Promethazine Hydrochloride (Antihistamine)

Class: First Generation Antihistamines
VA Class: CN309
CAS Number: 58-33-3
Brands: Phenadoz, Phenergan, Promethegan, Prometh VC

• Children <2 Years of Age


• 
  

  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}

  
  

• Respiratory Depression in Children <2 Years of Age


• 
  

  Postmarketing reports of respiratory depression, including fatalities, in pediatric patients <2 years of age receiving a wide range of weight-adjusted doses.^{117 133 134 135 136}

  
  

• Children ≥2 Years of Age


• 
  

  Administer with caution.^{117 132 133 134 135 136}

  
  


• 
  

  Use the lowest effective dose.^{117 132 133}

  
  


• 
  

  Avoid concomitant use with other respiratory depressant drugs.^{117 132 133}

  
  

• Warnings Regarding Parenteral Administration


• 
  

  Because of risk of severe tissue injury, including gangrene requiring amputation, following IV administration of promethazine, FDA states that the preferred route of administration is deep IM injection.^{139 140}

  
  

  Perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration of promethazine may result in irritation and tissue damage.^{139 140} Healthcare professionals should be alert for signs and symptoms of potential tissue injury, including burning or pain at the site of injection, phlebitis, swelling, and blistering.¹³⁹ (See IV Administration under Dosage and Administration and see Precautions Associated with Parenteral Administration under Cautions.)

  
  


• 
  

  FDA has notified healthcare professionals that a Boxed Warning describing these risks is being added to the prescribing information for promethazine hydrochloride.^{139 140}

  
  

Introduction

An ethylamino derivative of phenothiazine with potent first generation antihistaminic properties.^{134 136 a b}

Uses for Promethazine Hydrochloride (Antihistamine)

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}

Promethazine Hydrochloride (Antihistamine) Dosage and Administration

Administration

Administer orally, rectally, or by deep IM injection.^{117 136 a b} Also administered by IV injection.^{117 136 a b} However, FDA states that deep IM injection is the preferred method for administration of promethazine hydrochloride injection because of risks associated with IV administration (see Warnings Regarding Parenteral Administration under Boxed Warning).^{139 140}

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

IV Administration

If IV administration is required, administer through tubing of an IV infusion set that is known to be correctly functioning.¹³⁹

If patient complains of pain at the injection site during presumed IV injection, immediately discontinue injection and evaluate the possibility of intra-arterial placement of the needle or perivascular extravasation.^{117 139}

Promethazine hydrochloride injection is commercially available in 2 strengths: 25 mg/mL and 50 mg/mL.^{117 139} FDA states that the preparation containing 50 mg/mL is for IM injection only; the preparation containing 25 mg/mL may be administered by IM or IV injection.¹³⁹

Maximum concentration of the injection is 25 mg/mL.¹¹⁷

Rate of Administration

Maximum rate of IV administration is 25 mg/minute.^{117 139} (See Cardiovascular Effects under Cautions.)

Dosage

Dosages of promethazine hydrochloride by the various routes of administration are identical.^{a b}

Parenteral and rectal routes are used when oral administration is not feasible; institute oral therapy as soon as possible.^a

When used for management of common cold, administer only for short-term due to toxic potential of long-term therapy.^{128 129}

When used for allergic conditions, administer at bedtime because of pronounced sedative effects; adjust dosage to the smallest amount adequate to relieve symptoms.^{100 133 a}

Pediatric Patients

Common Cold

Oral

Children 2 to <6 years of age (as directed by a clinician): 1.56 mg every 4–6 hours.¹²⁸ (See Pediatric Use under Cautions.)

Children 6 to <12 years of age: 3.125 mg every 4–6 hours.¹²⁸

Children ≥12 years of age: 6.25 mg every 4–6 hours.^{128 129}

Allergic Conditions

Oral

Children ≥2 years of age: up to 25 mg at bedtime or up to 12.5 mg 3 times daily (should be adjusted to age and weight).^{100 a} Alternatively, 0.5 mg/kg at bedtime or 0.125 mg/kg as needed.^a

Rectal , IM, or IV

May be administered rectally, by deep IM, or IV^{117 133} in dosages identical to oral dosages.

Sedation

Preoperative or Postoperative Sedation

Oral, Rectal, IM, or IV

Children ≥2 years of age: 12.5–25 mg or 0.5–1.1 mg/kg.^{117 133 a}

Routine Sedation

Oral or Rectal

Children ≥2 years of age: 12.5–25 mg or 0.5–1.1 mg/kg.^{133 a}

Pain

Adjunct to Analgesics

Oral, Rectal, IM, or IV

Children ≥2 years of age: 12.5–25 mg or 0.5–1.1 mg/kg; reduce analgesic dosage accordingly.^{117 133 a}

Motion Sickness

Oral or Rectal

Children ≥2 years of age: 12.5–25 mg or 0.5 mg/kg administered at least 30–60 minutes prior to departure.¹³³ Administer a second dose 8–12 hours later if necessary; additional doses may be given on arising in the morning and before the evening meal for the duration of the journey.^{133 a}

Nausea and Vomiting

Oral or Rectal

Children ≥2 years of age: Usually, 1.1 mg/kg; should be adjusted to age, weight, and severity of condition.^{100 133} Alternatively, 0.25–0.5 mg/kg or 7.5–15 mg/m² 4–6 times daily.^b

IM or IV

Children ≥2 years of age: 0.25–0.5 mg/kg or 7.5–15 mg/m² 4–6 times daily.^b

Adults

Common Cold

Oral

6.25 mg every 4–6 hours.^{128 129}

Allergic Conditions

Oral

25 mg before retiring.^{100 133} Alternatively, 12.5 mg administered before meals and on retiring.^{133 a}

Rectal, IM, or IV

25 mg; dose may be repeated within 2 hours if necessary.^{117 133 a}

Transfusion Reactions

25 mg administered prior to or during a blood transfusion.^{117 133 a}

Sedation

Preoperative or Postoperative Sedation

Oral or Rectal

For preoperative sedation, a 50-mg dose may be administered the night before surgery and 50 mg usually is given before surgery.¹³³

For postoperative sedation, 25–50 mg is used.¹³³

IM or IV

25–50 mg.¹¹⁷

Routine Sedation

Oral, Rectal, IM, or IV

25–50 mg.^{100 117 133}

Sedation in Obstetric Patients

IM or IV

50 mg administered during the early stage of labor.¹¹⁷ When labor is established, 25–75 mg is given with a reduced dose of an opiate agonist.¹¹⁷ 25–50 mg doses may be repeated once or twice at 4-hour intervals if necessary.^{117 a}

Pain

Adjunct to Analgesics

Oral, Rectal, IM or IV

25–50 mg; reduce analgesic dosage accordingly.^{117 133 a}

Motion Sickness

Oral

25 mg administered at least 30–60 minutes prior to departure.^{100 133 a} Administer 25 mg 8–12 hours later if necessary; additional doses may be given on arising in the morning and before the evening meal for the duration of the journey.^{100 133 a}

Nausea and Vomiting

Oral, Rectal, IM, or IV

12.5–25 mg;^{100 117 133 b} administer additional doses of 12.5–25 mg every 4–6 hours if necessary;^{100 117 133 b} reduce dosage of analgesics and barbiturates accordingly.¹¹⁷

Hemolytic Disease of the Newborn†

Oral

3.7–5 mg/kg daily (given to the nearest 25-mg multiple) has been given initially in 4 divided doses after the first trimester or the 16th week of gestation in Rh-sensitized pregnant women.^a In extremely severe cases, maintenance dosage as high as 6.5 mg/kg daily has been used.^a

Prescribing Limits

Pediatric Patients

Common Cold

Oral

Maximum 9.36 mg in 24 hours for children 2 to <6 years of age.¹²⁸ (See Pediatric Use under Cautions.)

Maximum 18.75 mg in 24 hour for children 6 to <12 years of age.¹²⁸

Maximum 37.5 mg in 24 hours for children ≥12 years of age.^{128 129}

Adults

Common Cold

Oral

Maximum 37.5 mg in 24 hours.^{128 129}

Sedation

Sedation in Obstetric Patients

IM or IV

Maximum 100 mg during a 24-hour period of labor.¹¹⁷

Special Populations

Geriatric Patients

Use caution in dosage selection.¹³³ Parenteral dosage should be reduced.¹¹⁷

Cautions for Promethazine Hydrochloride (Antihistamine)

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

Nervous System Effects

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 reactions^{117 129 134} 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}

Respiratory Effects

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}

Hematologic Effects

Possible leukopenia, agranulocytosis, and thrombocytopenic purpura.^{117 a}

Precautions Associated with Parenteral Administration

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

Hepatic Effects

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

Possible cholestatic jaundice.^{117 133}

Sensitivity Reactions

Dermatologic and 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}

Sulfite Sensitivity

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

Cardiovascular Effects

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}

Other Precautions

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

Use of Fixed Combination

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

Specific Populations

Pregnancy

Category C.^{100 117 133}

Lactation

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

Pediatric Use

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 syndrome^{117 133} 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}

Geriatric Use

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

Hepatic Impairment

Use with caution.^{100 117 133 a b}

Common Adverse Effects

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

Interactions for Promethazine Hydrochloride (Antihistamine)

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
CNS depressants	Additive effects100 117 133 136	Either avoid concomitant use or reduce barbiturate dosage by ≥50% and narcotic dosage by 25–50% if administered concomitantly117 133
Epinephrine	Reversal of vasopressor effect of epinephrine133	Administer norepinephrine or phenylephrine if a vasopressor agent is required; epinephrine should not be used117
Anticholinergic agents	Additive anticholinergic effects 133	Use with caution117 133
MAO inhibitors	Increased extrapyramidal effects117 133
Immunologic urinary pregnancy tests	Possible test interference: false-positive Gravindex test and false-negative Prepurex and Dap test100 133 a

Promethazine Hydrochloride (Antihistamine) Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract^{100 133} 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 hours^{117 133 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

Stability

Storage

Oral

Tablets

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

Solution

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

Parenteral

Injection

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

Rectal

Suppositories

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

Solution Compatibility^HID

Compatible
Dextran 6% in dextrose 5%
Dextran 6% in sodium chloride 0.9%
Dextrose–Ringer’s injection combinations
Dextrose–Ringer’s injection, lactated, combinations
Dextrose–saline combinations
Dextrose 2½, 5, or 10% in water
Fructose 10% in sodium chloride 0.9%
Fructose 10% in water
Invert sugar 5 and 10% in sodium chloride 0.9%
Invert sugar 5 and 10% in water
Ionosol products
Ringer’s injection
Ringer’s injection, lactated
Sodium chloride 0.45 or 0.9%
Sodium lactate (1/6)M

Drug Compatibility

Admixture CompatibilityHID

Compatible
Amikacin sulfate
Ascorbic acid injection
Chloroquine phosphate
Hydromorphone HCl
Vitamin B complex with C
Incompatible
Aminophylline
Chloramphenicol sodium succinate
Chlorothiazide sodium
Furosemide
Heparin sodium
Hydrocortisone sodium succinate
Methohexital sodium
Penicillin G sodium
Pentobarbital sodium
Phenobarbital sodium
Thiopental sodium
Variable
Penicillin G potassium

Y-Site CompatibilityHID

Compatible
Amifostine
Amsacrine
Aztreonam
Bivalirudin
Ciprofloxacin
Cisplatin
Cladribine
Cyclophosphamide
Cytarabine
Dexmedetomidine HCI
Docetaxel
Doxorubicin HCl
Etoposide phosphate
Fenoldopam mesylate
Filgrastim
Fluconazole
Fludarabine phosphate
Gemcitabine HCl
Granisetron HCl
Hetastarch in lactated electrolyte injection (Hextend)
Linezolid
Melphalan HCl
Ondansetron HCl
Oxaliplatin
Pemetrexed disodium
Remifentanil HCl
Sargramostim
Teniposide
Thiotepa
Vinorelbine tartrate
Incompatible
Aldesleukin
Allopurinol sodium
Amphotericin B cholesteryl sulfate complex
Cefepime HCl
Doxorubicin HCl liposome injection
Foscarnet sodium
Lansoprazole
Methotrexate sodium
Piperacillin sodium–tazobactam sodium
Variable
Cefazolin sodium
Ceftizoxime sodium
Heparin sodium
Hydrocortisone sodium succinate
Potassium chloride
Vitamin B complex with C

ActionsActions

• 
  

  Blocks H₁-receptor sites,^{100 117 133} but does not block release of histamine.¹¹⁷

  
  


• 
  

  Produces either CNS stimulation or CNS depression (sedation); CNS depression is more common with therapeutic doses.^{134 136 a b}

  
  


• 
  

  Exhibits antiemetic, anticholinergic, and local anesthetic effects; also exhibits antimotion sickness action.^{100 117 133 134 136 a b}

  
  


• 
  

  Precise mechanism of the CNS effects unknown.^{a b} Antimotion sickness action apparently related to central anticholinergic effects.^a

  
  


• 
  

  Slight antitussive activity may result from anticholinergic and CNS-depressant effects.^a

  
  


• 
  

  Inhibits collagen-induced platelet aggregation in neonates whose mothers had received the drug during labor.¹⁰¹

  
  


• 
  

  Inhibits the ability of fetal macrophages to bind Rh-positive erythrocytes.^{106 107}

  
  


• 
  

  Inhibits phagocytosis and hexose monophosphate shunt activity in polymorphonuclear leukocytes.¹⁰⁸

  
  


• 
  

  Inhibits lysis of fetal Rh-positive erythrocytes mediated by lymphocytes and polymorphonuclear leukocytes.¹⁰⁹

  
  


• 
  

  Stabilizes the erythrocyte membrane against hemolysis.^{109 a}

  
  

Advice to Patients

• 
  

  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.)

  
  

Preparations

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

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