Nalmefene

Nalmefene is a prescription medication indicated for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression. Nalmefene is also intended for immediate administration as emergency therapy in settings where opioids may be present.

Nalmefene is available under the following different brand names: Zurnai.

Common side effects of Nalmefene include:

• feeling hot 
• dizziness 
• nausea
• headache 
• chills
• vomiting
• feeling pain from actions that aren’t typically painful such as lightly touching the skin (allodynia)
• irregular heartbeat (palpitations)
• ringing or buzzing in the ear (tinnitus) 
• ear discomfort
• feeling abnormal
• burning sensation
• hot flush and irritability

Serious side effects of Nalmefene include:

• sudden opioid withdrawal symptoms such as body aches, goose bumps, shivering or trembling, diarrhea, sweating, stomach cramping, increased heart rate, yawning, weakness, fever, nausea or vomiting, increased blood pressure, runny nose, nervousness, sneezing, restlessness or irritability

Rare side effects of Nalmefene include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult 

Injectable solution

• 1 mg/mL (single-dose 2-mL vial; generic)
• 1.5 mg/0.5 mL (autoinjector; Zurnai)

Pediatric dosage

Injectable solution

• 1.5 mg/0.5 mL (autoinjector; Zurnai)

Opioid overdose and reversal

Adult dosage

Autoinjector

• Initial dose: 1.5 mg IM or SC into the anterolateral aspect of the thigh, through clothing if necessary
• Repeat dosing
  • Seek emergency medical assistance as soon as possible after the first dose
  • Requirement for repeat doses depends upon the amount, type, and route of administration of the opioid being antagonized
  • If the patient responds and subsequently relapses back into respiratory depression before emergency assistance arrives, administer an additional dose using a new autoinjector and continue monitoring
  • If the desired response is not obtained after 2-5 minutes, administer an additional dose using a new autoinjector; if there is still no response and additional doses are available, administer additional doses every 2-5 minutes using a new autoinjector for each dose until emergency medical assistance arrives
  • Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance
  • Partial agonists or mixed agonists/antagonists (eg, buprenorphine): Reversal of respiratory depression may be incomplete and require repeated administration using a new autoinjector

1 mg/mL (vial)

Initial dose

• May administer IV (preferred), IM, or SC
• 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 the dose again to clinical effect using incremental doses to avoid over-reversal

Loss of IV access

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

Pediatric dosage

• Children below 12 years: Safety and efficacy not established
• Initial dose: 1.5 mg IM or SC into the anterolateral aspect of the thigh, through clothing if necessary
• Repeat dosing
  • Seek emergency medical assistance as soon as possible after the first dose
  • Requirement for repeat doses depends upon the amount, type, and route of administration of the opioid being antagonized
  • If the patient responds and subsequently relapses back into respiratory depression before emergency assistance arrives, administer an additional dose using a new autoinjector and continue monitoring
  • If the desired response is not obtained after 2-5 minutes, administer an additional dose using a new autoinjector; if there is still no response and additional doses are available, administer additional doses every 2-5 minutes using a new autoinjector for each dose until emergency medical assistance arrives
  • Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance
  • Partial agonists or mixed agonists/antagonists (eg, buprenorphine): Reversal of respiratory depression may be incomplete and require repeated administration using a new autoinjector

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Nalmefene has severe interactions with no other drugs
• Nalmefene has serious interactions with no other drugs
• Nalmefene has moderate interactions with no other drugs
• Nalmefene has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to nalmefene and any excipients in the product

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Nalmefene?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Nalmefene?”

Cautions

• Nalmefene, like all drugs in this class, is not the 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 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 and Lactation

• There was no evidence of impaired fertility or harm to the fetus
• There are no adequate and well-controlled studies in pregnant women
• Use during pregnancy only if needed
• Lactation
  • Nalmefene and its metabolites were secreted into rat milk, reaching concentrations approximately 3 times those in plasma at 1 hour and decreasing to about half the corresponding plasma concentrations by 24 hours following bolus administration
  • As no clinical information is available, exercise caution when administered to nursing women