Opvee (nalmefene HCl)

Dosage of nalmefene hydrochloride is expressed in terms of nalmefene.

Titrate dosage to reverse undesired opioid-induced effects. When adequate opioid reversal has been established, additional doses of nalmefene are not required and may cause unwanted reversal of analgesia or precipitate withdrawal.

Nalmefene hydrochloride may be administered by IV, IM, or subcutaneous (SUBQ) injection or intranasally.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Opioid Antagonists/Opioid Analgesics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Naltrexone, nalmefene, and samidorphan are opioid antagonists and thus inhibit the effects of opioid analgesics.(1-3)

CLINICAL EFFECTS: Concurrent administration or the administration of naltrexone within 7-10 days of opioids may induce acute abstinence syndrome or exacerbate a pre-existing subclinical abstinence syndrome.(1,4) Patients taking naltrexone may not experience beneficial effects of opioid-containing medications.(4) Samidorphan can precipitate opioid withdrawal in patients who are dependent on opioids. In patients who use opioids, delay initiation of samidorphan for a minimum of 7 days after last use of short-acting opioids and 14 days after last use of long-acting opioids.(3) Concurrent use of nalmefene tablets with opioid agonists may prevent the beneficial effects of the opioid.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of naltrexone states that the administration of naltrexone concurrently with opioids or to patients dependent on opioids is contraindicated.(1,4) Patients previously dependent on short-acting opioids should be opioid-free for a minimum of seven to ten days before beginning naltrexone therapy. Patients previously on buprenorphine or methadone may be vulnerable to withdrawal symptoms for as long as 2 weeks.(1,4) The manufacturer of naltrexone states that the naloxone challenge test, described in the naltrexone prescribing information, can be administered to determine if patients are opioid free.(1) The manufacturer of samidorphan states the concurrent use of samidorphan in patients using opioids or undergoing acute opioid withdrawal is contraindicated. Prior to initiating samidorphan, there should be at least a 7-day opioid free interval from the last use of short-acting opioids, and at least a 14-day opioid free interval from the last use of long-acting opioids.(3) The UK manufacturer of nalmefene tablets (for reduction of alcohol consumption) states the concurrent use of opioid analgesics is contraindicated.(2) Suspend the use of nalmefene tablets for 7 days prior to the anticipated use of opioids (e.g., elective surgery).(2)

DISCUSSION: A double-blind, randomized, placebo-control study evaluated pain relief and side effects of 35 opioid-naive patients undergoing cesarean section. All patients received spinal anesthesia (bupivacaine and morphine) and were randomized to also receive placebo, naltrexone 3 mg, or naltrexone 6 mg. Patients treated with naltrexone experienced shorter duration of pain relief (not statistically significant), however incidence of opioid-induced side effects was reduced. Patients in the naltrexone 6 mg group had lower rates of pruritus, vomiting, and somnolence (all statistically significant) compared to the placebo group.(5) In a double-blind, randomized, placebo-control trial ten recreational opioid users were studied to determine the effects of hydromorphone (4 mg and 16 mg), tramadol (87.5 mg, 175 mg, and 350 mg), and placebo after pretreatment with naltrexone (50 mg) or placebo. Results show that lower doses of hydromorphone and tramadol acted similar to placebo. Hydromorphone 16 mg alone caused euphoria and miosis which were blocked by naltrexone. Tramadol 350 mg produced a lower magnitude of euphoria and miosis compared to hydromorphone. Naltrexone partially diminished the euphoria caused by tramadol, while it enhanced some of the unpleasant monoaminergic effects (flushing, malaise, vomiting).(6) A case report describes a 28 year-old ex-heroin addict who was stable on methadone 100 mg daily and simultaneously stopped using heroin and began drinking alcohol. He was admitted to the hospital for alcohol detoxification and, by mistake, was given naltrexone 100 mg instead of methadone 100 mg. The patient experienced withdrawal symptoms including chills, agitation, muscle and abdominal pain, generalized piloerection, and dilated pupils. Treatment of withdrawal was titrated to treat symptoms and required administration 78 mg of parenteral hydromorphone, after which the patient experienced relief for the following six hours.(8) Intentional administration of an opioid antagonist, naloxone, with opioid analgesics has been performed with close monitoring to lower required opioid dose by inducing withdrawal. Three case reports describe patients who had improved pain relief on significantly reduced doses of opioid analgesics.(8) In a double-blind controlled trial, 267 trauma patients were randomized to receive 0.05 mg/kg intravenous morphine either alone or in combination with 5 mg naltrexone oral suspension. Evaluated endpoints include reduction of pain and incidence of side effects. Results indicate that ultra-low dose naltrexone does not alter opioid requirements for pain control, but does lower incidence of nausea [2 (1.16%) vs 16 (11.6%), p<0.001].(9)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity to nalmefene hydrochloride or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

The most common adverse effects of nalmefene hydrochloride injection (>=5% of patients) include nausea, vomiting, tachycardia, hypertension, feeling hot, headache, dizziness, chills, allodynia, palpitations, tinnitus, ear discomfort, feeling abnormal, burning sensation, hot flush, and irritability.

The most common adverse effects of nalmefene hydrochloride nasal spray (>=2% of patients) include nasal discomfort, headache, nausea, dizziness, hot flush, vomiting, anxiety, fatigue, nasal congestion, throat irritation, rhinalgia, decreased appetite, dysgeusia, erythema, and hyperhidrosis.

Rare or Very Rare

• Bradycardia
• Hypotension
• Myoclonus
• Opioid withdrawal symptoms

More Frequent

• Anorexia
• Dizziness
• Drug-induced hot flash
• Fatigue
• Headache disorder
• Hyperhidrosis
• Insomnia
• Nasal congestion
• Nasal pain
• Nausea
• Vomiting

Less Frequent

• Agitation
• Chills
• Diarrhea
• Dysgeusia
• Paresthesia
• Tachycardia
• Tremor
• Xerostomia

Rare or Very Rare

• Acute abdominal pain
• Acute cognitive impairment
• Depression
• Drowsy
• Erythema
• Pharyngitis
• Presyncope
• Symptoms of anxiety
• Urinary retention

No enhanced messaging available.

Safety and efficacy of nalmefene injection in single-dose vials have not been established in pediatric patients.

Safety and efficacy of nalmefene injection in auto-injectors (Zurnai(R)) and nalmefene nasal spray (Opvee(R)) have been established in pediatric patients >=12 years of age for the emergency treatment of known or suspected overdose manifested by respiratory and/or CNS depression. Use of these nalmefene dosage forms for this indication in this age group is based on studies performed in adult patients and a pharmacokinetic simulation. There have not been clinical studies to evaluate their use in pediatric patients. Safety and efficacy have not been established in pediatric patients <12 years of age.

Safety and efficacy of nalmefene injection in single-dose vials have not been established in neonates. Nalmefene should only be used in the resuscitation of neonates when, in the opinion of the treating clinician, the expected benefits outweigh the risk.

There is insufficient evidence with nalmefene in pregnant women to evaluate a drug-associated risk of major birth defects or miscarriage. Reproductive studies in rats and rabbits revealed no evidence of impaired fertility or embryotoxic effects, and no adverse effects on embryo-fetal development.

Opioid overdose is considered a medical emergency and can be fatal for the pregnant woman and fetus if left untreated. Treatment with nalmefene should not be withheld because of the potential concerns regarding the effects of nalmefene on the fetus.

There is no information regarding the presence of nalmefene and its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production. Nalmefene is distributed into the milk of rats. Use with caution in breastfeeding patients.

In general, dose selection of nalmefene hydrochloride injection in geriatric patients should be cautious, usually starting at the low end of the dose range, to reflect the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Clinical studies of nalmefene injection did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently from younger patients. Clinical studies of nalmefene nasal spray did not include patients >=65 years of age. Other clinical experience with nalmefene has not identified differences in responses between geriatric and younger patients.

Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function as well as concomitant diseases and drug therapy; therefore, systemic exposure to nalmefene may be higher in geriatric patients. Dosage of nalmefene hydrochloride injection should be selected with caution in geriatric patients.