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

ADVERSE REACTIONS

The safety of SUBOXONE has been 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 are 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.

In a comparative study, adverse event profiles were similar for subjects treated with 16 mg SUBOXONE or 16mg SUBUTEX. The following adverse events were reported to occur by at least 5% of patients in a 4-week study (Table 3).

Table 3. Adverse Events (≥5%) by Body System and Treatment Group in a 4-week Study

	N(%)	N(%)	N(%)
Body System / Adverse Event (COSTART Terminology)	SUBOXONE 16mg/day N=107	SUBUTEX 16mg/day N=103	Placebo N=107
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%)

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 4 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled study.

Table 4. 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 (4mg solution) approximates a 6 mg tablet dose "Moderate" dose (8mg solution) approximates a 12 mg tablet dose "High" dose (16mg 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%)	1 1 (6%)	6 (3%)	4 (2%)	26 (4%)
Pharyngitis	6 (3%)	7 (4%)	6 (3%)	9 (5%)	28 (4%)
Rhinitis	27(15%)	16(9%)	1 5 (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%)

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO SUBOXONE

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

Reported by a health professional (non-physician/pharmacist) from Sweden on 2007-02-11

Patient: 33 year old male

Reactions: Psychotic Disorder, Derealisation

Suspect drug(s):
Suboxone

Other drugs received by patient: Subutex

Possible Suboxone side effects / adverse reactions in 26 year old male

Reported by a consumer/non-health professional from Finland on 2007-02-20

Patient: 26 year old male

Reactions: Tooth Erosion, Dental Caries, Toothache, Rash Pruritic

Suspect drug(s):
Suboxone

Other drugs received by patient: Rivatril; Doxal; Insomin

Possible Suboxone side effects / adverse reactions in 31 year old male

Reported by a consumer/non-health professional from Finland on 2007-02-20

Patient: 31 year old male

Reactions: Irritability, Tooth Loss, Tooth Repair, Tooth Fracture, Pain

Suspect drug(s):
Suboxone

Other drugs received by patient: Xanor; Dormicum