SUBLOCADE

WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; SUBLOCADE RISK EVALUATION AND MITIGATION STRATEGY

BOXED WARNING SECTION

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. ( 5.1 ) Because of the risk of serious harm or death that could result from intravenous self-administration, 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. ( 5.2 )

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

SUBLOCADE 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. SUBLOCADE should be used as part of a complete treatment plan that includes counseling and psychosocial support.

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

SUBLOCADE injection is available in dosage strengths of 100 mg/0.5 mL and 300 mg/1.5 mL buprenorphine. Each injection is a sterile, clear, colorless to yellow to amber solution provided in a single-dose, prefilled syringe with a 19 gauge 5/8-inch needle.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

SUBLOCADE should not be administered to patients who have been shown to be hypersensitive to buprenorphine or any component of the ATRIGEL ® delivery system [see Warnings and Precautions ( 5.11 )] .

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

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 ( 5.7 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.8 )] Opioid Withdrawal [see Warnings and Precautions ( 5.9 , 5.12 )] Hepatitis, Hepatic Events [see Warnings and Precautions ( 5.10 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.11 )] Orthostatic Hypotension [see Warnings and Precautions ( 5.18 )] Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions ( 5.19 )] Elevation of Intracholedochal Pressure [see Warnings and Precautions ( 5.20 )]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

Table 5 includes clinically significant drug interactions with SUBLOCADE. Table 5 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 of a prescribed benzodiazepine or other 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 treatments [see Warnings and Precautions ( 5.4 , 5.5 )] . If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, as is recommended for all patients in treatment for opioid use disorder [see Warnings and Precautions ( 5.4 )]. Examples: Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids. Inhibitors of CYP3A4 Clinical Impact: The effects of co-administered CYP3A4 inhibitors on buprenorphine exposure in subjects treated with SUBLOCADE have not been studied and the effects may be dependent on the route of administration; however, such interactions have been established in studies using transmucosal buprenorphine. Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4; therefore, potential interactions may occur when SUBLOCADE is given concurrently with agents that affect CYP3A4 activity. The concomitant use of sublingual buprenorphine and CYP3A4 inhibitors (e.g., ketoconazole) can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects. Intervention: Patients who transfer to SUBLOCADE treatment from a regimen of transmucosal buprenorphine used concomitantly with CYP3A4 inhibitors [e.g., azole antifungals such as ketoconazole, macrolide antibiotics such as erythromycin, and HIV protease inhibitors (e.g., ritonavir, indinavir, and saquinavir)] should be monitored to ensure that the plasma buprenorphine level provided by SUBLOCADE is adequate. If patients already on SUBLOCADE require newly-initiated treatment with CYP3A4 inhibitors, the patients should be monitored for signs and symptoms of over-medication. Within 2 weeks of SUBLOCADE administration, if signs and symptoms of buprenorphine toxicity or overdose occur but the concomitant medication cannot be reduced or discontinued, it may be necessary to remove the depot and treat the patient with a formulation of buprenorphine that permits dose adjustments. Conversely, if a patient has been stabilized on SUBLOCADE in the setting of concomitant medication that is a CYP3A4 inhibitor, and the concomitant medication is discontinued, the patient should be monitored for withdrawal. If the dose of SUBLOCADE is not adequate in the absence of the concomitant medication, that patient should be transitioned back to a formulation of buprenorphine that permits dose adjustments. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The effects of co-administered CYP3A4 inducers on buprenorphine exposure in subjects treated with SUBLOCADE have not been studied. Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4; therefore, potential interactions may occur when SUBLOCADE is given concurrently with agents that affect CYP3A4 activity. CYP3A4 inducers may induce the 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 who transfer to SUBLOCADE treatment from a regimen of transmucosal buprenorphine used concomitantly with CYP3A4 inducers should be monitored to ensure that the plasma buprenorphine level provided by SUBLOCADE is adequate. If patients already on SUBLOCADE require newly-initiated treatment with CYP3A4 inducers, the patients should be monitored for withdrawal. If the dose of SUBLOCADE is not adequate in the absence of the concomitant medication, and the concomitant medication cannot be reduced or discontinued, that patient should be transitioned back to a formulation of buprenorphine that permits dose adjustments. Conversely, if a patient has been stabilized on SUBLOCADE in the setting of concomitant medication that is a CYP3A4 inducer, and the concomitant medication is discontinued, the patient should be monitored for signs and symptoms of over-medication. Within 2 weeks of SUBLOCADE administration, if the dose provided by SUBLOCADE is excessive in the absence of the concomitant inducer, it may be necessary to remove the SUBLOCADE and treat the patient with a formulation of buprenorphine that permits 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 CYP3A inducers, whereas delavirdine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and sublingual 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 treatment with SUBLOCADE should be 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 (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on sublingual 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 after sublingual administration, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in postmarketing reports of patients receiving sublingual 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 SUBLOCADE, the patient should be monitored for signs and symptoms of over-medication. It may be necessary to remove the depot 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 monitor the patient for signs and symptoms of serotonin syndrome, particularly during treatment initiation, and dur...

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

9 DRUG ABUSE AND DEPENDENCE

DRUG ABUSE AND DEPENDENCE SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

11 DESCRIPTION

DESCRIPTION SECTION

SUBLOCADE (buprenorphine extended-release) injection is a clear, viscous, colorless to yellow to amber, sterile solution for subcutaneous injection only . It is designed to deliver buprenorphine at a controlled rate over a one month period. The active ingredient in SUBLOCADE is buprenorphine free base, a mu-opioid receptor partial agonist and a kappa-opioid receptor antagonist. Buprenorphine is dissolved in the ATRIGEL ® delivery system at 18% by weight. The ATRIGEL ® delivery system is a biodegradable 50:50 poly(DL-lactide-co-glycolide) polymer and a biocompatible solvent, N -methyl-2-pyrrolidone (NMP). SUBLOCADE is provided in dosage strengths of 100 mg and 300 mg. Table 6 presents the delivered amounts of the raw materials and the approximate delivered volume for the two dosage strengths. Table 6 Amounts of Raw Materials and Delivered Volume for the Dosage Strengths Raw Materials in SUBLOCADE 100 mg Dosage 300 mg Dosage Buprenorphine 100 mg 300 mg Poly(DL-lactide-co-glycolide) 178 mg 533 mg N -methyl-2-pyrrolidone 278 mg 833 mg Approximate Delivered Volume 0.5 mL 1.5 mL The molecular weight of buprenorphine free base is 467.6, and its molecular formula is C 29 H 41 NO 4 . Chemically, buprenorphine is (2S)-2-[17-(Cyclopropylmethyl)-4,5α-epoxy-3-hydroxy-6-methoxy-6α,14-ethano-14α-morphinan-7α-yl]-3,3-dimethylbutan-2-ol. The structural formula is:

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

The key studies from the SUBLOCADE clinical development program that support its use in moderate to severe OUD are a Phase 3 double-blind efficacy and safety study (13-0001, NCT02357901), an opioid blockade study (13-0002, NCT02044094), and a study evaluating rapid induction of SUBLOCADE after an initial dose of transmucosal buprenorphine (Rapid Induction Substudy INDV-6000-401, NCT04995029).

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

SUBLOCADE injection is available as a sterile, clear, viscous, colorless to yellow to amber solution in a single dose, prefilled syringe with safety needle. SUBLOCADE, 100 mg/0.5 mL – NDC 12496-0100-1 SUBLOCADE, 300 mg/1.5 mL – NDC 12496-0300-1

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ).

SPL MEDGUIDE SECTION

SPL MEDGUIDE SECTION

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 02/2025 MEDICATION GUIDE SUBLOCADE (SUB-lo-kade) (buprenorphine extended-release) injection, for subcutaneous use, (CIII) What is the most important information I should know about SUBLOCADE? Because of the serious risk of potential harm or death from self-injecting SUBLOCADE into a vein (intravenously), it is only available through a restricted program called the SUBLOCADE REMS Program. SUBLOCADE is not available in retail pharmacies. Your SUBLOCADE injection will only be given to you by a certified healthcare provider. SUBLOCADE contains a medicine called buprenorphine. Buprenorphine is an opioid that can cause serious and life-threatening breathing problems, especially if you take or use certain other medicines or drugs. Talk to your healthcare provider about naloxone. Naloxone is a medicine that is available to people for the emergency treatment of an opioid overdose. If naloxone is given, you must call 911 or get emergency medical help right away to treat overdose or accidental use of an opioid. SUBLOCADE may cause serious and life-threatening breathing problems. Get emergency medical help right away if you : feel faint feel dizzy are confused feel sleepy or uncoordinated have blurred vision have slurred speech are breathing slower than normal cannot think well or clearly Do not take SUBLOCADE with certain medicines. Taking SUBLOCADE with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death. In an emergency, have family members tell emergency department staff that you are physically dependent on an opioid and are being treated with SUBLOCADE. You may have detectable levels of SUBLOCADE in your body for several months after stopping treatment with SUBLOCADE. What is SUBLOCADE? SUBLOCADE is a prescription medicine used to treat adults with moderate to severe addiction (dependence) to opioid drugs (prescription or illegal) who: have started treatment with a single dose of a buprenorphine medicine in the form of a sublingual tablet or buccal film (transmucosal) or are already being treated with buprenorphine. SUBLOCADE is part of a complete treatment plan that should include counseling and psychosocial support. Who should not receive SUBLOCADE? Do not receive SUBLOCADE if you are allergic to buprenorphine or any ingredients in the prefilled syringe (ATRIGEL® delivery system). See the end of this Medication Guide for a list of ingredients in SUBLOCADE. Before receiving SUBLOCADE, tell your healthcare provider about all your medical conditions, including if you have: trouble breathing or lung problems a curve in your spine that affects your breathing Addison's disease an enlarged prostate (men) problems urinating liver, kidney, or gallbladder problems alcoholism a head injury or brain problem mental health problems adrenal gland or thyroid gland problems Tell your healthcare provider if you are: pregnant or plan to become pregnant. If you receive SUBLOCADE while pregnant, your baby may have symptoms of opioid withdrawal at birth that could be life-threatening if not recognized and treated. Talk to your healthcare provider if you are pregnant or plan to become pregnant. breastfeeding or plan to breastfeed. SUBLOCADE can pass into your breast milk and harm your baby. Talk to your healthcare provider about the best way to feed your baby during treatment with SUBLOCADE. Monitor your baby for increased drowsiness and breathing problems if you breastfeed during treatment with SUBLOCADE. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Talk with your healthcare provider before starting any new medicines during or after stopping treatment with SUBLOCADE. How will I receive SUBLOCADE? You will receive SUBLOCADE by your healthcare provider as an injection just under the skin (subcutaneous) of your stomach (abdomen), thigh, buttock, or back of the upper arm. After the first two injections, you will receive SUBLOCADE monthly (with at least 26 days between doses). If you are not currently receiving buprenorphine treatment, your healthcare provider will give you a test dose of buprenorphine first to see if you are able to tolerate it, before switching to SUBLOCADE. SUBLOCADE is injected as a liquid. After the injection, SUBLOCADE changes to a solid form called a depot. The depot may be seen or felt as a small bump under your skin at the injection site for several weeks. The depot will get smaller over time. Do not try to remove the depot. Do not rub or massage the injection site. Try not to let any restrictive clothing such as belts, waistbands, or sleeves rub against the injection site. If you miss a dose of SUBLOCADE, see your healthcare provider to get your SUBLOCADE injection as soon as possible. What should I avoid while being treated with SUBLOCADE? Do not drive, operate heavy machinery, or perform any other dangerous activities until you know how SUBLOCADE affects you. SUBLOCADE can cause drowsiness and slow reaction times. SUBLOCADE can make you sleepy, dizzy, or lightheaded. This may happen more often in the first few days after your injection and when your dose is changed. You should not drink alcohol or take prescription or over-the-counter medicines that contain alcohol during treatment with SUBLOCADE, because this can lead to loss of consciousness or even death. What are the possible side effects of SUBLOCADE? SUBLOCADE can cause serious side effects, including: Trouble breathing. Taking SUBLOCADE with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants can cause breathing problems that can lead to coma and death. Sleepiness, dizziness, and problems with coordination. Physical dependence or abuse. Liver problems . Call your healthcare provider right away if you notice any of these symptoms: your skin or the white part of your eyes turns yellow (jaundice) dark or “tea-colored” urine light colored stools (bowel movements) loss of appetite pain, aching, or tenderness on the right side of your stomach area nausea Your healthcare provider should do blood tests to check your liver before you start and during treatment with SUBLOCADE. Allergic reaction. You may have a rash, hives, swelling of your face, wheezing, light-headedness, feeling faint or loss of consciousness. Call your healthcare provider or get emergency help right away. Opioid withdrawal. Call your healthcare provider right away if you get any of these symptoms: shaking sweating more than normal feeling hot or cold more than normal runny nose watery eyes goose bumps diarrhea vomiting muscle aches Decrease in blood pressure. You may feel dizzy when you get up from sitting or lying down. The most common side effects of SUBLOCADE include: constipation headache nausea injection site itching vomiting increase in liver enzymes tiredness injection site pain SUBLOCADE may affect fertility in males and females. Talk to your healthcare provider if this is a concern for you. These are not all the possible side effects of SUBLOCADE. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. General information about SUBLOCADE Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your doctor or pharmacist for information that is written for healthcare professionals. What are the ingredients in SUBLOCADE? Active ingredient: buprenorphine ATRIGEL ® Delivery system: biodegradable 50:50 poly(DL-lactide-co-glycolide) polymer and a biocompatible solvent, N -methyl-2-pyrrolidone (NMP). © 2025, Indivior UK Limited. All Rights Reserved. SUBLOCADE® is a registered trademark of Indivior UK Limited. Manufactured for Indivior Inc....

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Principal Display Panel - Sublocade 100 mg Carton Label NDC 12496-0100-1 Sublocade ® (buprenorphine extended-release) injection for subcutaneous use CIII 100 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Principal Display Panel - Sublocade 300 mg Carton Label NDC 12496-0300-1 Sublocade ® (buprenorphine extended-release) injection for subcutaneous use CIII 300 mg