promethazine hydrochloride
Anergan 50, Phenergan

Available forms
Available by prescription only
Injection: 25 mg/ml, 50 mg/ml
Suppositories: 12.5 mg, 25 mg, 50 mg
Syrup: 6.25 mg/5 ml
Tablets: 12.5 mg, 25 mg, 50 mg

Indications and dosages
 Motion sickness. Adults: 25 mg P.O. b.i.d.
Children older than age 2: 12.5 to 25 mg P.O. or P.R. b.i.d.
 Prevention and treatment of nausea and vomiting. Adults: 12.5 to 25 mg P.O., I.M., or P.R. q 4 hours, p.r.n.
Children older than age 2: 0.25 to 0.5 mg/kg, or 7.5 to 15 mg/m² I.M. or P.R. q 4 to 6 hours, p.r.n.
 Rhinitis, allergy symptoms. Adults: 12.5 mg P.O. before meals and h.s., or 25 mg P.O. h.s.
Children older than age 2: 6.25 to 12.5 mg P.O. t.i.d., or 25 mg P.O. or P.R. h.s.
 Sedation. Adults: 25 to 50 mg P.O., P.R., or I.M. h.s. or p.r.n.
Children older than age 2: 12.5 to 25 mg P.O., I.M., or P.R. h.s.
 Routine preoperative or postoperative sedation or as an adjunct to analgesics. Adults: 25 to 50 mg I.M., I.V., or P.O.
Children older than age 2: 12.5 to 25 mg or 0.5 to 1.1 mg/kg I.M., I.V., or P.O.
 Obstetric sedation. Adults: 50 mg I.M. or I.V. in early stages of labor, and 25 to 75 mg after labor is established; repeat q 2 to 4 hours, p.r.n. Maximum, 100 mg daily.

Pharmacodynamics
Antiemetic and antivertigo actions: The central antimuscarinic actions of antihistamines probably are responsible for their antivertigo and antiemetic effects; promethazine also is believed to inhibit the medullary chemoreceptor trigger zone.
Antihistamine action: Competes with histamine for the H₁-receptor, thereby suppressing allergic rhinitis and urticaria; drug doesn’t prevent the release of histamine.
Sedative action: Mechanism unknown; probably causes sedation by reducing stimuli to the brain-stem reticular system.

Pharmacokinetics
Absorption: Well absorbed from GI tract. Effects usually last 4 to 6 hours but may last for 12 hours.
Distribution: Distributed widely throughout body; crosses the placental barrier.
Metabolism: Metabolized in liver.
Excretion: Metabolites excreted in urine and feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug; in those with intestinal obstruction, prostatic hyperplasia, bladder neck obstruction, seizure disorders, coma, CNS depression, or stenosing peptic ulcerations; in newborns, premature neonates, and breast-feeding patients; and in acutely ill or dehydrated children.
  Use cautiously in patients with asthma or cardiac, pulmonary, or hepatic disease.

Interactions
Drug-drug. Epinephrine: Causes partial adrenergic blockade and further hypotension. Monitor blood pressure.
Levodopa: May block levodopa’s antiparkinsonian action. Monitor patient.
MAO inhibitors: Interferes with detoxification of antihistamines and phenothiazines; prolongs and intensifies sedative and anticholinergic effects. Avoid use together.
Other antihistamines or CNS depressants (such as anxiolytics, barbiturates, sleeping aids, tranquilizers): Causes additive CNS depression. Use together cautiously.
Drug-herb. Kava: Increases risk or severity of dystonic reactions. Discourage use together.
Yohimbe: Increases risk of toxicity. Discourage use together.
Drug-lifestyle. Alcohol use: Causes additive CNS depression. Discourage alcohol use.
Sun exposure: Causes photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: sedation, confusion, sleepiness, dizziness, disorientation, extrapyramidal symptoms, drowsiness.
CV: hypotension, hypertension.
EENT: blurred vision.
GI: nausea, vomiting, dry mouth.
GU: urine retention.
Hematologic: leukopenia, agranulocytosis, thrombocytopenia.
Metabolic: hyperglycemia.
Skin: photosensitivity, rash.

Effects on lab test results
• May increase blood glucose level.
• May decrease WBC, platelet, and granulocyte counts.

Overdose and treatment
Toxicity may cause CNS depression (sedation, reduced mental alertness, apnea, and CV collapse) or CNS stimulation (insomnia, hallucinations, tremors, or seizures). Atropine-like signs and symptoms, such as dry mouth, flushed skin, fixed and dilated pupils, and GI symptoms, are common, especially in children.
 Empty stomach by gastric lavage; don’t induce vomiting. Treat hypotension with vasopressors, and control seizures with diazepam or phenytoin; correct acidosis and electrolyte imbalance. Urinary acidification promotes excretion of drug. Don’t give stimulants.

Special considerations
• Pronounced sedative effects may limit use in some ambulatory patients.
• The 50-mg/ml concentration is for I.M. use only; inject deep into large muscle mass. Don’t administer drug S.C.; this may cause chemical irritation and necrosis. Drug may be administered I.V., in concentrations not to exceed 25 mg/ml and at a rate not to exceed 25 mg/minute. When using I.V. drip, wrap in aluminum foil to protect drug from light.
• Promethazine and meperidine (Demerol) may be mixed in same syringe.
• Stop drug 4 days before diagnostic skin tests to avoid preventing, reducing, or masking test response. Promethazine may cause either false-positive or false-negative pregnancy test results. It also may interfere with blood grouping in the ABO system.
Breast-feeding patients
• Antihistamines such as promethazine shouldn’t be used during breast-feeding. Many of these drugs appear in breast milk, exposing infants to risks of unusual excitability, especially premature infants and other neonates, who may experience seizures.
Pediatric patients
• Use cautiously in children with respiratory dysfunction. Safety and efficacy in children younger than age 2 haven’t been established. Don’t give drug to infants younger than age 3 months.
Geriatric patients
• Elderly patients are usually more sensitive to adverse effects of antihistamines and are especially likely to experience a greater degree of dizziness, sedation, hyperexcitability, dry mouth, and urine retention than younger patients. Symptoms usually respond to a decrease in dosage.

Patient education
• Warn patient about possible photosensitivity and ways to avoid it.
• When treating motion sickness, tell patient to take first dose 30 to 60 minutes before travel; on succeeding days, he should take dose upon arising and with evening meal.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use