Brixadi is the second (to Sublocade) long-acting injectable (LAI) of buprenorphine to be available in the US, expected release around September 2023.
Brixaldi been available for several years in Europe as Buvidal.
The subcutaneous injection is a low viscous solution that forms a crystalline gel depot that releases buprenorphine as it biodegrades. The depot is often palpable, although the lump is less prominent than seen with Sublocade.
❖ Mu opioid partial agonist
❖ Kappa opioid antagonist
❖ Subcutaneous LAI
❖ DEA Schedule III
FDA-approved for:
❖ Opioid dependence (moderate to severe)
Potential advantages of Brixadi over Sublocade:
More dosing options (weekly, monthly)
May be in injected in buttock, thigh, abdomen, or upper arm
Smaller needle and smaller volume of injected medication
May be started after a single 4 mg dose of transmucosal buprenorphine (rather than 7 days)
Does not have to be refrigerated
Disadvantages
Higher serum buprenorphine levels can be achieved with Sublocade
Sublocade can be surgically removed within 14 days of placement
Here are the buprenorphine mnemonics from Cafer's Psychopharmacology - Visualize to Memorize 270 Medication Mascots.
Buprenorphine LAI (BRIXADI)
BRIXADI (weekly) and BRIXADI (monthly) are different formulations with different inactive ingredients. Doses of BRIXADI (weekly) cannot be combined to yield an equivalent BRIXADI (monthly) dose.
Rotate injection sites for BRIXADI (weekly). Since injection in the upper arm was associated with approximately 10% lower plasma levels than other sites, this location should only be used after steady state has been achieved (4 consecutive doses).
The Brixadi needle cap may cause allergic reactions in latex-sensitive individuals
One of the inactive components of Brixadi (monthly) is N‐methyl‐2‐pyrrolidone (NMP, also found in Sublocade), which was teratogenic in animal studies.
Dosing: The maintenance dose of Brixadi must be individualized based on patient tolerability and/or efficacy. Maintenance is q 28 days for BRIXADI (monthly) monthly, and q 7 days for BRIXADI (weekly).
For patients not currently receiving buprenorphine:
Administer transmucosal buprenorphine 4 mg when objective signs of mild to moderate withdrawal appear.
If the test dose is tolerated without precipitated withdrawal, administer the first dose of BRIXADI (weekly), 16 mg subcutaneously in buttock, thigh, or abdomen (not upper arm).
Administer an additional dose of 8 mg BRIXADI (weekly) within 3 days of the first dose to achieve the recommended 24 mg BRIXADI (weekly) dose.
If needed, during this first week of treatment, administer an additional 8 mg dose of BRIXADI (weekly), waiting at least 24 hours after the previous injection, for a total weekly dose of 32 mg BRIXADI (weekly).
Administer subsequent BRIXADI (weekly) injections based on the total weekly dose established during Week One.
Dosage adjustments can be made at weekly appointments with the maximum BRIXADI (weekly) dose being 32 mg.
For patients already receiving buprenorphine:
Start with either BRIXADI (weekly) or BRIXADI (monthly).
SL buprenorphine (daily) | BRIXADI (weekly) | BRIXADI (monthly) |
≤ 6 mg | 8 mg | n/a |
8–10 mg | 16 mg | 64 mg |
12–16 mg | 24 mg | 96 mg |
18–24 mg | 32 mg | 128 mg |
An additional BRIXADI (weekly) 8 mg injection may be administered, based on clinical judgment during a dosing interval, up to a maximum dose of 32 mg per week of BRIXADI (weekly) or 128 mg per month of BRIXADI (monthly).
BRIXADI (weekly) may be administered up to 2 days before or after the weekly time point. BRIXADI (monthly) may be administered up to 1 week before or after the monthly time point.
Medication | SUBLOCADE | BRIXADI (weekly) | BRIXADI (monthly) |
Strengths | 100 mg / 0.5 mL 300 mg / 1.5 mL | 8 mg / 0.16 mL 16 mg / 0.32 mL 24 mg / 0.48 mL 32 mg / 0.64 mL | 64 mg / 0.18 mL 96 mg / 0.27 mL 128 mg / 0.36 mL |
Needle | 19-gauge 5/8 inch | 23-gauge ½ inch | 23-gauge ½ inch |
Detectable blood levels after last injection | 12 months or greater is possible after ~5 months of treatment | ~1 month | ~4 months |
Injection angle | 45° | 90° | 90° |
Able to remove surgically? | Within 14 days | no | no |
Dynamic interactions:
❖ Blocks full opioid agonists
❖ Blocked by opioid antagonists
(naloxone, naltrexone)
❖ Constipation
❖ Sedation
❖ Hypotension
❖ Decreased seizure threshold
❖ QT prolongation (at high dose)
❖ Serotonergic (mild)
Kinetic interactions:
❖ 3A4 substrate (fish)
❖ Delayed gastricemptying
Strongly consider prescribing naloxone upon initiation of a buprenorphine LAI. Advise patients and caregivers that naloxone may be administered for a known or suspected overdose with buprenorphine itself. Higher than normal doses of naloxone may be necessary due to high affinity of buprenorphine for the mu receptor. Repeated administration of naloxone may be necessary due to the long duration of action of the LAI.
Buprenorphine LAI (SUBLOCADE)
FDA-approved for:
❖ Opioid dependence (moderate to severe)
Used off label for:
❖ Chronic pain
Available since: 2018
Sublocade is a subcutaneous (SC) long-acting injectable (LAI) buprenorphine, injected into the abdomen monthly by a healthcare provider. It uses the same ATRIGEL delivery technology as Perseris (risperidone SC LAI). The injection is a viscous solution containing a polymer that forms a solid implant that releases buprenorphine as it biodegrades. The implant is palpable and often visible in nonobese individuals.
The injection of 0.5 or 1.5 mL of the medication with a large 19-gauge needle is painful. Local anesthesia, e.g., bupivacaine (no relation to buprenorphine) or lidocaine 2 cc SC can be used although it is not standard practice (Radosh et al, 2022).
If necessary, the Sublocade depot can be surgically excised within 14 days of injection, after which the residual plasma concentration will decrease gradually over weeks to months.
Serum buprenorphine level of 2 ng/mL is considered the minimum effective strength. Radosh et al (2022) report that at least 4–5 ng/mL is often needed.
With Sublocade 100 mg at steady state (achieved at ~5 months), average plasma buprenorphine concentration was 3.12 ng/mL, slightly higher than with the maximum approved sublingual dose of 24 mg/day (2.91 ng/mL).
With Sublocade 300 mg monthly at steady state, average plasma level was 6.54 ng/ML. This is double the 100 mg level, not triple as would be expected.
12 weeks into treatment with Sublocade, hydromorphone (Dilaudid) is no more likeable than placebo. However, the 2 ng/mL blood level is inadequate to block the effect of potent fentanyl analogues. Buprenorphine level of 7–8 ng/mL may be necessary, which would require 300 mg monthly Sublocade injections. The limiting side effect is usually somnolence/fatigue.
Lower serum concentrations in the early months may lead to breakthrough cravings or withdrawal symptoms. Supplementation with sublingual buprenorphine may be considered for the last few days of the month, on a temporary basis (Moreno et al, 2022).
If the patient reports somnolence or fatigue, check serum buprenorphine levels because a dose reduction may be indicated. More commonly, withdrawal symptoms can be experienced prior to the next injection, which may require a dose increase.
Patients may test positive for buprenorphine long after their last injection. Sublocade injection. fter steady-state has been achieved (~5 months), patients discontinuing SUBLOCADE may have detectable plasma and urine levels of buprenorphine for twelve months or longer”1 Patients may“ be falsely accused of still using buprenorphine
Injection-site reactions were reported in 13% of participants, mostly mild or moderate in severity, and lower in the second 6 months of treatment versus the first 6 months.
Skin ulceration may occur if the injection is given too superficially (intradermally). This subcutaneous injection should be given at 45° angle (15° would be intradermal).
Sublocade is available only through a Risk Evaluation and Mitigation Strategy (REMS) drug safety program because death from thromboembolism could result from intravenous self-administration.
One of the inactive components of Sublocade, N‐
methyl‐2‐pyrrolidone (NMP), was teratogenic in animal studies.
Dosing: The standard dose is 300 mg SC for the first two months, followed by 100 mg monthly maintenance doses. The minimal dosing interval is q 26 days, so the maximum is 300 mg q 26 days. A 150 mg or 200 mg dose can be approximated, off label. Prior to initiating Sublocade, tolerability needs to be established with 7 days of SL buprenorphine at 8–24 mg/day.