Penthrox Special Precautions

Renal disease: Methoxyflurane causes significant nephrotoxicity at high doses. Nephrotoxicity is also related to the rate of metabolism. Factors that increase the rate of metabolism such as drugs that induce hepatic enzymes can increase the risk of toxicity with methoxyflurane as well as sub-groups of people with genetic variations that may result in fast metaboliser status (see Interactions).
Nephrotoxicity is thought to be associated with inorganic fluoride ions, a metabolic breakdown product. Methoxyflurane impairs renal function in a dose-related manner. The lowest effective dose of methoxyflurane should be administered, especially in the elderly or patients with other known risk factors of renal disease.
An observational study in 1236 patients with trauma pain treated with methoxyflurane found that renal events were less frequent than in 1101 patients treated with other analgesics for trauma associated pain (0.7% versus 2.6%, p<0.001).
Liver disease: Methoxyflurane is metabolised in the liver, 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 or halothane anaesthesia.
PENTHROX should be used with care in patients with underlying hepatic conditions or with risks for hepatic dysfunction (such as enzyme inducers - see also Interactions).
An observational study on patients with trauma pain did not find a significant difference in occurrence of hepatic events between 1236 patients treated with methoxyflurane and 1101 patients treated with other analgesics for trauma associated pain (1.6% versus 2.1%, p=0.442).
Cardiovascular system depression/Use in elderly: Potential effects on blood pressure and heart rate are known class-effects of high dose methoxyflurane used in anaesthesia and other anaesthetics. They do not appear to be significant at the analgesic doses. There is no particular pattern to the patients' systolic BP levels after methoxyflurane administration as an analgesic across age groups. However, as the risk may potentially be increased for older people with hypotension and bradycardia, caution should be exercised in the elderly due to possible reduction in blood pressure.
Respiratory depression: Respiratory depression has been reported also from analgesic doses of methoxyflurane (Adverse Reactions).
Respiration should be monitored due to the risk for respiratory depression and hypoxia.
Central nervous system effects: Secondary pharmacodynamic effects including potential CNS effects such as sedation, euphoria, amnesia, ability to concentrate, altered sensorimotor coordination and change in mood are also known class-effects. Self-administration of methoxyflurane in analgesic doses will be limited by occurrence of CNS effects, such as sedation.
Whilst the possibility of CNS effects may be seen as a risk factor for potential abuse, reports of the latter are very rare in post marketing use.
Occupational exposure: Healthcare professionals who are regularly exposed to patients using PENTHROX inhalers should be aware of any relevant occupational health and safety guidelines for the use of inhalational agents. To reduce occupational exposure to methoxyflurane, the PENTHROX Inhaler should be used with the Activated Carbon (AC) Chamber. Patients should be instructed to exhale into the PENTHROX Inhaler so the exhaled vapour passes through the AC Chamber which adsorbs exhaled methoxyflurane. Multiple use of PENTHROX Inhaler without the AC Chamber creates additional risk. Elevation of liver enzymes, blood urea nitrogen and serum uric acid have been reported in exposed maternity ward staff in delivery wards when methoxyflurane was used in the past in obstetric patients at the time of labour and delivery. There have been reports of non-serious and transient reactions such as dizziness, headache, nausea or malaise, and reports of hypersensitivity reactions to methoxyflurane or other ingredients in healthcare professionals exposed to PENTHROX.
The derived maximum exposure limit (MEL) for methoxyflurane is 15 ppm expressed as an 8-hour time weighted average (8-hr TWA). The odour detection threshold for methoxyflurane ranges between 0.13 and 0.19 ppm which is well below the MEL. The exposure levels of medical staff involved in supervising the use of PENTHROX in hospital emergency triage rooms during an 8-hour shift were measured. The measurements showed levels (0.017 ppm, range 0.008 to 0.736 ppm) significantly lower than the MEL of 15 ppm.
Frequent repeated use: Due to the limitations on the dose of PENTHROX (maximum - 6 ml) and the duration of pain relief, PENTHROX is not appropriate for providing relief of break-through pain/exacerbations in chronic pain conditions. PENTHROX is also not appropriate for relief of trauma related pain in closely repeated episodes for the same patient.
Butylated hydroxytoluene: PENTHROX contains butylated hydroxytoluene (E321). Butylated hydroxytoluene may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes. See Description.
Effects on ability to drive and use machines: Methoxyflurane may have a minor influence on the ability to drive and use machines. Dizziness, somnolence and drowsiness may occur following the administration of methoxyflurane (see Adverse Reactions). A 15-minute inhalation of methoxyflurane in healthy volunteers induced an acute but short-lasting impairment of psychomotor and cognitive performance, which returns to normal within 30 minutes after cessation of inhalation.
Patients should be advised not to drive or operate machinery if they are feeling drowsy or dizzy.