Timothy O'Shea, MS, PharmD
Timothy O'Shea, MS, PharmD, is a Clinical Pharmacist working at a regional health insurance plan on the east coast. Additionally he works per diem at a nationwide retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. He completed his M.S. in Health Services Administration, with a focus on Health Economics and Outcomes, in 2018. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.
In November 2017, the FDA approved Indivior’s Sublocade, an extended-release buprenorphine injection for the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. With its approval, Sublocade became the first once-monthly buprenorphine injection for the treatment of OUD.
This article highlights several key therapeutics areas with Sublocade that every pharmacist should know.
Sublocade contains buprenorphine, a partial opioid agonist, and is indicated for the treatment of moderate-to-severe OUD in patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days.
Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support.
Limitations of Use
The safety and effectiveness of Sublocade have not been established in pediatric patients.
Additionally, Sublocade is not appropriate for use in opioid naïve patients or for treatment where Sublocade would be the first buprenorphine product used.
Mechanism of Action
Sublocade contains an extended-release formulation of buprenorphine, which is a partial agonist at the mu opioid receptor and an antagonist at the kappa opioid receptor. Buprenorphine displays high affinity at these receptions and therefore is not easily replaced by other opioids.
Formulation and Storage
Sublocade is available as a sterile, clear solution in a single dose, prefilled syringe with safety needle. It is available in 2 formulations: 100 mg/0.5 mL and 300 mg/1.5 mL.
It should be stored in refrigeration at 2 to 8°C (35.6 to 46.4°F). Once outside the refrigerator it may be stored in its original packaging at room temperature for up to 7 days prior to administration. If left at room temperature for longer than 7 days Sublocade should be discarded.
Only health care providers should prepare and administer Sublocade. Additionally, Sublocade is subject to a risk evaluation and mitigation strategy (REMS) program that includes a restricted distribution system to ensure that Sublocade is only administered by a healthcare provider. Therefore, this is not a medication that would typically be dispensed through retail pharmacy.
The recommended dose of Sublocade following induction and dose adjustment with transmuscosal buprenorphine is 300 mg monthly by subcutaneous injection in the abdominal region for the first 2 months followed by a maintenance dose of 100 mg monthly.
The maintenance dose may be increased 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.
A patient who misses a dose should receive the next dose as soon as possible, with the following dose given no less than 26 days later. Occasional delays in dosing up to 2 weeks are not expected to have a clinically significant impact on treatment effect.
Notably, Sublocade is only appropriate in adults who have initiated treatment on a transmucosal buprenorphine-containing product delivering the equivalent of 8 to 24 mg of buprenorphine daily. The patient may only be transitioned to this medication after a minimum of 7 days. Initiating treatment with Sublocade as the first buprenorphine product has not currently been studied.
The efficacy of Sublocade for the treatment of moderate to severe OUD was established in a phase 3 double-blind study and an opioid blockage study.
The phase 3 study was a 24-week, randomized, double-blind, placebo-controlled, multicenter trial in treatment-seeking patients who met the DSM5 criteria for moderate or severe OUD. Patients were randomly assigned to one of following dosing regimens: 6 once-monthly 300 mg doses, 2 once-monthly 300 mg doses followed by 4 once-monthly 100 mg doses, or 6 once-monthly SC injections of placebo. All patients received psychosocial support at least once a week. Prior to the first dose, treatment was initiated with Suboxone (buprenorphine/naloxone) sublingual film with doses adjusted from 8/2mg to 24/6 mg per day over a period of 7 to 14 days. Efficacy was evaluated over weeks 5 through 24 based on weekly urine drug screens combined with self?reported use of illicit opioid use.
A total of 504 patients were randomized into the study. Based on the cumulative distribution function (CDF) of the percentage of urine samples negative for illicit opioids combined with self-reports collected from week 5 through week 24, regardless of dose, Sublocade was statistically superior to the placebo group. Additionally, the proportion of patients achieving treatment success (defined as patients with ≥80% opioid?free weeks) was statistically significantly higher in both groups receiving Sublocade compared to the placebo group (28.4% [300 mg/100 mg], 29.1% [300 mg/300mg], 2% [placebo]).
The opioid blockage study evaluated the blockage of subjective opioid effects, pharmacokinetic, and safety of Sublocade in 39 patients with OUD. In the study, the average buprenorphine plasma concentrations of 2-3 ng/mL were associated with mu-opioid receptor occupancy ≥70%. Additionally, Sublocade was shown to be non-inferior to hydromorphone injections in terms of “drug liking.”
The most common adverse reactions of Sublocade reported in clinical trials include constipation, headache, nausea, injection site pruritus, vomiting, increased hepatic enzymes, fatigue, and injection site pain.
Sublocade has a boxed warning noting that serious harm or death could result if this medication is administered intravenously. Other warnings and precautions in the prescribing information include a risk of addiction, abuse, and misuse, respiratory depression, adrenal insufficiency, hepatic events, and opioid withdrawal with abrupt discontinuation.
Benzodiazepines and other central nervous system (CNS) depressants should be used with caution due to an increased risk of respiratory depression. Patients taking CPY3A4 inhibitors and substrates should be closely monitored for potential over- or under-dosing.
|Sublocade (buprenorphine)||Opioid dependence||SQ Injection||Monthly||N|
|Probuphine (buprenorphine)||Opioid dependence||Intradermal implant||6 months x 1 dose||N|
|Suboxone (buprenorphine and naloxone)||Opioid dependence||Sublingual tablet and film||Daily||Y (tablet), N (film)|
|Subutex (buprenorphine)||Opioid dependence||Sublingual tablet||Daily||Y|
|Zubsolv (buprenorphine and naloxone)||
|Bunavail (buprenorphine and naloxone)||Opioid dependence||Buccal film||Daily||N|
|Buprenex (buprenorphine)||Pain||IM or IV injection||Varies||Y|
|Belbuca (buprenorphine)||Pain||Film||Twice daily||N|
|Butrans (buprenorphine)||Pain||Transdermal patch||7 days on, 3 weeks off||N|
In clinical studies, Sublocade was shown to be effective in reducing illicit opioid use as compared to placebo and block ≥70% of mu-opioid receptors. Sublocade was relatively well-tolerated with most adverse effects attributed to injection site reactions and other effects common to all buprenorphine products. Sublocade is advantageous as a once monthly injection which can help remove the burden and decision of having to take another buprenorphine medication on a day-to-day basis. For some people, this may help improve adherence. Although Sublocade is the first once-monthly buprenorphine injection for the treatment of OUD another long-acting buprenorphine product, Probuphine, has been available on the market since 2016. Head to head studies would be beneficial to compare the efficacy of Sublocade versus other buprenorphine containing products.
- Understanding the Epidemic. CDC. https://www.cdc.gov/drugoverdose/epidemic/index.html. Accessed December 15, 2017
- Sublocade [Prescribing Information]. Indivior Inc. North Chesterfield, VA. November 2017.
- Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc.; December 15, 2017.
- Electronic Orange Book. Food and Drug Administration. Available at: http://www.fda.gov/cder/ob/default.htm/. Accessed December 20, 2017.