Methoxyflurane

Registered South African indications:

• Emergency relief of pain
  - By self-administration in conscious haemodynamically stable patients with trauma and associated pain, under supervision of healthcare professionals trained in methoxyflurane use
• Relief of pain in monitored conscious patients
  - Who require analgesia for surgical procedures such as the change of dressings

Contraindications

South African recommendations

• Hypersensitivity to methoxyflurane or any of its excipients
• Hypersensitivity to other inhalation anaesthetics
• Hypersensitivity to fluorinated anaesthetics
• A history of possible adverse reactions in either patient or relatives to any of the halogenated inhalational anaesthetic medicines
• Use as an anaesthetic medicine
• Renal impairment, including reduced glomerular filtration rate, urine output and reduced renal blood flow
• Renal failure
• Severe hepatic impairment
• Cardiovascular instability
• Respiratory depression
• Head injury or loss of consciousness
• Malignant hyperthermia: patients who are known to be or genetically susceptible to malignant hyperthermia
• Porphyria

Recommendations in other jurisdictions

• Hypersensitivity to methoxyflurane or any of its excipients
• Hypersensitivity to any fluorinated anaesthetic
• 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
• Use as an anaesthetic agent
• 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
• Malignant hyperthermia: patients who are known to be or genetically susceptible to malignant hyperthermia

Cautions

• Pregnancy
• Breastfeeding
• Mild to moderate hepatic impairment (South African recommendations)
• Hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Underlying hepatic conditions or with risks for hepatic dysfunction
• Occupational exposure
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inh (liq)

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Emergency relief of pain
- By self-administration in conscious haemodynamically stable patients with trauma and associated pain, under supervision of healthcare professionals trained in methoxyflurane use
Relief of pain in monitored conscious patients
- Who require analgesia for surgical procedures such as the change of dressings

• Inhaled (liq): Initial: Gentle breaths through inhaler to obtain analgesia; Thereafter: Normal breaths through the inhaler; Up to 6ml/day; Max: 15ml/week

If stronger analgesia is required, the patient can cover the dilutor hole on the AC chamber with a finger during use. See additional prescribing points for administration directions

If refilling the inhaler with a second bottle of methoxyflurane, this should occur only once and must be conducted in a well-ventilated area to reduce environmental exposure to methoxyflurane vapour

The lowest effective dosage of methoxyflurane to provide analgesia should be used, particularly for the elderly. The total weekly dose should not exceed 15ml. Administration on consecutive days is not recommended

The cumulative dose received by patients receiving intermittent doses of methoxyflurane for painful procedures (such as wound dressings) must be carefully monitored to ensure that the recommended dose of is not exceeded, as methoxyflurane may cause renal failure if the recommended dose is exceeded and it is generally irreversible

Paed. forms avail. in SA and covered in this monograph: inh (liq)

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Emergency relief of pain
- By self-administration in conscious haemodynamically stable patients with trauma and associated pain, under supervision of healthcare professionals trained in methoxyflurane use 6
Relief of pain in monitored conscious patients
- Who require analgesia for surgical procedures such as the change of dressings 

Younger than 1 year

• No information available

Between 1-11 years

• Inhaled (liq): Initial: Gentle breaths through inhaler to obtain analgesia; Thereafter: Normal breaths through the inhaler; Up to 3ml/day; Max: 15ml/week

Between 12-17 years

• See adult dosage

If stronger analgesia is required, the patient can cover the dilutor hole on the AC chamber with a finger during use. See additional prescribing points for administration directions

If refilling the inhaler with a second bottle of methoxyflurane, this should occur only once and must be conducted in a well-ventilated area to reduce environmental exposure to methoxyflurane vapour

The lowest effective dosage of methoxyflurane to provide analgesia should be used, particularly for children. The total weekly dose should not exceed 15ml. Administration on consecutive days is not recommended

The cumulative dose received by patients receiving intermittent doses of methoxyflurane for painful procedures (such as wound dressings) must be carefully monitored to ensure that the recommended dose of is not exceeded, as methoxyflurane may cause renal failure if the recommended dose is exceeded and it is generally irreversible

Pregnancy

• Caution; no evidence of risk in studies
• Animal studies do not indicate direct or indirect harmful effects with respect to reproductive 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 foetal 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 fetus. No fetal complications were reported to result from methoxyflurane analgesia in the mother in all the studies completed in obstetric analgesia. As with all medicines care should be exercised when administered during pregnancy especially the first trimester

Breastfeeding 

• Caution
• There is insufficient information on the excretion of methoxyflurane in human milk. Caution should be exercised when methoxyflurane is administered to a nursing mother

Renal Impairment 

• Contraindicated

Hepatic Impairment

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  Methoxyflurane, is metabolised in the liver and therefore increased exposures in patients with hepatic impairment can cause toxicity. It is advisable not to administer methoxyflurane to patients who have shown signs of liver damage, especially after previous methoxyflurane use or halothane anaesthesia
• Severe: Contraindicated

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Methoxyflurane, is metabolised in the liver and therefore increased exposures in patients with hepatic impairment can cause toxicity. It is advisable not to administer methoxyflurane to patients who have shown signs of liver damage, especially after previous methoxyflurane use or halothane anaesthesia
  Cautious clinical judgement should be exercised when methoxyflurane is to be used more frequently than on one occasion every 3 months

Elderly 

• Caution; no dose adjustment recommended 
  Initiate on lowest effective dose

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Amnesia
• Anxiety
• Depression
• Dizziness
• Dysarthria
• Dysgeusia
• Euphoria
• Headache
• Sensory neuropathy
• Somnolence
• Paraesthesia
• Fatigue

Cardiovascular Disorders

• Hypotension

Respiratory Disorders

• Coughing

Gastrointestinal Disorders

• Dry mouth
• Nausea
• Oral discomfort

Endocrine and Metabolic Disorders

• Increased appetite 
• Shivering

Skin and Subcutaneous Tissue Disorders

• Sweating

Sensory Disorders

• Diplopia

• CYP450 enzyme inducers 
• Central nervous system depressants
• Nephrotoxic agents
• Cardiac depressants

None routine

Administration directions

• Ensure the activated carbon chamber (where applicable) is inserted into the dilution hole on the top of the inhaler
• Remove the cap of the bottle by hand. Alternatively, use the base of the inhaler to loosen the cap with a 1⁄2 turn. Separate the inhaler from the bottle and remove the cap by hand
• Tilt the inhaler to a 45° angle and pour the total contents of one 3ml bottle into the base of the inhaler whilst rotating
• Place the wrist loop over the patient’s wrist. The patient inhales through the mouthpiece of the inhaler to obtain analgesia. The first few breaths should be gentle. Thereafter the patient breathes normally through the inhaler
• The patient exhales into the inhaler. The exhaled vapour passes through the AC chamber to absorb any exhaled methoxyflurane
• If stronger analgesia is required, the patient can cover the dilutor hole on the AC chamber with a finger during use
• If further pain relief is required, after the first bottle has been used, use a second bottle if available. Alternatively use a second bottle from a new combination pack. Use in the same way as the first bottle as described above. No need to remove the AC chamber. Put used bottle into the plastic bag provided
• The patient should be instructed to inhale intermittently to achieve adequate analgesia. Continuous inhalation will reduce duration of use. Patients should be administered the minimum dose to achieve analgesia

Methoxyflurane acts on the lipid matrix of neuronal membranes or other lipophilic sites and alters the activity of many ion channels and receptors required for cell-cell signalling across gap junctions.

Inhalation liquid (per ml) 99.9% m/m

• Penthrop (Equity) originator