Yes

Antiemetic

Symptomatic treatment of various allergic conditions; antiemetic; motion sickness; sedative; analgesic adjunct for control of postoperative pain; anesthetic adjunct

C

Clinical effects on the fetus: Crosses the placenta. Possible respiratory depression if drug is administered near time of delivery; behavioral changes, EEG alterations, impaired platelet aggregation reported with use during labor. Available evidence with use of occasional low doses suggests safe use during pregnancy.

Breast-feeding/lactation: No data available. American Academy of Pediatrics makes NO RECOMMENDATION.

Hypersensitivity to promethazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression; coma; intra-arterial or subcutaneous injection

May be sedating; use with caution in disorders where CNS depression is a feature. May impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (ie, operating machinery or driving). Effects with other sedative drugs or ethanol may be potentiated. Avoid use in Reye's syndrome. Use with caution in Parkinson's disease; hemodynamic instability; bone marrow suppression; predisposition to seizures; subcortical brain damage; and in severe cardiac, hepatic, renal, or respiratory disease. Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life threatening arrhythmias have occurred with therapeutic doses of phenothiazines. May cause orthostatic hypotension; use with caution in patients at risk of hypotension or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease).

Cardiovascular: Postural hypotension, tachycardia, dizziness, nonspecific QT changes

Central nervous system: Drowsiness, dystonias, akathisia, pseudoparkinsonism, tardive dyskinesia, neuroleptic malignant syndrome, seizures

Dermatologic: Photosensitivity, dermatitis, skin pigmentation (slate gray)

Endocrine & metabolic: Lactation, breast engorgement, false-positive pregnancy test, amenorrhea, gynecomastia, hyper- or hypoglycemia

Gastrointestinal: Xerostomia, constipation, nausea

Genitourinary: Urinary retention, ejaculatory disorder, impotence

Hematologic: Agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, aplastic anemia, thrombocytopenic purpura

Hepatic: Jaundice

Ocular: Blurred vision, corneal and lenticular changes, epithelial keratopathy, pigmentary retinopathy

Symptoms of overdose include CNS depression, respiratory depression, possible CNS stimulation, dry mouth, fixed and dilated pupils, hypotension

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, norepinephrine 0.1-0.2 mcg/kg/minute titrated to response may be tried. Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Critical cardiac arrhythmias often respond to I.V. phenytoin (15 mg/kg up to 1 g), while other antiarrhythmics can be used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management with diphenhydramine 1-2 mg/kg (adults) up to a maximum of 50 mg I.M. or I.V. slow push followed by a maintenance dose for 48-72 hours. When these reactions are unresponsive to diphenhydramine, benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

CYP2D6 enzyme substrate

Benztropine (and other anticholinergics) may inhibit the therapeutic response to promethazine and excess anticholinergic effects may occur

Chloroquine may increase promethazine concentrations

Cigarette smoking may enhance the hepatic metabolism of promethazine. Larger doses may be required compared to a nonsmoker.

Concurrent use of promethazine with an antihypertensive may produce additive hypotensive effects

Antihypertensive effects of guanethidine and guanadrel may be inhibited by promethazine

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Promethazine may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Promethazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce promethazine concentrations

Propranolol may increase promethazine concentrations

Sulfadoxine-pyrimethamine may increase promethazine concentrations

Promethazine and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

Promethazine and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Promethazine and trazodone may produce additive hypotensive effects

Protect from light and from freezing; compatible (when comixed in the same syringe) with atropine, chlorpromazine, diphenhydramine, droperidol, fentanyl, glycopyrrolate, hydromorphone, hydroxyzine hydrochloride, meperidine, midazolam, nalbuphine, pentazocine, prochlorperazine, scopolamine; incompatible when mixed with aminophylline, cefoperazone (Y-site), chloramphenicol, dimenhydrinate (same syringe), foscarnet (Y-site), furosemide, heparin, hydrocortisone, methohexital, penicillin G, pentobarbital, phenobarbital, thiopental

Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; competes with histamine for the H₁-receptor; reduces stimuli to the brainstem reticular system

Onset of effect: I.V.: Within 20 minutes (3-5 minutes with I.V. injection)

Duration: 2-6 hours

Metabolism: In the liver

Elimination: Principally as inactive metabolites in urine and in feces

Children:

Antihistamine: Oral, rectal: 0.1 mg/kg/dose every 6 hours during the day and 0.5 mg/kg/dose at bedtime as needed

Antiemetic: Oral, I.M., I.V., rectal: 0.25-1 mg/kg 4-6 times/day as needed

Motion sickness: Oral, rectal: 0.5 mg/kg/dose 30 minutes to 1 hour before departure, then every 12 hours as needed

Sedation: Oral, I.M., I.V., rectal: 0.5-1 mg/kg/dose every 6 hours as needed

Adults:

Antihistamine (including allergic reactions to blood or plasma):

Oral, rectal: 12.5 mg 3 times/day and 25 mg at bedtime

I.M., I.V.: 25 mg, may repeat in 2 hours when necessary; switch to oral route as soon as feasible

Antiemetic: Oral, I.M., I.V., rectal: 12.5-25 mg every 4 hours as needed

Motion sickness: Oral, rectal: 25 mg 30-60 minutes before departure, then every 12 hours as needed

Sedation: Oral, I.M., I.V., rectal: 25-50 mg/dose

Hemodialysis: Not dialyzable (0% to 5%)

Increase dietary intake of riboflavin; should be administered with food or water

Alters the flare response in intradermal allergen tests

Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called "epinephrine reversal" phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.

Significant hypotension may occur, especially when the drug is administered parenterally; orthostatic hypotension is due to alpha-receptor blockade, the elderly are at greater risk for orthostatic hypotension

Extrapyramidal reactions are more common in elderly with up to 50% developing these reactions after 60 years of age; drug-induced Parkinson's syndrome occurs often; akathisia is the most common extrapyramidal reaction in elderly

Increased confusion, memory loss, psychotic behavior, and agitation frequently occur as a consequence of anticholinergic effects

Antipsychotic associated sedation in nonpsychotic patients is extremely unpleasant due to feelings of depersonalization, derealization, and dysphoria

Take this drug as prescribed; do not increase dosage. Do not use alcohol or other CNS depressants or sleeping aids without consulting prescriber. May cause dizziness, drowsiness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, dry mouth, appetite disturbances (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report unusual weight gain, unresolved nausea or diarrhea, chest pain or palpitations, excess sedation or stimulation, or sore throat or difficulty breathing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Avoid S.C. administration, promethazine is a chemical irritation which may produce necrosis; avoid I.V. use; if necessary, may dilute to a maximum concentration of 25 mg/mL and infuse at a maximum rate of 25 mg/minute

Injection, as hydrochloride: 25 mg/mL (1 mL, 10 mL); 50 mg/mL (1 mL, 10 mL)

Suppository, rectal, as hydrochloride: 12.5 mg, 25 mg, 50 mg

Syrup, as hydrochloride: 6.25 mg/5 mL (5 mL, 120 mL, 240 mL, 480 mL, 4000 mL); 25 mg/5 mL (120 mL, 480 mL, 4000 mL)

Tablet, as hydrochloride: 12.5 mg, 25 mg, 50 mg

Blanc VF, Ruest P, Milot J, et al, "Antiemetic Prophylaxis With Promethazine or Droperidol in Paediatric Outpatient Strabismus Surgery," Can J Anaesth, 1991, 38(1):54-60.

Buck ML and Blumer JL, "Phenothiazine-Associated Apnea in Two Siblings," DICP, 1991, 25(3):244-7.

Cleghorn C and Bourke G, "Physostigmine for Promethazine Poisoning," Lancet, 1980, 2(8190):368-9.

DeGrandi T and Simon JE, "Promethazine-Induced Dystonic Reaction," Pediatr Emerg Care, 1987, 3(2):91-2.

Grunberg SM and Hesketh PJ, "Control of Chemotherapy-Induced Emesis," N Engl J Med, 1993, 329(24):1790-6.

Shawn DH and McGuigan MA, "Poisoning From Dermal Absorption of Promethazine," Can Med Assoc J, 1984, 130(11):1460-1.

Tavorath R and Hesketh PJ, "Drug Treatment of Chemotherapy-Induced Delayed Emesis," Drugs, 1996, 52(5):639-48.

Tortorice PV and O'Connell MB, "Management of Chemotherapy-Induced Nausea and Vomiting," Pharmacotherapy, 1990, 10(2):129-45.