WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; BRIXADI RISK EVALUATION AND
MITIGATION STRATEGY
- Serious harm or death could result if administered intravenously. BRIXADI forms a liquid crystalline
gel upon contact with body fluids and may cause occlusion, local tissue damage, and thrombo-embolic
events, including life-threatening pulmonary emboli, if administered intravenously.
- Because of the risk of serious harm or death that could result from intravenous self-administration,
BRIXADI is only available through a restricted program called the BRIXADI REMS. Healthcare settings
and pharmacies that order and dispense BRIXADI must be certified in this program and comply with the
REMS requirements.
BRIXADI (buprenorphine) extended-release injection (weekly, 50 mg/mL buprenorphine) and BRIXADI (monthly,
356 mg/mL buprenorphine) are different formulations. Doses of BRIXADI (weekly) cannot be combined to yield
an equivalent monthly dose.
BRIXADI is contraindicated in patients with hypersensitivity (e.g. anaphylactic shock) to buprenorphine or
any other ingredients in the solution for injection.
WARNINGS AND PRECAUTIONS
Addiction, Abuse, and Misuse: BRIXADI contains buprenorphine, a Schedule III controlled
substance that can be abused in a manner similar to other opioids. Monitor all patients for progression of
opioid dependence and addictive behaviors.
Respiratory and CNS Depression: Buprenorphine has been associated with life-threatening
respiratory depression and death. Use BRIXADI with caution in patients with compromised respiratory
function. 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.
Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose: Discuss the
availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver.
Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk
for opioid overdose, strongly consider prescribing naloxone for the emergency treatment of opioid overdose,
both when initiating and renewing treatment with BRIXADI. If naloxone is prescribed, educate patients and
caregivers on how to treat with naloxone, and emphasize the importance of calling 911 or getting emergency
medical help, even if naloxone is administered.
Concomitant Use of Benzodiazepines or other CNS Depressants: Concomitant use of
buprenorphine and benzodiazepines or other CNS depressants increase the risk of adverse reactions including
respiratory depression, overdose and death. Ensure that other healthcare providers prescribing
benzodiazepines or other CNS depressants are aware of the patient’s buprenorphine treatment and
coordinate care to minimize the risk associated with concomitant use. 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.
Neonatal Opioid Withdrawal Syndrome, Pregnancy, and Lactation: Neonatal opioid withdrawal
syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.
Healthcare providers should observe newborns for signs of NOWS and manage accordingly. Advise women that if
they are pregnant while being treated with BRIXADI, the baby may have signs of withdrawal at birth and that
withdrawal is treatable. Warn patients that buprenorphine passes into breast milk. Advise the nursing mother
taking buprenorphine to monitor the infant for increased drowsiness and breathing difficulties.
Adrenal Insufficiency: If adrenal insufficiency is diagnosed, treat with physiologic
replacement of corticosteroids, and wean patient off of the opioid.
Risk of Opioid Withdrawal with Abrupt Discontinuation: Patients who elect to discontinue
BRIXADI treatment should be monitored for withdrawal signs and symptoms with consideration given to the
product’s extended-release characteristics.
Risk of Hepatitis, Hepatic Events, and Use in Patients with Impaired Hepatic Function:
Liver function tests should be performed on all patients prior to initiation, during treatment, and if a
hepatic event is suspected. Because buprenorphine levels cannot be rapidly decreased, patients with
pre-existing moderate to severe hepatic impairment are not candidates for treatment with BRIXADI. Patients
who develop moderate to severe hepatic impairment while being treated with BRIXADI should be monitored for
signs and symptoms of toxicity or overdose of buprenorphine and may require a dose adjustment.
Hypersensitivity Reactions: Cases of bronchospasm, angioneurotic edema, and anaphylactic
shock have been reported in patients receiving buprenorphine-containing products. The BRIXADI needle cap is
synthetically derived from natural rubber latex which may cause allergic reactions in latex-sensitive
individuals.
Precipitation of Opioid Withdrawal in Patients Dependent on Full Opioid Agonists: BRIXADI
injection may precipitate opioid withdrawal signs and symptoms in individuals physically dependent on full
opioid agonists. In patients who are new entrants to treatment, to avoid precipitating an opioid withdrawal
syndrome, administer a 4 mg test dose of transmucosal buprenorphine when objective signs of mild to moderate
withdrawal appear and monitor for precipitated withdrawal before injecting BRIXADI.
Treatment of Emergent Acute Pain: Treat patients receiving BRIXADI with non-opioid
analgesic whenever possible. Patients requiring opioid therapy for analgesia may be treated with a
high-affinity full opioid analgesic under the supervision of a healthcare provider, with particular
attention to respiratory function. Advise patients of the importance of instructing their family members, in
the event of emergency, to inform the treating healthcare provider or emergency room staff that the patient
is being treated with BRIXADI. The above guidance should also be considered for any patient who has been
treated with BRIXADI within the last 6 months.
Patients at Risk for Arrhythmia: Thorough QT studies with buprenorphine products have
demonstrated QT prolongation ≤ 15 msec. This QTc prolongation effect does not appear to be mediated by
hERG channels. Based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone
in patients without risk factors. The risk of combining buprenorphine with other QT- prolonging agents is
not known.
Impairment of Ability to Drive and Operate Machinery: Caution patients about driving or
operating hazardous machinery until they are reasonably certain that BRIXADI does not adversely affect their
ability to engage in such activities.
Orthostatic Hypotension: Buprenorphine may produce orthostatic hypotension in ambulatory
patients.
Elevation of Cerebrospinal Fluid Pressure: Buprenorphine may elevate cerebrospinal fluid
pressure and should be used with caution in patients with head injury, intracranial lesions, and other
circumstances when cerebrospinal pressure may be increased.
Elevation of Intracholedochal Pressure: Buprenorphine has been shown to increase
intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients
with dysfunction of the biliary tract.
Effects in Acute Abdominal Conditions: Buprenorphine may obscure the diagnosis or clinical
course of patients with acute abdominal conditions.
ADVERSE REACTIONS
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.
To report SUSPECTED ADVERSE REACTIONS, contact Braeburn at 1-833-274-9234 or FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.
Please see FULL PRESCRIBING
INFORMATION, including BOXED WARNING, and MEDICATION GUIDE.
