Buprenorphine/naloxone, sold under the brand name Suboxone among others, is a fixed-dose
combination medication
A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...
that includes
buprenorphine
Buprenorphine, sold under the brand name Subutex among others, is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous a ...
and
naloxone
Naloxone, sold under the brand name Narcan among others, is an opioid antagonist, a medication used to reverse or reduce the effects of opioids. For example, it is used to restore breathing after an opioid overdose. Effects begin within two ...
.
It is used to treat
opioid use disorder
Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. ...
, and reduces the mortality of opioid use disorder by 50% (by reducing the risk of overdose on
full-agonist opioids such as
heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...
or
fentanyl
Fentanyl is a highly potent synthetic piperidine opioid primarily used as an analgesic (pain medication). It is 30 to 50 times more Potency (pharmacology), potent than heroin and 50 to 100 times more potent than morphine. Its primary Medici ...
).
It relieves cravings to use and withdrawal symptoms.
Buprenorphine/naloxone is available for use in two different forms,
under the tongue or
in the cheek.
Side effects may include respiratory depression (decreased breathing),
small pupils, sleepiness, and
low blood pressure
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
.
The risk of
overdose
A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014. with buprenorphine/naloxone (unless combined with other sedating substances) is exceedingly low, and lower than with
methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid used medically to treat chronic pain and opioid use disorder. Prescribed for daily use, the medicine relieves cravings and opioid withdrawal sym ...
,
[ but people are more likely to stop treatment on buprenorphine/naloxone than methadone.][ Buprenorphine (like methadone) is a treatment option during pregnancy.
At lower doses, buprenorphine results in the usual ]opioid
Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
effects; high doses beyond a certain level do not result in greater effects.[ This is believed to result in a lower risk of overdose than some other opioids.] Naloxone is an opioid antagonist
An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors.
Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to ...
that competes with and blocks the effect of other opioids (including buprenorphine) if given by injection. Naloxone is poorly absorbed when taken by mouth and is added to decrease the risk that people will misuse the medication by injection.[ Misuse by injection or use in the nose still occurs, and more recently the efficacy of naloxone in preventing misuse by injection has been brought into question and preparations including naloxone could even be less safe than preparations containing solely buprenorphine.] Rates of misuse in the U.S. appear to be lower than with other opioids.
The combination formulation was approved for medical use in the U.S. in 2002,[ and in the European Union in 2017.] A generic version was approved in the U.S. in 2018. In 2019, it was the 272nd most commonly prescribed medication in the U.S., with more than 1million prescriptions.
Medical uses
Buprenorphine/naloxone is used for the treatment of opioid use disorder
Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. ...
. Long-term outcomes are generally better with use of buprenorphine/naloxone than attempts at stopping opioid use altogether. This includes a lower risk of overdose with medication use. Due to the high binding affinity and low activation at the opioid receptor, cravings and withdrawal for opioids are decreased while preventing a person from getting high and relapsing on another opioid. The combination of the two medications is preferred over buprenorphine alone for maintenance treatment due to the presence of naloxone in the formulation, which is believed to help discourage intravenous use.[ However, the belief that the addition of naloxone provides this benefit has been called into question, and posters on drug-related online forums have stated that they were able to attain a high by injecting preparations of buprenorphine despite being combined with naloxone.]
Buprenorphine/naloxone is effective for treating opioid dependence and serves as a recommended first-line medication according to the U.S. National Institute on Drug Abuse
The National Institute on Drug Abuse (NIDA) is a United States federal government research institute whose mission is to "advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual ...
.[ The medication is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone. Both buprenorphine/naloxone and are substantially more effective than abstinence-based treatment.] As of October 2023 prescribers no longer need a Drug Addiction Treatment Act (DATA 2000) waiver to prescribe buprenorphine/naloxone for opioid dependence
Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. ...
. All practitioners who have a current DEA registration that includes Schedule III authority, may now prescribe buprenorphine for opioid use disorder in their practice if permitted by applicable state law. The Substance Abuse and Mental Health Services Administration
The Substance Abuse and Mental Health Services Administration (SAMHSA; pronounced ) is a branch of the U.S. Department of Health and Human Services (HHS). SAMHSA is charged with improving the quality and availability of treatment and rehabilitati ...
encourages practitioners to treat patients within their practices who require treatment for a substance use disorder. Because it may now be prescribed much more readily out of an office setting (as opposed to methadone, which requires specialized centers), buprenorphine/naloxone allows people more access to this medication and more freedom of administration. It also thus comes with more risks in this vulnerable population. Buprenorphine/naloxone may be recommended for socially stable people who use opioids who cannot retrieve medications from a center daily, who have another condition requiring regular primary care visits, or who have jobs or daily lives that require they maintain all their faculties and cannot take a sedating medication. Buprenorphine/naloxone is also recommended over methadone for people at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepine
Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...
s or other sedating substances, concomitant alcohol use disorder
Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World Hea ...
, those with a lower level of opioid tolerance, and those at high risk of prolonged QT interval
Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a Cardiac cycle, heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an cardiac arrhythmia, irregular heartb ...
. It is also helpful to use the medication in combination with psychosocial
The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is ...
support and counseling.
Available forms
Buprenorphine/naloxone is available in sublingual formulations (that is, products that are dissolved under the tongue). There is no evidence that the tablet formulation is easier to divert and use in ways other than intended by the prescriber compared to the film formulation, or that the tablet formulation has a higher risk for accidental ingestion by children. There are various pharmacokinetic
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...
differences between sublingual formulations.
Contraindications
Contraindications are severe respiratory
The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gr ...
or liver impairment
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Liver diseases
File:Ground glas ...
and acute alcoholism
Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...
. There are limited accounts of cross-reactivity with opioids, but there is a possibility. Serious central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
(CNS) and respiratory depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...
may also occur with concurrent use of CNS depressants
Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various area ...
, ingesting alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
, or other CNS-depressing factors while on buprenorphine/naloxone.
Adverse effects
Side effects are similar to those of buprenorphine and other opioids. In addition, naloxone can induce withdrawal symptoms in people who are chemically dependent on opioids. The most common side effects (in order of most to least common) of sublingual tablets include headache
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
s, opioid withdrawal
Opioid withdrawal is a set of symptoms arising from the sudden cessation or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs syndrome, naus ...
syndrome, pain, nausea, increased sweating, and difficulty sleeping
Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
. The most common side effects seen in film formulations are tongue pain, decreased sensation and redness in the mouth, headache, nausea, vomiting, excessive sweating
Hyperhidrosis is a medical condition in which a person exhibits excessive sweating, more than is required for the regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deteriorate the quality of life of the ...
, constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
, signs and symptoms of opioid withdrawal, sleeping difficulties, pain, and swelling of the extremities. Post-approval, the most frequently reported side effects of buprenorphine/naloxone in sublingual strip form (i.e. Suboxone strips) are peripheral edema
Peripheral edema is edema (accumulation of fluid causing swelling) in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body (those hanging distally), it may be called dependent ede ...
, stomatitis
Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration.
In its widest meaning, stomatitis can have a multitude of different c ...
, glossitis
Glossitis can mean soreness of the tongue, or more usually inflammation with depapillation of the dorsal surface of the tongue (loss of the lingual papillae), leaving a smooth and erythematous (reddened) surface, (sometimes specifically termed atro ...
, blistering of the mouth, and mouth ulcer
A mouth ulcer (aphtha), or sometimes called a canker sore or salt blister, is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanis ...
s (mouth sores). Use of buprenorphine/naloxone may also increase the risk of developing certain dental problems (including tooth decay
Tooth decay, also known as caries,The word 'caries' is a mass noun, and is not a plural of 'carie'.'' is the breakdown of teeth due to acids produced by bacteria. The resulting cavities may be a number of different colors, from yellow to black ...
and tooth loss).
Buprenorphine/naloxone has a milder side effect profile than methadone and limited respiratory effects, due to both agonist/antagonist effects. But buprenorphine/naloxone may be less safe than methadone in people with stable liver disease since it can elevate liver enzymes.
Dependence and withdrawal
When taken in excess, buprenorphine/naloxone can produce dysphoric symptoms for non-opioid-dependent/tolerant people because buprenorphine is a partial opioid agonist. The sublingual formulation of the buprenorphine/naloxone combination was designed to reduce the potential to inject the medication in comparison to buprenorphine alone. If the combination is taken sublingually, as directed, the addition of naloxone does not diminish buprenorphine's effects. When an opioid-dependent person dissolves and injects a combination sublingual tablet, it is believed that a withdrawal effect may be triggered because of naloxone's high parenteral bioavailability. However, the efficacy of naloxone in preventing misuse by injection has more recently been brought into question and preparations including naloxone could even be less safe than preparations containing solely buprenorphine. While this mechanism may act to deter intravenous injection, the Suboxone formulation can still produce an opioid agonist "high" if used sublingually by non-dependent persons, leading to opioid dependence.[Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction](_blank)
Treatment Improvement Protocol (TIP) 40. Laura McNicholas. US Department of Health and Human Services.
Interactions
Buprenorphine's sedating/narcotic effect is increased by other sedating substances, such as other opioids, benzodiazepines, first-generation antihistamines
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides r ...
, alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
, and antipsychotic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
s. Opioids and especially benzodiazepines also increase the risk of potentially lethal respiratory depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...
.
Strong inhibitors of the liver enzyme CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
, such as ketoconazole
Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...
, moderately increase buprenorphine concentrations; CYP3A4 inducers can theoretically decrease concentrations of buprenorphine.
Pharmacology
Mechanism of action
Buprenorphine binds strongly to opioid receptor
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostati ...
s and acts as a pain-reducing medication in the central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
(CNS). It binds to the μ-opioid receptor
The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical ...
with high affinity, which produces analgesic effects in the CNS. It is a partial μ-opioid receptor agonist and a weak κ-opioid receptor
The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP for its ligand ketazocine, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four re ...
antagonist. As a partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...
, buprenorphine binds and activates the opioid receptors, but has only partial efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...
at the receptor relative to a full agonist, even at maximal receptor occupancy. It is thus well-suited to treat opioid dependence, as it produces milder effects on the opioid receptor with lower dependence and habit-forming potential.
Naloxone is a pure opioid antagonist that competes with opioid molecules in the CNS and prevents them from binding to the opioid receptors. Naloxone's binding affinity
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usuall ...
is highest for the μ-opioid receptor, then the δ-opioid receptor
The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi alpha subunit, Gi/G0 and has enkephalins as it ...
, and lowest for the κ-opioid receptor. Naloxone has poor bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
, and is rapidly inactivated following oral administration. When injected, it exerts its full effects.
The principle behind its function as a deterrent is as follows: when taken sublingually as prescribed, buprenorphine's effects at the opioid receptor dominate, while naloxone's effects are negligible due to the low oral absorption. But when someone attempts to misuse the medication via either injection or inhalation, the naloxone is intended to act as an antagonist and either reduce the opioid's euphoric effects or even precipitate withdrawal in those dependent on opioids. This helps reduce the potential for deviating from the prescriber's intended use relative to buprenorphine, though it does not eradicate it. One reason that naloxone might have limited efficacy as an abuse-deterrent is that buprenorphine binds more tightly to the mu-opioid receptor than naloxone.
Pharmacokinetics
There are small differences in the pharmacokinetics between different sublingual buprenorphine/naloxone products. These differences may require changes in dose when a person switches from one product to another. The buprenorphine/naloxone sublingual film (e.g. trade name Suboxone) achieves higher buprenorphine maximum plasma concentrations (Cmax) and area under the curve
In mathematics, an integral is the continuous analog of a sum, which is used to calculate areas, volumes, and their generalizations. Integration, the process of computing an integral, is one of the two fundamental operations of calculus,Inte ...
(AUC, a measure of total drug exposure) than the original buprenorphine/naloxone sublingual tablets at equal doses. For example, at a buprenorphine/naloxone dose of 8 mg/2 mg, the buprenorphine Cmax after a single dose of the original tablet formulation is around 3 ng/mL whereas that of the 8 mg/2 mg film formulation is around 3.55 ng/mL. The Zubsolv trade name sublingual tablets have higher buprenorphine bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
than the original sublingual tablets, while the Bunavail trade name buccal films have the highest bioavailability. For example, a single dose of Bunavail 4.2 mg/0.7 mg achieves a Cmax around 3.41 ng/mL.
Buprenorphine
Buprenorphine is metabolized
Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
by the liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
, primarily via the cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
(CYP) isozyme
In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. di ...
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
, into norbuprenorphine
Norbuprenorphine is a major active metabolite of the opioid modulator buprenorphine. It is a μ-opioid, δ-opioid, and nociceptin receptor full agonist, and a κ-opioid receptor partial agonist. In rats, unlike buprenorphine, norbuprenorphin ...
. The glucuronidation
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...
of buprenorphine is primarily carried out by the UDP-glucuronosyltransferases (UGTs) UGT1A1
UDP-glucuronosyltransferase 1-1, also known as UGT-1A, is an enzyme that in humans is encoded by the ''UGT1A1'' gene.
UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT or UGT), an enzyme of the glucuroni ...
and UGT2B7
UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltran ...
, while norbuprenorphine is glucuronidated by UGT1A1
UDP-glucuronosyltransferase 1-1, also known as UGT-1A, is an enzyme that in humans is encoded by the ''UGT1A1'' gene.
UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT or UGT), an enzyme of the glucuroni ...
and UGT1A3
UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the ''UGT1A3'' gene.
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, ...
. These glucuronides are then eliminated mainly through excretion
Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...
into bile
Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
. The elimination half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...
of buprenorphine is 20 to 73 hours (mean 37 hours). Due to the mainly hepatic elimination, there is no risk of accumulation in people with kidney problems
Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
.
Naloxone
Naloxone is extensively inactivated by first-pass metabolism
The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...
in the liver, meaning that the use of buprenorphine/naloxone as prescribed should not lead to active naloxone in the blood (which, as an opioid antagonist, would reverse the effect of buprenorphine or other opioids).
Society and culture
Cost
While the cost of the medication buprenorphine/naloxone is greater than buprenorphine alone, one analysis predicted the overall costs would be less in the United States due to a lower risk of misuse.
Access in the United States
Before the Drug Addiction Treatment Act of 2000 (DATA), physicians were not allowed to prescribe narcotics to treat opioid dependence. People with narcotic dependence had to go to registered clinics to receive treatment. With DATA, Suboxone was the first medication approved for office-based treatment for opioid dependence.[ Suboxone has thus become widely used as a replacement for methadone as it can be prescribed by doctors in their offices, while methadone can only be provided at specialized addiction centers, of which there are a limited number, often making access difficult. Integrating Medication-Assisted Treatment into outpatient primary care practices improves patient access to Suboxone. Some physicians are also leading a movement to begin prescribing it out of the ]emergency department
An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the Acute (medicine), ...
(ED), as some small studies have shown ED-initiated Suboxone to be effective with people more likely to remain in addiction treatment compared to those either referred to addiction treatment programs or those receiving just a brief intervention in the department.
Access to Suboxone can be limited due to varying prior authorization
Prior authorization, or preauthorization, is a utilization management process used by some health insurance companies in the United States to determine if they will cover a prescribed procedure, service, or medication.
Overview
Prior authorisa ...
requirements across different insurer
Insurance is a means of protection from financial loss in which, in exchange for a fee, a party agrees to compensate another party in the event of a certain loss, damage, or injury. It is a form of risk management, primarily used to protect ...
s. Prior authorization is used by insurance companies to limit certain medications' use by requiring approval before the insurance company will pay for them. This can influence a person's financial access and adherence. Financial access is determined through prior authorization approval, which the prescriber must request before the person can start the medication. The time it takes to have the request approved can delay the person starting the medication. The prior authorization process can also affect adherence because approval is needed for every prescription. This presents the potential for a gap in treatment and withdrawal symptoms as the person waits for approval. Several insurance companies, as well as Medicaid
Medicaid is a government program in the United States that provides health insurance for adults and children with limited income and resources. The program is partially funded and primarily managed by U.S. state, state governments, which also h ...
in various states, have removed the use of prior authorization for Suboxone in an attempt to increase access to this treatment.
Controversies
In July 2019, the British company Reckitt Benckiser Group (RB Group) and its current/former affiliated entities (notably Indivior, which split from RB Group in 2014) settled with the US Department of Justice
The United States Department of Justice (DOJ), also known as the Justice Department, is a federal executive department of the U.S. government that oversees the domestic enforcement of federal laws and the administration of justice. It is equ ...
(DOJ) regarding the sale and marketing of brand name Suboxone (buprenorphine/naloxone). The non-prosecution agreement involves RB Group paying up to $1.4 billion, the largest settlement payment in U.S. history involving an opioid-class medication. This record was surpassed in October 2020, when Purdue Pharma reached an $8 billion settlement for claims related to injuries and deaths caused by the opioid epidemic, which includes criminal fines, forfeiture, and civil damages. The 2019 case alleged anti-competitive
Anti-competitive practices are business or government practices that prevent or reduce competition in a market. Antitrust laws ensure businesses do not engage in competitive practices that harm other, usually smaller, businesses or consumers. ...
behavior by RB Group and Indivior surrounding the expiration of their regulatory exclusivity for Suboxone sublingual tablets. The DOJ alleged that RB Group and Indivior employed a product hopping scheme (when a firm ceases production of a product upon expiration of regulatory exclusivity in favor of another product that still has regulatory exclusivity in order to prevent generic manufacturer competition) by misrepresenting that the Suboxone sublingual film formulation was safer than the sublingual tablet formulation because "children are less likely to be accidentally exposed to the film product". There was no scientific evidence for that claim. The company also sponsored a complaint to the FDA, expressing concern that buprenorphine/naloxone sublingual tablets (the very product they formerly produced) were unsafe, requesting that applications for regulatory approval of generic products by other pharmaceutical companies (their competitors) be rejected by the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
.
References
{{DEFAULTSORT:Buprenorphine Naloxone
Combination drugs
Drug rehabilitation
4,5-Epoxymorphinans
Kappa-opioid receptor antagonists
Drugs developed by Merck & Co.
Mu-opioid receptor agonists
Mu-opioid receptor antagonists
Oripavines
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Drugs developed by Schering-Plough
Semisynthetic opioids
Orphan drugs