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warnings and cautions
5 WARNINGS AND PRECAUTIONS Addiction, Abuse and Misuse: Buprenorphine can be abused in a similar manner to other opioids. Clinical monitoring appropriate to the patient’s level of stability is essential. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. ( 5.1 ) Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets. ( 5.2 , 5.3 ) Unintentional Pediatric Exposure: Store buprenorphine and naloxone sublingual tablets safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children. ( 5.4 ) Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy. ( 5.5 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.6 ) Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately. ( 5.7 ) Risk of Hepatitis; Hepatic Events: Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events. ( 5.8 ) Precipitation of Opioid Withdrawal Signs and Symptoms: An opioid withdrawal syndrome is likely to occur with parenteral misuse of buprenorphine and naloxone sublingual tablet by individuals physically dependent on full opioid agonists, or by sublingual administration before the agonist effects of other opioids have subsided. ( 5.10 ) Risk of Overdose in Opioid-Naïve Patients: Buprenorphine and naloxone sublingual tablet is not appropriate as an analgesic. There have been reported deaths of opioid naïve individuals who received a 2 mg sublingual dose. ( 5.11 ) 5.1 Addiction, Abuse, and Misuse Buprenorphine and naloxone sublingual tablets contain buprenorphine, a schedule III controlled substance that can be abused in a manner similar to other opioids, legal or illicit...
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adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Respiratory and CNS Depression [see Warnings and Precautions ( 5.2 , 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.6 )] Opioid Withdrawal [see Warnings and Precautions ( 5.7 , 5.10 )] Hepatitis, Hepatic Events [see Warnings and Precautions ( 5.8 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] Orthostatic Hypotension [see Warnings and Precautions ( 5.16 )] Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions ( 5.17 )] Elevation of Intracholedochal Pressure [see Warnings and Precautions ( 5.18 )] Adverse events commonly observed with administration of buprenorphine and naloxone sublingual tablets are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact PAI Pharma at 1-800-845-8210 or FDA at 1-800-FDA-1088, or www.fda.gov/medwatch. 6.1 Clinical Trial 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 buprenorphine and naloxone sublingual tablets was evaluated in 497 opioid-dependent subjects. The prospective evaluation of buprenorphine and naloxone sublingual tablets were supported by clinical trials using buprenorphine sublingual tablets 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 buprenorphine and naloxone sublingual tablets and buprenorphine sublingual tablets 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 Body System...
adverse reactions table
Table 1. Adverse Events (≥ 5%) by Body System and Treatment Group in a 4-week StudyBody System / Adverse Event (COSTART Terminology)N (%) Buprenorphine and Naloxone Sublingual Tablets 16 mg/day N=107 N (%) Placebo N=107Body as a WholeAsthenia7 (6.5%)7 (6.5%)Chills8 (7.5%)8 (7.5%)Headache39 (36.4%)24 (22.4%)Infection6 (5.6%)7 (6.5%)Pain24 (22.4%)20 (18.7%)Pain Abdomen12 (11.2%)7 (6.5%)Pain Back4 (3.7%)12 (11.2%)Withdrawal Syndrome27 (25.2%)40 (37.4%)Cardiovascular SystemVasodilation10 (9.3%)7 (6.5%)Digestive SystemConstipation13 (12.1%)3 (2.8%)Diarrhea4 (3.7%)16 (15.0%)Nausea16 (15.0%)12 (11.2%)Vomiting8 (7.5%)5 (4.7%)Nervous SystemInsomnia15 (14.0%)17 (15.9%)Respiratory SystemRhinitis5 (4.7%)14 (13.1%)Skin And AppendagesSweating15 (14.0%)11 (10.3%)
BUPRENORPHINE AND NALOXONE (BUPRENORPHINE HYDROCHLORIDE AND NALOXONE HYDROCHLORIDE) TABLET [PAI HOLDINGS, LLC DBA PHARMACEUTICAL ASSOCIATES, INC. AND DBA PAI PHARMA]