Promethazine (Phenergan)

Indications

  • Allergic Conditions
    • xxxx
  • Anti-Emetic (see Nausea and Vomiting, [[Nausea and Vomiting]])
  • Migraines (see Migraines, [[Migraines]])
  • Motion Sickness
  • Pruritus (see Pruritus, [[Pruritus]])
  • Psychosis (see Psychosis, [[Psychosis]]): weak anti-psychotic effects
  • Need for Sedation

Pharmacology

Chemical Structure

  • Phenothiazine Derivative

Pharmacologic Actions

  • First Generation Antihistamine (H1-Histamine Receptor Antagonist) (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])
  • Dopamine D2 Receptor Antagonist
  • Moderate Muscarinic Receptor Antagonist (Anti-Cholinergic): likely accounts for anti-emetic effect
  • 5-HT2A Receptor Antagonist
  • 5-HT2C Receptor Antagonist
  • Alpha-1 Adrenergic Receptor Antagonist

Metabolism

  • Hepatic: CYP2D6 (hydroxylation) and CYP2B6 (N-demethylation)
    • Significant first-pass effect

Administration

  • IV (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN
    • Onset of Action: 5 min
    • Duration of Action: 4-6 hrs (up to 12 hrs)
  • IM (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN
    • Onset of Action: 20 min
  • PO (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN
  • PR (Allergic Condition/Anti-Emetic): 12.5-25 mg q4-6 hrs PRN

Dose Adjustment

  • Hepatic: none
  • Renal: none

Risk of Extravasation Injury

  • Pain/Burning
  • Thrombophlebitis
  • Tissue Necrosis/Gangrene

Adverse Effects

Cardiovascular Adverse Effects

  • Orthostatic Hypotension (see Hypotension, [[Hypotension]])
  • QT Prolongation without Definite Association with Torsade (see Torsade, [[Torsade]])

Dermatologic Adverse Effects

  • Photosensitivity

Gastrointestinal Adverse Effects

  • Constipation (see Constipation, [[Constipation]]): due to anti-cholinergic effects

Neurologic Adverse Effects

Extrapyramidal Symptoms (see Extrapyramidal Symptoms, [[Extrapyramidal Symptoms]])

  • Akathisia (see Akathisia, [[Akathisia]]): motor restlessness
  • Dystonia (see Dystonia, [[Dystonia]])): continuous spasms and muscle contractions
  • Parkinsonism (see Parkinson’s Disease, [[Parkinsons Disease]]): rigidity, bradykinesia, tremor
  • Tardive Dyskinesia (see Tardive Dyskinesia, [[Tardive Dyskinesia]]): irregular, jerky movements

Other Neurologic Adverse Effects

  • Confusion/Delirium (see Delirium, [[Delirium]])
  • Dizziness (see Dizziness, [[Dizziness]])
  • Euphoria: rare (except with high intravenous doses or co-administration with opiates or central nervous system depressants)
  • Exacerbation of Myasthenia Gravis (see Myasthenia Gravis, [[Myasthenia Gravis]]): due to anti-cholinergic effects
  • Fatigue (see Fatigue, [[Fatigue]])
  • Irritability
  • Sedation (see Obtundation-Coma, [[Obtundation-Coma]]): common
  • Seizures (see Seizures, [[Seizures]]): rare

Ophthalmologic Adverse Effects

  • Blurred Vision (see Blurred Vision, [[Blurred Vision]]): due to anti-cholinergic effects

Otolaryngologic Adverse Effetcs

  • Dry Mouth (Xerostomia): due to anti-cholinergic effects

Pulmonary Adverse Effects

  • Respiratory Depression: may occur in children <2 y/o

Renal Adverse Effects

  • Urinary Retention (see Urinary Retention, [[Urinary Retention]]): due to anti-cholinergic effects

Other Adverse Effects


References

  • Influence of promethazine on cardiac repolarisation: a double-blind, midazolam-controlled study. Anaesthesia. 2009 Jun;64(6):609-14. doi: 10.1111/j.1365-2044.2009.05890.x [MEDLINE]