Allergan

Approved Indications

• Allergic Conditions:
• Seasonal and perennial allergic rhinitis
• Allergic conjunctivitis
• Urticaria and angioedema
• Anaphylactic reactions (as adjunct to epinephrine)
• Allergic reactions to blood or plasma
• Motion Sickness:
• Prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness
• Nausea and Vomiting:
• Prevention and control of nausea and vomiting associated with surgery, medications, and other causes
• Sedation:
• Preoperative, postoperative, or obstetric sedation
• Bedtime or daytime sedation for short-term use
• Surgical/Diagnostic Adjunct:
• Adjunct to analgesics and anesthetics in surgical or obstetric procedures
• Cough and Cold (Symptomatic Relief):
• Used in combination with other medications for symptomatic relief of cough and cold symptoms (not recommended for children under 6 years)

Clinically Accepted Off-Label Uses

• Vertigo and Ménière’s disease
• Migraine-associated nausea and vomiting
• Palliative care (nausea, agitation, sedation)
• Intractable hiccups (as adjunct)

Routes: Oral (tablet/syrup), Rectal (suppository), Intramuscular (IM), Intravenous (IV — with extreme caution)

Adults

• Allergy:
  Oral/IM/IV: 25 mg at bedtime or 12.5 mg before meals and at bedtime
  Maintenance: 25–50 mg/day in divided doses
• Motion Sickness:
  25 mg orally or rectally, taken 30–60 minutes before travel; repeat every 12 hours as needed
• Nausea and Vomiting:
  12.5–25 mg orally, IM, or rectally every 4–6 hours as required
• Sedation:
  25–50 mg orally or rectally at bedtime, or as a single preoperative dose

Pediatrics (≥2 years)

• General Dosing (Caution):
  0.1 mg/kg/dose every 6–8 hours orally or rectally (maximum single dose: 25 mg)

⚠️ Contraindicated in children under 2 years due to risk of fatal respiratory depression.

Elderly

• Use the lowest effective dose
• Increased risk of sedation, dizziness, and anticholinergic effects

Renal/Hepatic Impairment

• No formal dosage adjustment; use caution
• Monitor for signs of CNS toxicity or respiratory depression

Promethazine is a first-generation H1 receptor antagonist derived from phenothiazines. It competitively blocks histamine H1 receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Additionally, it has strong sedative, antiemetic, and anticholinergic properties. Its antiemetic effect is mediated by inhibition of the chemoreceptor trigger zone (CTZ) in the medulla. It also depresses the reticular activating system, contributing to its sedative effects. Its efficacy in motion sickness is due to antimuscarinic action in the vestibular system.

• Absorption:
  Rapid and well absorbed orally and rectally; IM injection results in reliable systemic levels
  Onset of action:
• Oral: 20–60 minutes
• IM: 20 minutes
• IV: 3–5 minutes (use with caution)
• Distribution:
  Widely distributed; crosses blood-brain barrier
  High protein binding (~90%)
• Metabolism:
  Hepatically metabolized primarily via CYP2D6 and CYP2B6
  Major metabolites: promethazine sulfoxide and N-desmethylpromethazine
• Elimination:
  Excreted mainly in urine as metabolites
  Elimination half-life: 10–19 hours

• Pregnancy:
• FDA Category C
• Use only if potential benefit justifies potential fetal risk
• No evidence of teratogenicity in humans, but use cautiously, especially in the first trimester
• Lactation:
• Excreted in breast milk
• May cause excessive sedation or irritability in infants
• Not recommended unless clearly needed; monitor infant if used

• Primary Class: H1 Antihistamine
• Subclass: First-generation, Phenothiazine derivative
• Additional Actions: Antiemetic, Sedative, Anticholinergic

• Hypersensitivity to promethazine or other phenothiazines
• Children under 2 years of age
• Comatose states or patients receiving large doses of CNS depressants
• Severe respiratory depression
• Bone marrow suppression
• Intra-arterial or subcutaneous injection (due to risk of tissue necrosis)
• Use with MAO inhibitors (within 14 days)

• Boxed Warnings:
• Pediatric Use: Risk of fatal respiratory depression in children <2 years
• Tissue Injury: Risk of severe tissue damage with IV administration (e.g., gangrene, necrosis)
• CNS Depression:
  Sedation and impaired mental alertness; avoid driving or hazardous activities
• Respiratory Depression:
  High doses or combined use with other CNS depressants increase risk
• Tissue Injury (Injection):
  Never administer intra-arterially or subcutaneously
  Avoid IV push; IM route preferred
• Seizure Risk:
  May lower seizure threshold; use caution in epileptic patients
• Anticholinergic Effects:
  Use with caution in glaucoma, prostatic hypertrophy, and GI obstruction

Common (by system):

• CNS: Drowsiness, dizziness, confusion, fatigue
• GI: Dry mouth, nausea, constipation
• Respiratory: Nasal congestion, respiratory depression (dose-dependent)
• Dermatologic: Photosensitivity, skin rash

Serious:

• Severe respiratory depression
• Neuroleptic malignant syndrome (rare)
• Extrapyramidal symptoms (e.g., dystonia, tremors)
• Tissue necrosis (with improper IV use)
• Seizures
• Hallucinations (especially in children)

Onset: Sedation within 20–60 minutes orally
Severity: Dose-dependent; more pronounced in elderly and pediatric populations

• CNS Depressants (e.g., alcohol, opioids, benzodiazepines):
  Additive sedation and respiratory depression
• MAO Inhibitors:
  Contraindicated; risk of severe hypotension, seizures, or respiratory failure
• QT-Prolonging Drugs (e.g., antiarrhythmics, macrolides):
  Increased risk of arrhythmias
• Anticholinergic Drugs:
  Enhanced effects (e.g., blurred vision, urinary retention)
• Enzyme Systems:
  Substrate of CYP2D6 and CYP2B6; inhibitors or inducers may affect plasma levels

• FDA (2023):
• Reinforced black box warning on tissue necrosis with IV administration
• Advised IM route as preferred parenteral option
• NICE (2023):
• Reaffirmed caution in pediatric use; recommends alternative agents in children <6 years unless essential
• CDC & AAP (2024):
• Warn against use of promethazine-containing cough/cold products in children

• Temperature: Store between 20°C and 25°C (68°F–77°F)
• Humidity: Keep in a dry place; avoid excessive humidity
• Light: Protect from light; store in original container
• Handling Precautions:
• Do not refrigerate injectable forms
• For IM use only when injection is necessary
• Avoid IV push; if IV is used, dilute and administer slowly in a large vein
• Shake oral syrup before use
• Shelf Life: Refer to manufacturer's label (typically 24–36 months)