What are the possible side effects of Buprecare?
Get emergency medical help if you have signs of an allergic reaction to Buprecare: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Like other narcotic medicines, Buprecare can slow your breathing. Death may occur if breathing becomes too weak.
Call your doctor at once if you have:
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chest pain, fast heart rate, trouble breathing;
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weak or shallow breathing, feeling like you might pass out;
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severe constipation;
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infertility, missed menstrual periods;
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impotence, sexual problems, loss of interest in sex;
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low cortisol levels - nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness;
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opioid withdrawal symptoms - shivering, goose bumps, increased sweating, feeling hot or cold, runny nose, watery eyes, diarrhea, muscle pain; or
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liver problems - nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.
Serious side effects may be more likely in older adults and those who are ill or debilitated.
Common Buprecare side effects may be more likely to occur, such as:
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constipation, nausea, vomiting;
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headache, dizziness, drowsiness;
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increased sweating;
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sleep problems (insomnia); or
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pain anywhere in your body.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Side effects of Buprecare in details
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 Buprecare 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 Buprecare and 138 subjects who received 12 monthly SC injections. Adverse events led to premature discontinuation in 4% of the group receiving Buprecare 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 Buprecare.
| Study 13-0001 (NCT02357901) Up to 6 Injections | Study 13-0003 (NCT02510014) | Total Subjects Exposed To Buprecare | |||||
|---|---|---|---|---|---|---|---|
| *Not included in total subjects exposed to Buprecare | |||||||
| † 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 Buprecare, already accounted for in Study 13-0001 section of table | |||||||
| Roll-Over Up to 6 Injections | De-Novo Up to 12 Injections | ||||||
| Buprecare 300/100 mg | Buprecare 300/300 mg | Placebo | From Buprecare 300/100 mg To Buprecare 300/Flex† | From Buprecare 300/300 mg To Buprecare 300/Flex† | From Placebo To Buprecare 300/Flex† | Buprecare 300/Flex | |
| N = 203 | N = 201 | N = 100* | N = 112‡ | N = 113‡ | N= 32 | N = 412 | N = 848 |
Table 2 shows the non-injection site-related adverse reactions (ADRs) for the groups receiving Buprecare 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 Buprecare, given by a healthcare provider in clinical trials, was consistent with the known safety profile of transmucosal Buprecare. Common adverse reactions associated with Buprecare 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 Buprecare 300/300-mg, Buprecare 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 Buprecare are grouped by System Organ Class (SOC).
| System Organ Class Preferred Term | PLACEBO | Buprecare 300/100 mg | Buprecare 300/300 mg |
|---|---|---|---|
| Count (%) | Count (%) | Count (%) | |
| *There were no cases of serious liver injury attributed to study drug. | |||
| 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) |
| Dizziness | 2 (2) | 5 (2.5) | 3 (1.5) |
| Somnolence | 0 | 10 (4.9) | 4 (2) |
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.
| *Patients received SUBOXONE film for a run-in period before they switched to Buprecare injection. | ||||||||
| Preferred term, n (%) | 13-0001 (Ph3DB) | 13-0003 (Ph3OL) | All Phase 3* | |||||
| Roll–over | De-novo | |||||||
| Buprecare 300/300 (N = 201) | Buprecare 300/100 (N = 203) | Placebo (N = 100) | Buprecare 300 → Buprecare 300/Flex (N = 113) | Buprecare 100 → Buprecare 300/Flex (N = 112) | Placebo → Buprecare 300/Flex (N = 32) | Buprecare 300/Flex (N = 412) | Total Buprecare (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%) |
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 Buprecare sublingual tablets was drug misuse or abuse. The most frequently reported systemic postmarketing adverse event with Buprecare/naloxone sublingual tablets and film was peripheral edema.
The following adverse reactions have been identified during post-approval use of Buprecare. 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 Buprecare.
Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.
What is the most important information I should know about Buprecare?
- Buprecare tablets may cause drowsiness or dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Buprecare tablets. Using Buprecare tablets alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.
- Avoid drinking alcohol or taking other medications that cause drowsiness (eg, sedatives, tranquilizers) while taking Buprecare tablets. Buprecare tablets will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.
- Do not inject Buprecare tablets. Doing so may cause severe withdrawal symptoms, severe breathing problems, and death.
- Buprecare tablets may cause dizziness, lightheadedness, or fainting. Alcohol, hot weather, exercise, and fever can increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Also, sit or lie down at the first sign of dizziness, lightheadedness, or weakness.
- Before you have any medical or dental treatments, emergency care, or surgery, tell the doctor or dentist that you are using Buprecare tablets.
- LAB TESTS, including liver function tests, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.
- Use Buprecare tablets with caution in the ELDERLY because they may be more sensitive to its effects, especially decreased breathing and drowsiness.
- Buprecare tablets is not recommended for use in CHILDREN younger than 16 years of age. Safety and effectiveness in this age group have not been confirmed.
- PREGNANCY and BREAST-FEEDING: Buprecare tablets may cause harm to the fetus. If you think you may be pregnant, discuss with your doctor the benefits and risks of using Buprecare tablets during pregnancy. Buprecare tablets is excreted in breast milk. Do not breast-feed while taking Buprecare tablets.
When used for long periods of time or at high doses, some people develop a need to continue taking Buprecare tablets. This is known as DEPENDENCE or addiction.
If you suddenly stop taking Buprecare tablets, you may experience WITHDRAWAL symptoms, including anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping.
Buprecare contraindications
Using Buprecare improperly will increase your risk of serious side effects or death. Even if you have used other narcotic medications, you may still have serious side effects from Buprecare. Follow all dosing instructions carefully.
Like other narcotic medicines, Buprecare can slow your breathing. Death may occur if breathing becomes too weak.
Never crush a tablet or other pill to mix into a liquid for injecting the drug into your vein. This practice has resulted in death with the misuse of Buprecare and similar prescription drugs.
Wear a medical alert tag or carry an ID card stating that you take Buprecare, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are being treated for narcotic addiction.
Avoid drinking alcohol, which can increase some of the side effects of Buprecare. Using too much of this medicine in addition to drinking alcohol can cause death.
Do not stop using Buprecare suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using Buprecare. You may need to use less and less before you stop the medication completely.
This medication may impair your thinking or reactions. Avoid driving or operating machinery until you know how Buprecare will affect you.
References
- DailyMed. "BUPRENORPHINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- European Chemicals Agency - ECHA. "Buprenorphine: The information provided here is aggregated from the "Notified classification and labelling" from ECHA's C&L Inventory. ". https://echa.europa.eu/information-o... (accessed September 17, 2018).
- KEGG. "Target-based classification of drugs". http://www.genome.jp/kegg-bin/get_ht... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Buprecare are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Buprecare. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported side effects
No survey data has been collected yetConsumer reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
