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Inhaled Analgesic — Acute Pain Pregnancy: UK SPC section 4.6: studies in animals have shown reproduction toxicity. Where methoxyflurane has been used for obstetric analgesia in pregnant women there has been a single report of neonatal respiratory depression associated with a high fetal level of methoxyflurane; however, when low concentrations were administered, or the duration of higher concentrations was kept short per recommended posology, methoxyflurane was found to have little effect on the foetus, and no fetal complications were reported in the obstetric analgesia studies. As with all medicines care should be exercised when administered during pregnancy, especially the first trimester. Breast-feeding: there is insufficient information on excretion in human milk — caution should be exercised when administered to a nursing mother. Fertility: no clinical data available; limited animal data do not indicate any effects on sperm morphology.

Methoxyflurane

Brand names: Penthrox

Methoxyflurane is an inhaled analgesic delivered via a hand-held inhaler used for the emergency short-term relief of moderate to severe pain associated with trauma in conscious adults.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Analgesic use: one bottle of 3 ml as a single dose, administered using the device provided. A second bottle should only be used where needed.
Route: Inhalation via the hand-held PENTHROX inhaler — self-administered under the supervision of a person trained in its administration. Use as an anaesthetic agent is contraindicated.
Frequency: Single dose, titrated by intermittent inhalation to adequate pain control. Onset of pain relief in adults should commence after 6-10 inhalations. Continuous inhalation of a 3 ml bottle provides analgesic relief for up to 25-30 minutes; intermittent inhalation may provide longer relief.
Max: No more than 6 ml in a single day; total dose to a patient in a week should not exceed 15 ml; administration on consecutive days is not recommended
VERBATIM UK SPC section 4.2: "Adults and children aged 6 years and older One bottle of 3 ml PENTHROX as a single dose, administered using the device provided. A second bottle should only be used where needed. The frequency at which PENTHROX can be safely used is not established (see section 4.4). The following administration schedule is recommended: no more than 6 ml in a single day, administration on consecutive days is not recommended, and the total dose to a patient in a week should not exceed 15 ml. In adults the onset of pain relief is rapid and should commence after 6-10 inhalations. In children additional inhalations may be required. Patients should be instructed to inhale intermittently to achieve adequate analgesia. Patients are able to assess their own level of pain and titrate the amount of PENTHROX inhaled for adequate pain control. Continuous inhalation of a bottle containing 3 ml provides analgesic relief for up to 25-30 minutes. Intermittent inhalation may provide longer analgesic relief. Patients should be advised to use the lowest possible dose to achieve pain relief." ADMINISTRATION: the Activated Carbon (AC) Chamber must be inserted into the dilutor hole on top of the inhaler; tilt the inhaler to 45 degrees and pour the total contents of one bottle into the base whilst rotating; if stronger analgesia is required the patient can cover the dilutor hole on the AC chamber with a finger during use. RENAL: "Methoxyflurane may cause renal failure if the recommended dose is exceeded. Caution should be exercised for patients diagnosed with clinical conditions that would pre-dispose to renal injury." HEPATIC: "Cautious clinical judgement should be exercised when PENTHROX is to be used more frequently than on one occasion every 3 months." The bundle's sections 4.4 and 4.8 both end at the source-fetch limit.

Paediatric dose

Route: Inhalation via the hand-held PENTHROX inhaler — self-administered under the supervision of a person trained in its administration
Frequency: Single dose, titrated by intermittent inhalation; in children additional inhalations may be required compared with adults
Max: No more than 6 ml in a single day; total dose in a week should not exceed 15 ml; administration on consecutive days is not recommended
THIS IS NOT A WEIGHT-BASED DOSE — no per-kg figure exists in the label, so dosePerKg is null. The UK SPC section 4.2 gives a single regimen for "Adults and children aged 6 years and older": "One bottle of 3 ml PENTHROX as a single dose, administered using the device provided. A second bottle should only be used where needed." "In children additional inhalations may be required." UNDER 6 YEARS: "The safety and efficacy of PENTHROX in children aged 0 to 6 years has not been established. Currently available data are described in section 5.1 but no recommendation on a posology can be made." Section 4.8: "The safety profile of PENTHROX in a placebo-controlled study in paediatrics (MEOF-002) aged 6 to < 18 years was consistent with the safety profile observed in adults. The majority of events were mild in intensity and non-serious with the most common being dizziness." Verify against a children's formulary and current prescribing references before use.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Use as an anaesthetic agent
  • Hypersensitivity to methoxyflurane, any fluorinated anaesthetic or to any of the excipients listed in section 6.1
  • Malignant hyperthermia: patients who are known to be or genetically susceptible to malignant hyperthermia
  • Patients or patients with a known family history of severe adverse reactions after being administered with inhaled anaesthetics
  • Patients who have a history of showing signs of liver damage after previous methoxyflurane use or halogenated hydrocarbon anaesthesia
  • Clinically significant renal impairment
  • Altered level of consciousness due to any cause including head injury, drugs, or alcohol
  • Clinically evident cardiovascular instability
  • Clinically evident respiratory depression

Side effects

  • Very common / common CNS reactions: dizziness, headache, somnolence — generally easily reversible
  • Common: nausea, dry mouth, oral discomfort, oral pruritus, salivary hypersecretion, vomiting
  • Common: euphoric mood, anxiety, depression, disturbance in attention, inappropriate affect, verbigeration, affect lability, agitation, confusional state
  • Common: cough; flushing, hypertension, hypotension
  • Common: dysgeusia, amnesia, dysarthria, paraesthesia, peripheral sensory neuropathy
  • Common: fatigue, feeling drunk, feeling abnormal, chills, feeling of relaxation; hyperhidrosis; increased appetite; vision impairment
  • Uncommon: hypoxia
  • Not known: hepatic failure, hepatitis, jaundice, liver injury (isolated post-marketing reports with analgesic use)
  • Not known: renal failure — serious dose-related nephrotoxicity has been associated with methoxyflurane when used in large doses over prolonged periods during general anaesthesia; the recommended maximum dose must not be exceeded
  • Not known: hypersensitivity; dissociation, restlessness, altered state of consciousness, nystagmus; choking, respiratory depression
  • Not known: hepatic enzyme increased, blood urea increased, blood uric acid increased, blood creatinine increased
  • The fetched section 4.8 ends at the source-fetch limit — this list is not complete

Monitoring

  • Use the lowest effective dose to control pain (section 4.4)
  • Use with caution in the elderly or other patients with known risk factors for renal disease, and in patients with clinical conditions which may pre-dispose to renal injury (section 4.4)
  • Nephrotoxicity is thought to be associated with inorganic fluoride ions; when administered as instructed for the analgesic indication a single 3 ml dose produces serum inorganic fluoride levels below 10 micromol/l, against the greater than 40 micromol/l at which significant nephrotoxicity occurred with anaesthetic use (section 4.4)
  • Factors that increase the rate of metabolism, such as hepatic enzyme inducers and fast-metaboliser genetic variants, can increase the risk of toxicity (sections 4.4 and 4.5)
  • Exercise cautious clinical judgement when use is required more frequently than on one occasion every 3 months; previous exposure to halogenated hydrocarbon anaesthetics at an interval of less than 3 months may increase the potential for hepatic injury (section 4.4)
  • Caution in the elderly due to possible reduction in blood pressure, as the risk of hypotension and bradycardia may potentially be increased (section 4.4)
  • The person trained in administering PENTHROX must provide and explain the Package Leaflet to the patient (section 4.2)

Clinical monograph

How it works

It is a volatile fluorinated agent that, at the low analgesic concentrations self-administered by inhalation, produces analgesia through actions on the central nervous system; the precise mechanism is not fully established.

Prescribing in practice

  • Total cumulative exposure must be limited because of the risk of dose-related nephrotoxicity and hepatotoxicity, and it is contraindicated in clinically significant renal impairment and in personal or family history of malignant hyperthermia.
  • It is self-administered by the patient through the inhaler under supervision, allowing them to titrate to effect; repeated use on consecutive days should be avoided.
  • Avoid concomitant use with agents that may worsen renal or hepatic toxicity; consult the SPC and follow exposure limits.

Monitoring

Monitor pain relief, conscious level, and ensure cumulative exposure limits are observed, with caution regarding renal and hepatic function.

Counselling the patient

  • Breathe through the inhaler to control your pain; take slow breaths and use more if you need it.
  • You may feel lightheaded or drowsy, which passes after you stop using it.
  • This is for short-term pain relief and should not be used repeatedly over consecutive days.

Evidence & guidelines

Methoxyflurane is licensed for emergency relief of moderate to severe trauma pain in conscious adults, supported by trial evidence such as the STOP! study and used within UK emergency and prehospital settings.

Reference: MHRA Approval Penthrox 2015; MHRA Paediatric Extension 2020; Coffey et al. Lancet 2017 (STOP! trial); SPC Penthrox; RCEMlearning Methoxyflurane module; NICE Evidence Review 2019; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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