Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (0)
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
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
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.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%
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
Images
Formulary
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