SUBLOCADE SIDE EFFECTS

  • Generic Name: buprenorphine injection for subcutaneous use
  • Brand Name: Sublocade
  • Drug Class: Analgesics, Opioid Partial Agonist
Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling

  • Addiction, Abuse, and Misuse
  • Respiratory and CNS Depression
  • Neonatal Opioid Withdrawal Syndrome
  • Adrenal Insufficiency
  • Opioid Withdrawal
  • Hepatitis, Hepatic Events
  • Hypersensitivity Reactions
  • Orthostatic Hypotension
  • Elevation of Cerebrospinal Fluid Pressure
  • Elevation of Intracholedochal Pressure

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of SUBLOCADE was evaluated in 848 opioid-dependent subjects. In these studies, there was a total of 557 subjects who received at least 6 monthly SC injections of SUBLOCADE and 138 subjects who received 12 monthly SC injections. Adverse events led to premature discontinuation in 4% of the group receiving SUBLOCADE compared with 2% in the placebo group (13-0001, NCT02357901).

In the Phase 3 open-label study (13-0003, NCT02510014), adverse events leading to drug dose reductions were reported in 7.3% of subjects receiving SUBLOCADE.

Table 1 Total Subjects Exposed to SUBLOCADE

Study 13-0001 (NCT02357901)
Up to 6 Injections
Study 13-0003 (NCT02510014) Total Subjects Exposed To SUBLOCADE
Roll-Over
Up to 6 Injections
De-Novo
Up to 12
Injections
SUBLOCADE 300/100 mg SUBLOCADE 300/300 mg Placebo From SUBLOCADE 300/100 mg To SUBLOCADE 300/Flex From SUBLOCADE 300/300 mg To SUBLOCADE 300/Flex From Placebo To SUBLOCADE 300/Flex SUBLOCADE 300/Flex
N = 203 N = 201 N = 100* N = 112 N = 113 N= 32 N = 412 N = 848
*Not included in total subjects exposed to SUBLOCADE
 FLEX = 300 mg initial dose with an option to receive either 100 mg or 300 mg for subsequent dosing per clinician’s discretion
 = Not included in total unique subjects exposed to SUBLOCADE, already accounted for in Study 13-0001 section of table

 

Table 2 shows the non-injection site-related adverse reactions (ADRs) for the groups receiving SUBLOCADE 300/300 mg (6 doses of 300 mg SC injections) 300/100 mg (300 mg SC injections for the first two doses followed by 4 doses of 100 mg SC injections) and placebo (volume-matched ATRIGEL® delivery system subcutaneous injections) reported following administration in the 6 month, double-blind, placebo-controlled study. The systemic safety profile for SUBLOCADE, given by a healthcare provider in clinical trials, was consistent with the known safety profile of transmucosal buprenorphine. Common adverse reactions associated with buprenorphine included constipation, nausea, vomiting, abnormal liver enzymes, headache, sedation and somnolence. Dose dependent hepatic effects observed in the Phase 3, double-blind study (13-0001, NCT02357901) included the incidence of ALT more than 3 times the upper limit of normal (> 3 × ULN) in 12.4%, 5.4%, and 4.0% of the SUBLOCADE 300/300-mg, SUBLOCADE 300/100-mg, and placebo groups, respectively. The incidence of AST > 3 × ULN was 11.4%, 7.9%, and 1.0%, respectively. Adverse drug reactions [by MedDRA Preferred Terms (PT)] reported in at least 2% of subjects receiving SUBLOCADE are grouped by System Organ Class (SOC).

Table 2 Adverse Reactions for Phase 3 Double-Blind Study: ≥2% of Subjects Receiving SUBLOCADE

System Organ Class Preferred Term PLACEBO
Count (%)
SUBLOCADE
300/100 mg
Count (%)
SUBLOCADE
300/300 mg
Count (%)
Total N = 100 N = 203 N = 201
Gastrointestinal disorders 12 (12%) 51 (25.1%) 45 (22.4%)
  Constipation 0 19 (9.4) 16 (8)
  Nausea 5 (5) 18 (8.9) 16 (8)
  Vomiting 4 (4) 19 (9.4) 11 (5.5)
General disorders and administration site conditions 17 (17%) 40 (19.7%) 49 (24.4%)
  Fatigue 3 (3) 8 (3.9) 12 (6)
Investigations* 2 (2%) 21 (10.3%) 19 (9.5%)
  Alanine aminotransferase increased (ALT) 0 2 (1) 10 (5)
  Aspartate aminotransferase increased (AST) 0 7 (3.4) 9 (4.5)
  Blood creatine phosphokinase increased (CPK) 1 (1) 11 (5.4) 5 (2.5)
  Gamma-glutamyl transferase increased (GGT) 1 (1) 6 (3) 8 (4)
Nervous system disorders 7 (7%) 35 (17.2%) 25 (12.4%)
  Headache 6 (6) 19 (9.4) 17 (8.5)
  Sedation 0 7 (3.4) 3 (1.5) 3 (1.5)
  Dizziness 2 (2) 5 (2.5) 3 (1.5)
  Somnolence 0) 10 (4.9) 4 (2)
*There were no cases of serious liver injury attributed to study drug.

 

Table 3 shows the injection site-related adverse events reported by ≥2 subjects in the Phase 3 studies. Most injection site adverse drug reactions (ADRs) were of mild to moderate severity, with one report of severe injection site pruritus. None of the injection site reactions were serious. One reaction, an injection site ulcer, led to study treatment discontinuation.

Table 3 Injection Site Adverse Drug Reactions Reported by ≥2 Subjects in the Phase 3 Studies

Preferred term, n
(%)
13-0001 (Ph3DB) 13-0003 (Ph3OL) All
P hase 3*
Roll–over De-novo
SUBLOCADE
300/300
SUBLOCADE
300/100
Placebo SUBLOCADE
300 →
SUBLOCADE
300/Flex
SUBLOCADE
100 →
SUBLOCADE
300/Flex
Placebo →
SUBLOCADE
300/Flex
SUBLOCADE
300/Flex
Total
SUBLOCADE
(N = 201) (N = 203) (N = 100) (N = 113) (N = 112) (N = 32) (N = 412) (N = 848)
Subjects with any injection site reactions 38 (18.9%) 28 (13.8%) 9 (9.0%) 6 (5.3%) 13 (11.6%) 2 (6.3%) 61 (14.8%) 140 (16.5%)
Injection site pain 12 (6.0%) 10 (4.9%) 3 (3.0%) 4 (3.5%) 2 (1.8%) `2 (6.3% 33 (8.0%) 61 (7.2%)
Injection site pruritus 19 (9.5%) 13 (6.4%) 4 (4.0%) 2 (1.8%) 6 (5.4%) 1 (3.1%) 17 (4.1%) 56 (6.6%)
Injection site erythema 6 (3.0%) 9 (4.4%) 0 1 (0.9%) 4 (3.6%) 0 21 (5.1%) 40 (4.7%)
Injection site induration 2 (1.0%) 2 (1.0%) 0 0 1 (0.9%) 0 7 (1.7%) 12 (1.4%)
Injection site bruising 2 (1.0%) 2 (1.0%) 0 0 0 0 2 (0.5%) 6 (0.7%)
Injection site swelling 1 (0.5%) 2 (1.0%) 0 1 (0.9%) 1 (0.9%) 0 1 (0.2%) 6 (0.7%)
Injection site discomfort 1 (0.5%) 1 (0.5%) 0 0 0 0 3 (0.7%) 5 (0.6%)
Injection site reaction 1 (0.5%) 0 0 0 3 (2.7%) 0 1 (0.2%) 5 (0.6%)
Injection site cellulitis 0 1 (0.5%) 0 0 0 0 2 (0.5%) 3 (0.4%)
Injection site infection 1 (0.5%) 0 1 (1.0%) 0 0 0 2 (0.5%) 3 (0.4%)
*Patients received SUBOXONE film for a run-in period before they switched to SUBLOCADE injection.

 

Longer-Term Experience

In an interim analysis of the ongoing open-label long-term safety study (13-0003), safety was evaluated for up to 12 injections over the course of a year. Adverse events were reported for 432 of 669 subjects during the treatment period. The overall adverse event profile was similar to the double-blind trial described above.

Postmarketing Experience

The most frequently reported systemic postmarketing adverse event observed with buprenorphine sublingual tablets was drug misuse or abuse. The most frequently reported systemic postmarketing adverse event with buprenorphine/naloxone sublingual tablets and film was peripheral edema.

The following adverse reactions have been identified during post-approval use of buprenorphine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serotonin Syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in SUBLOCADE.

Androgen Deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.

 

 

SRC: NLM .