FDA approves new dosage of buprenorphine and naloxone for opioid dependence

The U.S. Food and Drug Administration today approved Cassipa (buprenorphine and naloxone) sublingual film (applied under the tongue) for the maintenance treatment of opioid dependence. This action provides a new dosage strength (16 milligrams/4 milligrams) of buprenorphine and naloxone sublingual film, which is also approved in both brand name and generic versions and in various strengths.

“There’s an urgent need to ensure access to, and wider use and understanding of, medication-assisted treatment for opioid use disorder. The introduction of new treatment options has the potential to broaden access for patients. For example, the FDA recently described a streamlined approach to drug development for certain medication-assisted treatments that are based on buprenorphine. This streamlined approach can reduce drug development costs, so products may be offered at a lower price to patients and we can broaden access to treatment,” said FDA Commissioner Scott Gottlieb, M.D. “The FDA is committed to helping those with opioid use disorder transition to lives of sobriety. We’ve taken a number of steps to advance the development of new FDA-approved treatments for opioid dependence and encourage healthcare professionals to ensure patients are offered an adequate chance to benefit from these therapies. We’re also working to address the unfortunate stigma that’s sometimes associated with the use of opioid replacement therapy as one approach to the successful treatment of addiction. Despite what some may think, individuals who successfully transition onto medication-assisted treatment are not swapping one addiction for another. Opioid replacement therapy can be an important part of effective treatment. Opioid use disorder should be viewed similarly to any other chronic condition that is treated with medication.”

Medication-assisted treatment (MAT) is a comprehensive approach that combines FDA-approved medications (currently methadone, buprenorphine, or naltrexone) with counselling and other behavioural therapies to treat patients with opioid use disorder (OUD). Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper 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 treatment of their OUD cut their risk of death from all causes in half.

Improving access to prevention, treatment and recovery services, including the full range of MAT, is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis. Last month, the FDA issued draft guidance outlining new ways for drug developers to consider measuring and demonstrating the effectiveness and benefits of new or existing MAT products, building on another draft guidance issued in April outlining the agency’s current thinking about drug development and trial design issues relevant to the study of depot buprenorphine products (i.e., modified-release products for injection or implantation). In June, the agency also approved the first generic versions of Suboxone (buprenorphine and naloxone) sublingual film in multiple strengths.

Cassipa was approved through an abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act called the 505(b)(2) pathway. A new drug application submitted through this pathway may rely on the FDA’s finding that a previously approved drug is safe and effective or on published literature to support the safety and/or effectiveness of the proposed product if such reliance is scientifically justified. In the case of Cassipa, the manufacturer submitted a 505(b)(2) application that relied, in part, on the FDA’s finding of safety and effectiveness for Suboxone sublingual film to support approval. The applicant demonstrated that reliance on the FDA’s finding of safety and effectiveness for Suboxone was scientifically justified and provided Cassipa-specific pharmacokinetic data to establish the drug’s safety and efficacy for its approved uses.

Cassipa should be used as part of a complete treatment plan that includes counselling and psychosocial support and should only be used after patient induction and stabilization up to a dose of 16 milligrams of buprenorphine using another marketed product. Adverse events commonly observed with the buprenorphine and naloxone sublingual film are oral hypoesthesia (numbness), glossodynia (burning mouth), oral mucosal erythema (inflammation of oral mucous membrane), headache, nausea, vomiting, hyperhidrosis (excessive sweating), constipation, signs and symptoms of withdrawal, insomnia, pain and peripheral edema (accumulation of fluid causing swelling in lower limbs). These products may only be prescribed by Drug Addiction Treatment Act (DATA)-certified prescribers.

The FDA granted approval of Cassipa to Teva Pharmaceuticals USA Inc.

The FDA remains committed to addressing the national crisis of opioid addiction on all fronts, with a significant focus on decreasing exposure to opioids and preventing new addiction by taking steps to encourage more appropriate prescribing; supporting the treatment of those with OUD and promoting the development of improved as well as lower cost forms of MAT; fostering the development of novel pain treatment therapies that may not be as addictive as opioids, and the development of opioids more resistant to abuse and misuse; and taking action against those who contribute to the illegal importation and sale of opioid products. The agency will also continue to evaluate how drugs currently on the market are used, in both medical and illicit settings, and take regulatory action where needed.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.