Pronunciation: proe-METH-a-zeen HYE-droe-KLOR-ide
Class: Phenothiazine, nonselective

Trade Names

Phenadoz
- Suppositories, rectal 12.5 mg
- Suppositories, rectal 25 mg

Phenergan
- Injection, solution 25 mg/mL
- Injection, solution 50 mg/mL

Promethazine Hydrochloride
- Tablets, oral 12.5 mg
- Tablets, oral 25 mg
- Tablets, oral 50 mg
- Solution, oral 6.25 mg per 5 mL

Promethegan
- Suppositories, rectal 12.5 mg
- Suppositories, rectal 25 mg
- Suppositories, rectal 50 mg

Pharmacology

Competitively antagonizes histamine at H ₁ receptor sites. Produces antihistaminic, anti-motion sickness, sedative, antiemetic, and anticholinergic effects.

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Pharmacokinetics

Absorption

Well absorbed from the GI tract and after IM administration. T _max is 2 to 3 h (IM).

Distribution

Protein binding is 76% to 93%. Crosses the blood-brain barrier and placenta, and is distributed into breast milk.

Metabolism

Metabolized in the liver; sulfoxides and N-demethylpromethazine are the predominant metabolites.

Elimination

In the urine and bile, chiefly as metabolites. The half-life is approximately 5 to 14 h.

Onset

20 min (oral); 20 min (IM); 5 min (IV).

Duration

Duration of action is 4 to 6 h; may persist up to 12 h (oral).

Indications and Usage

Injection

Amelioration of allergic reactions to blood or plasma; in anaphylaxis as an adjunct to epinephrine and other standard measures after acute symptoms have been controlled; uncomplicated allergic conditions of the immediate type when other therapy is impossible or contraindicated; sedation and relief of apprehension and to produce light sleep from which 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; adjunct to analgesics for control of postoperative pain; preoperative, postoperative, and obstetric (during labor) sedation; IV in special surgical situations (eg, repeated bronchoscopy, ophthalmic surgery, poor-risk patients) with reduced amounts of meperidine or other narcotic analgesic as an adjunct to anesthesia and analgesia.

Oral/Rectal

For perennial and seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis; mild, uncomplicated skin manifestations of urticaria and angioedema; amelioration of allergic reactions to blood or plasma; dermographism; adjunctive therapy in anaphylactic reactions; preoperative, postoperative, or obstetric (during labor) sedation; prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery; adjunctive therapy to analgesics for postoperative pain; relief of apprehension and production of light sleep; active and prophylactic treatment of motion sickness; antiemetic therapy in postoperative patients.

Unlabeled Uses

Nausea and vomiting of pregnancy; opioid-induced nausea and vomiting.

Contraindications

Children younger than 2 y; comatose patients; known hypersensitivity or idiosyncratic reaction to promethazine or other phenothiazines; treatment of lower respiratory tract symptoms, including asthma (oral, rectal); intraarterial or subcutaneous injection (injection).

Dosage and Administration

Allergic conditions
Adults and Children 2 y and older

PO/PR 25 mg at bedtime or 12.5 mg before meals and at bedtime (4 times daily). Alternatively, 6.25 to 12.5 mg 3 times daily may be used. Adjust dose to the smallest amount adequate to reduce symptoms.

Adults

IM/IV 25 mg; may repeat dose within 2 h if needed. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to reduce symptoms.

Children 2 y and older

IM/IV Up to 12.5 mg; may repeat dose within 2 h as needed (max, 12.5 mg/dose). After initiation of treatment, dosage should be adjusted to the smallest amount adequate to reduce symptoms.

Antiemetic
Adults PO/PR

12.5 to 25 mg as needed every 4 to 6 h (use 25 mg during surgery and the postoperative period).

IM/IV

12.5 to 25 mg every 4 h as needed.

Children 2 y and older PO/PR

1 mg/kg every 4 to 6 h as needed. Adjust dose as needed. Do not use if unknown etiology.

IV/IV

Up to 6.25 to 12.5 mg; may repeat every 4 h as needed (max, 12.5 mg/dose).

Elderly

Dosage reduction may be required.

Motion sickness
Adults

PO/PR 25 mg twice daily with initial dose taken 30 min to 1 h before travel and repeated in 8 to 12 h if needed. Thereafter, 25 mg twice daily.

Children 2 y and older

PO/PR 12.5 to 25 mg twice daily with initial dose taken 30 min to 1 h before travel and repeated in 8 to 12 h if needed. Thereafter, 12.5 to 25 mg twice daily.

Obstetric sedation
Adults

IM/IV 50 mg in early stages of labor. When labor is established, 25 to 75 mg with reduced dose of narcotic may be repeated once or twice at 4 h intervals (max dose, 100 mg per 24 h).

Postoperative analgesia
Adults

PO/PR/IM/IV 25 to 50 mg with analgesics.

Children 2 y and older PO/PR

12.5 to 25 mg with analgesics.

IM/IV

1 mg/kg (max, 25 mg/dose) in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug.

Preoperative analgesia
Adults PO/PR

50 mg with an appropriately reduced dose of narcotic or barbiturate and the required amount of a belladonna alkaloid.

IM/IV

25 to 50 mg.

Children 2 y and older

PO/PR/IM/IV 1 mg/kg (max, 25 mg/dose) in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug.

Sedation
Adults

PO/PR/IM/IV 25 to 50 mg for nighttime, presurgical, or obstetrical sedation.

Children 2 y and older PO/PR

12.5 to 25 mg at bedtime, or pre- or postoperatively for sedation.

IM/IV

Up to 12.5 to 25 mg at bedtime (max, 25 mg/dose).

General Advice

Tablets and oral solution

• Administer without regard to meals. Administer with food if GI upset occurs.
• Measure and administer prescribed dose of oral solution using dosing syringe, dosing spoon, or dosing cup.

Suppositories

• For rectal administration only.
• Remove from foil wrap immediately prior to insertion.

Injection

• For deep IM (preferred) or IV administration only. Not for intradermal, subcutaneous, or intra-arterial administration.
• If drug must be administered IV, use caution. Do not inject directly into vein; inject through appropriate site in IV tubing of IV infusion set that is known to be functioning satisfactorily. Discontinue injection immediately if patient complains of pain at injection site.
• Do not exceed IV concentration of 25 mg/mL; do not exceed IV rate of 25 mg/min.

Storage/Stability

Store oral solution, tablets and injection between 68° and 77°F. Store suppositories in the refrigerator between 36° and 46°F. Protect from light.

Drug Interactions

Acitretin

The alcohol in promethazine oral solution may increase plasma concentrations and toxic effects (eg, teratogenic effects) of acitretin. Contraceptive measures must be employed for 3 y following cessation of acitretin.

Anticholinergics (eg, atropine, trihexyphenidyl)

May decrease action of promethazine. Use with caution.

Antipsychotic agents

The risk of NMS may be increased. Monitor the patient for symptoms of the syndrome. If an interaction is suspected, discontinue promethazine.

Cabergoline, pergolide

The pharmacologic effects may be decreased by coadministration with promethazine. Coadministration is not recommended.

Cefotetan, disulfiram, furazolidone, metronidazole

Because promethazine oral solution contains alcohol, an acute alcohol intolerance reaction may occur if one of these agents is given concurrently. When possible, advise patients to avoid concurrent use.

Cisapride

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased. Concurrent use is contraindicated.

CNS depressants (eg, alcohol, general anesthetics, narcotics, narcotic analgesics, sedatives/hypnotics, including barbiturates, tranquilizers, tricyclic antidepressants)

May have additive CNS depressant effects. Avoid such agents or administer in reduced dosages. When coadministered with promethazine, reduce the dose of barbiturates by at least half and the dose of narcotics by one-fourth to one-half.

Drugs that lower seizure threshold (eg, local anesthetics, narcotics, tramadol)

Promethazine may lower the seizure threshold. Use with caution in patients receiving other agents that may affect the seizure threshold.

Drugs with respiratory depressant effects

Increased respiratory depressant effects. Coadministration in pediatric patients has been associated with respiratory depression and sometimes death. Concurrent use should be avoided.

Epinephrine

Do not use to treat hypotension associated with promethazine overdose.

Levodopa

The pharmacologic effects of levodopa may be decreased. If concomitant use cannot be avoided, monitor the patient for reduced levodopa pharmacologic effect.

MAOIs (eg, phenelzine)

Adverse reactions, including an increased incidence of extrapyramidal symptoms, may occur. Use with caution. Monitor the clinical response.

Paroxetine

Promethazine plasma levels may be elevated, increasing the pharmacologic and adverse reactions. Observe the clinical response and adjust the promethazine dose as needed.

Tretinoin

The risk of photosensitivity may be increased. Do not coadminister.

Laboratory Test Interactions

Diagnostic pregnancy tests based on immunologic reactions between human chorionic gonadotropin (hCG) and anti-hCG may result in false-negative or false-positive interpretations; glucose tolerance tests may show an increase in blood glucose.

Adverse Reactions

Cardiovascular

Bradycardia; faintness; increased or decreased blood pressure; tachycardia.

CNS

Catatonic-like states; confusion; convulsive seizures; disorientation; dizziness; drowsiness; euphoria; excitation; extrapyramidal symptoms, including oculogyric crisis, tongue protrusion, and torticollis; fatigue; hallucinations; hysteria; incoordination; insomnia; lassitude; nervousness; NMS (potentially fatal); sedation; somnolence; tremors.

Dermatologic

Dermatitis; photosensitivity; urticaria.

EENT

Blurred vision; diplopia; nasal stuffiness; tinnitus.

GI

Dry mouth; jaundice; nausea; vomiting.

Hematologic-Lymphatic

Agranulocytosis; leukopenia; thrombocytopenia; thrombocytopenic purpura.

Local

Abscess; burning; edema; erythema; gangrene; injection-site phlebitis; pain; swelling; tissue necrosis.

Respiratory

Apnea (potentially fatal); asthma; respiratory depression (potentially fatal).

Miscellaneous

Angioneurotic edema; paradoxical reactions including hyperexcitability, abnormal movements, respiratory depression, nightmares, delirium, and agitated behavior.

Precautions

Warnings Respiratory depression Do not use promethazine in children younger than 2 y because of the potential for fatal respiratory depression. Postmarketing cases of respiratory depression, including fatalities, have been reported with use of promethazine in children younger than 2 y. Exercise caution when administering to children 2 y and older. It is recommended that the lowest effective dose of promethazine be used in children 2 y and older and that coadministration of other drugs with respiratory-depressant effects be avoided. Injection Promethazine injection can cause severe chemical irritation and damage to tissue 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, thrombophlebitis, tissue necrosis, and gangrene. In some cases, surgical intervention, including fasciotomy, skin graft, and/or amputation, have been required. Because of the risks of IV injection, the preferred route is deep IM injection. Subcutaneous injection is contraindicated.

Pregnancy

Category C . Administration within 2 weeks of delivery may inhibit platelet aggregation in the newborn.

Lactation

Undetermined.

Children

Contraindicated in children younger than 2 y. Use caution when administering to children 2 y and older. Not recommended for treatment of uncomplicated vomiting in children; use only when vomiting is prolonged and of known cause. Extrapyramidal symptoms that can occur secondary to IV use may be confused with CNS signs of undiagnosed primary disease (eg, encephalopathy, Reye syndrome). Avoid use in children with history of sleep apnea, family history of sudden infant death syndrome (SIDS), or hepatic diseases, and in children with Reye syndrome.

Elderly

Per the Beers list, promethazine may have potent anticholinergic properties. Non-anticholinergic antihistamines are preferred in elderly patients when treating allergic reactions. Promethazine is also considered a high-risk medication for elderly patients according to the Centers of Medicare and Medicaid Services.

Hepatic Function

Use with caution.

Special Risk Patients

Avoid use in patients with COPD and/or sleep apnea. Use drug with caution in patients with bone marrow depression, bronchial asthma, CV disease, hypertension, hyperthyroidism, or respiratory impairment. Also use with caution in patients with bladder neck obstruction, increased IOP, narrow-angle glaucoma, prostatic hypertrophy, pyloroduodenal obstruction, stenosing peptic ulcer, ulcer disease, or urinary retention.

Hazardous Tasks

May impair the mental or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery.

Tartrazine Sensitivity

Some of these products may contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions in certain susceptible persons.

Sulfite Sensitivity

Promethazine injection contains sodium metabisulfite, which can cause allergic reactions, including anaphylactic symptoms and life-threatening asthma episodes.

Hepatic effects

Administration has been associated with reported cholestatic jaundice.

Neuroleptic malignant syndrome

Has occurred and is potentially fatal.

Seizures

Promethazine hydrochloride may lower seizure threshold; use with caution in patients with known seizure disorders or when giving in combination with narcotics or local anesthetics that may alter seizure control.

Overdosage

Symptoms

Range from mild depression of the CNS and CV system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, extensor-plantar reflexes (Babinski reflex), stimulation, convulsions, paradoxical-type reaction characterized by hyperexcitability and nightmares, atropine-like signs and symptoms (eg, dry mouth, fixed, dilated pupils, flushing), and GI symptoms.

Patient Information

• Advise patients of the risk of respiratory depression, including potentially fatal respiratory depression in children younger than 2 y.
• Advise patients of the risk of severe tissue injury, including gangrene, with promethazine injection. Advise patients to report persistent or worsening pain or burning at the injection site.
• Advise patients to report any involuntary muscle movements.
• Advise patient that drug may cause drowsiness, or impaired judgment or thinking skills, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise patient to avoid prolonged exposure to the sun.

Copyright © 2009 Wolters Kluwer Health.