Note: Use of opioid antagonists in most emergency settings should be done in conjunction with establishment of a patent airway, ventilatory assistance, administration of oxygen, and circulatory access.
Opioid overdose:
Non–opioid-dependent patients: IV (preferred), IM, SUBQ: Initial: 0.5 mg; if needed, a second dose of 1 mg may be administered 2 to 5 minutes later (Kaplan 1999). If there is no clinical response following a total dose of 1.5 mg, it is unlikely that continued administration of nalmefene will be beneficial. Do not administer additional nalmefene once adequate initial reversal has been established.
Recurrent respiratory depression: Patients who achieved adequate reversal with the initial dosing regimen but experience recurrent respiratory depression may receive additional nalmefene using the same dosing strategy as described for initial therapy.
Opioid-dependent patients: IV (preferred), IM, SUBQ: Initial: 0.1 mg; if there is no evidence of withdrawal, administer 0.5 mg. If needed, a repeat dose of 1 mg may be administered 2 to 5 minutes later (Kaplan 1999). If there is no clinical response following a total dose of 1.6 mg, it is unlikely that continued administration of nalmefene will be beneficial. Do not administer additional nalmefene once adequate initial reversal has been established.
Recurrent respiratory depression: Patients who achieved adequate reversal with the initial dosing regimen but experience recurrent respiratory depression may receive additional nalmefene using the same dosing strategy as described for initial therapy.
No dosage adjustment necessary.
No dosage adjustment necessary.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection [preservative free]:
Generic: 1 mg/mL (2 mL)
Yes
IV: Administer via rapid IV push (preferred); IM or SUBQ administration may be utilized if IV access is lost or not readily available. In patients with kidney failure, consider slow administration over 60 seconds to minimize hypertension and dizziness.
Opioid overdose: For the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids; also indicated in the management of known or suspected opioid overdose.
Nalmefene may be confused with nalbuphine.
Nalmefene may precipitate opioid withdrawal syndrome in patients with opioid dependence or opioid use disorder. Symptoms may include abdominal cramps, agitation, diarrhea, fever, hypertension, irritability, nausea, pain, sweating, tachycardia, and vomiting. Withdrawal symptoms may require hospitalization, but are rarely life-threatening (Ref).
Mechanism: Related to the pharmacologic action; nalmefene acts as a competitive antagonist at opioid receptors, precipitating withdrawal (Ref).
Onset: Rapid; within 15 minutes to 3 hours (Ref).
Risk Factors:
• Higher doses or shorter intervals between doses ·
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Nausea (18%) (table 1)
Drug (Nalmefene) |
Comparator (Naloxone) |
Placebo |
Number of Patients (Nalmefene) |
Number of Patients (Naloxone) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
18% |
18% |
6% |
1,127 |
369 |
77 |
1% to 10%:
Cardiovascular: Hypertension (5%) (table 2) , hypotension (1%), tachycardia (5%) (table 3) , vasodilation (1%)
Drug (Nalmefene) |
Comparator (Naloxone) |
Placebo |
Number of Patients (Nalmefene) |
Number of Patients (Naloxone) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
5% |
7% |
0% |
1,127 |
369 |
77 |
Drug (Nalmefene) |
Comparator (Naloxone) |
Placebo |
Number of Patients (Nalmefene) |
Number of Patients (Naloxone) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
5% |
8% |
0% |
1,127 |
369 |
77 |
Gastrointestinal: Vomiting (9%) (table 4)
Drug (Nalmefene) |
Comparator (Naloxone) |
Placebo |
Number of Patients (Nalmefene) |
Number of Patients (Naloxone) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
9% |
7% |
4% |
1,127 |
369 |
77 |
Nervous system: Chills (1%), dizziness (3%)
Miscellaneous: Fever (3%) (table 5)
Drug (Nalmefene) |
Comparator (Naloxone) |
Placebo |
Number of Patients (Nalmefene) |
Number of Patients (Naloxone) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
3% |
4% |
0% |
1,127 |
369 |
77 |
<1%:
Cardiovascular: Bradycardia, cardiac arrhythmia
Dermatologic: Pruritus
Gastrointestinal: Diarrhea, xerostomia
Genitourinary: Urinary retention
Hepatic: Increased serum aspartate aminotransferase
Nervous system: Agitation, confusion, depression, drowsiness, myoclonus, nervousness, opioid withdrawal syndrome (Yéléhé-Okouma 2017), tremor
Respiratory: Pharyngitis
Hypersensitivity to nalmefene or any component of the formulation.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease or in patients receiving medications with potential adverse cardiovascular effects (eg, hypotension, pulmonary edema, arrhythmias); pulmonary edema and cardiovascular instability, including ventricular fibrillation, have been reported in association with abrupt reversal when using opioid antagonists.
Other warnings/precautions:
• Opioid overdose: When compared to naloxone, nalmefene has a longer duration of action at fully reversing doses; however, prolonged or recurrent respiratory depression is possible if the opioid involved is long-acting (eg, methadone, levo-alpha-acetylmethadol); recurrence of respiratory depression may occur even with an adequate initial response to nalmefene; continuously observe patients until there is no further risk of recurrent respiratory depression.
• Partial opioid agonist-induced respiratory depression: Reversal of respiratory depression secondary to a partial opioid agonist (eg, buprenorphine) may be incomplete; larger or repeat doses of nalmefene may be required.
• Postoperative reversal: Appropriate use: Excessive dosages should only be used with extreme caution after use of opioids in surgery. Abrupt postoperative reversal may result in nausea, vomiting, tachycardia, hypertension, seizures, and other cardiovascular events (including pulmonary edema and arrhythmias).
Substrate of CYP3A4 (minor), UGT1A3, UGT1A8, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Opioid Agonists: Nalmefene may diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modification
Outcome data following maternal use of nalmefene during pregnancy are limited and not specific to use following opioid exposure (Chick 2021; López-Pelayo 2020).
Based on data from other opioid antagonists, use may precipitate opioid withdrawal in the fetus in addition to the mother (ACOG 2017). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant patients if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).
It is not known if nalmefene is present in breast milk.
Respiratory rate, heart rate, BP, temperature, level of consciousness, arterial blood gas, or pulse oximetry.
As a 6-methylene analog of naltrexone, nalmefene acts as a competitive opioid receptor antagonist, thereby reversing the respiratory depression induced by opioids. When compared to naloxone, nalmefene has a longer duration of action and a higher affinity for opioid receptors (France 2021; Krieter 2019).
Onset: IV: 2 to 5 minutes; IM, SUBQ: 5 to 15 minutes.
Duration:
IV:
Partially reversing doses (ie, 1 mcg/kg): 30 to 60 minutes.
Fully reversing doses: >4 hours and relatively longer when compared to naloxone (Glass 1994).
Distribution: Vdss: 8.6 L/kg.
Protein binding: 45%.
Metabolism: Hepatic primarily via glucuronide conjugation to an inactive metabolite; also metabolized to trace amounts of an N-dealkylated metabolite (inactive). May undergo enterohepatic recycling (Dixon 1986).
Bioavailability: IM, SUBQ: ~100%
Half-life elimination: ~11 hours.
Time to peak: IM: 2.3 hours; SUBQ: 1.5 hours.
Excretion: Urine (<5% as unchanged nalmefene); feces (17%).
Altered kidney function: Plasma clearance was decreased by 27% and 25% in patients with end-stage renal disease (ESRD) during interdialysis and intradialysis, respectively. Elimination half-life was increased to 26 hours in patients with ESRD.
Hepatic function: Plasma clearance was decreased by 28.3% and elimination half-life was increased to ~12 hours in patients with liver disease.
Older adult: Age-related decreases in central volume of distribution may result in increased initial nalmefene concentrations.
Solution (Nalmefene HCl Injection)
1 mg/mL (per mL): $18.00
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