Buprenorphine and naloxone: uses, appearance and warnings

Buprenorphine and Naloxone Sublingual Tablets are indicated for the maintenance treatment of opioid dependence. Buprenorphine and Naloxone Sublingual Tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. Buprenorphine and Naloxone Sublingual Tablets contain buprenorphine, a partial opioid agonist, and naloxone, an opioid antagonist, and are indicated for the maintenance treatment of opioid dependence. ( 1 ) Buprenorphine and Naloxone Sublingual Tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support. ( 1 )

Buprenorphine and Naloxone Sublingual Tablets, USP are supplied as speckled-peach to peach, flat faced beveled edge tablets in two dosage strengths: • Buprenorphine 2 mg / naloxone 0.5 mg • Buprenorphine 8 mg / naloxone 2 mg Sublingual Tablet: • Buprenorphine 2 mg / naloxone 0.5 mg and • Buprenorphine 8 mg / naloxone 2 mg ( 3 )

Buprenorphine and Naloxone Sublingual Tablets, USP 2 mg/0.5 mg are supplied as speckled-peach to peach, flat faced beveled edge tablets with product identification “54” [above] “122” on one side and plain on the other. NDC 0054-0188-13: Bottle of 30 Tablets 8 mg/2 mg are supplied as speckled-peach to peach, flat faced beveled edge tablets with product identification “54” [above] “375” on one side and plain on the other. NDC 0054-0189-13: Bottle of 30 Tablets Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in USP. Store Buprenorphine and Naloxone Sublingual Tablets securely and dispose of properly [see Patient Counseling Information ( 17 )] .

Buprenorphine and Naloxone Sublingual Tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported [see Warnings and Precautions ( 5.9 )]. Hypersensitivity to buprenorphine or naloxone. ( 4 )

• Addiction, Abuse, and Misuse : Buprenorphine can be abused in a similar manner to other opioids. Clinical monitoring appropriate to the patient’s level of stability is essential. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. ( 5.1 ) • Respiratory Depression : Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential danger of self-administration of benzodiazepine or other CNS depressants while under treatment with Buprenorphine and Naloxone Sublingual Tablets. ( 5.2 , 5.3 ) • Unintentional Pediatric Exposure : Store Buprenorphine and Naloxone Sublingual Tablets safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children. ( 5.4 ) • Neonatal Opioid Withdrawal Syndrome : Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy. ( 5.5 ) • Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.6 ) • Risk of Opioid Withdrawal with Abrupt Discontinuation : If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately. ( 5.7 ) • Risk of Hepatitis, Hepatic Events : Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events. ( 5.8 ) • Precipitation of Opioid Withdrawal Signs and Symptoms : An opioid withdrawal syndrome is likely to occur with parenteral misuse of Buprenorphine and Naloxone Sublingual Tablets by individuals physically dependent on full opioid agonists, or by sublingual administration before the agonist effects of other opioids have subsided. ( 5.10 ) • Risk of Overdose in Opioid-Naïve Patients : Buprenorphine and Naloxone Sublingual Tablets are not appropriate as an analgesic. There have been reported deaths of opioid naïve individuals who received a 2 mg sublingual dose. ( 5.11 ) 5.1 Addiction, Abuse, and Misuse Buprenorphine and Naloxone Sublingual Tablets contain buprenorphine, a schedule III controlled substance that can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient’s level of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits [see Drug Abuse and Dependence ( 9.2 )]. 5.2 Life-Threatening Respiratory Depression and Central Nervous System (CNS) Depression Buprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressant, including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with Buprenorphine and Naloxone Sublingual Tablets [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )] . Use Buprenorphine and Naloxone Sublingual Tablets with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information ( 17 )] . Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration ( 2.7 )] . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose: Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider recommending or prescribing an opioid overdose reversal agent for the emergency treatment of an opioid overdose, both when initiating and renewing treatment with Buprenorphine and Naloxone Sublingual Tablets. Also consider recommending or prescribing such an agent if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose [see Dosage and Administration ( 2.2 )]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Advise patients and caregivers that an opioid overdose reversal agent, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with buprenorphine itself. …

The following serious adverse reactions are described elsewhere in the labeling: • Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] • Respiratory and CNS Depression [see Warnings and Precautions ( 5.2 , 5.3 )] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] • Adrenal Insufficiency [see Warnings and Precautions ( 5.6 )] • Opioid Withdrawal [see Warnings and Precautions ( 5.7 , 5.10 )] • Hepatitis, Hepatic Events [see Warnings and Precautions ( 5.8 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] • Orthostatic Hypotension [see Warnings and Precautions ( 5.16 )] • Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions ( 5.17 )] • Elevation of Intracholedochal Pressure [see Warnings and Precautions ( 5.18 )] Adverse events commonly observed with administration of buprenorphine/naloxone are oral hypoesthesi …

Table 3 includes clinically significant drug interactions with Buprenorphine and Naloxone Sublingual Tablets. Table 3. Clinically Significant Drug Interactions with Buprenorphine and Naloxone Sublingual Tablets Benzodiazepines or Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. Intervention: Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. …