Buprenorphine Hydrochloride
Tablet · Sublingual, Intramuscular, Intravenous
Uses
Buprenorphine Sublingual Tablets are indicated for the treatment of opioid dependence and is preferred for induction. Buprenorphine Sublingual Tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. Buprenorphine Sublingual Tablets contain buprenorphine, a partial opioid agonist, and is indicated for the treatment of opioid dependence and is preferred for induction. ( 1 ) Buprenorphine Sublingual Tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support. ( 1 )
Dosage and administration
Administer Buprenorphine Sublingual Tablets sublingually as a single daily dose. ( 2.1 ) Strongly consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) at the time buprenorphine sublingual tablets are initiated or renewed because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose. ( 2.2 ) To avoid precipitating withdrawal, induction with Buprenorphine Sublingual Tablets should be undertaken when objective and clear signs of withdrawal are evident. ( 2.3 ) Buprenorphine and naloxone sublingual film or buprenorphine and naloxone sublingual tablets are generally initiated after two days of buprenorphine sublingual tablets titration. ( 2.4 ) Administer Buprenorphine Sublingual Tablets as directed in the Full Prescribing information. ( 2.3 , 2.4 , 2.5 ) Buprenorphine Sublingual Tablets must be administered whole. Do not cut, chew, or swallow Buprenorphine Sublingual Tablets. ( 2.5 ) When discontinuing treatment, gradually taper to avoid signs and symptoms of withdrawal. ( 2.9 ) 2.1 Important Dosage and Administration Instructions Buprenorphine Sublingual Tablets are administered sublingually as a single daily dose. Buprenorphine Sublingual Tablets do not contain naloxone and is preferred for use only during induction. Following induction, buprenorphine and naloxone sublingual film or buprenorphine and naloxone sublingual tablets are preferred due to the presence of naloxone when clinical use includes unsupervised administration. The use of Buprenorphine Sublingual Tablets for unsupervised administration should be limited to those patients who cannot tolerate buprenorphine and naloxone sublingual film or buprenorphine and naloxone sublingual tablet; for example, those patients who have been shown to be hypersensitive to naloxone. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits. 2.2 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 overdose reversal agent for the emergency treatment of opioid overdose, both when initiating and renewing treatment with Buprenorphine 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 Warnings and Precautions ( 5.2 )]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Warnings and Precautions ( 5.2 )]. 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 opioid overdose reversal agents, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with Buprenorphine Sublingual Tablets itself. Higher than normal doses and repeated administration of an opioid overdose reversal agent may be necessary due to the long duration of action of Buprenorphine Sublingual Tablets and its affinity for the mu receptor [see Overdosage ( 10 )] . 2.3 Induction Prior to induction, consideration should be given to the type of opioid dependence (i.e., long- or short-acting opioid products), the time since last opioid use, and the degree or level of opioid dependence. Patients dependent on heroin or other short-acting opioid products : At treatment initiation, the first dose of Buprenorphine Sublingual Tablets should be administered only when objective and clear signs of moderate opioid withdrawal appear, and not less than 4 hours after the patient last used an opioid. It is recommended that an adequate treatment dose, titrated to clinical effectiveness, should be achieved as rapidly as possible. The dosing on the initial day of treatment may be given in 2 mg to 4 mg increments if preferred. In some studies, gradual induction over several days led to a high rate of dropout of buprenorphine patients during the induction period. In a one-month study, patients received 8 mg of Buprenorphine Sublingual Tablets on Day 1 and 16 mg Buprenorphine Sublingual Tablets on Day 2. From Day 3 onward, patients received either buprenorphine and naloxone sublingual tablets or Buprenorphine Sublingual Tablets at the same buprenorphine dose as Day 2 based on their assigned treatment. Induction in the studies of buprenorphine solution was accomplished over 3-4 days, depending on the target dose. Patients dependent on methadone or other long-acting opioid products : Patients dependent upon methadone or other long-acting opioid products may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioid products; therefore, the first dose of Buprenorphine Sublingual Tablets should only be administered when objective and clear signs of moderate opioid withdrawal appear, and generally not less than 24 hours after the patient last used a long-acting opioid product. There is little controlled experience with the transfer of methadone-maintained patients to buprenorphine. Available evidence suggests that withdrawal signs and symptoms are possible during induction onto buprenorphine.
Dosage forms and strengths
Buprenorphine Sublingual Tablets are supplied as a white to off white round convex tablet in four dosage strengths: buprenorphine 2 mg, buprenorphine 4 mg, buprenorphine 8 mg, and buprenorphine 12 mg Sublingual tablet: buprenorphine 2 mg, buprenorphine 4 mg, buprenorphine 8 mg and buprenorphine 12 mg. ( 3 )
Contraindications
Buprenorphine Sublingual Tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see Warnings and Precautions ( 5.9 )] . Hypersensitivity to buprenorphine. ( 4 )
Warnings and precautions
Addiction, Abuse, and Misuse : Buprenorphine can be abused in a similar manner to other opioids. 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 benzodiazepines or other CNS depressants while under treatment with Buprenorphine Sublingual Tablets ( 5.2 , 5.3 ) Unintentional Pediatric Exposure : Store Buprenorphine 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 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 Sublingual Tablets are NOT appropriate as an analgesic. There have been reported deaths of opioid naïve individuals who received a 2 mg sublingual dose of buprenorphine. ( 5.11 ) 5.1 Addiction, Abuse, and Misuse Buprenorphine 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 misuses by self-injection or were associated with the concomitant use of benzodiazepines or other CNS depressants, including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with Buprenorphine Sublingual Tablets. [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )]. Use Buprenorphine 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 ( 2.9 )] . 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 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 Sublingual Tablets itself. Higher than normal doses and repeated administration of an opioid overdose reversal agent may be necessary due to the long duration of action of Buprenorphine Sublingual Tablets and its affinity for the mu-opioid receptor [see Overdosage ( 10 )] .
Side effects
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 are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Advagen Pharma Ltd, at 866-488-0312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Buprenorphine Sublingual Tablets was supported by clinical trials using buprenorphine sublingual tablets, buprenorphine and naloxone sublingual tablets and other trials using buprenorphine sublingual solutions. In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction. Few differences in adverse event profile were noted between buprenorphine sublingual tablets or buprenorphine administered as a sublingual solution. The following adverse events were reported to occur by at least 5% of patients in a 4-week study ( Table 1 ). Table 1. Adverse Events ≥5% by Body System and Treatment Group in a 4-week Study N(%) N(%) Body System / Adverse Event (COSTART Terminology) Buprenorphine Sublingual Tablets 16 mg/day N=103 Placebo N=107 Body as a Whole Asthenia 5 (4.9%) 7 (6.5%) Chills 8 (7.8%) 8 (7.5%) Headache 30 (29.1%) 24 (22.4%) Infection 12 (11.7%) 7 (6.5%) Pain 19 (18.4%) 20 (18.7%) Pain Abdomen 12 (11.7%) 7 (6.5%) Pain Back 8 (7.8%) 12 (11.2%) Withdrawal Syndrome 19 (18.4%) 40 (37.4%) Cardiovascular System Vasodilation 4 (3.9%) 7 (6.5%) Digestive System Constipation 8 (7.8%) 3 (2.8%) Diarrhea 5 (4.9%) 16 (15.0%) Nausea 14 (13.6%) 12 (11.2%) Vomiting 8 (7.8%) 5 (4.7%) Nervous System Insomnia 22 (21.4%) 17 (15.9%) Respiratory System Rhinitis 10 (9.7%) 14 (13.1%) Skin and Appendages Sweating 13 (12.6%) 11 (10.3%) The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine solution, over a range of doses in four months of treatment. Table 2 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled study. Table 2. Adverse Events (≥5%) by Body System and Treatment Group in a 16-week Study Body System/ Adverse Event (COSTART Terminology) Buprenorphine Dose* Very Low* (N=184) Low* (N=180) Moderate* (N=186) High* (N=181) Total* (N=731) N (%) N (%) N (%) N (%) N (%) Body as a Whole Abscess 9 (5%) 2 (1%) 3 (2%) 2 (1%) 16 (2%) Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%) Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%) Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%) Flu Syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%) Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%) Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%) Injury Accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%) Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%) Pain Back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%) Withdrawal Syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%) Digestive System Constipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%) Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%) Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%) Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%) Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%) Nervous System Anxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%) Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%) Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%) Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%) Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%) Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%) Respiratory System Cough Increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%) Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 28 (4%) Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%) Skin and Appendages Sweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%) Special Senses Runny Eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%) * Sublingual solution. Doses in this table cannot necessarily be delivered in tablet form, but for comparison purposes: "Very low" dose (1 mg solution) would be less than a tablet dose of 2 mg. "Low" dose (4 mg solution) approximates a 6 mg tablet dose. "Moderate" dose (8 mg solution) approximates a 12 mg tablet dose. "High" dose (16 mg solution) approximates a 24 mg tablet dose. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of buprenorphine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequently reported post-marketing adverse events with buprenorphine sublingual tablets not observed in clinical trials, excluding drug exposure during pregnancy, was drug misuse or abuse.
Drug interactions
Table 3 includes clinically significant drug interactions with Buprenorphine Sublingual Tablets. Table 3. Clinically Significant Drug Interactions with Buprenorphine 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 CNS depressant or decreasing to the lowest effective dose may be appropriate. Before co-prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments [see Warnings and Precautions ( 5.2 , 5.3 )] . If concomitant use is warranted, strongly consider recommending or prescribing an opioid overdose reversal agent, as is recommended for all patients on buprenorphine treatment for opioid use disorder [see Warnings and Precautions ( 5.2 )] . Examples : Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Inhibitors of CYP3A4 Clinical Impact : The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of buprenorphine sublingual tablets is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see Clinical Pharmacology ( 12.3 )] , potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine. Intervention : If concomitant use is necessary, consider dosage reduction of buprenorphine sublingual tablets until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the buprenorphine sublingual tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples : Macrolide antibiotics (e.g.,erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir). CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology ( 12.3 )], potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see Clinical Pharmacology ( 12.3 )], which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression. Intervention : If concomitant use is necessary, consider increasing the buprenorphine sublingual tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider buprenorphine sublingual tablets dosage reduction and monitor for signs of respiratory depression. Examples : Rifampin, carbamazepine, phenytoin Antiretrovirals: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Clinical Impact: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delavirdine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects. Intervention : Patients who are on chronic buprenorphine sublingual tablets treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Examples : efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in post-marketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly. Intervention : Monitor patients taking buprenorphine sublingual tablets and atazanavir with and without ritonavir, and reduce dose of buprenorphine sublingual tablets if warranted. Examples : atazanavir, ritonavir Antiretrovirals: Nucleoside reverse transcriptase inhibitors (NRTIs) Clinical Impact: Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected. Intervention : None Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention : If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Buprenorphine if serotonin syndrome is suspected.
Use in specific populations
Lactation: Buprenorphine passes into mother’s milk. ( 8.2 ) Geriatric Patients: Monitor for sedation or respiratory depression. ( 8.5 ) Severe Hepatic Impairment: Consider reducing the starting and titration incremental dose by half and monitor for signs and symptoms of toxicity or overdose. ( 8.6 ) 8.1 Pregnancy Risk Summary The data on use of buprenorphine, the active ingredient in Buprenorphine Sublingual Tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. There are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data ] . Observational studies have reported on congenital malformations among buprenorphine- exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see Data ] . Reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. Pre-and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. In a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see Data ] . Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Dose Adjustment during Pregnancy and the Postpartum Period Dosage adjustments of buprenorphine, such as a higher doses, may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. Dosing should be based on individual response, and withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. Fetal/neonatal adverse reactions Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with Buprenorphine Sublingual Tablets. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth. The duration and severity of neonatal opioid withdrawal syndrome may vary. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. [see Warnings and Precautions ( 5.5 )] . Labor or Delivery Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid induced respiratory depression in the neonate. Data Human Data: Studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. Limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. Several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. Interpretation of data is complicated further by the lack of information on untreated opioid- dependent pregnant women, who would be the most appropriate group for comparison. Rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. However, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. In a multicenter, double-blind, randomized, controlled trial [Maternal Opioid Treatment: Human Experimental Research (MOTHER)] designed primarily to assess neonatal opioid withdrawal effects, opioid- dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups.
Pregnancy
8.1 Pregnancy Risk Summary The data on use of buprenorphine, the active ingredient in Buprenorphine Sublingual Tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. There are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data ] . Observational studies have reported on congenital malformations among buprenorphine- exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see Data ] . Reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. Pre-and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. In a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see Data ] . Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Dose Adjustment during Pregnancy and the Postpartum Period Dosage adjustments of buprenorphine, such as a higher doses, may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. Dosing should be based on individual response, and withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. Fetal/neonatal adverse reactions Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with Buprenorphine Sublingual Tablets. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth. The duration and severity of neonatal opioid withdrawal syndrome may vary. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. [see Warnings and Precautions ( 5.5 )] . Labor or Delivery Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid induced respiratory depression in the neonate. Data Human Data: Studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. Limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. Several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. Interpretation of data is complicated further by the lack of information on untreated opioid- dependent pregnant women, who would be the most appropriate group for comparison. Rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. However, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. In a multicenter, double-blind, randomized, controlled trial [Maternal Opioid Treatment: Human Experimental Research (MOTHER)] designed primarily to assess neonatal opioid withdrawal effects, opioid- dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups. A total of 28 of the 86 women in the buprenorphine group (33%) and 16 of the 89 women in the methadone group (18%) discontinued treatment before the end of pregnancy. Among women who remained in treatment until delivery, there was no difference between buprenorphine-treated and methadone-treated groups in the number of neonates requiring NOWS treatment or in the peak severity of NOWS.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Buprenorphine Sublingual Tablets has not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use Clinical studies of buprenorphine sublingual tablets, buprenorphine and naloxone sublingual film, or buprenorphine and naloxone sublingual tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe Buprenorphine Sublingual Tablets should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose.
Overdosage
Clinical Presentation The manifestations of acute overdose include pinpoint pupils, sedation, hypotension, hypoglycemia, respiratory depression, and death. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose In the event of overdose, the respiratory and cardiac status of the patient should be monitored carefully. When respiratory or cardiac functions are depressed, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluids, vasopressors, and other supportive measures should be employed as indicated. In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. An opioid overdose reversal agent may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary. The long duration of action of buprenorphine sublingual tablets should be taken into consideration when determining the length of treatment and medical surveillance needed to reverse the effects of an overdose. Insufficient duration of monitoring may put patients at risk.
Description
Buprenorphine Sublingual Tablets are a white to off white round convex, tablet debossed with ˄ on 2 mg, ˄ on 8 mg on one side and plain on the B9 B10 other side, debossed with 24 on one side and ˄ on other side of 4 mg, debossed with L52 on one side and ˄ on other side of 12 mg. It contains buprenorphine HCl, a partial agonist at the mu-opioid receptor, and is available in four dosage strengths, buprenorphine 2 mg, buprenorphine 4 mg, buprenorphine 8 mg and buprenorphine 12 mg (as the free base, equivalent to 2.16 mg buprenorphine hydrochloride USP, 4.3 mg buprenorphine hydrochloride USP, 8.64 mg buprenorphine hydrochloride USP and 12.96 mg buprenorphine hydrochloride USP). Each tablet also contains lactose monohydrate, mannitol, corn starch, citric acid anhydrous, sodium citrate dihydrate and magnesium stearate. Chemically, buprenorphine HCl is (2S)-2-[17-Cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6-methoxy-6α,14-ethano-14α-morphinan-7α-yl]-3,3-dimethylbutan -2-ol hydrochloride. It has the following chemical structure: Buprenorphine HCl has the molecular formula C 29 H 41 NO 4 ∙HCl and the molecular weight is 504.10. It is a white or off-white crystalline powder, sparingly soluble in water, freely soluble in methanol, soluble in alcohol and practically insoluble in cyclohexane. "Image Description"
Mechanism of action
12.1 Mechanism of Action Buprenorphine Sublingual Tablets contain buprenorphine, a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor.
How supplied
Buprenorphine sublingual tablets containing 2 mg buprenorphine (as the free base, equivalent to 2.16 mg buprenorphine hydrochloride, USP) are white to off white round convex, tablet debossed with ‘˄’ on one side and plain on the other side and are supplied as: B9 Bottles of 30 with child resistant cap……………..NDC 72888-182-30 Bottles of 90 with child resistant cap……………..NDC 72888-182-90 Buprenorphine sublingual tablets containing 4 mg buprenorphine (as the free base, equivalent to 4.32 mg buprenorphine hydrochloride, USP) are white to off white round convex, tablet debossed with ‘24’ on one side and ‘˄’ on other side and are supplied as: Bottles of 30 with child resistant cap……………..NDC 72888-509-01 Bottles of 90 with child resistant cap……………..NDC 72888-509-02 Buprenorphine sublingual tablets containing 8 mg buprenorphine (as the free base, equivalent to 8.64 mg buprenorphine hydrochloride, USP) are white to off white round convex, tablet debossed with ‘˄’ on one side and plain on the other side and are supplied as: B10 Bottles of 30 with child resistant cap……………..NDC 72888-183-30 Bottles of 90 with child resistant cap……………..NDC 72888-183-90 Buprenorphine sublingual tablets containing 12 mg buprenorphine (as the free base, equivalent to 12.96 mg buprenorphine hydrochloride, USP) are white to off white round convex, tablet debossed with ‘L52’ on one side and ‘˄’ on other side and are supplied as: Bottles of 30 with child resistant cap……………..NDC 72888-510-01 Bottles of 90 with child resistant cap……………..NDC 72888-510-02 Store at 20°C to 25°C (68°F to 77°F); excursion permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature.]. Protect from moisture. Dispense in a tight, light-resistant container as defined in USP. Store Buprenorphine Sublingual Tablets securely and dispose of properly [see Patient Counseling Information ( 17 )].
Storage
Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store Buprenorphine Sublingual Tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions ( 5.1 , 5.4 ), Drug Abuse and Dependance ( 9.2 )]. Inform patients that leaving Buprenorphine Sublingual Tablets unsecured can pose a deadly risk to others in the home. Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused Buprenorphine Sublingual Tablets should be disposed of by flushing the unused medication down the toilet, if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.
Patient information
Advise patients to read the FDA-approved patient labeling ( Medication Guide ) Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store Buprenorphine Sublingual Tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions ( 5.1 , 5.4 ), Drug Abuse and Dependance ( 9.2 )]. Inform patients that leaving Buprenorphine Sublingual Tablets unsecured can pose a deadly risk to others in the home. Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused Buprenorphine Sublingual Tablets should be disposed of by flushing the unused medication down the toilet, if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines. Safe Use Before initiating treatment with Buprenorphine Sublingual Tablets, explain the points listed below to caregivers and patients. Instruct patients to read the Medication Guide each time Buprenorphine Sublingual Tablets are dispensed because new information may be available. Inform patients and caregivers that potentially fatal additive effects may occur if Buprenorphine Sublingual Tablets are used with benzodiazepines or other CNS depressants. (e.g., alcohol, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), counsel patients that such medications should not be used concomitantly unless supervised by a health care provider [see Warnings and Precautions ( 5.2 , 5.3 ), Drug Interactions ( 7 )]. 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 Warnings and Precautions ( 5.2 )] . 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 are at risk for relapse, discuss the importance of having access to an opioid overdose reversal agent. Also discuss the importance of having access to an opioid overdose reversal agent if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter (some products), or as part of a community-based program) [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.3 )]. There are important differences among the opioid overdose reversal agents. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Educate patients and caregivers on how to recognize the signs and symptoms of an opioid overdose. Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if an opioid overdose reversal agent is administered. Repeat administration may be necessary, particularly for overdose involving buprenorphine sublingual tablets, [See Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 ), Overdosage ( 10 )] . Advise patients and caregivers: how to treat with an opioid overdose reversal agent in the event of an opioid overdose to tell family and friends about their opioid overdose reversal agent and to keep it in a place where family and friends can easily access it in an emergency to read the Patient Information (or other educational material) that will come with their opioid overdose reversal agent. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Advise patients that Buprenorphine Sublingual Tablet contains an opioid that can be a target for people who abuse prescription medications or street drugs, to keep their tablets in a safe place, and to protect them from theft. Instruct patients to keep Buprenorphine Sublingual Tablet in a secure place, out of the sight and reach of children. Accidental or deliberate ingestion by a child may cause respiratory depression that can result in death. Advise patients to seek medical attention immediately if a child is exposed to Buprenorphine Sublingual Tablets. Serotonin Syndrome: Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare provider if they are taking, or plan to take serotonergic medications [see Drug Interactions ( 7 )]. Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions ( 5.6 )]. Advise patients to never give Buprenorphine Sublingual Tablet to anyone else, even if he or she has the same signs and symptoms. It may cause harm or death.
Label text from the FDA structured product label by Advagen Pharma Ltd (revised Jul 17, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Buprenorphine Hydrochloride in 13 products
Buprenorphine Hydrochloride NDC products (13)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-7559 | Buprenorphine Hydrochloride 8 mg/1 Tablet | A-S Medication Solutions | ANDA · DEA CIII |
| 72888-182 | Buprenorphine Hydrochloride 2 mg/1 Tablet | Advagen Pharma Ltd | ANDA · DEA CIII |
| 72888-183 | Buprenorphine Hydrochloride 8 mg/1 Tablet | Advagen Pharma Ltd | ANDA · DEA CIII |
| 72888-509 | Buprenorphine Hydrochloride 4 mg/1 Tablet | Advagen Pharma Ltd | ANDA · DEA CIII |
| 72888-510 | Buprenorphine Hydrochloride 12 mg/1 Tablet | Advagen Pharma Ltd | ANDA · DEA CIII |
| 0143-9246 | Buprenorphine Hydrochloride .324 mg/mL Injection | Hikma Pharmaceuticals USA Inc. | ANDA · DEA CIII |
| 0409-2012 | Buprenorphine Hydrochloride .3 mg/mL Injection, Solution | Hospira, Inc. | ANDA · DEA CIII |
| 0121-1019 | Buprenorphine Hydrochloride 2 mg/1 Tablet | PAI Holdings, LLC dba PAI Pharma | ANDA · DEA CIII |
| 0121-2038 | Buprenorphine Hydrochloride 8 mg/1 Tablet | PAI Holdings, LLC dba PAI Pharma | ANDA · DEA CIII |
| 42023-179 | Buprenorphine Hydrochloride .324 mg/mL Injection | Par Health USA, LLC | ANDA · DEA CIII |
| 70518-4570 | Buprenorphine Hydrochloride 2 mg/1 Tablet | REMEDYREPACK INC. | ANDA · DEA CIII |
| 70518-4571 | Buprenorphine Hydrochloride 8 mg/1 Tablet | REMEDYREPACK INC. | ANDA · DEA CIII |
| 70069-027 | Buprenorphine Hydrochloride .324 mg/mL Injection | Somerset Therapeutics, LLC | ANDA · DEA CIII |
Buprenorphine Hydrochloride recalls
- D-0596-2026 Jun 24, 2026 · Class II · Ongoing
Crystallization; identified as Buprenorphine free base - D-0527-2026 May 20, 2026 · Class II · Ongoing
Crystallization; identified as Buprenorphine free base - D-0564-2024 Jul 3, 2024 · Class II · Ongoing
Lack of Assurance of Sterility-The potential for incomplete crimp seals. - D-0087-2024 Nov 15, 2023 · Class II · Terminated
Crystallization; identified as Buprenorphine free base - D-1533-2020 Sep 2, 2020 · Class II · Terminated
Sub-potent Drug: Out-of-Specification assay results found at 3 month stability testing. - D-0698-2017 May 17, 2017 · Class II · Terminated
Crystallization: due to the presence of white, crystalline particulates, adhered to the side and bottom of the glass vials, which are comprised of principally dextrose and the buprenorphine active component. - D-1604-2014 Oct 1, 2014 · Class II · Terminated
Failed Impurities/Degradation Specification: Out of Specification results for pseudobuprenorphine impurity at the 9-month stability time point.
Frequently asked questions
What is Buprenorphine Hydrochloride used for?
Buprenorphine Sublingual Tablets are indicated for the treatment of opioid dependence and is preferred for induction. Buprenorphine Sublingual Tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. Buprenorphine Sublingual Tablets contain buprenorphine, a partial opioid agonist, and is indicated for the treatment of opioid dependence and is…
What are the side effects of Buprenorphine Hydrochloride?
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… See the full label for the complete list.
Who makes Buprenorphine Hydrochloride?
Buprenorphine Hydrochloride is listed by 8 labelers in the FDA NDC directory, including A-S Medication Solutions, Advagen Pharma Ltd, Hikma Pharmaceuticals USA Inc., Hospira, Inc..
Has Buprenorphine Hydrochloride been recalled?
The FDA enforcement database lists 7 recalls for Buprenorphine Hydrochloride, most recently D-0596-2026 (class ii): Crystallization; identified as Buprenorphine free base