nalmefene (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 2mg/2mL (single-dose vial; generic)

Opioid Overdose and Reversal

Indicated in the management of known or suspected opioid overdose

Also, indicated for complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids

Initial dose

  • Non-opioid dependent patients: 0.5 mg/70 kg; may administer a second dose of 1 mg/70 kg 2-5 minutes later if necessary
  • Suspected opioid dependency: Administer a challenge dose of 0.1 mg/70 kg initially; if no evidence of withdrawal within 2 minutes, the recommended dosing should be followed
  • If no clinical response after administering a total dose of 1.5 mg/70 kg, additional nalmefene is unlikely to have an effect
  • Do not give more nalmefene than is required to restore respiratory rate to normal, thus minimizing the likelihood of cardiovascular stress and precipitated withdrawal syndrome
  • If respiratory depression recurs, titrate dose again to clinical effect using incremental doses to avoid over-reversal

Dosage Modifications

Loss of IV access

  • Single intramuscular (IM) or subcutaneous (SC) 1-mg doses have been shown to effective within 5-15 min of administration

Renal impairment

  • Renal failure substantially reduces clearance of nalmefene; for single episodes of opioid antagonism, deliver incremental doses slowly (over 60 seconds) to minimize hypertension and dizziness following abrupt administration

Hepatic impairment

  • All severities: Hepatic disease substantially reduces clearance of nalmefene; for single episodes of opioid antagonism, no dosage adjustment necessary

Dosing Considerations

Nalmefene had no effect in cases where opioids were not responsible for sedation and hypoventilation

Only treat when likelihood of an opioid overdose is high, based on a history of opioid overdose or clinical presentation of respiratory depression with concurrent pupillary constriction

Patients tolerant to or physically dependent opioids

  • May cause acute withdrawal symptoms in individuals who have some degree of tolerance to and dependence on opioids
  • Closely observe for symptoms of withdrawal following administration
  • Administer subsequent doses with intervals of at least 2-5 minutes between doses to allow the full effect of each incremental dose of nalmefene to be reached

Safety and efficacy not established

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Interactions

Interaction Checker

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                    Adverse Effects

                    >10%

                    Nausea (18%)

                    1-10%

                    Vomiting (9%)

                    Tachycardia (5%)

                    Hypertension (5%)

                    Postoperative pain (4%)

                    Fever (3%)

                    Dizziness (3%)

                    Headache (1%)

                    Chills (1%)

                    Hypotension (1%)

                    Vasodilation (1%)

                    <1%

                    Transient increases in creatinine phosphatase kinase (0.5%)

                    Cardiovascular: Bradycardia, arrhythmia

                    Digestive: Diarrhea, dry mouth

                    Nervous system: Somnolence, depression, agitation, nervousness, tremor, confusion, withdrawal syndrome, myoclonus

                    Respiratory: Pharyngitis

                    Skin: Pruritus

                    Urogenital: Urinary retention

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                    Warnings

                    Contraindications

                    Hypersensitivity to nalmefene and any excipients in the product

                    Cautions

                    Nalmefene, like all drugs in this class, is not primary treatment for ventilatory failure

                    Treatment with this drug should follow, not precede, establishment of a patent airway, ventilatory assistance, administration of oxygen, and establishment of circulatory access

                    Pulmonary edema, cardiovascular instability, hypotension, hypertension, ventricular tachycardia, and ventricular fibrillation reported in connection with opioid reversal; in many cases, these effects appear to be the result of abrupt reversal of opioid effects

                    Use with caution in patients at high cardiovascular risk or who have received potentially cardiotoxic drugs

                    Use extreme caution in patients with known physical dependence on opioids or following surgery involving high doses of opioids; imprudent use or excessive doses of opioid antagonists in the postoperative setting has been associated with hypertension, tachycardia, and excessive mortality in patients at high risk for cardiovascular complications

                    Preclinical studies have shown that nalmefene at doses up to 10 mg/kg (437x maximum recommended human dose) produced incomplete reversal of buprenorphine-induced analgesia in animal models; nalmefene may not completely reverse buprenorphine-induced respiratory depression

                    Risk of recurrent respiratory depression

                    • Accidental overdose with long-acting opioids (eg, methadone, levo-alpha-acetylmethadol [LAAM]) may result in prolonged respiratory depression
                    • Be aware that a recurrence of respiratory depression is possible, even after an apparently adequate initial response to nalmefene treatment
                    • Observe treated patients until, in the opinion of the physician, there is no reasonable risk of recurrent respiratory depression

                    Drug interaction overview

                    Flumazenil
                    • Coadministration of both flumazenil and nalmefene produced fewer seizures than expected in a study in rodents, based on the expected effects of each drug alone
                    • An adverse interaction from the coadministration of the two drugs is not expected, but physicians should remain aware of the potential risk of seizures from agents in these classes
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                    Pregnancy & Lactation

                    Pregnancy

                    There was no evidence of impaired fertility or harm to the fetus

                    There are no adequate and well-controlled studies in pregnant females

                    Use during pregnancy only if clearly needed

                    Lactation

                    Nalmefene and its metabolites were secreted into rat milk, reaching concentrations ~3x those in plasma at 1 hr and decreasing to about half the corresponding plasma concentrations by 24 hr following bolus administration

                    As no clinical information is available, exercise caution when administered to nursing females

                    Pregnancy Categories

                    A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                    B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                    C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                    D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                    X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                    NA: Information not available.

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                    Pharmacology

                    Mechanism of Action

                    An opioid antagonist, is a 6-methylene analogue of naltrexone, prevents or reverses effects of opioids, including respiratory depression, sedation, and hypotension

                    Studies have shown that nalmefene hydrochloride injection has a longer duration of action than naloxone at fully reversing doses

                    Absorption

                    Peak plasma time

                    • IM: 2.3 hr
                    • SC: 1.5 hr

                    Peak plasma concentration (IV)

                    • 19-32 years: 3.7 ng/mL
                    • 62-80 years: 5.8 ng/mL

                    AUC

                    • 19-32 years: 16.6 ng·hr/mL
                    • 62-80 years: 17.3 ng·hr/mL

                    Bioavailability

                    • IM: 101.5%
                    • SC: 99.7%

                    Distribution

                    • Vd (steady-state): 8.6 L/kg

                    Vdc

                    • 19-32 years: 3.9 L/kg
                    • 62-80 years: 2.8 L/kg

                    Metabolism

                    Metabolized by liver, primarily by glucuronide conjugation

                    Metabolized to trace amounts of an N-dealkylated metabolite

                    Metabolites: Nalmefene glucuronide (inactive); N-dealkylated metabolite (minimal pharmacological activity)

                    Elimination

                    Systemic clearance: 0.8 L⋅hr/kg

                    Renal clearance: 0.08 L⋅hr/kg

                    Half-life

                    • 19-32 years: 10.8 hr
                    • 62-80 years: 9.4 hr

                    Excretion

                    • Feces: 17%
                    • Urine: <5%
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                    Administration

                    Administration

                    Take proper steps to prevent use of the incorrect concentration

                    May administer IV bolus (preferred), SC, or IM

                    Discard unused portion

                    Storage

                    Store at 20-25ºC (68-77ºF) in original carton

                    Protect from light

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                    Images

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                    Patient Handout

                    A Patient Handout is not currently available for this monograph.
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                    Formulary

                    FormularyPatient Discounts

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                    The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                    Tier Description
                    1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                    2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                    3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                    4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                    5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                    6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                    NC NOT COVERED – Drugs that are not covered by the plan.
                    Code Definition
                    PA Prior Authorization
                    Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                    QL Quantity Limits
                    Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                    ST Step Therapy
                    Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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                    Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.