WARNINGS
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.
o SUBLOCADE is not available in retail pharmacies.
o 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.
• Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse opioid overdose. If naloxone or nalmefene 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:
o feel faint
o feel dizzy
o have blurred vision
o have slurred speech
o are confused
o are breathing slower than normal
o feel sleepy or uncoordinated
o cannot think well or clearly
• Do not take SUBLOCADE with certain medicines. Taking SUBLOCADE with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), 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.
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).
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.
USES
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.
HOW TO USE
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 are the possible side effects of SUBLOCADE?
SUBLOCADE can cause serious side effects, including:
• Trouble breathing. Taking SUBLOCADE with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) 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:
o your skin or the white part of your eyes turns yellow (jaundice)
o dark or “tea-colored” urine
o loss of appetite
o pain, aching, or tenderness on the right side of your stomach area
o light colored stools (bowel movements) o 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:
o shaking o goose bumps
o sweating more than normal o diarrhea
o feeling hot or cold more than normal
o vomiting
o runny nose o muscle aches
o watery eyes
• 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
• vomiting
• headache
• increase in liver enzymes
• nausea
• tiredness
• injection site itching
• 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.
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, Nmethyl-2-pyrrolidone (NMP).
OVERDOSE
Please call your healthcare provider for more information.
MISSED DOSE
If you miss a dose of SUBLOCADE, see your healthcare provider to get your SUBLOCADE injection as soon as possible
STORAGE
Store refrigerated at 2-degrees C to 8-degrees C (35.6-degrees F to 46.4-degrees F).
Once outside the refrigerator this product may be stored in its original packaging at room temperature, 15-degrees C to 30-degrees C (59-degrees F to 86-degrees F), for up to 12 weeks prior to administration. Discard SUBLOCADE if left at room temperature for longer than 12 weeks.
SUBLOCADE 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.
NOTES
Medication Guide: revision date 12/2025
Prescribing Information: revision date 12/2025
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]. 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]. Examples: Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), and other opioids.
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 newlyinitiated 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. 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)
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 during dose adjustment of the serotonergic drug. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine 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 SUBLOCADE 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 SUBLOCADE 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. 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 as 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 SUBLOCADE is used concomitantly with anticholinergic drugs.
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.
