SUBOXONE SIDE EFFECTS

  • Generic Name: buprenorphine hcl and naloxone hcl
  • Brand Name: Suboxone
  • Drug Class: Analgesics, Opioid Partial Agonist, Opioid Antagonists
Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

The following serious adverse reactions are described elsewhere in 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 SUBOXONE sublingual film is supported by clinical trials using SUBUTEX® (buprenorphine) sublingual tablets and SUBOXONE (buprenorphine and naloxone) sublingual tablets, and other trials using buprenorphine sublingual solutions, as well as an open-label study in 194 patients treated with SUBOXONE sublingual film administered sublingually and 188 patients treated with the film administered buccally. In total, safety data from clinical studies are available from over 3000 opioid-dependent subjects exposed to buprenorphine at doses in the range used in the treatment of opioid dependence. Few differences in the adverse event profile were noted with regard to sublingually and bucally administered SUBOXONE sublingual film, SUBOXONE sublingual tablets, SUBUTEX sublingual tablets and a buprenorphine ethanolic sublingual solution.

The most common adverse event (>1%) associated with the sublingual administration of the SUBOXONE sublingual film was oral hypoesthesia. Other adverse events were constipation, glossodynia, oral mucosal erythema, vomiting, intoxication, disturbance in attention, palpitations, insomnia, withdrawal syndrome, hyperhidrosis, and blurred vision.

The most common adverse events associated with the buccal administration were similar to those observed with sublingual administration of the film.

Other adverse event data were derived from larger, controlled studies of SUBOXONE sublingual tablets and SUBUTEX sublingual tablets and of buprenorphine sublingual solution. In a comparative study of SUBOXONE sublingual tablets and SUBUTEX sublingual tablets, adverse event profiles were similar for subjects treated with 16 mg/4 mg SUBOXONE sublingual tablets or 16 mg SUBUTEX sublingual tablets. The following adverse events were reported to occur by at least 5% of patients in a 4 week study of SUBOXONE sublingual tablets and SUBUTEX sublingual tablets.

Table 1: Adverse Events (≥5%) by Body System and Treatment Group in a 4 Week Study

Body System/ Adverse Event (COSTART Terminology) SUBOXONE sublingual tablets 16 mg/4 mg/day
N=107 n (%)
SUBUTEX sublingual tablets 16 mg/day
N=103 n (%)
Placebo
N=107 n (%)
Body as a Whole
Asthenia 7 (6.5%) 5 (4.9%) 7 (6.5%)
Chills 8 (7.5%) 8 (7.8%) 8 (7.5%)
Headache 39 (36.4%) 30 (29.1%) 24 (22.4%)
Infection 6 (5.6%) 12 (11.7%) 7 (6.5%)
Pain 24 (22.4%) 19 (18.4%) 20 (18.7%)
Pain abdomen 12 (11.2%) 12 (11.7%) 7 (6.5%)
Pain back 4 (3.7%) 8 (7.8%) 12 (11.2%)
Withdrawal syndrome 27 (25.2%) 19 (18.4%) 40 (37.4%)
Cardiovascular System
Vasodilation 10 (9.3%) 4 (3.9%) 7 (6.5%)
Digestive System
Constipation 13 (12.1%) 8 (7.8%) 3 (2.8%)
Diarrhea 4 (3.7%) 5 (4.9%) 16 (15.0%)
Nausea 16 (15.0%) 14 (13.6%) 12 (11.2%)
Vomiting 8 (7.5%) 8 (7.8%) 5 (4.7%)
Nervous System
Insomnia 15 (14.0%) 22 (21.4%) 17 (15.9%)
Respiratory System
Rhinitis 5 (4.7%) 10 (9.7%) 14 (13.1%)
Skin And Appendages
Sweating 15 (14.0%) 13 (12.6%) 11 (10.3%)
Abbreviations: COSTART = Coding Symbols for Thesaurus of Adverse Reaction Terms.

 

The adverse event profile of buprenorphine was also characterized in the dose-controlled study of a buprenorphine ethanolic solution, over a range of doses in four months of treatment. Table 2 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled trial.

Table 2: Adverse Events (≥5%) by Body System and Treatment Group in a 16 Week Study

Body System/ Adverse Event (COSTART Terminology) Buprenorphine Dose
Very Low*
N=184 n (%)
Low*
N=180 n (%)
Moderate*
N=186 n (%)
High*
N=181 n (%)
Total*
N=731 n (%)
Body as a Whole
Abscess 9 (5%) 2 (1%) 3 (2%) 2 (1%) 16 (2%)
Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%)
Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%)
Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%)
Flu syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%)
Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%)
Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%)
Injury accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%)
Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%)
Pain back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%)
Withdrawal syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%)
Digestive System
Constipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%)
Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%)
Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%)
Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%)
Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%)
Nervous System
Anxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%)
Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%)
Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%)
Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%)
Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%)
Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%)
Respiratory System
Cough increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%)
Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 28 (4%)
Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%)
Skin and Appendages
Sweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%)
Special Senses
Runny eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%)
*Sublingual solution. Doses in this table cannot necessarily be delivered in tablet form, but for comparison purposes:
“Very low” dose (1 mg solution) would be less than a tablet dose of 2 mg
“Low” dose (4 mg solution) approximates a 6 mg tablet dose
“Moderate” dose (8 mg solution) approximates a 12 mg tablet dose
“High” dose (16 mg solution) approximates a 24 mg tablet dose

 

The safety of SUBOXONE sublingual film during treatment induction is supported by a clinical trial using 16 patients treated with SUBOXONE sublingual film and 18 treated with a buprenorphine-only sublingual film. Few differences in the adverse event profiles were noted between SUBOXONE sublingual film and the buprenorphine-only sublingual film.

The most common adverse event occurring during treatment induction and the 3 days following induction using SUBOXONE sublingual film was restlessness. Other adverse events were anxiety, piloerection, stomach discomfort, irritability, headache, rhinorrhea, cold sweat, arthralgia, and lacrimation increased.

Four subjects left the study early on the first day of sublingual film administration. However, there was no evidence to suggest that any of the four subjects experienced precipitated withdrawal secondary to the administration of buprenorphine or buprenorphine/naloxone sublingual films.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of SUBOXONE sublingual film. 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.

The most frequently reported postmarketing adverse events were peripheral edema, stomatitis, glossitis, and blistering and ulceration of the mouth or tongue.

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 SUBOXONE sublingual film.

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

Local reactions: glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis

 

SRC: NLM .