What are the contraindications to Penthrox (methoxyflurane)?

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Last updated: October 22, 2025View editorial policy

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Contraindications to Penthrox (Methoxyflurane)

Methoxyflurane (Penthrox) is contraindicated in patients with a history of kidney disease, liver disease, or those at risk for renal impairment due to its potential nephrotoxicity, even at analgesic doses.

Absolute Contraindications

  • Renal impairment: Methoxyflurane can cause dose-dependent nephrotoxicity, making it unsuitable for patients with existing kidney disease or dysfunction 1
  • Liver disease: Patients with hepatic impairment should avoid methoxyflurane due to rare reports of hepatotoxicity 1
  • Hypersensitivity: Any known hypersensitivity to methoxyflurane or other fluorinated anesthetics 2
  • Malignant hyperthermia: Patients with known or genetic predisposition to malignant hyperthermia 2

Relative Contraindications and Precautions

  • Concurrent use with nephrotoxic drugs: Medications that may affect kidney function could potentially increase the risk of renal damage 1
  • Elderly patients: While methoxyflurane can be used in elderly patients, caution is advised due to potentially decreased renal function; dose adjustment may be required 3
  • Tetracycline antibiotics: Concurrent use with tetracyclines (minocycline, doxycycline) should be avoided due to potential drug interactions 3
  • Pregnancy: Use during pregnancy should be avoided unless clearly necessary (similar to other anesthetic agents) 2

Drug Interactions

  • Enzyme inducers: Medications that induce liver enzymes may affect methoxyflurane metabolism 1
  • Tetracyclines: Minocycline and doxycycline have documented interactions with methoxyflurane 3
  • CNS depressants: Caution when using with other central nervous system depressants, as this may potentiate sedative effects 3

Monitoring and Safety Considerations

  • Occupational exposure: Healthcare providers should be aware of occupational exposure limits (MEL of 15 ppm as an 8-hour time-weighted average) 1
  • Administration environment: Should be used in well-ventilated areas to minimize staff exposure 1
  • Dosage limitations: Strict adherence to recommended dosage is essential to prevent nephrotoxicity 2
  • Self-administration: Must be supervised by healthcare personnel trained in its use 4

Clinical Pearls

  • The odor threshold for methoxyflurane (0.13-0.19 ppm) is well below toxic levels, serving as a warning mechanism for excessive exposure 1
  • Despite historical concerns about nephrotoxicity from its use as an anesthetic, low-dose methoxyflurane for analgesia has demonstrated a favorable safety profile when used according to guidelines 4, 5
  • Methoxyflurane provides rapid onset of pain relief and is particularly useful in trauma settings 4, 5
  • When properly administered at analgesic (rather than anesthetic) doses, methoxyflurane has minimal side effects, with drowsiness (13%) and nausea (7%) being most common 5

By understanding these contraindications and taking appropriate precautions, methoxyflurane can be safely used as an effective analgesic for moderate-to-severe trauma-related pain in appropriate patients.

References

Research

The Reincarnation of Methoxyflurane.

Journal of anesthesia history, 2020

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 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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