Dosing & Uses
Dosage Forms & Strengths
injection, long-acting subcutaneous: Schedule III
- 100mg/0.5mL prefilled syringe
- 300mg/1.5mL prefilled syringe
Opioid Use Disorder
Indicated for moderate-to-severe opioid use disorder (OUD) in adults who have initiated treatment with a transmucosal buprenorphine-containing product and have been on a stable dose of transmucosal buprenorphine treatment for ≥7 days
Prescribe as part of a complete treatment plan that includes counseling and psychosocial support
300 mg SC once monthly for the first 2 months, followed by a maintenance dose of 100 mg/month
May increase maintenance dose to 300 mg monthly for patients who tolerate the 100-mg dose, but do not demonstrate a satisfactory clinical response, as evidenced by self-reported illicit opioid use or urine drug screens positive for illicit opioid use
Also see Administration
Dosing Considerations
Patient selection
- Appropriate patients for buprenorphine long-acting SC are adults who have initiated treatment on a transmucosal buprenorphine-containing product delivering the equivalent of 8-24 mg/day for at least 7 days
Clinical supervision
- Periodic assessment is necessary to determine effectiveness of the treatment plan and overall patient progress
- When evaluating, examine the injection site for signs of infection or evidence of tampering or attempts to remove the depot
- Owing to the chronic nature of opioid use disorder, the need for continuing medication-assisted treatment should be reevaluated periodically
- There is no maximum recommended duration of maintenance treatment
- For some patients, treatment may continue indefinitely
- If considering stopping treatment, the clinical status of the patient should be considered
Removal of the depot
- If the depot must be removed, it can be surgically excised under local anesthesia within 14 days of injection; only the most recently injected depot can be removed
- Removal should be handled with adequate security, accountability, and proper disposal, per facility procedure for a Schedule III drug product and pharmaceutical biohazardous waste, and per applicable federal, state, and local regulations
- The residual plasma concentrations from previous injections decreases gradually over subsequent months
- Following removal, monitor for signs and symptoms of withdrawal
<17 years: Safety and efficacy not established
Clinical trials did not include sufficient numbers of individuals aged ≥65 y to determine whether they responded differently than younger individuals
Owing to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine long-acting SC injection should be made cautiously in individuals aged ≥65 y
If prescribed in geriatric patients, monitor for signs and symptoms of toxicity or overdose
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Injection site reactions (5.3-11.6%)
1-10%
Headache (8.5-9.4%)
Constipation (8-9.4%)
Vomiting (5.5-9.4%)
Nausea (8-8.9%)
Fatigue (3.9-6%)
CPK increased (2.5-5.4%)
ALT increased (1-5%)
Somnolence (2-4.9%)
AST increased (3.4-4.5%)
GGT increased (3-4%)
Sedation (1.5-3.4%)
Dizziness (1.5-2.5%)
Postmarketing Reports
Serotonin syndrome during concomitant use of opioids with serotonergic drugs
Adrenal insufficiency with use >1 month
Anaphylaxis
Androgen deficiency with long-term opioid use
Warnings
Black Box Warnings
Serious harm or death resulting from IV administration
- For abdominal subcutaneous (SC) injection only
- Serious harm or death could result if administered intravenously (IV)
- The drug forms a solid mass upon contact with body fluids and may cause occlusion, local tissue damage, and thromboembolic events, including life-threatening pulmonary emboli, if administered IV instead of SC
- The long-acting delivery is achieved by Atrigel, a biodegradable polymer and biocompatible solvent that is designed to deliver buprenorphine at a controlled rate over a 1-month period
Sublocade REMS program
- Because of the risk of serious harm or death that could result from IV self-administration, the drug is only available through a restricted program called the Sublocade risk evaluation and mitigation strategy (REMS) program
- Healthcare settings and pharmacies that order and dispense Sublocade must be certified in this program and comply with the REMS requirements
- Further information available at www.SublocadeREMS.com or call 1-866-258-3905
- REMS requirements
- Healthcare settings and pharmacies that order and dispense Sublocade must be certified in the REMS program
- Certified healthcare settings and pharmacies must establish processes and procedures to verify Sublocade is provided directly to a healthcare provider for administration by a healthcare provider, and the drug is not dispensed to the patient
- Certified healthcare settings and pharmacies must not distribute, transfer, loan, or sell Sublocade
Contraindications
Documented hypersensitivity to buprenorphine or Atrigel delivery system components
Cautions
Risk of serious harm or death with IV administration (see Black Box Warnings)
Only available through a restricted access program called the Sublocade REMS program (see Black Box Warnings)
Buprenorphine is a schedule III controlled substance that can be abused in a manner similar to other opioids
Neonatal withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy, whether that use is medically authorized or illicit; unlike opioid withdrawal syndrome in adults, NOWS may be life-threatening if not recognized and treated in the neonate (also see Pregnancy)
Adrenal insufficiency reported with opioid use, more often with use exceeding 1 month; if diagnosed, treat with physiologic replacement doses of corticosteroids and wean patient off the opioid to allow adrenal recovery
Hypersensitivity reported and may include angioneurotic edema and anaphylactic shock; common signs and symptoms include rashes, hives, and pruritus (see Contraindications)
Because of the partial opioid agonist properties of buprenorphine, it may precipitate opioid withdrawal signs and symptoms in persons who are currently physically dependent on full opioid agonists (eg, heroin, morphine, methadone) before the effects of the full opioid agonist have subsided
Emergent acute pain should be treated with a nonopioid analgesic whenever possible; patients requiring opioid therapy for analgesia may be treated with a high‐affinity full opioid analgesic under the supervision of a physician, with particular attention to respiratory function; higher doses may be required for analgesic effect
Deaths reported if used in opioid-naïve individuals who received a 2 mg-dose as a sublingual tablet
Prolonged QTc interval observed in some patients participating in clinical trials; consider these observations in clinical decisions when prescribing buprenorphine to patients with hypokalemia, hypomagnesemia, or clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia; avoid the 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
May impair mental or physical abilities; caution patients regarding driving or operating machinery
Orthostatic hypotension may occur
May elevate CSF pressure; caution with head injury, intracranial lesions, and other circumstances when CSF pressure may be increased; buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation
Opioids increase intracholedochal pressure; caution with biliary tract dysfunction
May obscure the diagnosis or clinical course of acute abdominal conditions
Can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed
Patients who elect to discontinue treatment should be monitored for withdrawal signs and symptoms; consider transmucosal buprenorphine if needed to treat withdrawal after discontinuing long-acting injection
Risk of opioid withdrawal
- Buprenorphine is a partial agonist at the mu-opioid receptor and long-term administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation
- The withdrawal syndrome is milder than that seen with full agonists and may be delayed in onset
- Owing to the long half-life of buprenorphine long-acting SC injection, withdrawal signs and symptoms emerge after about 1 month following discontinuation
Hepatitis and hepatic events
- Cytolytic hepatitis and hepatitis with jaundice reported
- Abnormalities range from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy
- Liver function tests, prior to initiation of treatment, are recommended to establish a baseline
- Monthly monitoring of liver function during treatment, particularly with the 300-mg maintenance dose, is also recommended
- In a pharmacokinetic study with transmucosal buprenorphine, buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment
Respiratory depression
- Associated with life-threatening respiratory depression and death; many, but not all, postmarketing reports regarding coma and death involved misuse by self‐injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressants, including alcohol
- Caution with compromised respiratory function (eg, COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, preexisting respiratory depression)
- Owing to its extended‐release characteristics, if discontinued as a result of compromised respiratory function, monitor patients for ongoing buprenorphine effects for several months
Drug interaction overview
- Muscle relaxants: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk of respiratory depression
- Diuretics: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone
- Anticholinergics: Coadministration may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
- Medications that prolong QT interval (eg, Class IA or Class III antiarrhythmic medications: Buprenorphine may enhance the effects of drugs that cause QT prolongation; coadministration may increase the effects
- Benzodiazepines or other CNS depressants
- Concomitant use with benzodiazepines or other CNS depressants, including alcohol, increases the risk of adverse reactions including overdose, respiratory depression, profound sedation, and death
- For patients in buprenorphine treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia
- 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 benzodiazepine or other CNS depressant or decreasing to the lowest effect dose may be appropriate
- Coadministration with CYP3A4 inhibitors or inducers
- Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4
- CYP3A4 inhibitors (eg, azole antifungals, macrolide antibiotics, protease inhibitors [atazanavir, ritonavir], delavirdine) can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects
- CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, etravirine) 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
- Coadministration with serotonergic drugs
- MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma); do not use buprenorphine while taking MAOIs or within 14 days of stopping MAOIs (eg, phenelzine, tranylcypromine, linezolid)
Pregnancy
Pregnancy
Data are limited regarding use in pregnancy; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure
There are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations
Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes (eg, low birth weight, preterm birth, fetal death)
Additionally, untreated opioid addiction often results in continued or relapsing illicit opioid use
Fetal/neonatal adverse reactions
- Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine
- Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight
- Signs of neonatal withdrawal usually occur in the first days after birth
- The duration and severity of neonatal opioid withdrawal syndrome may vary
- Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly
Labor or delivery
- Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor
- As with all opioids, use of buprenorphine prior to delivery may result in respiratory depression in the newborn; closely monitor neonates for signs of respiratory depression
- An opioid antagonist (eg, naloxone) should be available for reversal of opioid-induced respiratory depression in the neonate
Lactation
Based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine are present in low levels in human milk and infant urine
Available data have not shown adverse reactions in breastfed infants, although caution is advised
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor
Absorption
Peak plasma time: 24 hr
Steady-state plasma concentrations
- Steady-state is reached after 4 injections of 100 mg or 300 mg, or 2 injections of 300 mg
- Peak plasma concentration: 4.88 ng/mL (100 mg/dose); 10.12 ng/mL (300 mg/dose)
- Minimum plasma concentration: 2.48 ng/mL (100 mg/dose); 5.01 ng/mL (300 mg/dose)
- Average plasma concentration (steady-state): 3.21 ng/mL (100 mg/dose); 6.54 ng/mL (300 mg/dose)
Distribution
Protein bound: 96%, primarily to alpha and beta globulin
Metabolism
Metabolized to its major metabolite, norbuprenorphine, by CYP3A4
Norbuprenorphine can further undergo glucuronidation
Elimination
Half-life: 43-60 days
Excretion: 30% (<1% unchanged) urine; 69% (33% unchanged) feces
Administration
SC Preparation
Only healthcare providers should prepare and administer
As a universal precaution, always wear gloves
Administer once monthly with a minimum of 26 days between doses
Initiating treatment with buprenorphine long-acting SC injection as the first buprenorphine product has not been studied
Initiate treatment only following induction and dose adjustment with a transmucosal buprenorphine‐containing product (see Adult Dosing)
Remove buprenorphine long-acting SC injection from the refrigerator prior to administration; requires at least 15 minutes to reach room temperature
Do not open the foil pouch until the patient has arrived for his or her injection; do not attach needle until time of injection
Administer each injection only using the syringe and safety needle included with the product
SC Administration
For abdominal SC injection only; do not administer IV or IM
Subcutaneous tissue should be free of skin conditions (eg, nodules, lesions, excessive pigment); not for injection into an area where skin is irritated, reddened, bruised, infected or scarred in any way
Missed or delayed doses
- A patient who misses a dose should receive the next dose as soon as possible, with the following dose given no sooner than 26 days later
- Occasional delays in dosing up to 2 weeks are not expected to have a clinically significant impact on treatment effect
Storage
Refrigerate at 2-8°C (35.6-46.4°F)
Once outside the refrigerator, this product may be stored in its original packaging at room temperature at 15-30°C (59-86°F) for up to 7 days prior to administration
Discard if left at room temperature >7 days
Images
Patient Handout
Formulary
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