buprenorphine/samidorphan

Action and Spectrum

Actions and Spectrum:  

buprenorphine is a partial opioid receptor agonist used to treat opioid addiction and manage pain. It works by binding to the same receptors in the brain that opioids bind to, but it produces less of a euphoric effect and less respiratory depression than full opioid agonists. Buprenorphine also has a long half-life, which means it can be taken less frequently than other opioid medications. 

samidorphan, on the other hand, is an opioid receptor antagonist that works by blocking the effects of opioids on the brain. It is added to buprenorphine to reduce the potential for abuse and overdose. samidorphan is also thought to enhance the therapeutic effects of buprenorphine by blocking a specific opioid receptor that is associated with negative side effects such as depression and anxiety. 

The spectrum of buprenorphine/samidorphan is primarily related to its effects on the central nervous system. It can produce a range of therapeutic effects, including pain relief, reduced anxiety, and improved mood. However, it can also produce side effects such as drowsiness, constipation, and nausea. The medication has a relatively long half-life, meaning it can produce prolonged effects and requires less frequent dosing than other opioid medications. 

Drug Interaction

Adverse Reaction

Black Box Warning

Black Box Warning:  

The black box warning for buprenorphine/samidorphan is related to the potential risk of respiratory depression, which can be fatal. Respiratory depression is a severe side effect of opioid medications that can lead to breathing difficulties and death. 

The warning states that buprenorphine/samidorphan should only be prescribed by healthcare providers who are certified in the treatment of opioid use disorder and are knowledgeable in the use of opioid medications.

The medication should also be administered in a healthcare setting where trained personnel can monitor the patient’s breathing and other vital signs. 

The black box warning also advises against the use of buprenorphine/samidorphan in patients who are not already tolerant to opioids, as it can cause severe respiratory depression and death in these individuals. 

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: buprenorphine/samidorphan is contraindicated in patients who have a known hypersensitivity to buprenorphine, samidorphan, or any of its components. 

Respiratory Depression: buprenorphine/samidorphan should not be used in patients with acute or severe respiratory depression, which may lead to respiratory arrest and death.  

Central Nervous System (CNS) Depression: buprenorphine/samidorphan is contraindicated in patients with significant CNS depression, including coma or head injury, as it may increase the risk of respiratory depression.  

MAO Inhibitors: buprenorphine/samidorphan should not be used with monoamine oxidase (MAO) inhibitors or within 14 days of discontinuing MAO inhibitors. Concomitant use can lead to serotonin syndrome, a potentially life-threatening condition.  

Gastrointestinal (GI) Obstruction: buprenorphine/samidorphan should not be used in patients with known or suspected GI obstruction, including paralytic ileus.  

Hepatic Impairment: buprenorphine/samidorphan is contraindicated in patients with severe hepatic impairment, as it may cause increased buprenorphine exposure and result in respiratory depression. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

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: 

buprenorphine/samidorphan is a combination medication used to treat opioid use disorder (OUD) and major depressive disorder (MDD). buprenorphine is a partial agonist at the mu-opioid receptor, while samidorphan is an opioid antagonist. 

Pharmacodynamics: 

The pharmacodynamic mechanism of buprenorphine/samidorphan is that buprenorphine activates the mu-opioid receptor, which helps to alleviate withdrawal symptoms and reduce cravings associated with opioid use disorder. At the same time, it partially activates the receptor, which limits the degree of euphoria and respiratory depression that full opioid agonists can produce. 

MOA:  

The mechanism of action of buprenorphine is complex and involves its interactions with multiple opioid receptors, including mu, delta, and kappa receptors. As a partial agonist at the mu-opioid receptor, buprenorphine produces less of an opioid effect than full agonists like morphine or heroin, but still provides some degree of pain relief and reduces the craving for opioids. At the same time, buprenorphine also acts as an antagonist at the kappa-opioid receptor, which can help to reduce the risk of certain side effects, such as sedation and respiratory depression.  

Pharmacokinetics: 

Absorption:  

buprenorphine/samidorphan is administered orally in the form of tablets. The bioavailability of buprenorphine after oral administration is approximately 30%, while that of samidorphan is approximately 60%. The peak plasma concentrations of buprenorphine and samidorphan are reached within 1-2 hours after oral administration. 

Distribution:  

buprenorphine/samidorphan is extensively bound to plasma proteins, with buprenorphine binding approximately 96% to plasma proteins and samidorphan binding approximately 98% to plasma proteins. The volume of distribution of buprenorphine is approximately 3.7 L/kg, while that of samidorphan is approximately 3.2 L/kg.  

Metabolism:  

buprenorphine is primarily metabolized by the liver via N-dealkylation and glucuronidation. The major metabolites of buprenorphine are norbuprenorphine, buprenorphine-3-glucuronide, and buprenorphine-6-glucuronide. samidorphan is primarily metabolized by the liver via oxidative metabolism, mediated by cytochrome P450 enzymes. The major metabolites of samidorphan are hydroxysamidorphan and N-desmethylsamidorphan.  

Excretion and elimination: 

buprenorphine and its metabolites are excreted in the urine and feces. Approximately 70% of a buprenorphine dose is excreted in the feces, while approximately 30% is excreted in the urine. samidorphan and its metabolites are primarily excreted in the urine, with approximately 60% of a samidorphan dose excreted in the urine and approximately 40% excreted in the feces. The elimination half-life of buprenorphine is approximately 24-60 hours, while that of samidorphan is approximately 15-20 hours. 

Adminstartion

Administration:  

Patient Assessment: Before starting treatment with buprenorphine/samidorphan, the patient’s medical history, current medications, and drug use history should be assessed. Additionally, a physical examination and laboratory tests may be necessary to determine the appropriate dose of buprenorphine/samidorphan.  

Induction: buprenorphine/samidorphan is typically started when the patient is experiencing mild to moderate opioid withdrawal symptoms. The initial dose of buprenorphine/samidorphan may vary depending on the patient’s opioid use history and the severity of their withdrawal symptoms.  

Dosing: buprenorphine/samidorphan is usually administered once a day in the form of a sublingual tablet. The dosage may be adjusted based on the patient’s response to treatment.  

Monitoring: Patients should be closely monitored for any side effects or adverse reactions to buprenorphine/samidorphan. They should also be monitored for signs of opioid withdrawal or relapse. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: buprenorphine/samidorphan 

Why do we use buprenorphine/samidorphan?  

buprenorphine/samidorphan is a medication used to treat adults with moderate-to-severe symptoms of depression that have not responded to other treatments. It is a combination of two drugs: buprenorphine and samidorphan. 

buprenorphine is a partial opioid agonist that helps to reduce cravings and withdrawal symptoms in people who are dependent on opioids. It is also used as a pain reliever.   

samidorphan is an opioid antagonist that works to counteract the effects of buprenorphine, helping to prevent abuse and addiction.  

The combination of buprenorphine and samidorphan is thought to provide a more balanced approach to treating opioid dependence and depression. It can help to reduce cravings and withdrawal symptoms while also improving mood and reducing the risk of abuse and addiction.