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FDA Approves Buprenorphine Implant for Opioid Addiction

May 26, 2016
The Food and Drug Administration has added a long-term treatment options for patients with opioid dependence and addiction.

The US Food and Drug Adminstration has approved Probuphine, the first buprenorphine implant "for the maintenance treatment of opioid dependence." Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low-to-moderate doses of other forms of buprenorphine (ie, Suboxone).

Prior to today's action by the agency, the treatment of opioid dependence consisted of either an pill or buccal film formulations that needed to be taken on a daily basis. The new formulation "provides a new treatment option for people in recovery," noted the agency. An independent FDA advisory committee supported the approval of Probuphine in a meeting held earlier this year.

"Opioid abuse and addiction have taken a devastating toll on American families. We must do everything we can to make new, innovative treatment options available that can help patients regain control over their lives,” said FDA Commissioner Robert M. Califf, MD. “Today’s approval provides the first-ever implantable option to support patients’ efforts to maintain treatment as part of their overall recovery program.”

“The AMA is pleased the FDA approved a new implantable option to help treat patients with substance use disorders. With nearly 2.5 million Americans addicted to prescription opioids and heroin, patients will benefit from increased options for medication-assisted treatment," said Patrice A. Harris, MD, chair-elect of the American Medical Association in a statement.

“The approval by FDA, however, is only one of many steps we must take to rein in our spiraling opioid [including heroin] crisis," she added. "As physicians, we must avoid initiating opioids for new patients with chronic noncancer pain unless the expected benefits are anticipated to outweigh the risks; we must limit the amount of opioids prescribed for post-operative care and acutely-injured patients; and we must register for and use our state Prescription Drug Monitoring Programs to assist in the care of patients when considering the use of controlled substances. There is no panacea to the opioid crisis.”

Medication-Assisted Treatment

Expanding the use and availability of medication-assisted treatment (MAT) options like buprenorphine is an important component of the FDA’s opioid action plan and one of three top priorities for the US Department of Health and Human Services’ Opioid Initiative aimed at reducing prescription opioid and heroin related overdose, death and dependence.

MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine, or naltrexone) with counseling and other behavioral therapies to treat patients with opioid use disorder. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use, without causing the cycle of highs and lows associated with opioid misuse or abuse.

At sufficient doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their opioid use disorder cut their risk of death from all causes in half.

“Scientific evidence suggests that maintenance treatment with these medications in the context of behavioral treatment and recovery support are more effective in the treatment of opioid use disorder than short-term detoxification programs aimed at abstinence,” said Nora Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health. “This product will expand the treatment alternatives available to people suffering from an opioid use disorder.”

According to the FDA, Probuphine should be used as part of a complete treatment program that includes counseling and psychosocial support. Probuphine consists of 4, one-inch-long rods that are implanted under the skin on the inside of the upper arm and provide treatment for six months.

Administering Probuphine requires specific training because it must be surgically inserted and removed. Only a health care provider who has completed the training and become certified through a restricted program called the Probuphine Risk Evaluation and Mitigation Strategy (REMS) program should insert and remove the implants.

If further treatment is needed, new implants may be inserted in the opposite arm for one additional course of treatment. The FDA is requiring postmarketing studies to establish the safety and feasibility of placing the Probuphine implants for additional courses of treatment.

Safety and Efficacy

The safety and efficacy of Probuphine were demonstrated in a randomized clinical trial of adults who met the clinical criteria for opioid dependence and were considered stable after prior buprenorphine treatment. A response to MAT was measured by urine screening and self-reporting of illicit opioid use during the six month treatment period. Sixty-three percent of Probuphine-treated patients had no evidence of illicit opioid use throughout the 6 months of treatment—similar to the 64% of those who responded to sublingual buprenorphine alone.

The most common side effects included implant-site pain, itching, and redness, as well as headache, depression, constipation, nausea, vomiting, back pain, toothache and oropharyngeal pain. The safety and efficacy of Probuphine have not been established in children or adolescents less than 16 years of age, noted the FDA. Clinical studies of Probuphine did not include participants over the age of 65.

Probuphine has a boxed warning that provides important safety information for health care professionals, including a warning that insertion and removal of Probuphine are associated with the risk of implant migration, protrusion, expulsion and nerve damage resulting from the procedure. Probuphine must be prescribed and dispensed according to the Probuphine REMS program because of the risks of surgical complications and because of the risks of accidental overdose, misuse and abuse if an implant comes out or protrudes from the skin. As part of this program, Probuphine can only be prescribed and dispensed by health care providers who are certified with the REMS program and have completed live training, among other requirements.

Probuphine implants contain a significant amount of drug that can potentially be expelled or removed, resulting in the potential for accidental exposure or intentional misuse and abuse if the implant comes out of the skin. Patients should be seen during the first week after insertion and a visit schedule of no less than once-monthly is recommended for continued counseling and psychosocial support.

Probuphine is marketed by San Francisco-based Titan Pharmaceuticals Inc. and Braeburn Pharmaceuticals based in Princeton, New Jersey.

Last updated on: March 5, 2019

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