buprenorphine buccal

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action: 

• Mu-Opioid Receptor Agonism: buprenorphine is a partial agonist at the mu-opioid receptors in the central nervous system. It binds to these receptors, activating them to produce analgesic effects and alleviate opioid withdrawal symptoms. However, buprenorphine’s partial agonist activity has a ceiling effect, meaning that beyond a specific dose, increasing the dosage does not result in a proportional increase in opioid effects. This property reduces the risk of respiratory depression and overdose associated with full opioid agonists. 
• Kappa-Opioid Receptor Antagonism: buprenorphine also has antagonist activity at the kappa-opioid receptors. By blocking these receptors, buprenorphine may help modulate pain perception and provide additional analgesic effects. 

Spectrum of Activity: 

• Opioid Dependence Treatment: buprenorphine buccal is indicated for treating opioid dependence. It can be used as a maintenance treatment, where it helps reduce cravings, alleviate withdrawal symptoms, and block the effects of other opioids. buprenorphine buccal is often part of a comprehensive treatment program that includes counseling and psychosocial support. 
• Chronic Pain Management: buprenorphine buccal is also utilized to manage chronic pain, particularly in individuals at risk for opioid misuse or abuse. buprenorphine’s unique pharmacological profile, including its partial agonist activity and ceiling effect, allows for analgesic effects while minimizing the risk of respiratory depression and other adverse effects associated with full opioid agonists. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Open-label titration phase 

Nausea, both opioid-naïve and opioid-tolerant (33%) 

Constipation, opioid-naïve (13%) 

Nausea, opioid-naive (50%) 

Nausea, opioid-tolerant (17%) 

Constipation, opioid-naïve and opioid-tolerant (11%)  

1-10% 

Open-label titration phase 

Dizziness (6%) 

Constipation, opioid-tolerant (8%) 

Somnolence (6%) 

Headache (8%) 

Drug withdrawal syndrome: (1%) 

Vomiting (7%)  

Post-marketing reports 

Hepatotoxicity 

Anaphylaxis 

Adrenal insufficiency 

Serotonin syndrome 

Androgen deficiency 

Black Box Warning

Black box warning: 

• The risks associated with opioid analgesics include addiction, abuse, and misuse, which can lead to overdose and death. Healthcare providers should assess each patient’s risk before prescribing opioids and monitor patients regularly for signs of these behaviors or conditions. 
• Life-threatening respiratory depression is another serious risk of opioid analgesics. Healthcare providers should monitor patients, especially during initiation or after a dose increase, for respiratory depression. 
• Accidental exposure to opioids, even in a single dose, can be fatal, especially in children. It is essential to store and dispose of opioid medications correctly to prevent accidental ingestion by others. 
• Prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome in newborns. Healthcare providers should inform pregnant patients about the risk and ensure that appropriate treatment is available. 
• Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, can cause severe sedation, respiratory depression, coma, and death. Healthcare providers should limit prescribing opioids with these substances to patients with inadequate alternative treatment options.  
• Dosages and durations of use should be minimized, and patients should be monitored for signs of respiratory depression and sedation. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: buprenorphine buccal should not be used in individuals with known hypersensitivity or severe allergic reactions to buprenorphine or other ingredients in the medication. 
• Respiratory Depression: buprenorphine buccal is contraindicated in patients with severe respiratory depression, as it can further suppress respiration and potentially lead to life-threatening respiratory depression. 
• Acute or Severe Bronchial Asthma: buprenorphine buccal is contraindicated in individuals with acute or severe bronchial asthma or other respiratory conditions that significantly compromise respiratory function. 
• Paralytic Ileus: The use of buprenorphine buccal is contraindicated in patients with paralytic ileus, a condition where the normal movement of the intestines is absent or impaired. 

Caution: 

• Respiratory depression: buprenorphine buccal can cause respiratory depression, mainly when used in high doses or combination with other respiratory depressants. Caution should be exercised when prescribing buprenorphine buccal to patients with compromised respiratory function, such as those with chronic obstructive pulmonary disease (COPD), asthma, or respiratory insufficiency. 
• Dependency and Withdrawal: buprenorphine is an opioid partial agonist, and its use can lead to physical dependence. Patients should be closely monitored for signs of opioid dependence, and gradual tapering may be necessary when discontinuing treatment to minimize withdrawal symptoms. 
• Hepatic impairment: buprenorphine is metabolized in the liver, and caution should be exercised when prescribing buprenorphine buccal to patients with hepatic impairment. Patients may need dose adjustments to avoid excessive drug accumulation and potential adverse effects. 
• Renal impairment: buprenorphine elimination is not significantly affected by renal function. However, caution should still be exercised when prescribing buprenorphine buccal to patients with severe renal impairment, as this population has limited clinical experience. 
• CNS Depression and Impaired Alertness: buprenorphine buccal can cause sedation and impair mental and physical abilities. Patients should be advised to avoid activities that require mental alertness, such as driving or operating heavy machinery until they know how the medication affects them. 
• Adverse Reactions in Pediatric Patients: buprenorphine buccal is not approved for use in pediatric patients below the age of 18 years. Safety and effectiveness in this population have yet to be established. 

Pregnancy / Lactation

Pregnancy consideration: Opioids, including buprenorphine, can cross the placenta, leading to respiratory depression and psychophysiological effects in neonates. The use of opioids is generally not recommended in women immediately before and during labor. 

Lactation: Excretion of the drug in human breast milk is known. Caution should be exercised when administering opioid therapy to nursing women. 

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: 

buprenorphine binds to and activates mu-opioid receptors in the brain, spinal cord, and other areas of the central nervous system. It acts as a partial agonist, producing opioid effects but with a ceiling effect, limiting its maximal effect even at higher doses. This property reduces the risk of respiratory depression compared to full opioid agonists. 

Pharmacodynamics: 

The pharmacodynamics of buprenorphine buccal: 

• Mu-opioid receptor binding: buprenorphine binds to the mu-opioid receptors in the central nervous system, producing analgesic effects. As a partial agonist, it has a high affinity for the receptor but produces a limited maximal effect compared to full agonists like morphine. This property helps to minimize the risk of respiratory depression and other opioid-related side effects. 
• Analgesic effect: buprenorphine buccal is primarily used to manage moderate to severe pain. Binding to the mu-opioid receptors in the brain and spinal cord reduces pain perception and alters the emotional response to pain. 
• Partial agonist activity: buprenorphine acts as a partial agonist, which means it has both agonist and antagonist properties at the mu-opioid receptor. It produces a ceiling effect, where increasing the dose beyond a certain point does not result in additional analgesia. This property reduces the risk of overdose and abuse potential. 
• Receptor modulation: buprenorphine can displace other full opioid agonists from the mu-opioid receptors and occupy them for an extended period. This characteristic is known as receptor binding affinity and allows buprenorphine to block the effects of other opioids, such as heroin or oxycodone. It is used in medication-assisted treatment (MAT) for opioid dependence to reduce cravings and withdrawal symptoms. 
• Respiratory depression: Although buprenorphine has a reduced risk of respiratory depression compared to full agonists, it can still cause respiratory depression, especially at higher doses.  

Pharmacokinetics: 

Absorption 

When administered via the buccal route, buprenorphine is absorbed through the mucous membranes of the oral cavity. It undergoes rapid absorption, with a portion of the drug entering the bloodstream through the oral mucosa. The buccal route provides a relatively high bioavailability for buprenorphine. 

Distribution 

buprenorphine is extensively distributed throughout the body. It has a high lipid solubility, allowing it to cross the blood-brain barrier and distribute into various tissues, including the central nervous system. Buprenorphine binds extensively to plasma proteins, primarily to albumin. 

Metabolism 

buprenorphine is extensively metabolized in the liver primarily through hepatic metabolism. The main metabolic pathway is N-dealkylation, catalyzed by the cytochrome P450 enzyme system, particularly CYP3A4. The major metabolite formed is norbuprenorphine, which has partial agonist activity at the mu-opioid receptor. 

Elimination and Excretion 

The metabolites of buprenorphine, including norbuprenorphine, are primarily eliminated through urine and, to a lesser extent, through feces. Only a tiny fraction of the parent drug is excreted unchanged. The elimination half-life of buprenorphine is variable and can range from 20 to 73 hours, depending on individual factors and dosing. 

Adminstartion

Administration: 

buprenorphine buccal is a formulation of buprenorphine designed for administration through the buccal mucosa, which refers to the area inside the cheek. Here’s a general overview of the administration of buprenorphine buccal: 

• Preparation: Before administering buprenorphine buccal, it’s important to ensure the hands are clean and dry. The medication package should be checked for any signs of damage or tampering. 
• Placement: The buprenorphine buccal film or tablet is placed inside the mouth against the cheek or between the cheek and gum. The medication should be positioned so that it adheres to the mucous membrane. It’s essential to avoid chewing, swallowing, or cutting the film or tablet, as it may affect the drug’s intended absorption. 
• Adherence: The buccal film or tablet should be held in place until it fully dissolves or disintegrates. This process may take a few minutes, and avoiding eating or drinking during this time is important to ensure proper absorption. 
• Avoidance of excessive saliva: Excessive saliva production or swallowing may reduce the effectiveness of buprenorphine buccal. To minimize these effects, avoiding talking, chewing gum, or smoking while the medication is in the mouth is recommended. 
• Disposal: After the film or tablet has completely dissolved or disintegrated, any remaining residue can be swallowed or rinsed away with water.

Patient Information Leaflet

Patient information leaflet 

Generic Name: buprenorphine buccal 

Why do we use buprenorphine buccal? 

buprenorphine buccal is primarily used for the management of moderate to severe pain. It is a formulation of buprenorphine designed to be administered through the buccal mucosa (inside the cheek).  

• Pain management: buprenorphine buccal is indicated for treating moderate to severe pain in patients who require around-the-clock opioid analgesia for an extended period. It is typically used when other non-opioid analgesics are inadequate or not tolerated. 
• Chronic pain: buprenorphine buccal may be used in patients with chronic pain conditions, such as cancer or chronic non-cancer pain, where long-term opioid therapy is necessary. 
• Opioid dependence treatment: Besides its analgesic properties, buprenorphine is also used in medication-assisted treatment (MAT) programs for opioid dependence. However, it’s important to note that buprenorphine buccal is not explicitly indicated for this purpose. Instead, buprenorphine for opioid dependence treatment is typically administered through other formulations, such as sublingual tablets or implants.