Brixadi
Buprenorphine · Injection · Subcutaneous
Uses
1 INDICATIONS AND USAGE BRIXADI is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. BRIXADI should be used as part of a complete treatment plan that includes counseling and psychosocial support. BRIXADI contains buprenorphine, a partial opioid agonist. BRIXADI is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. ( 1 ) BRIXADI should be used as part of a complete treatment plan that includes counseling and psychosocial support. ( 1 )
Dosage and administration
Only healthcare providers should prepare and administer BRIXADI. ( 2.1 ) BRIXADI (weekly) and BRIXADI (monthly) are different formulations. Doses of BRIXADI (weekly) cannot be combined to yield an equivalent BRIXADI (monthly) dose. ( 2.1 ) BRIXADI should be injected slowly, into the subcutaneous tissue of the buttock, thigh, abdomen, or upper arm ( 2.1 ) Strongly consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) at the time BRIXADI is 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 ) Injection sites for BRIXADI (weekly) should be alternated/rotated for each injection. ( 2.7 ) See Full Prescribing Information for administration instructions. ( 2.7 ) 2.1 Important Dosage and Administration Instructions FOR SUBCUTANEOUS INJECTION ONLY. DO NOT ADMINISTER BRIXADI INTRAVENOUSLY, INTRAMUSCULARLY, OR INTRADERMALLY [see Warnings and Precautions (5.1) , Instructions for Use (2.6) ]. BRIXADI exists in two formulations. Doses of BRIXADI (weekly) cannot be combined to yield a monthly dose. Only healthcare providers should prepare and administer BRIXADI. Administer BRIXADI as a single injection. Do not divide. BRIXADI should be injected slowly, into the subcutaneous tissue of the buttock, thigh, abdomen, or upper arm. In patients who are not currently receiving buprenorphine treatment, for BRIXADI (weekly), the upper arm site should only be used after steady-state has been achieved (4 consecutive doses) [see Instructions for Use (2.6) ]. Injection in the arm site was associated with approximately 10% lower plasma levels than other sites. Injection sites should be alternated/rotated between injections for BRIXADI (weekly) [see Instructions for Use (2.6) ]. For all patients, the dose of BRIXADI must be individualized based on patient tolerability and/or efficacy. BRIXADI (weekly) should be administered in 7-day intervals. BRIXADI (monthly) should be administered in 28-day intervals. For patients not currently receiving buprenorphine treatment, begin with a test dose of 4 mg transmucosal buprenorphine to establish that buprenorphine is tolerated without precipitated withdrawal, and then transition to BRIXADI (weekly). Initiating treatment with BRIXADI as the first buprenorphine product has not been studied. Initiating treatment with BRIXADI (monthly) in new entrants to treatment has not been studied [see Dosage and Administration (2.3) ] . Patients who are currently being treated with other buprenorphine-containing products can start treatment with either BRIXADI (weekly) or BRIXADI (monthly) [see Dosage and Administration (2.3) ] . Administer each injection using only the syringe and safety needle included with the product [see Instructions for Use (2.6) ] . Caution: The BRIXADI needle cap is synthetically derived from natural rubber latex which may cause allergic reactions in latex-sensitive individuals [see Warnings and Precautions (5.10) ] . To avoid missed doses, the weekly dose may be administered up to 2 days before or after the weekly time point, and the monthly dose may be administered up to 1 week before or after the monthly time point. If a dose is missed, the next dose should be administered as soon as practically possible. 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 prescribing or recommending an overdose reversal agent for the emergency treatment of opioid overdose, both when initiating and renewing treatment with BRIXADI. Also consider prescribing or recommending 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 (5.4) ]. 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 (5.4) ]. 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 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 and its affinity for the mu receptor [see Overdosage (10) ] . 2.3 Recommended Dosing Patients Not Currently Receiving Buprenorphine Treatment The recommended weekly dose in patients not currently receiving buprenorphine treatment is 24 mg of BRIXADI (weekly) titrated up over the first week of treatment as follows: To avoid precipitating an opioid withdrawal syndrome, administer a test dose of transmucosal buprenorphine 4 mg when objective signs of mild to moderate withdrawal appear. If the dose of transmucosal buprenorphine is tolerated without precipitated withdrawal, administer the first dose of BRIXADI (weekly), 16 mg. Administer an additional dose of 8 mg BRIXADI (weekly) within 3 days of the first dose to achieve the recommended 24 mg BRIXADI (weekly) dose. If needed, during this first week of treatment, administer an additional 8 mg dose of BRIXADI (weekly), waiting at least 24 hours after the previous injection, for a total weekly dose of 32 mg BRIXADI (weekly).
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS BRIXADI is a sterile, yellowish to yellow-clear liquid solution and is provided as two different formulations, one for weekly and one for monthly administration in pre-filled, single-dose, syringes, with 23 gauge ½ inch needles, available in the following dosage strengths. Table 3: BRIXADI (weekly) Strengths BRIXADI (weekly) 50 mg/mL buprenorphine Dosage Strength Dosage Volume 8 mg 0.16 mL 16 mg 0.32 mL 24 mg 0.48 mL 32 mg 0.64 mL Table 4: BRIXADI (monthly) Strengths BRIXADI (monthly) 356 mg/mL buprenorphine Dosage Strength Dosage Volume 64 mg 0.18 mL 96 mg 0.27 mL 128 mg 0.36 mL BRIXADI is a weekly and monthly injection provided in a pre-filled single-dose syringe with a 23 gauge ½ inch needle. ( 3 ) BRIXADI (weekly) is available in 8 mg/0.16 mL, 16 mg/0.32 mL, 24 mg/0.48 mL, and 32 mg/0.64 mL; BRIXADI (monthly) is available in 64 mg/0.18 mL, 96 mg/0.27 mL, and 128 mg/0.36 mL.
Contraindications
4 CONTRAINDICATIONS BRIXADI is contraindicated in patients with hypersensitivity (e.g., anaphylactic shock) to buprenorphine, or any other ingredients in the solution for injection [see Warnings and Precautions (5.10) ]. Hypersensitivity to buprenorphine or any other ingredients in BRIXADI. ( 4 )
Warnings and precautions
Addiction, Abuse, and Misuse: Buprenorphine can be abused in a manner similar to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. ( 5.3 ) Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with BRIXADI. ( 5.4 , 5.5 ) Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy. ( 5.6 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.7 ) Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment with BRIXADI is discontinued, monitor patients for withdrawal and treat appropriately. ( 5.8 ) Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to and during treatment. ( 5.9 ) Latex Allergy: The packaging of this product contains natural rubber latex which may cause allergic reactions. ( 5.10 ) Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Administer a test dose of transmucosal buprenorphine and monitor for precipitated withdrawal before injecting BRIXADI. ( 5.11 ) Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic whenever possible. If opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect. ( 5.12 ) 5.1 Risk of Serious Harm or Death with Intravenous Administration Intravenous injection presents significant risk of serious harm or death as BRIXADI forms a liquid crystalline gel upon contact with body fluids. Occlusion, local tissue damage, and thrombo-embolic events, including life-threatening pulmonary emboli, could result if administered intravenously [see Warnings and Precautions (5.2) , Drug Abuse and Dependence (9.2) ] . Do not administer intravenously, intramuscularly, or intradermally. 5.2 BRIXADI Risk Evaluation and Mitigation Strategy (REMS) BRIXADI is available only through a restricted program called the BRIXADI REMS because of the risk of serious harm or death that could result from intravenous self-administration. The goal of the REMS is to mitigate serious harm or death that could result from intravenous self-administration by ensuring that healthcare settings and pharmacies are certified and only dispense BRIXADI directly to a healthcare provider for administration by a healthcare provider. Notable requirements of the BRIXADI REMS include the following: Healthcare Settings and Pharmacies that order and dispense BRIXADI must be certified in the BRIXADI REMS. Certified Healthcare Settings and Pharmacies must establish processes and procedures to verify BRIXADI is provided directly to a healthcare provider for administration by a healthcare provider, and the drug is not dispensed to the patient. Certified Healthcare Settings and Pharmacies must not distribute, transfer, loan, or sell BRIXADI. Further information is available at www.BRIXADIREMS.com or by calling 1-833-274-9234. 5.3 Addiction, Abuse, and Misuse BRIXADI contains buprenorphine, a Schedule III controlled substance that can be abused in a manner similar to other opioids. Buprenorphine is sought by people with opioid use disorder and is subject to criminal diversion. Monitor all patients for progression of opioid use disorder and addictive behaviors [see Drug Abuse and Dependence (9.2) ] . 5.4 Life-Threatening Respiratory and Central Nervous System (CNS) Depression Buprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, postmarketing 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 drugs including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with BRIXADI [see Drug Interactions (7) , Warnings and Precautions (5.5) , Patient Counseling Information (17) ] . Use BRIXADI 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) . Due to its extended-release characteristics, if BRIXADI is discontinued as a result of compromised respiratory function, monitor patients for ongoing buprenorphine effects for approximately 1 month for BRIXADI (weekly) and for approximately 4 months for BRIXADI (monthly). 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, monitor patient during treatment and consider dose reduction using best practices for opioid taper. [see Clinical Supervision (2.5) ]. 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 prescribing or recommending an opioid overdose reversal agent for the emergency treatment of an opioid overdose, both when initiating and renewing treatment with BRIXADI.
Side effects
The following adverse reactions are discussed in more detail in other sections of the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.3) ] Respiratory and CNS Depression [see Warnings and Precautions (5.4) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.6) ] Adrenal Insufficiency [see Warnings and Precautions (5.7) ] Opioid Withdrawal [see Warnings and Precautions (5.8 , 5.11) ] Hepatitis, Hepatic Events [see Warnings and Precautions (5.9) ] Hypersensitivity Reactions [see Warnings and Precautions (5.10) ] Orthostatic Hypotension [see Warnings and Precautions (5.17) ] Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions (5.18) ] Elevation of Intracholedochal Pressure [see Warnings and Precautions (5.19) ] Adverse reactions commonly associated with BRIXADI administration (in ≥5% of patients) were injection site pain, headache, constipation, nausea, injection site erythema, injection site pruritus, insomnia, and urinary tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Braeburn at 1-833-274-9234 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 BRIXADI was evaluated in 440 opioid-dependent patients across two, Phase 3 clinical studies: one double-blind, active-control (n=213) and one open-label (n=227). In these studies, a total of 305 patients were exposed to BRIXADI for at least 24 weeks and 132 patients were exposed for at least 48 weeks. In the first 12-week phase of the double-blind, double-dummy, active-controlled study, patients received BRIXADI (weekly) (16, 24, 32 mg) or matching placebo injections after a one-week titration. In the second 12-week phase of the study, patients remaining in the study received BRIXADI (monthly) (64, 96, 128, or 160 mg) or matching placebo injections. The 160 mg monthly dose is not an approved dose. Those randomized to receiving placebo injections were the active control groups and received sublingual buprenorphine/naloxone tablets at corresponding doses to BRIXADI. Patients receiving active BRIXADI injections also received placebo sublingual tablets. Adverse reactions led to premature discontinuation in 10 (4.7%) patients in the group receiving BRIXADI compared to 5 (2.3%) patients in the sublingual buprenorphine/naloxone group, during the double-blind study. Adverse reactions commonly reported after BRIXADI administration (≥5%, regardless of dose and regimen) in the double-blind study, were injection site pain (9.9%), headache (7.5%), constipation (7.5%), nausea (7.0%), injection site erythema (6.6%), injection site pruritus (6.1%), Insomnia (5.6%), and urinary tract infection (5.2%). Table 5 shows the adverse reactions for BRIXADI compared with the active-control group (SL BPN/NX) in the double-blind study. Table 5: Adverse Reactions in the Phase 3 Double-Blind Study: ≥ 2% of Patients Receiving BRIXADI (Excluding Injection Site Reactions). System Organ Class (SOC) BRIXADI Total = This group includes all subjects exposed to varying doses of both the BRIXADI (weekly) and BRIXADI (monthly) formulations. SL BPN/NX = SL BPN/NX denotes the active comparator: patients assigned to daily buprenorphine with sham (placebo) injections. Patients randomized to this group could also receive a 'booster' injection of BRIXADI (weekly), 8mg, per protocol. All patients in Study 421 received a single test dose of 4mg SL BPN/NX before randomization into either arm. Preferred Term (PT) = report of adverse reactions that occurred in ≥ 2% of the patients randomized to BRIXADI in Study HS-11-421. Patients are represented once per PT (N=213) n(%) (N=215) n(%) Cardiac disorders 6 (2.8%) 9 (4.2%) Tachycardia 5 (2.3) 5 (2.3) Gastrointestinal disorders 43 (20.2%) 45 (20.9%) Constipation 16 (7.5) 16 (7.4) Diarrhea 6 (2.8) 7 (3.3) Nausea 15 (7.0) 17 (7.9) Vomiting 9 (4.2) 8 (3.7) Infections and infestations 42 (19.7%) 50 (23.3%) Urinary tract infection 11 (5.2) 10 (4.7) Upper respiratory tract infection 9 (4.2) 9 (4.2) Musculoskeletal and connective tissue disorders 20 (9.4%) 22 (10.2%) Arthralgia 7 (3.3) 3 (1.4) Nervous system disorders 27 (12.7%) 27 (12.6%) Headache 16 (7.5) 17 (7.9) Psychiatric disorders 20 (9.4%) 20 (9.3%) Anxiety 6 (2.8) 7 (3.3) Insomnia 12 (5.6) 6 (2.8) Injection site reactions in the double-blind study are presented in Table 6 below. The majority of injection site-related adverse events were mild or moderate in severity. No injection site reactions were reported as severe intensity. Table 6: Injection site reactions in the Double-Blind Phase 3 Study: ≥ 2% of Patients Receiving BRIXADI Preferred Term (PT) = Injection site reactions (ISR) that occurred in ≥2% of patients receiving BRIXADI, in the controlled trial, HS-11-421. Patients are represented once per PT. BRIXADI Total = This group includes patients exposed to varying doses of both the BRIXADI weekly and monthly formulations. (N=213) n(%) SL BPN/NX = SL BPN/NX denotes the active comparator: subjects assigned to daily buprenorphine with sham (placebo) injections. Patients randomized to this group could also receive a supplemental 'booster' injection of BRIXADI (weekly), 8mg, per protocol. (N=215) n(%) Administration site reactions = The ISRs that occurred in ≥2% of the patients randomized to BRIXADI were reported under the HGLT of Administration site reactions. However, ISRs were also identified under the Bacterial infectious disorders HGLT (of which, there were three injection site related cellulitis reactions in the BRIXADI group and one in the SL BPN/NX group, respectively) but those numbers did not rise to level of reporting.
Drug interactions
Table 7: Clinically Significant Drug Interactions Benzodiazepines and 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 a prescribed benzodiazepine or CNS depressant or decreasing to the lowest effective dose may be appropriate. Similarly, cessation of other CNS depressants is preferred when possible. Before co-prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatment [see Warnings and Precautions (5.5) ] . 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 (5.4) ]. Examples: Alcohol, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), and other opioids. Inhibitors of CYP3A4 Clinical Impact: The effects on buprenorphine exposure in patients treated with BRIXADI have not been studied, and the effects may be dependent on the route of administration. Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4; therefore, potential interactions may occur when BRIXADI is given concurrently with agents that affect CYP3A4 activity [see Clinical Pharmacology (12.3) ]. 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 BRIXADI is achieved. Intervention: Patients Converted to BRIXADI Treatment from a Regimen of Transmucosal Buprenorphine used Concomitantly with CYP3A4 Inhibitors: Monitor to ensure that the plasma buprenorphine level provided by BRIXADI is adequate. Patients Already on BRIXADI who Require Newly-Initiated Treatment with a CYP3A4 Inhibitor : Monitor for signs and symptoms of over-medication. If signs and symptoms of buprenorphine toxicity or overdose occur but the concomitant medication cannot be reduced or discontinued, reduce the dose of BRIXADI. If available doses do not permit achievement of the desired dose, it may be necessary to discontinue treatment with BRIXADI and treat the patient with a formulation of buprenorphine that permits more precise dose adjustments. Patients Stabilized on BRIXADI in the Setting of Concomitant Medication That is a CYP3A4 Inhibitor, and the Concomitant Medication is Discontinued : Monitor for withdrawal and consider a dosage adjustment of BRIXADI. If the dose of BRIXADI cannot be adjusted to an adequate level in the absence of the concomitant medication, transition the patient back to a formulation of buprenorphine that permits more precise dose adjustments. Examples: azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., erythromycin), and protease inhibitors (e.g., ritonavir, indinavir, and saquinavir) CYP3A4 Inducers Clinical Impact: The effects of co-administered CYP3A4 inducers on buprenorphine exposure in patients treated with BRIXADI have not been studied. Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4; therefore, potential interactions may occur when BRIXADI is given concurrently with agents that affect CYP3A4 activity [see Clinical Pharmacology (12.3) ] . CYP3A4 inducers may induce metabolism of buprenorphine and, therefore, may cause increased clearance of the drug which could lead to a decrease in buprenorphine plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome. Intervention: Patients Converted to BRIXADI Treatment from a Regimen of Transmucosal Buprenorphine used Concomitantly with CYP3A4 Inducers: Monitor to ensure that the plasma buprenorphine level provided by BRIXADI is adequate. Patients Already on BRIXADI who Require Newly-Initiated Treatment with a CYP3A4 Inducer : Monitor for withdrawal. If the dose of BRIXADI is not adequate in the presence of the concomitant medication, and the concomitant medication cannot be reduced or discontinued, adjust the dose of BRIXADI. If the dose of BRIXADI cannot be adjusted to an adequate level, transition the patient back to a formulation of buprenorphine that permits more precise dose adjustments. Patients Stabilized on BRIXADI in the setting of Concomitant Medication that is a CYP3A4 Inducer, and the Concomitant Medication is Discontinued : Monitor for signs and symptoms of over-medication. If the dose provided by BRIXADI is excessive in the absence of the concomitant inducer, consider reducing the dose of BRIXADI. If the dose of BRIXADI cannot be adjusted to an adequate level, transition the patient back to a formulation of buprenorphine that permits more precise dose adjustments [see Clinical Pharmacology (12.3) ] . Examples: Rifampin, carbamazepine, phenytoin, phenobarbital 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 CYP3A4 inducers, whereas delaviridine is a CYP3A4 inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delviradine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamics effects.
Use in specific populations
Lactation : Buprenorphine passes into the mother's milk. ( 8.2 ) Geriatric Patients: Monitor for sedation or respiratory depression. ( 8.5 ) Moderate to Severe Hepatic Impairment: Not recommended. ( 5.14 , 8.6 ) 8.1 Pregnancy Risk Summary The data on use of buprenorphine, the active ingredient in BRIXADI 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 sublingual buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data ]. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses 21 times and equal to, respectively, the mean daily dose of 4.6 mg buprenorphine delivered by either 32 mg BRIXADI (weekly) or 128 mg BRIXADI (monthly). Pre- and post-natal development studies in rats demonstrated increased neonatal deaths at doses approximately equal to and above and dystocia at 11 times the mean daily dose of 4.6 mg buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses 4 times and greater than the mean daily dose of 4.6 mg of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses 2 and 21 times the mean daily dose of 4.6 mg 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 risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. BRIXADI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 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 may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. 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 BRIXADI. 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 (5.6) ]. Labor or Delivery Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. As with all opioids, use of buprenorphine prior to delivery may result in respiratory depression in the newborn. Closely monitor neonates for signs of respiratory depression. An opioid antagonist such as naloxone or nalmefene, should 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. Buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs 10.4 mg), had shorter hospital stays (10.0 days vs 17.5 days), and shorter duration of treatment for NOWS (4.1 days vs 9.9 days) compared to the methadone-exposed group.
Pregnancy
8.1 Pregnancy Risk Summary The data on use of buprenorphine, the active ingredient in BRIXADI 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 sublingual buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data ]. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses 21 times and equal to, respectively, the mean daily dose of 4.6 mg buprenorphine delivered by either 32 mg BRIXADI (weekly) or 128 mg BRIXADI (monthly). Pre- and post-natal development studies in rats demonstrated increased neonatal deaths at doses approximately equal to and above and dystocia at 11 times the mean daily dose of 4.6 mg buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses 4 times and greater than the mean daily dose of 4.6 mg of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses 2 and 21 times the mean daily dose of 4.6 mg 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 risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. BRIXADI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 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 may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. 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 BRIXADI. 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 (5.6) ]. Labor or Delivery Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. As with all opioids, use of buprenorphine prior to delivery may result in respiratory depression in the newborn. Closely monitor neonates for signs of respiratory depression. An opioid antagonist such as naloxone or nalmefene, should 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. Buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs 10.4 mg), had shorter hospital stays (10.0 days vs 17.5 days), and shorter duration of treatment for NOWS (4.1 days vs 9.9 days) compared to the methadone-exposed group.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of BRIXADI have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use Clinical studies of BRIXADI did not include sufficient numbers of subjects aged 65 or older to determine whether they respond differently to the drug than younger patients. Other reported clinical experience with buprenorphine has not identified differences in responses between the geriatric 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 BRIXADI 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 buprenorphine 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 considered as indicated. 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. Clinicians should consider the potential role and contribution of buprenorphine, other opioids, and other CNS depressant drugs in a patient's clinical presentation.
Description
(buprenorphine) extended-release injection is a sterile, yellowish to yellow clear liquid provided in a single-dose, pre-filled syringe intended for subcutaneous injection only . BRIXADI is designed to deliver buprenorphine at a controlled rate over either one week or one month. The active ingredient in BRIXADI is buprenorphine free base, a partial opioid agonist. BRIXADI is provided in multiple doses with two durations (weekly and monthly). BRIXADI (weekly; 8, 16, 24, 32 mg) consists of 50 mg/mL buprenorphine. The inactive ingredients include dehydrated alcohol (12% v/v), glycerol dioleate (43% v/v), and soybean phosphatidylcholine (41% w/v). BRIXADI (monthly; 64, 96, 128 mg) consists of 356 mg/mL buprenorphine. The inactive ingredients include glycerol dioleate (24% v/v), methylpyrrolidone (31% v/v), and soybean phosphatidylcholine (15% w/v). Upon injection, BRIXADI spontaneously transforms from a low viscous solution to a liquid crystalline gel that encapsulates buprenorphine and releases it at a steady rate as the depot biodegrades. Different drug product strengths, or doses, are accomplished by different syringe fill volumes [see Dosage Forms and Strengths (3) ]. The molecular weight of buprenorphine free base is 467.65 g/mol, and its molecular formula is C29H41NO4. Chemically, buprenorphine is: (2S)-2-[17-(Cyclopropylmethyl)-4,5α-epoxy-3-hydroxy-6α,14-ethano-14α-morphinan-7α-yl]-3,3-dimethylbutan-2-ol. The structural formula is: Chemical Structure
Mechanism of action
12.1 Mechanism of Action BRIXADI contains buprenorphine, a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor.
How supplied
Weekly and monthly BRIXADI is available as a sterile, yellowish to yellow clear liquid solution in a single dose, prefilled safety syringe. The BRIXADI needle cap is synthetically derived from natural rubber latex, which may cause allergic reactions in latex sensitive individuals. Store BRIXADI at room temperature at 20°C to 25°C (68°F to 77° F); with excursions permitted at 15°C to 30° C (59°F to 86°F) [see USP Controlled Room Temperature]. BRIXADI is a Schedule III drug product. Handle with adequate security and accountability. After administration, syringes should be properly disposed, per facility procedure for a Schedule III drug product, and per applicable federal, state, and local regulations. BRIXADI Weekly 50 mg/mL buprenorphine Dosage Volume NDC 8 mg 0.16 mL 58284-208-01 58284-208-91 16 mg 0.32 mL 58284-216-01 58284-216-91 24 mg 0.48 mL 58284-224-01 58284-224-91 32 mg 0.64 mL 58284-232-01 58284-232-91 BRIXADI Monthly 356 mg/mL buprenorphine Dosage Volume NDC 64 mg 0.18 mL 58284-264-01 58284-264-91 96 mg 0.27 mL 58284-296-01 58284-296-91 128 mg 0.36 mL 58284-228-01 58284-228-91
Storage
Store BRIXADI at room temperature at 20°C to 25°C (68°F to 77° F); with excursions permitted at 15°C to 30° C (59°F to 86°F) [see USP Controlled Room Temperature]. BRIXADI is a Schedule III drug product. Handle with adequate security and accountability. After administration, syringes should be properly disposed, per facility procedure for a Schedule III drug product, and per applicable federal, state, and local regulations. BRIXADI Weekly 50 mg/mL buprenorphine Dosage Volume NDC 8 mg 0.16 mL 58284-208-01 58284-208-91 16 mg 0.32 mL 58284-216-01 58284-216-91 24 mg 0.48 mL 58284-224-01 58284-224-91 32 mg 0.64 mL 58284-232-01 58284-232-91 BRIXADI Monthly 356 mg/mL buprenorphine Dosage Volume NDC 64 mg 0.18 mL 58284-264-01 58284-264-91 96 mg 0.27 mL 58284-296-01 58284-296-91 128 mg 0.36 mL 58284-228-01 58284-228-91
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Instruct patients to read the Medication Guide each time BRIXADI is administered because new information may be available. Safe Use Before initiating treatment with BRIXADI, explain the points listed below to patients and caregivers. BRIXADI Risk Evaluation and Mitigation Strategy (REMS) Advise patients that because of the risk of serious harm or death due to intravenous self-administration, BRIXADI is available only through a restricted distribution program called the BRIXADI REMS. Healthcare settings and pharmacies are certified and only dispense BRIXADI directly to a healthcare provider for administration by a healthcare provider [see Warnings and Precautions (5.2) ] . Life Threatening 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 Warnings and Precautions 5.4) ] . 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 householdmembers (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 (5.4) ]. 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. 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. [see Dosage and Administration (2.2) , Warnings and Precautions (5.4) , 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. Interaction with Benzodiazepines and other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if BRIXADI is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.5) and Drug Interactions (7) ]. Serotonin Syndrome Inform patients that BRIXADI 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 physicians if they are taking, or plan to take serotonergic medications [see Drug Interactions (7) ]. Adrenal Insufficiency Inform patients that BRIXADI 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 (5.7) ]. Anaphylaxis Inform patients that anaphylaxis has been reported with buprenorphine. Advise patients how to recognize such a reaction and when to seek medical attention [see Warnings and Precautions (5.10) ] . Latex Allergy The BRIXADI needle cap is synthetically derived from natural rubber latex which may cause allergic reactions in latex-sensitive individuals [see Warnings and Precautions (5.10) ] . Dependence and Withdrawal Inform patients that BRIXADI can cause drug dependence and that withdrawal signs and symptoms may occur when the medication is discontinued [see Warnings and Precautions (5.11) ]. Driving or Operating Heavy Machinery Caution patients that BRIXADI may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving or operating hazardous machinery. Instruct patients not to drive or operate hazardous machinery until they are reasonably certain that BRIXADI therapy does not adversely affect their ability to engage in such activities [see Warnings and Precautions (5.16) ]. Orthostatic Hypotension Inform patients that, like other opioids, BRIXADI may produce orthostatic hypotension in ambulatory individuals [see Warnings and Precautions (5.17) ]. Long Duration of Action Inform patients that they may have detectable levels of buprenorphine for a prolonged period of time after treatment with BRIXADI.
Label text from the FDA structured product label by Braeburn Inc. (revised Dec 31, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Buprenorphine in 7 products
Brixadi NDC products (7)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 58284-208 | Buprenorphine 8 mg/.16mL Injection | Braeburn Inc. | NDA · DEA CIII |
| 58284-216 | Buprenorphine 16 mg/.32mL Injection | Braeburn Inc. | NDA · DEA CIII |
| 58284-224 | Buprenorphine 24 mg/.48mL Injection | Braeburn Inc. | NDA · DEA CIII |
| 58284-228 | Buprenorphine 128 mg/.36mL Injection | Braeburn Inc. | NDA · DEA CIII |
| 58284-232 | Buprenorphine 32 mg/.64mL Injection | Braeburn Inc. | NDA · DEA CIII |
| 58284-264 | Buprenorphine 64 mg/.18mL Injection | Braeburn Inc. | NDA · DEA CIII |
| 58284-296 | Buprenorphine 96 mg/.27mL Injection | Braeburn Inc. | NDA · DEA CIII |
Frequently asked questions
What is Brixadi used for?
1 INDICATIONS AND USAGE BRIXADI is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. BRIXADI should be used as part of a complete treatment plan that includes counseling and psychosocial support. BRIXADI contains…
What are the side effects of Brixadi?
The following adverse reactions are discussed in more detail in other sections of the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.3) ] Respiratory and CNS Depression [see Warnings and Precautions (5.4) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.6) ] Adrenal Insufficiency [see Warnings and Precautions (5.7) ] Opioid Withdrawal [see Warnings… See the full label for the complete list.
Who makes Brixadi?
Brixadi is listed by 1 labeler in the FDA NDC directory, including Braeburn Inc..