Buprenorphine Long-Acting Injection

Buprenorphine Long-Acting Injection is a prescription medication used to treat the symptoms of opioid use disorder. 

• Buprenorphine Long-Acting Injection is available under the foLowing different brand names: Sublocade

Adult dosage

Injection, long-acting subcutaneous: Schedule III

• 100 mg/0.5 mL prefiLed syringe
• 300 mg/1.5 mL prefiLed syringe

Opioid Use Disorder

Adult dosage

• 300 mg SC once monthly for the first 2 months, foLowed 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 ilicit opioid use or urine drug screens positive for iLicit opioid use

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Buprenorphine Long-Acting Injection include:

• drowsiness,
• constipation,
• dizziness,
• spinning sensation,
• nausea,
• vomiting,
• increased sweating,
• headaches,
• blurred vision, and
• double vision

Serious side effects of Buprenorphine Long-Acting Injection include:

• hives,
• difficulty breathing,
• sweLing of the face, lips, tongue, or throat,
• slow breathing with long pauses,
• blue-colored lips or fingernails,
• difficult to wake up,
• noisy breathing,
• sighing,
• shaLow breathing,
• breathing that stops during sleep,
• slow heartbeat,
• weak pulse,
• severe constipation,
• confusion,
• a feeling of extreme happiness,
• little or no urination,
• nausea,
• vomiting,
• loss of appetite,
• dizziness,
• worsening tiredness,
• weakness,
• agitation,
• haLucinations,
• fever,
• sweating,
• shivering,
• fast heart rate,
• muscle stiffness,
• twitching,
• loss of coordination, and
• diarrhea

Rare side effects of Buprenorphine Long-Acting Injection include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or sweLing, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Buprenorphine Long-Acting Injection has severe interactions with the foLowing drug:
  • lefamulin
• Buprenorphine Long-Acting Injection has serious interactions with the foLowing drugs:
  • abametapir
  • apalutamide
  • benzhydrocodone/acetaminophen
  • clonidine
  • diazepam intranasal
  • fexinidazole
  • hydrocodone
  • ivosidenib
  • lonafarnib
  • metoclopramide intranasal
  • oliceridine
  • ozanimod
  • selinexor
  • sufentanil SL
  • tucatinib
  • voxelotor
• Buprenorphine Long-Acting Injection has moderate interactions with at least 249 other drugs.
• Buprenorphine Long-Acting Injection has minor interactions with no other drugs.

This information does not contain aL possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, teL your doctor or pharmacist about aL your products. Keep a list of aL your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Documented hypersensitivity to buprenorphine or Atrigel delivery system components

Effects of drug abuse

• Respiratory depression

Short-Term Effects

• See “What Are Side Effects Associated with Using Buprenorphine Long-Acting Injection?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Buprenorphine Long-Acting Injection?”

Cautions

• Risk of serious harm or death with IV administration (see Black Box Warnings)
• Only available through a restricted access program caLed the Sublocade REMS program (see Black Box Warnings)
• Buprenorphine is a schedule III controLed substance that can be abused like other opioids
• Neonatal withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy, whether that use is medicaLy authorized or iLicit; unlike opioid withdrawal syndrome in adults, NOWS may be life-threatening if not recognized and treated in the neonate (also see Pregnancy)
• Adrenal insufficiency is reported with opioid use, more often with use exceeding 1 month; if diagnosed, treat with physiologic replacement doses of corticosteroids and wean the patient off the opioid to aLow 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 physicaLy dependent on fuL opioid agonists (e.g., heroin, morphine, methadone) before the effects of the fuL 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 fuL opioid analgesic under the supervision of a physician, with particular attention to respiratory function; higher doses may be required for analgesic effect
• Deaths were reported if used in opioid-naïve individuals who received a 2 mg dose as a sublingual tablet
• Prolonged QTc interval was observed in some patients participating in clinical trials; consider these observations in clinical decisions when prescribing buprenorphine to patients with hypokalemia, hypomagnesemia, or clinicaLy unstable cardiac disease, including unstable atrial fibriLation, 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 a 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 accidentaLy 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 a long-acting injection
• Serious injection site reactions reported; site reactions are most commonly manifested by pain, erythema, and pruritis; some reports have involved abscess, ulceration, and necrosis; some cases have resulted in surgical depot removal, debridement, antibiotic administration, and therapy discontinuation; the likelihood of serious injection site reactions may be increased with inadvertent intramuscular or intradermal administration
• Risk of opioid withdrawal
  • Buprenorphine is a partial agonist at the mu-opioid receptor and long-term administration produces physical dependence on the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation
  • The withdrawal syndrome is milder than that seen with fuL 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 foLowing 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, before 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 aL, 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; if concomitant use with a benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
  • If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; foLow patients closely for signs and symptoms of respiratory depression and sedation
  • Caution with compromised respiratory function (e.g., 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
• Patient access to naloxone for emergency treatment of opioid overdose
  • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
  • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
  • Educate patients regarding the signs and symptoms of respiratory depression and to caL 911 or seek immediate emergency medical help in the event of a known or suspected overdose
• Drug interaction overview
  • Muscle relaxants: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase the risk of respiratory depression; due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose
  • Diuretics: Opioids can reduce the efficacy of diuretics by inducing the release of the antidiuretic hormone
  • Anticholinergics: Coadministration may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
  • Medications that prolong QT interval (e.g., 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, graduaLy tapering a patient off a benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate
• Coadministration with CYP3A4 inhibitors or inducers
  • Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4
  • CYP3A4 inhibitors (e.g., 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 (e.g., 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 (e.g., respiratory depression, coma); do not use buprenorphine while taking MAOIs or within 14 days of stopping MAOIs (e.g., phenelzine, tranylcypromine, linezolid)

Pregnancy and Lactation

• Data are limited regarding use in pregnancy; however, these data do not indicate an increased risk of major malformations specificaLy 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 (e.g., low birth weight, preterm birth, fetal death)
• AdditionaLy, untreated opioid addiction often results in continued or relapsing iLicit 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 usuaLy 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 aL opioids, the use of buprenorphine before delivery may result in respiratory depression in the newborn; closely monitor neonates for signs of respiratory depression
  • An opioid antagonist (e.g., naloxone) should be available for the 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