Action and Spectrum

Mechanism of action

buprenorphine is a partial opioid agonist, which means it activates the same receptors in the brain as full opioid agonists (such as heroin or morphine), but to a lesser extent. This results in a milder form of pain relief and a lower potential for overdose than full opioid agonists

naloxone is an opioid antagonist, which means it blocks the effects of opioids. It is combined with buprenorphine to counteract potential misuse or abuse of the medication. It is formulated so that it is not active when taken as directed (sublingually or buccally). However, if the medication is crushed and then injected, the naloxone will counteract the effects of buprenorphine, making it less appealing for abuse

Combining buprenorphine and naloxone (such as Suboxone) treats opioid dependence. buprenorphine provides a mild form of pain relief that can help manage withdrawal symptoms and cravings, while naloxone serves as a deterrent to misuse or abuse

Spectrum

The spectrum of activity of buprenorphine and naloxone covers the management of opioid dependence and the treatment of opioid withdrawal symptoms

Drug Interaction

Adverse Reaction

Frequency defined:

>10%

Withdrawal symptoms (24-25.2%)

Pain (22.4%)

Hyperhidrosis (14%)

Constipation (5-12.1%)

Headache (28-36.4%)

Insomnia (14-23%)

Nausea (7-15%)

Asthenia (6.5-14%)

Abdominal pain (11.2%)

1-10%

Peripheral edema (9.3%)

Vomiting (4-7.5%)

Diarrhea (10%)

Chills (6-7.5%)

Post marketing reports

Anaphylaxis

Hepatotoxicity

Glossitis

Oral hypoesthesia stomatitis

Adrenal insufficiency

Serotonin syndrome

Glossodynia

Black Box Warning

Contraindication / Caution

Contraindications

• buprenorphine and naloxone are contraindicated in individuals with severe respiratory depression, acute or severe bronchial asthma, or hypercapnia
• buprenorphine and naloxone are contraindicated in individuals with moderate or severe hepatic impairment, as the metabolism and elimination of the drug may be altered
• buprenorphine and naloxone are contraindicated in individuals with head injury or increased intracranial pressure
• buprenorphine is contraindicated in individuals with a history of alcohol or drug abuse unless it is part of a comprehensive treatment program

Caution

• Respiratory depression: It can cause respiratory depression, particularly in high doses or in individuals who are not tolerant to opioids.
• Hepatic or renal impairment: It should be used with caution in individuals with liver or kidney disease, as the metabolism and elimination of the drug may be altered.
• Substance abuse should be used with caution in individuals with a history of substance abuse, as there is a risk of abuse or dependence.
• Pregnancy and breast-feeding: It should be used with caution during pregnancy and breastfeeding, as the effects of the drug on the developing fetus or nursing infant are not well known
• Concurrent use of other central nervous systems (CNS) depressants: It should be used with caution in individuals taking other CNS depressants, as the combined effects may lead to excessive sedation or respiratory depression

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 available 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 buprenorphine and naloxone involves the actions of these drugs at the mu, delta, and kappa opioid receptors in the central nervous system (CNS) and their effects on various physiological and behavioral processes

Pharmacodynamics

buprenorphine is a semisynthetic opioid that acts as a mixed agonist-antagonist at mu and delta opioid receptors in the central nervous system (CNS). This means that it partially activates the receptors, producing some of the effects of an opioid agonist, but also partially blocks the receptors, producing some of the effects of an opioid antagonist. It has a high affinity for the mu opioid receptors and low efficacy, meaning that it binds strongly to the receptors but has a limited ability to activate them. This results in a ceiling effect, where the effects of buprenorphine level off at higher doses, reducing the risk of respiratory depression and overdose

naloxone, on the other hand, is a potent opioid antagonist that acts specifically at mu opioid receptors. It blocks the effects of opioids by binding to the receptors and preventing them from being activated. When administered parenterally, naloxone rapidly reverses the effects of full opioid agonists, producing opioid withdrawal signs and symptoms in individuals who are physically dependent on these drugs. This is why naloxone is often used with buprenorphine to treat opioid dependence, counteract the effects of other opioids, and reduce the risk of abuse or overdose

Pharmacokinetics

Absorption:

Suboxone, Zubsolv, and Bunavail are all formulations of buprenorphine and naloxone and are taken orally. The bioavailability of these formulations may differ, with Zubsolv providing equivalent buprenorphine exposure to Suboxone 8/2 mg but with 12% lower naloxone exposure and Bunavail providing equivalent buprenorphine exposure to Suboxone 8/2 mg but with 33% lower naloxone exposure. The coadministration of liquids can reduce the systemic exposure of both buprenorphine and naloxone, with the extent of reduction depending on the pH of the liquid

Half-life:

The half-life of buprenorphine in Suboxone is 24-42 hours, while the half-life of naloxone is 2-12 hours. The half-life of buprenorphine in Zubsolv and Bunavail is similarly in the range of 24-42 hours and 16.4-27.5 hours, respectively, while the half-life of naloxone is 2-12 hours and 1.9-2.4 hours, respectively

Distribution

buprenorphine and naloxone are protein-bound, with buprenorphine primarily bound to alpha and beta globulin (96%) and naloxone primarily bound to albumin (45%)

Metabolism

N-dealkylation metabolizes Buprenorphine via CYP3A4 to norbuprenorphine (active metabolite) and glucuronidation. Naloxone is metabolized by direct glucuronidation to naloxone-3-glucuronide, as well as by N-dealkylation and reduction of the 6-oxo group

Elimination/Excretion

buprenorphine is excreted in the urine (30%) and feces (69%)

Adminstartion

Administration

• buprenorphine and naloxone are administered as part of a combination product, such as Suboxone, Zubsolv, or Bunavail
• Suboxone and Zubsolv are sublingual (under the tongue) films that dissolve slowly and are meant to be absorbed through the mucous membranes in the mouth
• Bunavail is a buccal (in the cheek) film that adheres to the inside of the cheek and is also meant to be absorbed through the mucous membranes in the mouth
• It is essential to follow the instructions for use provided by the manufacturer and to avoid consuming food or drink immediately before or after taking the product
• It is also essential to store these products in a safe place, as they can be abused and have a high potential for overdose if taken in more significant amounts than prescribed

Patient Information Leaflet

Patient information leaflet

Generic Name: buprenorphine and naloxone

Pronounced:[BUE-pre-NOR-feen-and-nal-OX-one ]

Why do we use buprenorphine and naloxone?

buprenorphine and naloxone are used for the treatment of opioid dependence or addiction. buprenorphine is a partial opioid agonist that provides pain relief and reduces cravings and withdrawal symptoms in individuals addicted to opioids. naloxone, on the other hand, is an opioid antagonist that helps to prevent the abuse of buprenorphine by reversing the effects of the drug if it is injected or misused