A new contraindication has been added to the product information of Doryx® (doxycycline). This product is now contraindicated with the concurrent use of methoxyflurane due to reports of fatal renal toxicity when methoxyflurane is co-administered with tetracycline.

Doxycycline is a tetracycline antibiotic indicated for a number of conditions including community-acquired pneumonia, acute bacterial sinusitis, chronic prostatitis, pelvic inflammatory disease, and acne. Methoxyflurane is an inhalational anaesthetic that can cause renal failure on its own when administered at high doses. However, it is now only used in subanaesthetic doses for rapid-onset short-term analgesia. While this medication may be administered in a monitored setting for analgesia during surgical procedures, it is also carried by defence force personnel, surf lifesaving departments, and other emergency services in the form of the Penthrox® ‘green whistle.’ Methoxyflurane is, therefore, often administered in situations where a full medical history may not be readily available.

While the mechanism of this interaction is not fully understood, it is thought to be a class effect. Therefore, caution is recommended with other brands of doxycycline, minocycline, and tetracycline (not currently marketed in Australia). There is also the possibility that methoxyflurane may enhance the nephrotoxic potential of other agents such as gentamicin, colistin, and amphotericin B.

The Database of Adverse Event Notifications managed by the Therapeutic Goods Administration has received only two reports of renal failure associated with the use of methoxyflurane since 1971. While neither of these cases was fatal, methoxyflurane-associated renal failure is generally irreversible. Careful attention to the contraindications, precautions, and dosing instructions listed in the Penthrox® product information is advised.


  1. Department of Health. Database of Adverse Event Notifications. Woden: Therapeutic Goods Administration; 2018.
  2. Doryx® (doxycycline) Australian approved product information. Salisbury South: Mayne Pharma. Approved November 2018.
  3. Penthrox® (methoxyflurane) Australian approved product information. Scoresby: Medical Developments International. Approved October 2018.

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