PROBUPHINE® (buprenorphine) Implant
for the treatment of Opioid Addiction
Market in progress
|Preclinical||Phase 1||Phase 2||Phase 3||Market|
Probuphine is a subdermal implant utilizing Titan's proprietary ProNeura drug delivery platform. Probuphine is the first and only product on the market for maintenance treatment of opioid addiction that provides non-fluctuating blood levels of buprenorphine around the clock for a period of six months following a single treatment procedure.
WARNING: IMPLANT MIGRATION, PROTUSION, EXPULSION and NERVE DAMAGE ASSOCIATED WITH INSERTION and REMOVAL. Probuphine is only available through the PROBUPHINE REMS Program.
Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.
Effective as maintenance treatment for opioid dependence.
The implant provides continuous delivery of buprenorphine for up to six months.
Patient treatment is a subdermal implant, removing the opportunity for theft, child overdose or diversion.
Ease of Use
Patients receive the Probuphine implant every six months. The insertion and removal procedure is performed in an outpatient setting.
What is Opioid Addiction?
Opioid addiction is a medical condition that is increasingly recognized as a global epidemic by world health authorities. Addiction is a primary, chronic disease of brain reward, motivation, memory and neurobiological circuitry. It is characterized by cravings, accompanied by a lack of impulse control, as well as cycles of relapse and remission. If left untreated, addiction is a progressive disease that often results in disability or premature death.
Opioid addiction requires long-term treatment plans and medical care; abstinence is rarely a successful therapeutic approach. The current gold standard for medication assisted therapy (MAT) in the U.S. is buprenorphine. Challenges with MAT include diversion and abuse associated with daily medications.
Given the significant health epidemic of opioid addiction in the U.S., federal officials are seeking ways to ensure greater access to safe and effective treatments for the disease, while minimizing the risk of diversion and abuse. The U.S. Health and Human Services (HHS) Department recently announced that it will move to expand access to MAT by revising the regulations related to the prescribing of buprenorphine to treat opioid dependence. The current cap on the number of patients that can be treated with buprenorphine products by a physician limits the availability of this important medication assisted therapy. The HHS revision to the regulation will provide a balance between expanding the supply of buprenorphine-based treatment, encouraging use of evidence-based MAT, and minimizing the risk of drug diversion.
Treatment options that help minimize the risk of abuse and diversion, such as Titan's Probuphine implant, increasingly play a crucial role in the maintenance treatment of patients suffering from opioid addiction.
Oral buprenorphine dominates the current opioid addiction market
U.S. sales of daily oral formulations of buprenorphine, 2015
U.S. buprenorphine prescriptions have exceeded those of methadone
A pivotal Phase 3 double-blind, double dummy clinical study of 177 patients met the pre-specified endpoint of non-inferiority as well as all secondary endpoints (Rosenthal, R., Lofwall, M., Kim, S., Chen,M., Beebe, K., Vocci, F. et al. (2016) Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: a randomized clinical trial. JAMA 316: 282-290.). Data from that trial also indicate that patients who were clinically stable on 8mg or less of buprenorphine per day maintained stability when transferred to Probuphine and were more likely to sustain abstinence from illicit opioids throughout the six months than those being treated with sublingual buprenorphine. The efficacy and safety of Probuphine were also studied in several other clinical trials, including a 163-patient, placebo-controlled study over a 24-week period (published in the Journal of the American Medical Association (JAMA)), and a follow on study of 287 patients (published in the journal Addiction).
For Heathcare Providers
Healthcare providers certified to prescribe buprenorphine products who would like more information about Probuphine or the certification process for prescribing Probuphine may contact Titan or may learn more at www.probuphineREMS.com.
Certification Process for Prescribing Probuphine
Through the PROBUPHINE REMS Program, Titan provides eligible health care providers with the necessary training and certification.
- Information on Probuphine and selection of suitable patients
- Proper methods for inserting and removing the Probuphine implant
- Hands-on training using a meat simulation model
Healthcare Professionals that have been Certified to Prescribe, implant and remove Probuphine:
Medical Specialties of Healthcare Professionals that have been Certified include:
- Correctional Medicine
- Occupational medicine
- Internal medicine
- Family medicine
- Surgery + subspecialties
Benefits of Probuphine
- Lower risk of diversion
- Additional option for medication-assisted treatment (MAT)
- Frequent travelers (No need for daily administration?)
- Fewer office visits
Patients are expected to begin treatment with oral buprenorphine formulations to determine their dosages before physicians can decide if Probuphine is the right treatment.
Indication & Important Safety Information
INDICATIONS AND USAGE
PROBUPHINE® (buprenorphine) implant is for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product (i.e., < 8 mg per day of Subutex or Suboxone sublingual tablet equivalent or generic equivalent).
PROBUPHINE should be used as part of a complete treatment program to include counseling and psychosocial support.
PROBUPHINE is not appropriate for new entrants to treatment and patients who have not achieved and sustained prolonged clinical stability, while being maintained on buprenorphine 8 mg per day or less of a Subutex or Suboxone sublingual tablet or generic equivalent.
IMPORTANT SAFETY INFORMATION
WARNING: IMPLANT MIGRATION, PROTRUSION, EXPULSION and NERVE DAMAGE ASSOCIATED WITH INSERTION and REMOVAL
Risk Associated with Insertion and Removal
Insertion and removal of PROBUPHINE are associated with the risk of implant migration, protrusion, 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.
Because of the risks associated with insertion and removal, PROBUPHINE is available only through a restricted program called the PROBUPHINE REMS Program. 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 PROBUPHINE implants. Patients must be monitored to ensure that PROBUPHINE is removed by a healthcare provider certified to perform insertions.
PROBUPHINE is contraindicated in patients with a history of hypersensitivity to buprenorphine or any other ingredients in PROBUPHINE (e.g., EVA).
SUMMARY OF WARNINGS AND PRECAUTIONS
- Respiratory and CNS Depression: Significant respiratory depression and death have occurred in association with buprenorphine particularly when taken by the intravenous (IV) route in combination with benzodiazepines or other CNS depressants (including alcohol). Consider dose reduction of CNS depressants when used concomitantly.
- Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome(NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.
- Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.
- Unintentional Pediatric Exposure: In the event an implant protrudes or comes out, keep the implant away from children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children.
- Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately.
- Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to initiation and during treatment.
- Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Verify that patient is clinically stable on transmucosal buprenorphine and not dependent on full agonists before inserting PROBUPHINE.
- Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic whenever possible. If opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect.
- Impairment of Ability to Drive and Operate Machinery: PROBUPHINE may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery.
- Other systemic effects: PROBUPHINE may cause orthostatic hypotension in ambulatory patients.
- Effects in Acute Abdominal Conditions: As with other opioids, buprenorphine may obscure the diagnosis or clinical course of patients with acute abdomincal conditions.
- Infection at Implant Site: Infection may occur at the site of the insertion or removal. Excessive palpation may increase an opportunity for infection. Improper removal carries risk of implant-site infection.
- General Precautions: PROBUPHINE should also be administered with caution in patients with a history of keloid formation, connective tissue disease, e.g., scleroderma or history of recurrent MRSA infections.
To report SUSPECTED ADVERSE REACTIONS, contact Titan at 1-844- 859-6341 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch