Buprenorphine implant

Avoid drinking alcohol. Dangerous side effects could occur.

Buprenorphine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Using other drugs that make you sleepy or slow your breathing can cause dangerous side effects or death while buprenorphine implants are in your body. Ask your doctor before taking a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Many drugs can interact with buprenorphine, and some drugs should not be used while you have the implants in your body. Tell your doctor about all your current medicines and any you start or stop using, especially:

• an antibiotic, antifungal, or antiviral medicine;

• any type of antidepressant, sedative, or tranquilizer;

• heart or blood pressure medication;

• seizure medication; or

• tuberculosis medicine.

This list is not complete and many other drugs can interact with buprenorphine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

• If you have an allergy to buprenorphine or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood; or stomach or bowel block or narrowing.
• If you have liver disease.
• If you or a family member have a long QT on ECG.
• If you are taking any of these drugs: Butorphanol, nalbuphine, or pentazocine.
• If you are using another drug that has the same drug in it.
• If you are taking any of these drugs: Certain drugs to treat a heartbeat that is not normal like amiodarone, disopyramide, dofetilide, procainamide, quinidine, or sotalol.
• If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking buprenorphine implant within 14 days of those drugs can cause very bad high blood pressure.
• If you are taking any of these drugs: Linezolid or methylene blue.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take buprenorphine implant with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.
• Check with your pharmacist about how to throw out unused drugs.

Parenteral:
13 years or older:
Initial dose: 0.3 mg deep IM or slow IV (over at least 2 minutes) ; may repeat initial dose once after 30 to 60 minutes if required
Maintenance dose: 0.3 mg deep IM or slow IV at up to 6-hour intervals as needed
Maximum dose: 0.3 mg

2 to 12 years: 2 to 6 mcg/kg IM or slow IV every 4 to 6 hours; some patients may not need to be remedicated for 6 to 8 hours

Comments:
-Fixed interval or round the clock dosing should not be used until the proper inter-dose interval has been established.
-Use extra caution with IV administration, especially the first dose

Use: For the relief of moderate to severe pain

Aged 16 years or older: To be used as part of a complete treatment plan to include counseling and psychosocial support:

Buprenorphine TRANSMUCOSAL Products for Opioid Dependence (BTOD):
Induction dose:
-Day 1: 8 mg sublingually once a day
-Day 2: 16 mg sublingually once a day
Maintenance dose: 4 to 24 mg/day; dose adjustments may be made in increments/decrements of 2 or 4 mg to a level that suppresses opioid withdrawal symptoms and holds the patient in treatment.

Comments:
-To avoid precipitating withdrawal during induction, initiation should occur when clear signs of withdrawal are evident, preferably when moderate objective signs of opioid withdrawal appear.
-Following induction, combination buprenorphine/naloxone is preferred; use of buprenorphine alone should be limited to those patients who cannot tolerate naloxone.

Use: For the treatment of opioid dependence, preferably induction only.

Buprenorphine IMPLANT for Subdermal Administration:
-For opioid tolerant patients only
-Insert 1 dose subdermally in the inner side of the upper arm
-Remove implant at the end of the sixth month

Comments:
-Insertions and removals of implant should be performed by a certified healthcare provider.
-One dose consists of 4 implants; each implant contains buprenorphine 74.2 mg (equivalent to 80 mg buprenorphine hydrochloride).
-After 1 insertion in each arm, most patients should be transitioned back to transmucosal product for continued treatment; there is no experience with inserting additional implants into other sites in the arm or into a previously-used site.

Use: For the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a BTOD.

Patients chosen for implant use should meet all of the following criteria:
-Achieved and sustained prolonged clinical stability on an acceptable BTOD maintenance dose for 3 months or longer without any need for supplemental dosing or adjustments
Acceptable BTOD maintenance doses include:
--buprenorphine sublingual tablets (Subutex[R]) or generic equivalent at 8 mg or less per day
--buprenorphine/naloxone sublingual tablets (Suboxone[R]) or generic equivalent at 8 mg/2 mg or less per day
--buprenorphine/naloxone buccal film (Bunavail[R]) at 4.2 mg/0.7 mg or less per day
--buprenorphine/naloxone sublingual tablets (Zubsolv[R]) at 5.7 mg/1.4 mg or less per day
-Patients should not be tapered to a lower dose for the sole purpose of transitioning to the implant.

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Buprenorphine Transmucosal Products for Opioid Dependence (BTOD), Suboxone(R)/Subutex(R), Extended-Release and Long-Acting (ER/LA) Opioid Analgesics and Probuphine(R) implant. Each includes a medication guide and elements to assure safe use. Additionally BTOD, Suboxone(R)/Subutex(R), and Probuphine(R) require an implementation system. For additional information: www.fda.gov/REMS

US BOXED WARNINGS: Transdermal Patch
ADDICTION, ABUSE, AND MISUSE:
-This drug exposes patients and other users to the risks of opioid addiction, abuse, or misuse which can lead to overdose and death. Assess each patient's risk before prescribing; regularly monitor for these behaviors or conditions.
LIFE-THREATENING RESPIRATORY DEPRESSION:
-Respiratory depression with fatal outcome can occur. Monitor closely upon initiation or following a dose increase. Misuse or abuse by chewing, swallowing, snorting, or injecting buprenorphine extracted from the transdermal patch will result in uncontrolled delivery of the drug and pose a significant risk of overdose and death.
NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use during pregnancy can result in this life-threatening syndrome if not recognized and treated promptly. Treatment requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment will be available.
ACCIDENTAL EXPOSURE:
-Accidental ingestion to even 1 dose, especially in children, can be fatal.

US BOXED WARNING: Implant for Subdermal Administration
IMPLANT MIGRATION, PROTRUSION, EXPULSION, and NERVE DAMAGE ASSOCIATED WITH INSERTION and REMOVAL:
-Risk Associated with Insertion and Removal: Insertion and removal of this drug is associated with the risk of implant migration, protrusion, and expulsion resulting from the procedure. Rare but serious complications including nerve damage and migration resulting in embolism and death may result from improper insertion of drug implants inserted in the upper arm. Additional complications may include local migration, protrusion, and expulsion. Incomplete insertions or infections may lead to protrusion or expulsion. All healthcare providers must successfully complete a live training program on the insertion and removal procedures and become certified, prior to performing insertions or prescribing implants. Patients must be monitored to ensure that the implant is removed by a healthcare provider certified to perform insertions. Further information is available at www.PROBUPHINEREMS.com or 1-844-859-6341.

Drug Addiction Treatment Act:
Under the Drug Addiction Treatment Act (DATA) codified at 21 US Code 823(G), use of this product in the treatment of opioid dependence is limited to physicians who meet qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe or dispense this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

Safety and efficacy of the injection have not been established in patients younger than 2 years.
Safety and efficacy of the sublingual or implant for subdermal administration have not been established in patients younger than 16 years.
Safety and efficacy of transdermal products have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III

• Buprenorphine acts on mu opioid receptors to provide pain relief.
• Buprenorphine belongs to the class of medicines known as narcotic analgesics. It may also be called an opioid analgesic. An analgesic is a drug that is used to relieve pain. Sublingual buprenorphine should be reserved for the treatment of opioid addiction.

• Transdermal patches should be applied to a clean, dry, rash-free, hairless or nearly hairless area of skin on the upper chest, back, or arm, or side of the chest. Hair may need to be clipped prior to application (not shaved). Only use water to clean the area of skin prior to application because other substances (such as soaps, oils, or gels) may alter the absorption of the drug. Transdermal system should be worn continuously for seven days and then subsequent systems applied to different sites after removal of the previous system. Discard used patches carefully and out of reach of children or pets.
• Avoid exposing the site where the patch is located to excessive heat (such as electric blankets, saunas, or prolonged direct sunlight) as this may cause a faster-than-normal release of buprenorphine, increasing the risk of overdosage and death.
• Sublingual tablets must be placed under the tongue and allowed to dissolve; swallowing the tablets reduces how much buprenorphine is actually absorbed. Drinking warm fluids prior to administration may help with the dissolution of buprenorphine. Always try to take your tablets the same way to ensure blood levels of buprenorphine remain consistent.
• Sublingual strips should be placed side-by-side on the tongue (minimize overlapping) and allowed to dissolve. Avoid talking, chewing or swallowing while a strip is dissolving.
• Use buprenorphine strictly as directed by your doctor. Do not use on an "as needed" basis or increase or decrease the dosage without your doctor's advice.
• Some forms of buprenorphine have a REMS (Risk Evaluation and Mitigation Strategy) associated with them which means you will need to fill in a patient enrolment form with your Healthcare prescriber. Always read the medication guide prescribed with buprenorphine.
• If you are taking buprenorphine for severe pain, tell your doctor if you begin to have breakthrough pain.
• When used to treat drug addiction, it is important that you take advantage of any social support and counseling services offered to you as withdrawal from opioids is a long and often difficult process and a successful outcome is dependent upon a multi-targeted approach.
• Tell your doctor if you experience any difficulty with breathing or shortness of breath after taking buprenorphine, especially within the first 24 to 72 hours of initiating therapy.
• Avoid sudden discontinuation of buprenorphine. The dosage of buprenorphine must be tapered off slowly to minimize withdrawal symptoms which include restlessness, runny nose and eyes, muscle pain and insomnia. When the time comes to discontinue buprenorphine, your doctor will advise you on a tapering schedule.
• Rise carefully from a sitting to a standing position to minimize blood pressure lowering effects from buprenorphine which may result in dizziness increasing your risk of falls.
• Always talk to your doctor or pharmacist before buying anything over-the-counter to check if it is compatible with buprenorphine.

• The analgesic effect after IV administration usually occurs within 10-30 minutes; peak analgesic effects occur within 60 minutes. The analgesic effect of buprenorphine usually lasts for an average of six hours but duration may vary between individuals.
• It takes about three days for transdermal buprenorphine to reach a steady level.
• Sublingual preparations of buprenorphine vary in the time they take to dissolve (from just a few minutes to up to 12 minutes). people should not eat, drink, or talk during this time. Some relief from withdrawal symptoms should be expected within 30 minutes of the first dose. It may take several doses before the full effects are seen. A decrease in the response to buprenorphine may indicate that a higher dosage is needed.

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