AdultPediatricDosage Forms & Strengths intranasal solution 2.7mg/0.1mL; each unit-dose nasal spray delivers a single 2.7 mg-dose Opioid Overdose Indicated for emergency treatment of known or suspected opioid (natural or synthetic) overdose in adults as manifested by respiratory and/or central nervous system (CNS) depression Seek emergency care immediately after use Administer 1 spray (2.7 mg) intranasally into nose as soon as possible Administer additional doses, using a new nasal spray with each dose, if patient is nonresponsive or relapses into respiratory depression after response May readminister dose every 2-5 min until emergency medical assistance arrives Consider additional supportive and/or resuscitative measures Dosage Modifications Renal impairment For single doses, no dosage adjustment is necessary Renal impairment reduces clearance of nalmefene Hepatic impairment For single doses, no dosage adjustment is necessary Hepatic impairment reduces clearance of nalmefene Dosage modifications to partial agonists or mixed agonists/antagonists Reversal of respiratory depression by partial agonists or mixed agonist/antagonists (eg, buprenorphine, pentazocine) may be incomplete and require repeated administration of nalmefene intranasal Dosing Considerations For immediate administration as emergency therapy in settings where opioids may be present Not a substitute for emergency medical careDosage Forms & Strengths intranasal solution 2.7mg/0.1mL; each unit-dose nasal spray delivers a single 2.7 mg-dose Opioid Overdose Indicated for emergency treatment of known or suspected overdose induced by natural or synthetic opioids in adults and pediatric patients aged ≥12 years, as manifested by respiratory and/or central nervous system depression <12 years: Safety and efficacy not established ≥12 years For intranasal use only Seek emergency care immediately after use Administer 1 spray (2.7 mg) intranasally into nose as soon as possible Administer additional doses, using a new nasal spray with each dose, if patient is nonresponsive or relapses into respiratory depression after response May readminister dose every 2-5 min until emergency medical assistance arrives Consider additional supportive and/or resuscitative measures Dosage Modifications Renal impairment For single doses, no dosage adjustment is necessary Renal impairment reduces clearance of nalmefene Hepatic impairment For single doses, no dosage adjustment is necessary Hepatic impairment reduces clearance of nalmefene Dosage modifications to partial agonists or mixed agonists/antagonists Reversal of respiratory depression by partial agonists or mixed agonist/antagonists (eg, buprenorphine, pentazocine) may be incomplete and require repeated administration of nalmefene intranasal Dosing Considerations For immediate administration as emergency therapy in settings where opioids may be present Not a substitute for emergency medical careInteraction CheckerEnter a drug name and nalmefene intranasalNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (0)Serious - Use Alternative (0)Monitor Closely (0)Minor (0) >10% 2.7 mg Headache (6.7-55.7%) Nasal discomfort (8.2-42.7%) Nausea (3.4-36.1%) Hot flush (8-19.7%) Dizziness (5.6-14.8%) Anxiety (4.7-11.5%) Vomiting (2.2-11.5%) 5.4 mg Rhinalgia (8.7-25%) Nausea (4.2-21.7%) Nasal congestion (4.3-16.7%) Nasal discomfort (12.5-13%) 1-10% 2.7 mg Hyperhidrosis (2-6.6%) Nasal congestion (3.3-4.5%) Throat irritation (3.4-4.9%) Fatigue (3.4-4.9%) Erythema (2-3.4%) Rhinalgia (1.6-3.4%) Dyspnea (1.3-3.3%) Oropharyngeal pain (1.3-3.3%) Paresthesia (1.3-3.3%) Agitation (1.3-3.3%) Chills (1.3-3.3%) Claustrophobia (1.3-3.3%) Dysgeusia (1.1-3.3%) Decreased appetite (1.1-3.3%) Abdominal pain (1.1-1.6%) Dry mouth (0.7-1.6%) Insomnia (0.7-1.1%) Rhinitis (0.7-1.1%) 5.4 mg Presyncope (4.3%) Headache (4.3%) Dry mouth (4.3%) Vomiting (4.3%) Insomnia (4.3%) Chest discomfort (4.3%) Rhinitis (4.3%) Dry eye (4.3%) Tachycardia (4.3%) Oropharyngeal pain (4.2-4.3%) Erythema (4.2-4.3%) Paresthesia (4.2-4.3%) Dizziness (4.2%) Constipation (4.2%) Hyperhidrosis (4.2%) Urticaria (4.2%) <1% Bradycardia Arrhythmia Diarrhea Dry mouth Somnolence Depression Agitation Nervousness Tremor Confusion Withdrawal syndrome Myoclonus Pharyngitis Pruritus Urinary retention Postmarketing Reports Abrupt reversal of opioid depression: Nausea, vomiting, sweating, tremulousness, seizures, and cardiovascular instability including tachycardia, hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest Death, coma, and encephalopathy reported as sequelae of these events; events primarily occurred in patients who had pre-existing cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects In persons who were opioid dependent, abrupt reversal of opioid effects has precipitated an acute withdrawal syndrome Signs and symptoms included: Body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shiver or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia In neonates, opioid withdrawal symptoms also included convulsions, excessive crying, and hyperactive reflexes Contraindications Hypersensitivity to nalmefene or to any of other ingredients Cautions Reversal of respiratory depression by partial agonists or mixed agonist/antagonists (eg, buprenorphine, pentazocine) may be incomplete; repeated doses of nalmefene intranasal may be necessary to antagonize buprenorphine owing to long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor Risk of recurrent respiratory and CNS depression Recurrence of respiratory depression is possible, even after an adequate initial response to nalmefene intranasal Always seek out emergency medical assistance immediately after administering first dose and continue to monitor patient Additional doses may be necessary if symptoms of opioid overdose recur Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance Precipitation of severe opioid withdrawal May precipitate opioid withdrawal in patients who are opioid dependent Signs and symptoms include body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure Abrupt postoperative reversal of opioid depression after use may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest After use, monitor patients with preexisting cardiac disease or patients who have received medications associated with cardiovascular effects such as hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in an appropriate healthcare setting In neonates, opioid withdrawal may be life threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes Monitor for developing signs and symptoms of opioid withdrawal Use an alternative opioid antagonist product that can be titrated to effect and, where applicable, dosed according to weight Risk of opioid overdose from attempts to overcome the blockade Unlikely to produce acute withdrawal symptoms in nonopioid-dependent patients Use in patients who are opioid dependent may precipitate opioid withdrawal Attempting to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids could lead to opioid intoxication and death Inform patients of the potential consequences of trying to overcome the opioid blockade Get emergency medical assistance as soon as possible after using nalmefene nasal spray regardless of withdrawal symptoms Pregnancy Do not withhold life-sustaining therapy for opioid overdose There are no available data on nalmefene use in pregnant females to evaluate for a drug-associated risk of major birth defects or miscarriage Animal data No embryotoxic effects on embryofetal development were observed in rats and rabbits treated with nalmefene at exposures at least 6x (rats) and up to 20x (rabbits) the exposure at two human nasal doses of 5.4 mg Clinical considerations An opioid overdose is a medical emergency and can be fatal for the pregnant female and fetus if left untreated Lactation There are no data on presence of nalmefene and its metabolites in human milk, the effects of nalmefene on breastfed children, or effects on milk production Nalmefene and its metabolites are present in rat milk When a drug is present in animal milk, drug is likely present in human milkPregnancy 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. 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 Absorption Bioavailability: 0.806 (relative to IM) Peak plasma concentration 2.7-mg dose (1 spray in 1 nostril): 9.75 ng/mL 5.4-mg dose (1 spray in each nostril): 18.9 ng/mL 5.4-mg dose (2 sprays in 1 nostril): 16.1 ng/mL Peak plasma time 2.7-mg dose (1 spray in 1 nostril): 0.267 hr 5.4-mg dose (1 spray in each nostril): 0.25 hr 5.4-mg dose (2 sprays in 1 nostril): 0.25 hr AUC (0-inf) 2.7-mg dose (1 spray in 1 nostril): 45.8 ng⋅hr/mL 5.4-mg dose (1 spray in each nostril): 88.1 ng⋅hr/mL 5.4-mg dose (2 sprays in 1 nostril): 83.8 ng⋅hr/mL Distribution Vd: 3.9 L/kg Vd (steady-state): 8.6 L/kg Blood-to-plasma ratio: 1.3 Metabolism Metabolized by the liver, primarily by glucuronide conjugation Metabolized to trace amounts of an N-dealkylated metabolite Nalmefene glucuronide is inactive and N-dealkylated metabolite has minimal pharmacological activity Elimination Clearance: 75.7 L/hr Half-life 2.7-mg dose (1 spray in 1 nostril): 11.4 hr 5.4-mg dose (1 spray in each nostril): 11.3 hr 5.4-mg dose (2 sprays in 1 nostril): 11.3 hr Excretion Nalmefene and its metabolites are excreted in urine Urine: <5% unchanged Feces: 17% Intranasal Administration Place patient in supine position Before administering, ensure device nozzle is inserted in patient’s nose and provide support to back of the neck to allow head to tilt back Do not prime or test device before administering Press firmly on plunger and remove nozzle from nose after use If patient responds (eg, waking up to voice or touch, starts breathing normally), place patient on their side (recovery position) as shown in prescribing information and call for emergency medical assistance immediately after administering first dose Storage Store in blister and cartons provided Store at controlled room temperature 15-25ºC (59-77ºF); excursions permitted to 4- 40ºC (39-104ºF) Do not freeze Protect from light Do not open individual blister packs or test nasal spray devices before use No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. 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. View explanations for tiers and restrictions 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. OR Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription. Plans Select State: Alabama Alaska Arizona Arkansas California Colorado Connecticut Delaware District of Columbia Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota Ohio Oklahoma Oregon Pennsylvania Puerto Rico Rhode Island South Carolina South Dakota Tennessee