Buprenorphine/naloxone, sold under the brand name Suboxone among others, is a combination medication that includes buprenorphine and naloxone. It is used to treat opioid use disorder together with counselling. It decreases withdrawal symptoms for about 24 hours. Buprenorphine/naloxone is available for use under the tongue or in the cheek.
Side effects may include respiratory depression (decreased breathing), small pupils, sleepiness, and low blood pressure. Risk of overdose is less with buprenorphine/naloxone than with methadone, however, people are more likely to stop treatment on buprenorphine/naloxone than methadone. Methadone is generally preferred when treatment is required during pregnancy.
Buprenorphine, at lower doses, results in the usual opioid effects, however, 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 a opioid antagonist that competes with and blocks the effect of other opioids if given by injection.
The combination was approved for medical use in the United States in 2002. The addition of naloxone is to decrease the risk that people will misuse the medication by injection. Misuse by injection or in the nose, however, still occurs. Rates of misuse in the United States appear to be lower than with other opioids. In the United States the wholesale cost as of 2017 is between 2.32 and 3.15 USD per day. In the United Kingdom a similar dose costs the NHS 0.90 to 2.72 pounds per day in 2015.
Video Buprenorphine/naloxone
Medical uses
Buprenorphine/naloxone is used for the treatment of opioid use disorder. Long term outcomes are generally better with use of buprenorphine/naloxone than attempts at stopping all opioid use. 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 patient from getting high and relapsing on another opioid. The combination of the two drugs is the preferred medication over buprenorphine alone for maintenance treatment due to the presence of naloxone in the formulation, which helps function as an abuse deterrent, especially against intravenous use.
Buprenorphine/naloxone has been found to be effective for treating opioid dependence, and serves as a recommended first line medication according to the U.S. National Institute on Drug Abuse. The medication is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, which are both substantially more effective than abstinence-based treatment.
Because it may be prescribed out of an office setting (as opposed to methadone which requires specialized centers), buprenorphine/naloxone allows for more freedom of patient administration, but thus also comes with more risks in this vulnerable population. Buprenorphine/naloxone may be recommended for socially stable opioid users who may not be able to retrieve medications from a center daily, if they have another condition requiring regular primary care visits, or if their jobs or daily lives require they maintain all their faculties and cannot take a sedating medication. Buprenorphine/naloxone is also recommended over methadone in people who may be at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepines or other sedating drugs, concomitant alcohol abusers, those with a lower level of opioid tolerance, and those at high risk of prolonged QT interval. It is also helpful to use the medication in combination with psychosocial support and counseling for the patient.
Maps Buprenorphine/naloxone
Contraindications
Contraindications are severe respiratory or liver impairment and acute alcoholism. There are limited accounts of cross-reactivity with opioids, but there is a possibility. Serious CNS and respiratory depression may also occur with concurrent use of CNS depressants, ingesting alcohol, or other CNS depressing factors while on buprenorphine/naloxone.
Adverse effects
Side effects are basically the same as those of buprenorphine and other opioids. In addition, naloxone can induce withdrawal symptoms in people who are addicted to opioids. The most common side effects (in order of most common to least common) of sublingual tablets include: headaches, withdrawal syndrome, pain, increased perspiration, vasodilation, and vomiting. The most common side effects seen in film formulations are glossodynia, oral hypoesthesia, oral mucosa erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.
Buprenorphine/naloxone has a milder side effect profile than methadone, and has limited respiratory effects, due to both agonist/antagonist effects. However, buprenorphine/naloxone may be less safe than methadone in patients with stable liver disease, since it can elevate liver enzymes.
Dependence and withdrawal
Buprenorphine/naloxone, when taken in excess, can produce dysphoric symptoms for non opioid-dependent/tolerant individuals due to buprenorphine being a partial opioid agonist. The sublingual formulation of the buprenorphine/naloxone combination was designed to reduce abuse potential via the injection route in comparison to buprenorphine alone. If the combination is taken via the sublingual route, as directed, the addition of naloxone does not diminish the effects of buprenorphine. When the combination sublingual tablet is dissolved and injected by opioid-dependent individuals, a withdrawal effect may be triggered due to the high parenteral bioavailability of naloxone. While this mechanism can potentially act to deter abuse, the Suboxone formulation still has potential to produce an opioid agonist "high" if abused sublingually by non-dependent persons, leading to dependence on opioids.
Interactions
The sedating/narcotic effect of buprenorphine is increased by other sedating drugs such as other opioids, benzodiazepines, first generation antihistamines, alcohol, and antipsychotics. In addition, opioids and especially benzodiazepines increase the risk for potentially lethal respiratory depression.
Strong inhibitors of the liver enzyme CYP3A4, such as ketoconazole, moderately increase buprenorphine concentrations; CYP3A4 inducers can theoretically decrease concentrations of buprenorphine.
Pharmacology
Mechanism of action
Buprenorphine binds to the ?-opioid receptor with high affinity and produces analgesic effects in the central nervous system (CNS). It is a partial ? agonist and it is a weak ?-opioid receptor antagonist. As the dose of buprenorphine increases, its analgesic effects reach a plateau, and then it starts to act like an antagonist. As a partial agonist, buprenorphine binds and activates the opioid receptors, but has only partial efficacy at the receptor relative to a full agonist, even at maximal receptor occupancy. It is thus well-suited to treat opiate dependence, as it produces milder effects on the opioid receptor with lower dependence and abuse 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 is highest for the ?-opioid receptor, then the ?-opioid receptor, and lowest for the ?-opioid receptor. Naloxone has rather poor bioavailability, and is rapidly inactivated following oral administration.
Because of the differing bioavailability between the two drugs in this combination, buprenorphine/naloxone works as an abuse deterrent: when taken sublingually as prescribed, the buprenorphine effects at the opioid receptor dominate, while the naloxone effects are negligible due to the low oral absorption. However, when someone attempts to misuse the drug either via injection or inhalation, the naloxone is able to act as an antagonist and either block the euphoric effects of the opioid or even precipitate withdrawal in those currently dependent on opioids. This has the overall effect of helping to reduce the abuse potential of buprenorphine/naloxone.
Society and culture
Access in the United States
Before the Drug Addiction Treatment Act of 2000 (DATA), physicians weren't allowed to prescribe narcotics to treat opioid dependence. People with narcotic dependence would have 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.
Access to Suboxone can be limited due to varying prior authorization requirements across different insurers. Prior authorization is used by insurance companies to limit the use of certain medications by requiring approval before the insurance company will pay for the drug. This can influence patient financial access and adherence. Financial access is determined through prior authorization approval, which the prescriber must request before the patient can start the drug. The time it takes to have the request approved can delay the patient in starting the medication. The prior authorization process can also impact adherence, because the approval is needed for every prescription or every couple months. This presents the potential for a gap in treatment and withdrawal symptoms as the patient waits for approval. Several insurance companies, as well as Medicaid in various states, have removed the use of prior authorization for Suboxone in the attempt to increase access to this treatment.
See also
- Methadone
- Buprenorphine/samidorphan
- Buprenorphine/naltrexone
References
Source of the article : Wikipedia
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