Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is rapid and of a short duration. Use is only recommended with direct medical supervision. Common side effects include anxiety, headache, sleepiness, cough, and nausea. Serious side effects may include kidney problems, liver problems, low blood pressure, and malignant hyperthermia. It is unclear if it is safe in either pregnancy or breastfeeding. It is only recommended in those who have a normal level of consciousness and stable blood pressure and heart rate. It is classified as a volatile anaesthetic. It was first made in 1948 by William T. Miller and Kenneth W Drew and came into medical use in the 1960s. It was used as a general anesthetic from its introduction in 1960 until the late 1970s. In 1999, the manufacturer discontinued methoxyflurane in the United States, and in 2005 the Food and Drug Administration withdrew it from the market. It is still used in New Zealand, Australia, Ireland, and the United Kingdom for pain. Methoxyflurane is used for relief of moderate or severe pain as a result of trauma. It may also be used for short episodes of pain as a result of procedures. Each dose lasts approximately 30 minutes. Pain relief begins after 6–8 breaths and continues for several minutes after stopping inhalation. The maximum recommended dose is 6 milliliters per day or 15 milliliters per week because of the risk of kidney problems, and it is not recommended to be used on consecutive days. Despite the potential for kidney problems when used at anesthetic doses, no significant adverse effects have been reported when it is used at the lower doses (up to 6 milliliters) used for pain relief. Due to the risk of kidney toxicity, methoxyflurane is contraindicated in people with pre-existing kidney disease or diabetes mellitus, and is not recommended to be administered in conjunction with tetracyclines or other potentially nephrotoxic or enzyme-inducing drugs.

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