What are the side effects of Phenergan (promethazine)?

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Side Effects of Phenergan (Promethazine)

Phenergan (promethazine) has numerous significant side effects including drowsiness, sedation, confusion, extrapyramidal symptoms, respiratory depression, hypotension, and potentially fatal neuroleptic malignant syndrome. 1

Common Side Effects

Central Nervous System Effects

  • Drowsiness (most prominent CNS effect) 1
  • Sedation and somnolence
  • Dizziness and confusion
  • Blurred vision
  • Fatigue and lassitude
  • Nervousness and insomnia

Cardiovascular Effects

  • Blood pressure changes (increased or decreased) 1
  • Tachycardia or bradycardia
  • Faintness
  • Hypotension (especially with rapid IV administration) 2

Gastrointestinal Effects

  • Dry mouth 1
  • Nausea and vomiting
  • Jaundice

Respiratory Effects

  • Respiratory depression (potentially fatal) 1
  • Apnea (potentially fatal)
  • Nasal stuffiness
  • Asthma exacerbation

Serious Adverse Effects

Extrapyramidal Symptoms

  • Oculogyric crisis (abnormal eye movements) 1
  • Torticollis (neck twisting)
  • Tongue protrusion
  • Dystonic reactions ranging from restlessness to oculogyric crises 2

Severe Reactions

  • Neuroleptic malignant syndrome (potentially fatal) 1, 3
  • Seizures 1, 4
  • Hallucinations 1
  • Paradoxical reactions (hyperexcitability, agitation) 1
  • Tissue damage with extravasation or inadvertent intra-arterial injection (FDA black box warning) 3

Hematologic Effects

  • Leukopenia 1
  • Thrombocytopenia
  • Thrombocytopenic purpura
  • Agranulocytosis

Special Population Considerations

Pediatric Patients

  • Children may experience paradoxical reactions characterized by hyperexcitability and nightmares 1
  • Increased risk of adverse effects in children under 2 years of age 4
  • Reports of possible association with apparent life-threatening events or sudden infant death syndrome in very young children 4

Elderly Patients

  • Increased sensitivity to anticholinergic effects 5
  • Higher risk of sedation and confusion
  • Altered drug metabolism with prolonged half-life
  • Increased risk of extrapyramidal side effects

Drug Interactions

  • Enhanced sedation when combined with:

    • Alcohol 1
    • Sedatives/hypnotics (including barbiturates)
    • Narcotics and narcotic analgesics
    • General anesthetics
    • Tricyclic antidepressants
    • Tranquilizers
  • May interfere with diagnostic pregnancy tests (false-negative or false-positive results) 1

  • May increase blood glucose levels 1

  • Interaction with MAOIs causing increased extrapyramidal effects 1

Precautions

  • Use with caution in patients with:

    • Narrow-angle glaucoma 1
    • Prostatic hypertrophy
    • Stenosing peptic ulcer
    • Pyloroduodenal obstruction
    • Bladder-neck obstruction
    • Cardiovascular disease
    • Impaired liver function
  • Avoid epinephrine for treating hypotension associated with promethazine overdose 1

  • Avoid prolonged sun exposure due to photosensitivity risk 1

Promethazine should be used only when clearly needed and with careful consideration of its significant side effect profile, particularly in vulnerable populations such as young children and the elderly.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Replacement of Promethazine With Ondansetron for Treatment of Opioid- and Trauma-Related Nausea and Vomiting in Tactical Combat Casualty Care.

Journal of special operations medicine : a peer reviewed journal for SOF medical professionals, 2015

Guideline

Treatment of Panic Disorder

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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