nalmefene intranasal

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action:  

nalmefene acts as a competitive antagonist at opioid receptors, primarily targeting the mu-opioid receptors in the central nervous system. It has a high affinity for these receptors, displacing opioid agonists from their binding sites. By blocking the mu-opioid receptors, nalmefene prevents the opioid agonists from exerting their effects, such as analgesia and respiratory depression. 

Spectrum of Activity:  

nalmefene exhibits a broad spectrum of activity due to its antagonist properties. Some critical aspects of its spectrum of activity include: 

• Opioid Overdose Reversal: nalmefene is primarily used for the emergency management of opioid overdose. By rapidly binding to and blocking opioid receptors, it can reverse the respiratory depression and central nervous system depression associated with opioid overdose. nalmefene can effectively counteract the effects of various opioid drugs, including morphine, heroin, and synthetic opioids like fentanyl. 
• Alcohol Dependence: nalmefene has also been studied for its potential use in reducing alcohol consumption in individuals with alcohol dependence. By blocking the endogenous opioids released upon alcohol consumption, it is thought to reduce the rewarding effects and cravings associated with alcohol use. This may help in reducing alcohol intake and promoting abstinence. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

2.7 mg 

Nasal discomfort (8.2-42.7%) 

Hot flush (8-19.7%) 

Anxiety (4.7-11.5%) 

Headache (6.7-55.7%) 

Nausea (3.4-36.1%) 

Dizziness (5.6-14.8%) 

Vomiting (2.2-11.5%) 

5.4 mg 

Nausea (4.2-21.7%) 

Nasal discomfort (12.5-13%) 

Rhinalgia (8.7-25%) 

Nasal congestion (4.3-16.7%) 

1-10%  

2.7 mg 

Nasal congestion (3.3-4.5%) 

Fatigue (3.4-4.9%) 

Rhinalgia (1.6-3.4%) 

Oropharyngeal pain (1.3-3.3%) 

Agitation (1.3-3.3%) 

Throat irritation (3.4-4.9%) 

Erythema (2-3.4%) 

Dyspnea (1.3-3.3%) 

Paresthesia (1.3-3.3%) 

Hyperhidrosis (2-6.6%) 

5.4 mg 

Headache (4.3%) 

Vomiting (4.3%) 

Chest discomfort (4.3%) 

Dry eye (4.3%) 

Oropharyngeal pain (4.2-4.3%) 

Dry mouth (4.3%) 

Insomnia (4.3%) 

Rhinitis (4.3%) 

Tachycardia (4.3%) 

Presyncope (4.3%)  

<1% 

Arrhythmia 

Dry mouth 

Depression 

Nervousness 

Confusion 

Bradycardia 

Diarrhea 

Somnolence 

Agitation 

Tremor 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: nalmefene intranasal should not be used in individuals with known hypersensitivity or allergy to nalmefene or any of the components of the formulation. Allergic reactions can range from mild skin reactions to more severe systemic reactions, including anaphylaxis. 
• Opioid Dependence: nalmefene intranasal is contraindicated in individuals who are physically dependent on opioids. Since nalmefene is an opioid receptor antagonist, its use in opioid-dependent individuals can precipitate withdrawal symptoms and potentially exacerbate the withdrawal syndrome. 
• Opioid Analgesia: nalmefene intranasal is not intended for use as an analgesic or for pain relief. Using it in individuals who require ongoing opioid analgesia may result in the reversal of pain relief and potentially lead to acute withdrawal symptoms. 
• Severe Respiratory Depression: nalmefene intranasal should not be administered to individuals with severe respiratory depression, as it may worsen the condition. The abrupt reversal of opioid effects can lead to respiratory distress and compromise. 
• Pediatric Use: The use of nalmefene intranasal is not recommended for children under the age of 18 years due to limited data on safety and efficacy in this population. 
• Pregnancy and Breastfeeding: The safety of nalmefene intranasal in pregnant or breastfeeding individuals has not been established.  

Caution: 

• Hepatic impairment: nalmefene is primarily metabolized in the liver, so caution should be exercised when administering nalmefene intranasal to individuals with hepatic impairment. Dose adjustments or close monitoring of liver function may be necessary in such cases. 
• Renal Impairment: Although renal impairment is not expected to affect nalmefene’s pharmacokinetics significantly, caution is advised when using nalmefene intranasal in individuals with severe renal impairment. Monitoring renal function may be appropriate in these cases. 
• Cardiovascular Disease: nalmefene can have cardiovascular effects, including increases in heart rate and blood pressure. Individuals with pre-existing cardiovascular conditions, such as hypertension, arrhythmias, or ischemic heart disease, should be closely monitored during treatment with nalmefene intranasal. 
• Respiratory Conditions: nalmefene can cause withdrawal symptoms and worsen respiratory depression in individuals with compromised respiratory function, such as those with chronic obstructive pulmonary disease (COPD) or other respiratory disorders. Caution should be exercised in such cases, and close monitoring of respiratory function is advised. 
• Central Nervous System (CNS) Depression: nalmefene can cause sedation and drowsiness. Therefore, caution should be exercised when using nalmefene intranasal in individuals concurrently using other CNS depressants, such as alcohol, benzodiazepines, or other opioids. The combined effects of these substances may increase the risk of respiratory depression and sedation. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

The pharmacology of nalmefene intranasal: 

• Duration of Action: nalmefene has a more prolonged action duration than naloxone, another opioid antagonist commonly used for overdose reversal. This extended duration of action allows for sustained opioid receptor blockade, reducing the risk of recurrent respiratory depression after the initial reversal. 
• Receptor Selectivity: nalmefene exhibits a high affinity for the mu-opioid receptors but also has some affinity for the kappa-opioid receptors. However, it has a lower affinity for the kappa-opioid receptors compared to its affinity for the mu-opioid receptors. This selectivity contributes to its opioid receptor antagonism and overdose reversal effects. 

Pharmacodynamics: 

• Duration of Action: nalmefene has a more prolonged action duration than naloxone, another opioid antagonist commonly used for overdose reversal. This extended duration of action allows for sustained opioid receptor blockade, reducing the risk of recurrent respiratory depression after the initial reversal. 
• Receptor Selectivity: nalmefene exhibits selectivity for mu-opioid receptors, although it also has some affinity for kappa-opioid receptors. However, its affinity for the mu-opioid receptors is higher than its affinity for kappa-opioid receptors. This selectivity contributes to its antagonism of opioid effects and its ability to reverse opioid overdose. 
• Withdrawal Symptoms: nalmefene can precipitate acute withdrawal symptoms in individuals physically dependent on opioids. When administered to individuals with opioid dependence, it displaces opioid agonists from the receptors, leading to an abrupt decrease in opioid activity, which can result in withdrawal symptoms. 
• Cardiovascular Effects: nalmefene can cause cardiovascular effects, such as increases in heart rate and blood pressure. These effects are mediated by the antagonism of the mu-opioid receptors, which can activate other neural pathways involved in cardiovascular regulation. 

Pharmacokinetics: 

Absorption 

nalmefene intranasal is administered through the nasal mucosa and is absorbed into the systemic circulation. The absorption process begins when the medication is sprayed or administered as a nasal spray. The nasal mucosa has a rich blood supply, which facilitates the absorption of the drug into the bloodstream. 

Distribution 

Once absorbed, nalmefene is distributed throughout the body via systemic circulation. It readily crosses the blood-brain barrier and other tissues, including the liver. nalmefene is highly bound to plasma proteins, primarily albumin, which can influence its physical distribution. 

Metabolism 

nalmefene is primarily metabolized in the liver through various metabolic pathways. The main pathway involves the conversion of nalmefene to its major active metabolite, nalmefene-3-glucuronide, through glucuronidation. Other minor metabolic pathways, including N-dealkylation and N-oxidation, may also occur. The metabolism of nalmefene involves enzymes primarily from the cytochrome P450 (CYP) family, including CYP3A4 and CYP2C8. 

Elimination and Excretion  

nalmefene and its metabolites are primarily eliminated from the body through the urine. The glucuronide conjugate, nalmefene-3-glucuronide, and other metabolites are excreted into the urine. A small portion of the drug and its metabolites may also be eliminated in the feces. The elimination half-life of nalmefene is approximately 8 to 12 hours. 

Adminstartion

Administration: 

• Preparation: Before using the nasal spray, ensure the product is stored correctly and at the recommended temperature. Read the instructions and check the expiration date. 
• Priming: Some nasal spray devices may require priming before the first use or if it has not been used for a certain period. Priming helps to ensure the proper functioning of the device. Follow the specific priming instructions provided with the product. 
• Nasal Administration: The following steps are typically involved in administering nalmefene intranasal: 

1. Gently blow your nose to clear the nasal passages. 
2. Remove the cap from the nasal spray device. 
3. Hold the device with your thumb at the bottom and your index and middle fingers on the sides. 
4. Tilt your head slightly forward and keep the device upright.
5. Insert the nozzle into one nostril, closing the other with your finger. 
6. Aim the nozzle slightly away from the center of the nose, towards the ear on the same side. 
7. Breathe gently through your nose and press firmly on the pump to release the spray while inhaling. h. Repeat the process for the other nostril if required. 
8. After administration, remove the nozzle from the nostril and breathe gently through the nose.

• Post-Administration: Recap the nasal spray device, if applicable. Avoid blowing your nose immediately after administration to allow the medication to remain in the nasal passages. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: nalmefene intranasal 

Why do we use nalmefene intranasal? 

nalmefene intranasal is primarily indicated for the emergency management of known or suspected opioid overdose. It is used to rapidly reverse the respiratory depression and central nervous system depression associated with opioid overdose. Here are the primary uses of nalmefene intranasal: 

• Opioid Overdose Reversal: nalmefene intranasal is administered to individuals experiencing an opioid overdose to reverse the effects of opioids quickly. It works by competitively binding to opioid receptors, displacing and blocking the opioids from activating these receptors. This leads to the reversal of respiratory depression and the restoration of normal breathing and consciousness.