NALMEFENE HYDROCHLORIDE

Clinical summary

Indications and usage INDICATIONS AND USAGE Nalmefene hydrochloride injection is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Nalmefene hydrochloride injection is indicated in the management of known or suspected opioid overdose. Dosage and administration DOSAGE AND ADMINISTRATION Important Information - Dosage Form Nalmefene hydrochloride injection is supplied in a 2 mL vial as a 1 mg/mL concentration suitable for the management of overdose. Proper steps should be taken to prevent use of the incorrect concentration. General Principles Nalmefene hydrochloride injection should be titrated to reverse the undesired effects of opioids. Once adequate reversal has been established, additional administration is not required and may actually be harmful due to unwanted reversal of analgesia or precipitated withdrawal. Duration of Action The duration of action of nalmefene hydrochloride injection is as long as most opioid analgesics. The apparent duration of action of nalmefene hydrochloride injection will vary, however, depending on the half-life and plasma concentration of the narcotic being reversed, the presence or absence of other drugs affecting the brain or muscles of respiration, and the dose of nalmefene hydrochloride injection administered. Partially reversing doses of nalmefene hydrochloride injection (1 mcg/kg) lose their effect as the drug is redistributed through the body, and the effects of these low doses may not last more than 30 to 60 minutes in the presence of persistent opioid effects. Fully reversing doses (1 mg/70 kg) have been shown to last many hours in both experimental and clinical studies, but may complicate the management of patients who are in pain, at high cardiovascular risk, or who are physically dependent on opioids. The recommended doses represent a compromise between a desirable controlled reversal and the need for prompt response and adequate duration of action. Using higher dosages or shorter intervals between incremental doses is likely to increase the incidence and severity of symptoms related to acute withdrawal such as nausea, vomiting, elevated blood pressure, and anxiety. Patients Tolerant to or Physically Dependent on Opioids Nalmefene hydrochloride injection may cause acute withdrawal symptoms in individuals who have some degree of tolerance to and dependence on opioids. These patients should be closely observed for symptoms of withdrawal following administration of the initial and subsequent injections of nalmefene hydrochloride injection. Subsequent doses should be administered with intervals of at least 2 to 5 minutes between doses to allow the full effect of each incremental dose of nalmefene hydrochloride injection to be reached. Management of Known or Suspected Opioid Overdose The recommended initial dose of nalmefene hydrochloride injection for non-opioid dependent patients is 0.5 mg/70 kg. If needed, this may be followed by a second dose of 1 mg/70 kg, 2 to 5 minutes later. If a total dose of 1.5 mg/70 kg has been administered without clinical response, additional nalmefene hydrochloride injection is unlikely to have an effect. Patients should not be given more nalmefene hydrochloride injection than is required to restore the respiratory rate to normal, thus minimizing the likelihood of cardiovascular stress and precipitated withdrawal syndrome. If there is a reasonable suspicion of opioid dependency, a challenge dose of nalmefene hydrochloride injection 0.1 mg/70 kg should be administered initially. If there is no evidence of withdrawal in 2 minutes, the recommended dosing should be followed. Nalmefene hydrochloride injection had no effect in cases where opioids were not responsible for sedation and hypoventilation. Therefore, patients should only be treated with nalmefene hydrochloride injection when the likelihood of an opioid overdose is high, based on a history of opioid overdose or the clinical presentation of respiratory depression with concurrent pupillary constriction. Repeated Dosing Nalmefene hydrochloride injection is the longest acting of the currently available parenteral opioid antagonists. If recurrence of respiratory depression does occur, the dose should again be titrated to clinical effect using incremental doses to avoid over-reversal. Hepatic and Renal Disease Hepatic disease and renal failure substantially reduce the clearance of nalmefene (see Pharmacokinetics ). For single episodes of opioid antagonism, adjustment of nalmefene hydrochloride injection dosage is not required. However, in patients with renal failure, the incremental doses should be delivered slowly (over 60 seconds) to minimize the hypertension and dizziness reported following the abrupt administration of nalmefene to such patients. Loss of Intravenous Access Should intravenous access be lost or not readily obtainable, a pharmacokinetic study has shown that a single dose