Suboxone (Buprenorphine Hydrochloride / Naloxone Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

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.

Adverse Events in Clinical Trials - SUBOXONE Sublingual Tablets

The safety of SUBOXONE was evaluated in 497 opioid-dependent subjects. The prospective evaluation of SUBOXONE was supported by clinical trials using SUBUTEX (buprenorphine tablets without naloxone) and other trials using buprenorphine sublingual solutions. In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction.

Few differences in adverse event profile were noted between SUBOXONE and SUBUTEX or buprenorphine administered as a sublingual solution.

The following adverse events were reported to occur by at least 5% of patients in a 4-week study (Table 1).

Table 1. Adverse Events >5% by Body System and Treatment Group in a 4-week Study

	N (%)	N (%)
Body System / Adverse Event (COSTART Terminology)	SUBOXONE 16 mg/day N=107	Placebo N=107
Body as a Whole
Asthenia	7 (6.5%)	7 (6.5%)
Chills	8 (7.5%)	8 (7.5%)
Headache	39 (36.4%)	24 (22.4%)
Infection	6 (5.6%)	7 (6.5%)
Pain	24 (22.4%)	20 (18.7%)
Pain Abdomen	12 (11.2%)	7 (6.5%)
Pain Back	4 (3.7%)	12 (11.2%)
Withdrawal Syndrome	27 (25.2%)	40 (37.4%)
Cardiovascular System
Vasodilation	10 (9.3%)	7 (6.5%)
Digestive System
Constipation	13(12.1%)	3 (2.8%)
Diarrhea	4 (3.7%)	16 (15.0%)
Nausea	16 (15.0%)	12 (11.2%)
Vomiting	8 (7.5%)	5 (4.7%)
Nervous System
Insomnia	15 (14.0%)	17 (15.9%)
Respiratory System
Rhinitis	5 (4.7%)	14 (13.1%)
Skin And Appendages
Sweating	15 (14.0%)	11 (10.3%)

The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine 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 study.

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)	Low* (N=180)	Moderate* (N=186)	High* (N=181)	Total* (N=731)
	N (%)	N (%)	N (%)	N (%)	N (%)
*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
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%)

Adverse Events – Post-marketing Experience with SUBOXONE Sublingual Tablets

The most frequently reported post-marketing adverse event not observed in clinical trials was peripheral edema.

REPORTS OF SUSPECTED SUBOXONE SIDE EFFECTS / ADVERSE REACTIONS

Possible Suboxone side effects / adverse reactions in 33 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 33 year old female

Reactions: Hypersensitivity, Urinary Incontinence, Faecal Incontinence, Mental Disorder, Disturbance in Attention, Amnesia

Adverse event resulted in: hospitalization

Suspect drug(s):
Klonopin
    Dosage: unknown dosing details
    Indication: Product Used FOR Unknown Indication

Suboxone
    Dosage: suboxone sublingual film. dosage unknown.
    Indication: Product Used FOR Unknown Indication

Possible Suboxone side effects / adverse reactions in 61 year old male

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 61 year old male

Reactions: Hepatic Neoplasm Malignant, Feeling of Body Temperature Change, Hyperhidrosis

Suspect drug(s):
Suboxone
    Dosage: sublingual film - dosing information unknown
    Indication: Product Used FOR Unknown Indication

Suboxone
    Dosage: sublingual film - dosing information unknown

Possible Suboxone side effects / adverse reactions in 27 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 27 year old female

Reactions: Diarrhoea, Memory Impairment, Asthenia, Convulsion

Suspect drug(s):
Suboxone