SUBLOCADE® Long-Term Safety Data Published in Journal of Clinical Psychopharmacology
Slough, UK and Richmond, VA, April 16, 2020 – Indivior PLC (LON: INDV) today announced
the publication of long-term safety data for SUBLOCADE® (buprenorphine extended-release)
injection, for subcutaneous use (CIII).
The manuscript entitled "Treating Opioid Use Disorder with a Monthly Subcutaneous
Buprenorphine Depot Injection: 12-month Safety, Tolerability and Efficacy Analysis" was
published online on April 9, 2020 and will appear in an upcoming print issue of the Journal
of Clinical Psychopharmacology.1
This open-label multicenter study (NCT 02510014) in adults with moderate or severe opioid
use disorder (OUD) enrolled 257 participants from a previously conducted placebocontrolled, double-blind Phase III trial (Rollover group) and 412 De Novo participants not
previously treated with SUBLOCADE. By study end, 60.7% participants completed the study
and received up to 12 injections. The main findings were as follows:
- The safety profile of up to 12-month SUBLOCADE treatment was consistent with that of transmucosal buprenorphine, with the exception of the anticipated injection-site reactions.1
- Overall, 66.8% of participants reported >1 treatment-emergent adverse event (TEAE). Injection-site TEAEs (13.2% of participants), were mostly mild or moderate in severity.
- An integrated analysis of the double-blind and open-label study participants showed that the incidence of TEAEs, including injection-site TEAEs, were lower in the second 6 months of treatment versus the first 6 months.
- There were no unexpected safety signals detected and no TEAEs potentially related to respiratory depression.
- The hepatic safety profile of SUBLOCADE was comparable to that reported for transmucosal buprenorphine and longer exposure to the highest 300 mg maintenance dose of SUBLOCADE did not worsen hepatic laboratory assessments. There were no cases of hepatocellular injury indicated by increased AST/ALT with jaundice and no removal of SUBLOCADE was required.
- Efficacy was evaluated using Urine Drug Screen for opioids plus self-reported illicit opioid use combined into a single endpoint. After 12 months of SUBLOCADE treatment, 61.5% of the Rollover participants and 75.8% of the De Novo participants were free of illicit opioid use.
“Recent research has shown that treatment is most helpful when it addresses opioid use
disorder as a chronic disease that requires services and support structures over an extended
period of time,” said Christian Heidbreder, PhD, Indivior’s Chief Scientific Officer. “Data from
this open-label study provide additional scientific evidence in support of the long-term
safety profile of SUBLOCADE and may help clinicians to determine how best they can help
patients achieve and maintain recovery.”
ABOUT SUBLOCADE2
INDICATION AND USAGE
SUBLOCADE® (buprenorphine extended-release) injection, for subcutaneous use (CIII) is
indicated for the treatment of moderate to severe opioid use disorder in patients who have
initiated treatment with a transmucosal buprenorphine-containing product followed by a
dose adjustment period for a minimum of seven days.
SUBLOCADE should be used as part of a complete treatment program that includes
counseling and psychosocial support.
ABOUT SUBLOCADE2
INDICATION AND USAGE
SUBLOCADE® (buprenorphine extended-release) injection, for subcutaneous use (CIII) is
indicated for the treatment of moderate to severe opioid use disorder in patients who have
initiated treatment with a transmucosal buprenorphine-containing product followed by a
dose adjustment period for a minimum of seven days.
SUBLOCADE should be used as part of a complete treatment program that includes
counseling and psychosocial support.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; SUBLOCADE RISK EVALUATION AND MITIGATION STRATEGY
- Serious harm or death could result if administered intravenously. SUBLOCADE forms a solid mass 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 selfadministration, SUBLOCADE is only available through a restricted program called the SUBLOCADE REMS Program. Healthcare settings and pharmacies that order and dispense SUBLOCADE must be certified in this program and comply with the REMS requirements.
Prescription use of this product is limited under the Drug Addiction Treatment Act.
SUBLOCADE should only be prepared and administered by a healthcare provider.
CONTRAINDICATIONS
SUBLOCADE should not be administered to patients who have been shown to be hypersensitive to buprenorphine or any component of the ATRIGEL® delivery system.
WARNINGS AND PRECAUTIONS
Addiction, Abuse, and Misuse: SUBLOCADE 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 patients for conditions indicative of diversion or progression of
opioid dependence and addictive behaviors.
Risk of Life-Threatening Respiratory Depression and Concomitant Use of Benzodiazepines
or Other CNS Depressants with Buprenorphine: Buprenorphine has been associated with
life‐threatening respiratory depression, overdose, and death, particularly when misused by
self-injection or with concomitant use of benzodiazepines or other CNS depressants,
including alcohol. Warn patients of the potential danger of self-administration of
benzodiazepines, other CNS depressants, opioid analgesics, and alcohol while under
treatment with SUBLOCADE. Counsel patients that such medications should not be used
concomitantly unless supervised by a healthcare provider.
Use 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).
Opioids can cause sleep-related breathing disorders; e.g., central sleep apnea (CSA), sleeprelated hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion.
Consider decreasing the opioid using best practices for opioid taper if CSA occurs.
Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome
(NOWS) is an expected and treatable outcome of prolonged use of opioids during
pregnancy. NOWS may be life-threatening if not recognized and treated in the
neonate. Newborns should be observed for signs of NOWS and managed
accordingly. Advise pregnant women receiving opioid addiction treatment with
SUBLOCADE of the risk of neonatal opioid withdrawal syndrome.
Adrenal Insufficiency: Adrenal insufficiency has been reported with opioid use. If
adrenal insufficiency is diagnosed, treat with physiologic replacement doses of
corticosteroids. Wean the patient off the opioid.
Discontinuation of SUBLOCADE Treatment: Due to the long-acting nature of
SUBLOCADE, if treatment is discontinued, monitor patients for several months for
withdrawal and treat appropriately.
Inform patients that they may have detectable levels of buprenorphine for a
prolonged period of time after treatment with SUBLOCADE. Considerations of drugdrug interactions, buprenorphine effects, and analgesia may continue to be relevant
for several months after the last injection.
Risk of Hepatitis, Hepatic Events: Because cases of cytolytic hepatitis and hepatitis
with jaundice have been observed in individuals receiving buprenorphine, monitor
liver function tests prior to treatment and monthly during treatment.
Hypersensitivity Reactions: Hypersensitivity to buprenorphine-containing products
have been reported most commonly as rashes, hives, and pruritus. Some cases of
bronchospasm, angioneurotic edema, and anaphylactic shock have also been
reported.
Precipitation of Opioid Withdrawal in Patients Dependent on Full Agonist Opioids:
Buprenorphine may precipitate opioid withdrawal signs and symptoms in persons
who are currently physically dependent on full opioid agonists such as heroin,
morphine, or methadone before the effects of the full opioid agonist have subsided.
Verify that patients have tolerated and are dose adjusted on transmucosal
buprenorphine before subcutaneously injecting SUBLOCADE.
Risks Associated With Treatment of Emergent Acute Pain: When patients need
acute pain management, or may require anesthesia, treat patients receiving
SUBLOCADE currently or within the last 6 months with a non-opioid analgesic
whenever possible. If opioid therapy is required, patients may be treated with a
high-affinity full opioid analgesic under the supervision of a physician, with particular
attention to respiratory function, as higher doses may be required for analgesic
effect and therefore, a higher potential for toxicity exists with opioid administration.
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 physically dependent on an opioid and that the patient is being
treated with SUBLOCADE.
Use in Opioid Naïve Patients: Because death has been reported for opioid naïve
individuals who received buprenorphine sublingual tablet, SUBLOCADE is not
appropriate for use in opioid naïve patients.
Use in Patients With Impaired Hepatic Function: Because buprenorphine levels
cannot be rapidly decreased, SUBLOCADE is not recommended for patients with preexisting moderate to severe hepatic impairment. Patients who develop moderate to
severe hepatic impairment while being treated with SUBLOCADE should be
monitored for several months for signs and symptoms of toxicity or overdose caused
by increased levels of buprenorphine.
Use in Patients at Risk for Arrhythmia: Buprenorphine has been observed to
prolong the QTc interval in some patients participating in clinical trials. Avoid use of
buprenorphine in patients with a history of Long QT Syndrome or an immediate
family member with this condition or those taking Class IA antiarrhythmic
medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic
medications (e.g., sotalol, amiodarone, dofetilide), or other medications that
prolong the QT interval.
Impairment of Ability to Drive or Operate Machinery: SUBLOCADE may impair the
mental or physical abilities required for the performance of potentially dangerous
tasks such as driving a car or operating machinery. Caution patients about driving or
operating hazardous machinery until they are reasonably certain that SUBLOCADE
does not adversely affect their ability to engage in such activities.
Orthostatic Hypotension: Buprenorphine may produce orthostatic hypotension.
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. Buprenorphine can produce miosis and changes in the level of
consciousness that may interfere with patient evaluation.
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.
Unintentional Pediatric Exposure: Buprenorphine can cause severe, possibly fatal,
respiratory depression in children who are accidentally exposed to it.
ADVERSE REACTIONS: Adverse reactions commonly associated with SUBLOCADE
(≥5% of subjects) during clinical trials were constipation, headache, nausea,
vomiting, increased hepatic enzymes, fatigue, and injection site pain and pruritus.
This is not a complete list of potential adverse events. Please see the full Prescribing
Information for a complete list.
DRUG INTERACTIONS
CYP3A4 Inhibitors and Inducers: Monitor patients starting or ending CYP3A4
inhibitors or inducers for potential over- or under-dosing.
Serotonergic Drugs: If concomitant use with serotonergic drugs is warranted,
monitor for serotonin syndrome, particularly during treatment initiation, and during
dose adjustment of the serotonergic drug.
Consult the full Prescribing Information for SUBLOCADE for more information on
potentially significant drug interactions.
USE IN SPECIFIC POPULATIONS
Pregnancy: Opioid-dependent women on buprenorphine maintenance therapy may
require additional analgesia during labor.
Lactation: Buprenorphine passes into the mother’s milk. Advise breastfeeding
women to monitor the infant for increased drowsiness and breathing difficulties.
Fertility: Chronic use of opioids may cause reduced fertility. It is not known whether
these effects on fertility are reversible.
Geriatric Patients: Monitor geriatric patients receiving SUBLOCADE for sedation or
respiratory depression.
To report pregnancy or side effects associated with taking SUBLOCADE, please call 1-877-
782-6966.
For more information about SUBLOCADE, see the full Prescribing Information including
BOXED WARNING, and Medication Guide. For REMS information visit www.
sublocadeREMS.com.
About Opioid Use Disorder (OUD)
Opioid addiction isn’t a moral weakness. Opioid addiction is a chronic disease called Opioid Use Disorder (OUD)3 in which people develop a pattern of using opioids that can lead to negative consequences.4 Opioid addiction may affect the parts of the brain that control impulses, judgment, and decision-making.4,5 Patients become trapped in a cycle of opioid use, which produces changes in brain function that can reduce their ability to control their use.4,6
In 2018, an estimated 10.3 million people aged 12 or older misused opioids in the past year, including 9.9 million prescription pain reliever misusers and 808,000 heroin users. Approximately 506,000 people misused prescription pain relievers and used heroin in the past year.7 SUBLOCADE is not indicated for use in children younger than 18 years of age. Buprenorphine, the active ingredient of SUBLOCADE can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it.
About Indivior
Indivior is a global pharmaceutical company working to help change patients’ lives by developing
medicines to treat addiction and serious mental illnesses. Our vision is that all patients around the world
will have access to evidence-based treatment for the chronic conditions and cooccurring disorders of
addiction. Indivior is dedicated to transforming addiction from a global human crisis to a recognized and
treated chronic disease. Building on its global portfolio of opioid dependence treatments, Indivior has a
pipeline of product candidates designed to both expand on its heritage in this category and potentially
address other chronic conditions and co-occurring disorders of addiction, including alcohol use disorder.
Headquartered in the United States in Richmond, VA, Indivior employs more than 800 individuals
globally and its portfolio of products is available in over 40 countries worldwide. Visit www.indivior.com
to learn more. Connect with Indivior on LinkedIn by visiting www.linkedin.com/company/indivior.
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Jason Thompson
Indivior Vice President, Investor Relations
+1 804-402-7123
Jason.Thompson@indivior.com