burning and/or pain and evaluate for arterial injection or perivascular extravasation. Although there is no proven successful management of unintentional intra-arterial injection or perivascular extravasation, sympathetic block and heparinization have been used in the acute management of unintentional intra-arterial injection based on results from animal studies. Vesicant; for IV administration (not the preferred route of administration), ensure proper needle or catheter placement prior to and during administration; avoid extravasation.

Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects. Disease-related concerns:

Use with caution in patients with bone marrow suppression; leukopenia and agranulocytosis have been reported.

Use with caution in patients with cardiovascular disease.

Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade.

Use with caution in patients with hepatic impairment; cholestatic jaundice has been reported with use. Avoid use in pediatric patients with signs and symptoms of hepatic disease (extrapyramidal symptoms caused by promethazine may be confused with CNS signs of hepatic disease).

Use with caution in patients with myasthenia gravis; condition may be exacerbated by cholinergic blockade.

Use with caution in patients with Parkinson disease; may have increased risk of tardive dyskinesia.

Avoid use in patients with compromised respiratory function or in patients at risk for respiratory failure (eg, COPD, sleep apnea); may lead to potentially fatal respiratory depression.

Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Respiratory depression, including fatalities, have been reported in children Antiemetics are not recommended for the treatment of uncomplicated vomiting in pediatric patients; limit use to prolonged vomiting of known etiology. Avoid use in children who may have Reye syndrome or hepatic disease as adverse reactions caused by promethazine may be confused with signs of primary disease. Dosage form specific issues:

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Injection may contain sodium metabisulfite; may cause allergic reaction.