brixadi

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…

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…

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 )

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.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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. Intervention: It is recommended that patients who are on BRIXADI treatment have their dose monitored for increase or decrease in therapeutic effects 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 (e.g., nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetics and no significant pharmacodynamics effects. Other PIs with CYP3A4 inhibitory activity (e.g., 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 postmarketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly. Intervention: If treatment with atazanavir with and without ritonavir must be initiated in a patient already treated with BRIXADI, the patient should be monitored for signs and symptoms of over-medication. It may be necessary to discontinue treatment with BRIXADI and treat the patient with a sublingual buprenorphine product that permits rapid dose adjustments. 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 during dose adjustment of the serotonergic drug. Discontinue BRIXADI if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, S-HT3 receptor antagonists, drugs that affect serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e. cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monomaine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Intervention: The use of BRIXADI is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: Phenelzine, tranylcypromine, linezolid Muscle Relaxants Clinical Impact: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients receiving muscle relaxants and BRIXADI for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, strongly consider recommending or prescribing an opioid overdose reversal agent, as is recommended for all patients on buprenorphine treatment for opioid use disorder. [see Dosage and Administration (2.2) , Warnings and Precautions (5.4 , 5.5) ] . Examples: Cyclobenzaprine, metaxolone Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when BRIXADI is used concomitantly with anticholinergic drugs. CYP3A4 Inhibitors and Inducers: Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over or under dosing. ( 7 ) Serotonergic Drugs: If concomitant use is warranted, monitor for serotonin syndrome, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. ( 7 )