Promethazine Hydrochloride

Nasal Allergies and the Common Cold

Management of seasonal allergic rhinitis (e.g., hay fever) and perennial (nonseasonal) allergic rhinitis.100 133 136

Management of seasonal nonallergic (vasomotor) rhinitis.133

Symptomatic relief of rhinorrhea and sneezing associated with the common cold.c

Other Allergic Conditions

Adjunct to epinephrine and other standard measures in the treatment of anaphylactic reactions after the acute manifestations have been controlled.100 117 133 136

Used IM for management of other uncomplicated allergic reactions of the immediate type when oral therapy is impossible or contraindicated.117

Prevention and treatment of mild, uncomplicated skin manifestations of urticaria and angioedema.100 133 136

Management of allergic conjunctivitis caused by foods or inhaled allergens.133 136

Treatment of mild transfusion reactions not caused by ABO incompatibility or pyrogens.100 117 133 136 c

Treatment of dermatographism.100 133 136

Sedation

Treatment to produce sedation in surgery and obstetrics (during labor); reduces preoperative tension and anxiety, facilitates sleep.100 117 133 136

Routine sedation.100 117 133 136 b

Pain

Adjunct to analgesics (e.g., opiates) for management of pain (e.g., postoperative).100 117 133 136 b

Used IV as adjunct to analgesics (e.g., opiates) and anesthesia during surgery (e.g., bronchoscopy, ophthalmic surgery) and in poor-risk patients.117

Motion Sickness

Prevention and treatment of nausea, vomiting, and/or vertigo associated with motion sickness.100 117 133 136 a

Nausea and Vomiting

Prevention and management of nausea and vomiting of various etiologies (e.g., anesthesia, surgery, postoperative).100 117 133 136 b

Hemolytic Disease of the Newborn†

May ameliorate hemolytic disease of the newborn† (erythroblastosis fetalis) when administered during pregnancy in Rh-sensitized women.102 103 104 105

Contraindications

• Pediatric patients <2 years of age.117 132 133 134 135 136 (See Boxed Warning.)

• Concomitant administration of large doses of other CNS depressants.a (See Specific Drugs under Interactions.)

• Comatose patients.100 117 133 136

• Known hypersensitivity or idiosyncrasy to promethazine or other phenothiazines.100 117 133 136

• Treatment of lower respiratory symptoms (e.g., asthma).100 133 136

• FDA states that sub-Q or intra-arterial injection is contraindicated.139 140 (See Precautions Associated with Parenteral Administration under Cautions.)

• Some manufacturers state that promethazine also is contraindicated in patients with bone marrow depression, angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, or bladder neck obstruction;136 a b others state that the drug be used with caution in these patients.100 117 133

Warnings/Precautions

Warnings

Possible impairment of ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).100 117 133 136

Possible extrapyramidal reactions117 129 134 with high doses.117 129

Possible increased severity of seizures in epileptic patients; use with caution, if at all, in patients with seizure disorders.100 117 133 136 a

Possible neuroleptic malignant syndrome (NMS), characterized by hyperpyrexia, muscle rigidity, altered mental status, evidence of autonomic instability (e.g., irregular pulse or BP, tachycardia, diaphoresis, cardiac dysrhythmias).117 133 134 136 Immediately discontinue therapy and initiate supportive and symptomatic therapy if NMS develops.117 133

Possible fatal respiratory depression.117 133 134 135 136

Possible suppression of cough reflex.a

Use with caution in patients who are having an asthmatic attack and in those with acute or chronic respiratory impairment (e.g., COPD), particularly children.136 a b (See Pediatric Use under Cautions.)

Use with caution, if at all, in patients with a history of sleep apnea.100 117 119 124 133 136

Possible leukopenia, agranulocytosis, and thrombocytopenic purpura.117 a

Severe chemical irritation and damage to tissues (e.g., burning, pain, erythema, swelling, severe spasm of distal vessels, thrombophlebitis, venous thrombosis, phlebitis, abscesses, tissue necrosis, gangrene) may occur with administration of the injection, regardless of the route of administration.30 31 117 139 140 141 142 143 144

Because IV administration has been associated with severe tissue injury, including gangrene requiring amputation, FDA states that deep IM injection is the preferred method for administration.139 140

Possible irritation and damage from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration.30 31 117 139 140 141 142

Possible nerve damage (ranging from temporary sensory loss to palsies and paralysis).117 139 Injection near or into a nerve may result in permanent tissue damage.117 Surgical intervention (e.g., fasciotomy, skin graft, amputation) may be needed.117 139 140 141 144

Possible severe chemical irritation following unintentional intra-arterial administration; may result in impairment of circulation and gangrene requiring amputation.117

If IV administration is required, use extreme care when administering IV; avoid extravasation or unintentional intra-arterial injection.117 (See IV Administration under Dosage and Administration.)

FDA states that sub-Q or intra-arterial administration of promethazine hydrochloride is contraindicated.139 140 Intra-arterial administration may cause chemical irritation that may be severe and cause severe arteriospasm, possibly resulting in impairment of circulation and gangrene requiring amputation.117

Because promethazine discolors blood on contact; aspiration of dark blood at the site of injection does not rule out the possibility of intra-arterial placement of the needle.117

During IV administration, observe for signs and symptoms of potential tissue injury, including burning or pain at the site of injection, phlebitis, swelling, and blistering; inform patients that adverse effects may occur immediately (i.e., while receiving the injection) or may develop hours to days after an injection of promethazine.139

Immediately stop injection if pain at the injection site occurs during presumed IV injection; evaluate the possibility of intra-arterial placement of the needle or perivascular extravasation.117 139

Sympathetic block and administration of heparin may be used for acute management of extravasation or inadvertent intra-arterial injection.117

Possible obstructive jaundice; usually reversible following discontinuance of therapy.100 117

Possible cholestatic jaundice.117 133

Sensitivity Reactions

Possible photosensitivity; further therapy may be contraindicated if this effect develops.133 a b

Possible urticaria, dermatitis, dermatologic reactions, and angioedema.117 134 136

Some commercially available formulations of promethazine injection may contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.117 a b

General Precautions

Possible tachycardia, bradycardia, and faintness with parenteral use.117

Rapid IV administration may produce a transient fall in BP; administer slowly.a

Use with caution in patients with cardiovascular disease.100 117 133 a b

Possible increased BP; administer with extreme caution, if at all, to patients in hypertensive crisis.a b

Shares the toxic potentials of antihistamines and phenothiazines; observe the usual precautions of these agents.a b

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Category C.100 117 133

Not known whether promethazine is distributed into milk.100 117 133 Discontinue nursing or the drug.117 133

Use of promethazine is contraindicated in pediatric patients <2 years of age, because of risk of developing potentially fatal respiratory depression.117 132 133 134 135 136 (See Boxed Warning.)

Excessively high dosages may cause sudden death in pediatric patients.117 133 Possible cardiac arrest, hallucinations, oversedation, agitation, dystonic reactions, apnea, dermatologic reactions, neuroleptic malignant syndrome, and seizures with therapeutic doses and overdosage.117 133 134

Use with caution in pediatric patients ≥2 years of age.117 133 134 135 136

Avoid concomitant use with other respiratory depressant drugs in children ≥2 years of age, because respiratory depression and death may occur.133

In children ≥2 years of age, the drug may be used for prolonged vomiting of known etiology; use not recommended in children with vomiting of unknown etiology.117 133 136

Possible increased susceptibility to dystonias in acutely ill or dehydrated children; use not recommended in these children.133 a

Avoid use in children ≥2 years of age with signs and symptoms suggestive of Reye’s syndrome117 133 or other hepatic disease.117 133

Use not recommended in children ≥2 years of age with asthma, liver disease, seizure disorder, or glaucoma, unless otherwise directed by a clinician.128 136 b

Possible sleep apnea and sudden infant death syndrome (SIDS) in infants and young children.119 123 (See Respiratory Effects under Cautions.) Use with caution in children with a history of sleep apnea, those with a family history of SIDS, and those who are less prone than usual to spontaneous arousal from sleep.100 123 124 a b

Possible marked drowsiness that may be potentiated by other CNS depressants (e.g., sedatives, tranquilizers); use these drugs only under the direction of a clinician.133 136 a (See Nervous System Effects under Cautions.)

Possible increased risk of CNS stimulant effects; close supervision recommended for children performing hazardous activities (e.g., bike riding).100 133 a

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.133

Increased risk of sedative effects and confusion.117 133 Select dosage with caution (usually starting at low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.133 Dosage of the injection should be reduced.117

Close observation recommended.d

Use with caution.100 117 133 a b

Common Adverse Effects

Pronounced sedative effects, drowsiness, confusion, disorientation.100 117 133 136

Absorption

Bioavailability

Well absorbed from the GI tract100 133 and from parenteral sites.117 a b

Onset

Onset of sedative effects occurs within 20 minutes following oral, rectal, or IM administration;100 117 133 a b following IV administration, sedative effects occur within 3–5 minutes.117 a b

Duration

Duration of sedative effects usually about 2–8 hours117 133 a b (depending on the dose and route of administration);a b effects may persist for 12 hours.100 117 133

Distribution

Extent

Widely distributed in body tissues.a b

Compared with other organs, lower concentrations of the drug are found in the brain, but this concentration is higher than the plasma concentration.a b

Readily crosses the placenta.115 116 a b

It is not known if promethazine is distributed into milk.100 117 133 a b

Plasma Protein Binding

93% protein bound (determined by gas chromatography)126 and 76–80% bound (determined by high-performance liquid chromatography).125

Elimination

Metabolism

Metabolized in the liver.100 117 133 a b

Elimination Route

Excreted slowly in urine (mainly) and feces, principally as inactive promethazine sulfoxide and glucuronides.100 117 133 a b

Half-life

9–16 hours (following IV use) and about 9.8 hours (following IM use).117

Storage

Oral

Tight, light-resistant containers at 20–25°C.133 Protect from light.133

Tight, light-resistant containers at 15–30°C.100 Protect from light.100 Avoid freezing.a

Parenteral

Tight, light-resistant containers preferably at 20–25°C (may be exposed to 15–30°C).117

Rectal

Well-closed containers at 2–8°C.133 Protect from light.133

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

• Importance of informing parents and caregivers that promethazine should not be used in pediatric patients <2 years of age.134 135 136

• Importance of informing parents and caregivers to use the drug with caution and obtain a clinician's advice about administration of any promethazine dosage form in pediatric patients ≥2 years of age.136

• Risk of drowsiness; avoid alcohol and other CNS depressants and use caution when driving, operating machinery, or engaging in other hazardous tasks.100 117 133 136

• Importance of informing caregivers that pediatric patients performing hazardous activities (e.g., bike riding) should be closely supervised, because children may be at increased risk for experiencing CNS stimulant effects.100 117 133

• Importance of informing clinicians of any involuntary muscle movements or unusual sensitivity to sunlight.100 117 133

• Importance of avoiding prolonged exposure to sun.117 133

• Importance of promptly informing clinicians of any pain at the injection site during IV injection or other symptoms (e.g., erythema, swelling, blistering) occurring within days of IV injection.117 139

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.117 133 136

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.117 133 136 a

• Importance of informing patients of other important precautionary information.117 133 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name