Nalmefene Hydrochloride Injection

Pharmacological action Nalmefene is an opioid receptor antagonist and a 6-methylene analog of naltrexone. Nalmefene can inhibit or reverse the respiratory depression, sedation and hypotension effects of opioid drugs. Pharmacodynamic studies have shown that the duration of action of nalmefene is longer than that of naloxone at a complete reversal dose. Nalmefene has no opioid agonist activity and does not produce respiratory depression, hallucinogenic effects or pupil constriction. No pharmacological effect was observed when nalmefene was administered in the absence of opioid agonists. No tolerance, physical dependence or abuse tendency of nalmefene was observed in the study. In opioid-dependent subjects, nalmefene can produce acute withdrawal symptoms. Toxicological studies The results of the nalmefene Ames test, mouse lymphoma test, mouse micronucleus test, and rat bone marrow cytogenetic test for genetic toxicity were all negative. In the human lymphocyte metaphase test, a weak but statistically significant gene disruption effect was observed in the presence of exogenous metabolic activation, but not in the absence of exogenous metabolic activation. Reproductive toxicity: When nalmefene was orally administered to rats at a dose of up to 1200 mg/m2/day, no effects on fertility, reproductive behavior, and offspring survival were observed. When nalmefene was orally administered to rats and rabbits at doses of up to 1200 mg/m2/day and 2400 mg/m2/day, respectively, and when nalmefene was intravenously administered to rabbits at doses of up to 96 mg/m2/day (114 times the human dose), no impairment of fertility or effects on the fetus were observed.

The main ingredient of this product is nalmefene hydrochloride, its chemical name is: 17-cyclopropylmethyl-4,5α-epoxy-6-methylenemorphinan-3,14-diol hydrochloride, and its structural formula is: Molecular formula: C21H25NO3·HCl Molecular weight: 375.9 Excipients are sodium chloride and water for injection.

This product is a colorless clear liquid.

Nalmefene is used to completely or partially reverse the effects of opioids, including respiratory depression caused by natural or synthetic opioids. It is mainly used for emergency awakening of known or suspected opioid overdose or poisoning, acute craniocerebral and spinal cord injury, cerebral ischemia, cerebral infarction and other neurological damage diseases. It is also used for awakening after coma, shock and postoperative anesthesia, alcohol poisoning, and relapse prevention after drug detoxification.

Nalmefene injection is generally given intravenously, and can also be injected intramuscularly or subcutaneously. General principles: This product can reverse the undesirable opioid effects by dose titration. Because it is not expected to reverse the loss of pain and cause harm or withdrawal reactions, the drug should not be continued once a sufficient reversal effect is achieved. Recommended dose for reversing postoperative opioid inhibition: Use a dose concentration of 100 micrograms/ml, see the initial dose in Table 1. The purpose of postoperative nalmefene treatment is to reverse the excessive inhibitory effects of opioids, not to cause complete reversal and acute pain. The initial dose is 0.25 micrograms/kg, and the dose can be increased by 0.25 micrograms/kg after 2 to 5 minutes. Stop the drug immediately when the expected opioid reversal effect is achieved. Cumulative doses greater than 1.0 micrograms/kg will not increase the efficacy. Table 1: Reversal of the depressant effects of postoperative opioids Body weight mL of nalmefene used (at a concentration of 100 mg/mL) 50 kg 0.125 60 kg 0.150 70 kg 0.175 80 kg 0.200 90 kg 0.225 100 kg 0.250 For patients with known high cardiovascular risk, dilute nalmefene with sodium chloride injection or sterile water for injection in a 1:1 ratio and use 0.1 microgram/kg as the initial dose and escalating doses. Patients with opioid tolerance or physical dependence: Nalmefene can cause acute withdrawal symptoms in patients with opioid tolerance or physical dependence. These patients should be closely observed for withdrawal symptoms during initial or continued use. The next dose should be repeated at least 2-5 minutes later to increase the dose to achieve maximum therapeutic effect. Repeated administration: If respiratory depression recurs, the dose should be increased to achieve clinical therapeutic effect. Over-reversal should be avoided when increasing the dose.

For healthy users, nalmefene is well tolerated without serious adverse reactions, even at doses of 15 times or more than the recommended dose. For a small number of patients, when the dose of this product exceeds the recommended dose, the symptoms produced by nalmefene show a reversal of the effects of endogenous opioids (such as other anesthetic antagonists previously reported). These symptoms (nausea, chills, myalgia, irritability, abdominal cramps and joint pain) are often transient and have a low incidence. After using clinically recommended doses in patients who have undergone surgery or opioid overdose, expected opioid withdrawal symptoms occurred, and it was later discovered that these patients had used opioids. The withdrawal symptoms that occur with the use of nalmefene are similar to those that occur with other opioid antagonists. The withdrawal symptoms that occur with low doses after surgery are transient, and the withdrawal symptoms that occur with high doses in patients with drug overdose last for a long time. It is reported that the frequency of tachycardia and nausea after the use of nalmefene after surgery is the same as that of the use of bioequivalent doses of naloxone. The incidence of these two adverse reactions is low when the dose can only partially reverse the effects of opioids, and their incidence increases with increasing doses. Therefore, the recommended dose is no more than 1.0 μg/kg for postoperative use and no more than 1.5 mg/70 kg for the treatment of opioid overdose. According to foreign clinical trial literature, the common adverse reactions to nalmefene are listed as follows: Common adverse reactions with an incidence of no more than 1% (all patients, clinical cases used) Adverse reactions Nalmefene (1127 cases) Naloxone (369 cases) Placebo (77 cases) Nausea 18% 18% 6% Vomiting 9% 7% 4% Tachycardia 8% 8% - Hypertension 5% 7% - Postoperative pain 4% 4% N/A Fever 3% 4% - Dizziness 3% 4% 1% Headache 1% 1% 4% Chills 1% 1% - Hypotension 1% 1% - Vasodilation 1% 1% - Adverse reactions with an incidence of less than 1% Cardiovascular system: bradycardia, arrhythmia Digestive tract: diarrhea, dry mouth Nervous system: drowsiness, neurasthenia, agitation, nervousness, tremor, confusion, withdrawal symptoms, muscle spasm Respiratory tract: pharyngitis Skin: itching Urinary tract: urinary retention When the dosage of this product exceeds the recommended dose, the incidence of adverse reactions increases. Laboratory Results: In studies of patients receiving medication postoperatively, transient increases in CPK values have been reported in 0.5%. The increase was thought to be related to the surgery and not to the use of nalmefene. Increases in AST were observed in 0.3% of patients receiving nalmefene or naloxone. It is not known whether this finding is clinically significant. No hepatitis or liver injury was observed with nalmefene or naloxone in clinical trials.

Nalmefene is contraindicated in patients with drug allergies.

Precautions for children: The efficacy and safety of this product for pediatric patients have not been established. The efficacy and safety of this product for neonatal patients have not been established. Nalmefene can only be used for neonatal resuscitation, and clinicians believe that its expected benefits outweigh the risks. Precautions for pregnancy and lactation: In reproductive studies, rats and rabbits were given oral doses of 1200 mg/m2/day and 2400 mg/m2/day of nalmefene, respectively, and rabbits were given intravenous doses of 96 mg/m2/day of nalmefene (114 times the human dose), and no effects on reproductive capacity or harm to the fetus were found. However, sufficient relevant controlled trials have not been conducted on pregnant women. Because the results of animal reproductive studies cannot predict human responses, this product can only be used in pregnant patients when it is determined that it must be used. Nalmefene and its metabolites can be secreted into rat milk, reaching three times the blood drug concentration 1 hour after a large amount of medication, and reducing to half the blood drug concentration in 24 hours. Because there are no relevant clinical reports, care should be taken when using nalmefene in lactating patients. Elderly precautions: After intravenous injection of 0.5-2 mg nalmefene to elderly male volunteers, AUC was proportional to the dose. After intravenous injection of 1 mg nalmefene, there was no significant difference in plasma clearance, apparent distribution volume or half-life between the young group (19-32 years old) and the elderly group (62-80 years old). The concentration of nalmefene in the elderly group was higher, so the apparent central distribution volume decreased (young group: 3.9±1.1L/kg, elderly group: 2.8±1.1L/kg), and the degree of decrease was related to age. At the same time, the initial plasma concentration of nalmefene in the elderly group increased transiently, so it is necessary to consider adjusting the dose.

Nalmefene can cause sensory loss when used after benzodiazepines, inhaled anesthetics, muscle relaxants, and muscle relaxant antagonists. This product can also be used in outpatient settings for conscious sedation and in emergency situations of multiple drug overdoses. No harmful drug interactions have been observed. Preclinical studies have shown that flumazenil and nalmefene can induce seizures in animals. Combining flumazenil and nalmefene produces fewer seizures than expected in rodent studies because the drugs alone can achieve the desired effect. Based on these data, adverse reactions cannot be expected from the combination of these two drugs, but physicians should be informed that nalmefene may cause seizures when used in combination with these drugs.

Sealed, store in a cool dark place (avoid light and not exceed 20℃).

1ml:0.1mg

24 months

Lingbao City Yuxi Pharmaceutical Co., Ltd.

• Founded in:

  1999-05-19

• Address:

  West section of Station Road, Lingbao City

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  914112827066645112

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