PENTHROX

). 1 Pregnant Women). 1 Pediatrics Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use. 4 Geriatrics). 2 CONTRAINDICATIONS PENTHROX (methoxyflurane) is contraindicated in patients, with: • an altered level of consciousness, due to any cause, including head injury, drugs, or alcohol • clinically significant renal impairment • a history of liver dysfunction after previous methoxyflurane use or other halogenated anesthetics • hypersensitivity to methoxyflurane or other halogenated anesthetics or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

For a complete listing see

1 Adverse Reaction Overview The most common reactions are related to the CNS system, including dizziness, headache and somnolence. Serious dose-related nephrotoxicity has been associated with methoxyflurane when used at high doses over prolonged periods.

There have been reports of renal failure and increased blood urea nitrogen/creatinine levels following PENTHROX use. There have also been reports of increased hepatic enzymes and very rare reports of hepatoxicity, including hepatic injury and failure, with inhalation of methoxyflurane at analgesic doses.

The recommended maximum dose for PENTHROX should not be exceeded (see 4 DOSAGE AND ADMINISTRATION and 7 WARNINGS AND PRECAUTIONS). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Table 2 shows treatment-emergent adverse events (TEAEs) experienced by ≥ 1% of patients with trauma and associated pain from a placebo-controlled trial, Study MEOF-001.

The safety population in this study was defined as those patients who were randomized to treatment and received at least one dose of PENTHROX (149 patients) or placebo (149 patients). 6%) female. 2%). At least one AE was experienced by 50% of the patients in the study.

9%). In this study, PENTHROX had no clinically relevant effects on vital signs, such as blood pressure, heart rate and rhythm or respiratory rate. 7) Laboratory investigations in Study MEOF-001 revealed that serum AST and ALT were not elevated in patients treated with PENTHROX, compared to placebo.

, Renal). Dosing limitations should be followed meticulously to prevent or limit risk of nephrotoxicity (see 2 CONTRAINDICATIONS and 4 DOSAGE AND ADMINISTRATION). • Very rare cases of hepatotoxicity have been reported with methoxyflurane inhalation when used for analgesic purposes (see 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS, Hepatic).

1 Dosing Considerations • PENTHROX (methoxyflurane) use should be self-administered under supervision of a healthcare practitioner, trained in its administration, using the hand-held PENTHROX Inhaler. • Avoid use of PENTHROX in patients taking CNS depressants, such as opioids, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines or alcohol (see 9 DRUG INTERACTIONS).

• Also, avoid PENTHROX with potentially nephrotoxic drugs, such as, contrast agents, NSAIDs, some antibiotics (see 9 DRUG INTERACTIONS). • PENTHROX should not be used for the treatment of chronic or repetitive pain (see 1 INDICATIONS).

2 Recommended Dose and Dosage Adjustment The lowest effective dosage of PENTHROX to provide analgesia should be used. The recommended dose is a single administration of a 3 mL bottle. On finishing the 3 mL dose, another 3 mL may be used, if necessary.

The maximum recommended dose is: • 6 mL (2 bottles) in a single administration or over a 48-hour period; • 15 mL (5 bottles) over a 3-month period Expected onset of pain relief is rapid with a median onset of 5 minutes. 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 provides analgesic relief for up to 25-30 minutes, or approximately 1 hour when administered intermittently.

Patients should be advised to take the lowest possible dose to achieve pain relief. 4 Administration PENTHROX is a portable, lightweight, non-invasive inhaler for self-administration (single patient use). Instructions on the preparation of the PENTHROX Inhaler and correct administration are provided below: 1.

PENTHROX (methoxyflurane) is contraindicated in patients, with: • an altered level of consciousness, due to any cause, including head injury, drugs, or alcohol • clinically significant renal impairment • a history of liver dysfunction after previous methoxyflurane use or other halogenated anesthetics • hypersensitivity to methoxyflurane or other halogenated anesthetics or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • known or genetically susceptible to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives • clinically evident hemodynamic instability • clinically evident respiratory impairment Use of PENTHROX as an anesthetic agent is contraindicated.

Product Monograph PENTHRO X® (methoxyflurane volatile liquid for inhalation) Page 5 of 33