FDA Approves Zimhi (naloxone hydrochloride) Injection for the Treatment of Opioid Overdose

In continuation of my update on naloxone hydrochloride, Adamis Pharmaceuticals Corporation (Nasdaq: ADMP) announced   the U.S. Food and Drug Administration (FDA)   approval of  Adamis’ Zimhi™ (naloxone HCL Injection, USP) 5 mg/0.5 mL product. Zimhi is a high-dose naloxone injection product FDA-approved for use in the treatment of opioid overdose.

Naloxone is an opioid antagonist and is generally considered the drug of choice for immediate administration for opioid overdose. It works by blocking or reversing the effects of the opioid, including extreme drowsiness, slowed breathing, or loss of consciousness. Common opioids include morphine, heroin, tramadol, oxycodone, hydrocodone and fentanyl.

According to statistics published by the Centers for Disease Control and Prevention (CDC), drug overdoses resulted in approximately 96,779 deaths in the United States during the 12-month period ending March 2021, which was a 29% increase over the prior 12-month period. Drug overdoses are now the leading cause of death for Americans under age 50, with more powerful synthetic opioids, like fentanyl and its analogues, responsible for the largest number of those deaths.

Dr. Jeffrey Galinkin, an anesthesiologist, and former member of the FDA Advisory Committee for Anesthetics, Analgesics and Addiction Products, commented, “I am pleased to see this much needed high dose naloxone product will become part of the treatment tool kit as a countermeasure to the continued surge in fentanyl related deaths. The higher intramuscular doses of naloxone in Zimhi should result in more rapid and higher levels of naloxone in the systemic circulation, which in turn, should result in more successful resuscitations.”

Dr. Dennis J. Carlo, President and CEO of Adamis, stated, “We are very excited by this approval and are working with our commercial partner, US WorldMeds, to make this much-needed, lifesaving product readily available to the market. Zimhi provides the highest systemic levels of naloxone compared to any of the nasal or intramuscular products currently available.”

P. Breckinridge Jones, Sr., CEO of US WorldMeds, added, “We are pleased with the approval and now look forward to commercially marketing Zimhi in the United States. US WorldMeds has a proven track-record of successfully commercializing pharmaceutical products and have a First-in-Class and only FDA-approved product, LUCEMYRA® (lofexidine), for the treatment of withdrawal symptoms associated with abrupt opioid discontinuation. We are confident we can leverage our existing commercial infrastructure and presence in the opioid dependence market to speed the uptake of Zimhi and combat the growing opioid crisis. We are preparing for the full commercial launch of ZIMHI which is planned for the first quarter of 2022.”\

Naloxone Prescribing Increasing but Still Very Low

In continuation of my update on Naloxone

Naloxone prescribing has increased but is still very low among patients at risk for opioid overdose, according to a study recently published in the Journal of General Internal Medicine.

Lewei (Allison) Lin, M.D., from the University of Michigan in Ann Arbor, and colleagues compared adults who received opioids and naloxone from January 2014 to June 2017 to those who received opioids without naloxone using a U.S.-wide health insurance claims dataset. A total of 3,963 opioid+naloxone and 19,815 opioid-only patients were matched based on gender, age, month/year of opioid fill, and number of opioid claims.

The researchers found that high opioid daily dosage (50 to <90 morphine milligram equivalents [MME] and ≥90 MME versus <50 MME: adjusted odds ratios, 2.43 and 3.94, respectively), receiving concurrent benzodiazepines (adjusted odds ratio, 1.27), and having a diagnosis of opioid use disorder (adjusted odds ratio, 1.56) were key factors associated with naloxone fills. There was an increase in the percentage of patients receiving naloxone, but by the last six months of the study period, less than 2 percent of patients in any of the key overdose risk factor groups received naloxone.

"Increasing naloxone availability is one of the most promising interventions to reduce opioid overdose," the authors write. "These findings suggest there is substantial further work needed to increase naloxone for patients at risk for opioid overdose."

One author disclosed financial ties to the pharmaceutical industry.

https://link.springer.com/article/10.1007%2Fs11606-019-05423-7

https://en.wikipedia.org/wiki/Naloxone

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose

In continuation of my update on naloxone 

   

The first generic naloxone nasal spray to treat opioid overdose has received approval from the U.S. Food and Drug Administration.

Teva Pharmaceuticals' lifesaving product is also the first generic naloxone nasal spray approved for use by people without medical training. There was already a brand-name spray (Narcan) for emergency use by untrained people, such as family members and bystanders.

The need is urgent. On average, more than 130 Americans die every day from overdoses of opioids -- including prescription painkillers such as fentanyl, oxycodone (OxyContin), hydrocodone (Vicodin) and morphine, as well as illegal drugs such as heroin or drugs sold as heroin, the FDA said.

"In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible," said Dr. Douglas Throckmorton, deputy center director for regulatory programs in the FDA's Center for Drug Evaluation and Research.

"In addition to this approval of the first generic naloxone nasal spray, moving forward we will prioritize our review of generic drug applications for naloxone," he added.

When someone overdoses on opioids, breathing may become shallow or stop completely, leading to death if no one intervenes. If administered quickly, naloxone can counter the effects within minutes.

Throckmorton said in an agency news release that the FDA is also helping drugmakers pursue approval of an over-the-counter naloxone product, and "exploring other ways to increase availability of naloxone products intended for use in the community."

The FDA is also considering whether naloxone should be routinely prescribed along with all or some opioid prescriptions in order to reduce the risk of overdose.

"Altogether, these efforts have the potential to put a vital tool for combating opioid overdose in the hands of those who need it most -- friends and families of opioid users, as well as first responders and community-based organizations," Throckmorton said.

Nearly 400,000 people in the United States died of opioid overdoses between 1999 and 2017, according to the U.S. Centers for Disease Control and Prevention.

"We're committed to working with other federal, state and local officials, as well as health care providers, patients and communities across the country to combat the staggering human and economic toll created by opioid abuse and addiction," Throckmorton said in the news release.

 Ref : https://en.wikipedia.org/wiki/Naloxone

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose  

Naloxone Nasal Spray Works Best to Stop Opioid OD...

In continuation of my update on naloxone

A one-step nasal spray is the easiest form of naloxone to give someone suffering an opioid overdose, researchers say.

Increased public availability of naloxone, also known by the brand name Narcan, is considered a key way to reduce opioid overdose deaths. But there's more than one way to administer it, and it wasn't clear which method would be most successful when given by a bystander.

In this study, 138 adults watched a two-minute video demonstrating how to administer naloxone using one of the three methods -- two nasal sprays and one intramuscular shot. Each participant then selected one method to administer naloxone to a mannequin.

The study participants had a higher rate of success with the single-step nasal spray than with an intramuscular naloxone injection. They administered the one-step nasal spray faster than either a multi-step atomized spray or shot.

"With training, nasal sprays in general had a higher degree of success than the shot," said study author William Eggleston. He's a clinical assistant professor in the School of Pharmacy and Pharmaceutical Sciences at Binghamton University in New York.

"Even if it seemed to us it was a no-brainer that we should be using nasal sprays, we had no data before, so now we have some to support that," he said in a university news release.

https://en.wikipedia.org/wiki/Naloxone#/media/File:Naloxone.svg

Cassipa Approved for Opioid Dependence

In continuation of my update on buprenorphine and naloxone

                                           

Cassipa (buprenorphine and naloxone), a film designed to be placed under the tongue, has been approved to treat opioid dependence, the agency said in a news release.

Both buprenorphine and naloxone have been approved previously for this purpose.

"Opioid replacement therapy can be an important part of effective treatment," said FDA Commissioner Dr. Scott Gottlieb. "Opioid use disorder should be viewed similarly to any other chronic condition that is treated with medication."

The newly approved drug duo should be part of a complete treatment plan that includes counseling and psychosocial support to treat people with opioid use disorder. Cassipa may only be dispensed by approved prescribers, the agency said.

Side effects of the drugs include oral numbness, burning mouth, inflammation of the mouth's mucous membrane, headache, nausea, vomiting, excessive sweating and constipation.

Cassipa is produced by Teva Pharmaceuticals USA, based in New Jersey. Its parent company is located in Israel.

https://en.wikipedia.org/wiki/Buprenorphine

https://en.wikipedia.org/wiki/Naloxone

FDA Approves Sublocade (buprenorphine) Once-Monthly Injection for Opioid Use Disorder

In continuation of my update on Sublocade (buprenorphine)

The U.S. Food and Drug Administration today approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.

Buprenorphine for the treatment of OUD is currently approved to administer as a tablet or film that dissolves in the mouth, or as an implant. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade at a meeting held last month.

"Given the scale of the opioid crisis, with millions of Americans already affected, the FDA is committed to expanding access to treatments that can help people pursue lives of sobriety. Everyone who seeks treatment for opioid use disorder deserves the opportunity to be offered the treatment best suited to the needs of each individual patient, in combination with counseling and psychosocial support, as part of a comprehensive recovery plan,” said FDA Commissioner Scott Gottlieb, M.D. “As part of our ongoing work in supporting the treatment of those suffering from addiction to opioids, the FDA plans to issue guidance to expedite the development of new addiction treatment options. We’ll continue to pursue efforts to promote more widespread use of existing, safe and effective FDA-approved therapies to treat addiction.”

Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (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.

OUD is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress and includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition.

MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with 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 their OUD cut their risk of death from all causes in half.

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film (absorbed under the tongue). Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group.

The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose).

Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.

FDA Approves Sublocade (buprenorphine) Once-Monthly Injection for Opioid Use Disorder

Expand prescribing of buprenorphine for opioid abuse? Experts weigh pros and cons....

In continuation of my update on Buprenorphine

Buprenorphine is a critical part of treatment for the growing epidemic of opioid abuse--but also carries the potential for misuse and diversion. The debate over whether 'to expand or not to expand' prescribing of buprenorphine for opioid abuse is discussed in an expert review in the Journal of Psychiatric Practice, published by Wolters Kluwer.

Based on the strong evidence of effectiveness, "We should not limit or impede the use and expansion of buprenorphine therapy," write Drs. Xiaofan Li, Daryl Shorter, and Thomas Kosten, of the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. They propose specific strategies to promote buprenorphine use while ensuring quality of care and reducing the risk of diversion and abuse.

Focus on Expanding Buprenorphine Use 'Safely and Effectively'

A "partial agonist" of the μ-opioid receptor in the brain, buprenorphine has similar actions to other opioids, but with less potential for abuse and a more favorable safety profile. Because it reduces demand for opioids, buprenorphine therapy is an effective deterrence strategy to combat opioid abuse. The authors cite studies suggesting that access to buprenorphine therapy can sharply reduce heroin mortality--including reductions of more than 50 percent in France and 37 percent in Baltimore.

Compared to methadone--long the standard for treating opioid and heroin addiction--buprenorphine poses lower risks related to diversion and non-medical use. The most commonly prescribed form of buprenorphine includes the opioid antagonist (blocker) naloxone, decreasing the potential for intravenous abuse.

But there are strict controls on prescribing of buprenorphine, which is classified as a Schedule III controlled substance in the United States. To prescribe buprenorphine in office-based settings, physicians must receive a Drug Enforcement Agency (DEA) waiver, complete special training, and comply with limits on the number of treated patients.

While medical use of buprenorphine has skyrocketed over the past decade, most prescribers are located in urban areas. It is estimated that 53 percent of US counties do not have any physician with a DEA waiver to prescribe buprenorphine.

Measures to make buprenorphine treatment more accessible have been proposed, such as allowing prescribing by qualified advanced nurse practitioners and physician assistants and loosening limits on number of patients treated. But these measures have been controversial, reflecting legitimate concerns about increased potential for diversion and abuse. Data show that, as use of buprenorphine to treat opioid use disorder has increased, so have the rates of misuse and diversion.

Drs. Li, Shorter, and Kosten raise special concern about the recent emergence of intravenous buprenorphine abuse. They write, "This real-world, almost paradoxical, phenomenon demonstrates the complexity inherent in the treatment of addictive disorders--a medication intended to treat substance use disorder that has its own abuse potential, upon gaining popularity and increased availability, will inevitably be explored by drug abusers for reward and reinforcement purposes."

Earlier this year, President Obama announced an initiative to increase access to effective medications for treating opioid addiction--specifically, buprenorphine and naloxone. Drs. Li, Shorter, and Kosten outline strategies to expand effective treatment with buprenorphine while reducing the risks of diversion and abuse, including:

• Additional support for physicians with high caseloads and other measures to help prescribers comply with guidelines.
• Continuing medical education targeting improvements in office-based therapy for opioid abuse.
• Policies and regulations promoting safe practice.
• Financial incentives coupled with mandatory enforcement of essential components of safe practice.
• More active pharmacy involvement, including supervised dispensing.
• Identification of groups at high risk of intravenous buprenorphine abuse.

"The question is not whether or not to expand buprenorphine prescribing," the authors add. "It is how to expand buprenorphine prescribing safely and effectively."

Ref :1. http://journals.lww.com/practicalpsychiatry/pages/articleviewer.aspx?year=2016&amp;issue=05000&amp;article=00004&amp;type=abstract

 http://dx.doi.org/10.1097/PRA.0000000000000154

Expand prescribing of buprenorphine for opioid abuse? Experts weigh pros and cons 

BDSI announces FDA approval of BUNAVAIL sNDA for manufacturing specification change

BioDelivery Sciences International, Inc. (NASDAQ: BDSI) announced that the U.S. Food and Drug Administration (FDA) has approved the company's Supplemental New Drug Application (sNDA) for a manufacturing specification change for BUNAVAIL® (buprenorphine and naloxone) buccal film (CIII).

The approval allows for the immediate release of BUNAVAIL inventory to wholesalers. BDSI will be shipping product to wholesalers this morning which should make product available in pharmacies as early as Friday.

The newly released product supplies are expected to satisfy current and anticipated demand, which has increased following the October 1 initiation of a contract providing exclusive, preferred formulary status for BUNAVAIL for Medicaid patients in the state of Tennessee.

"All of us at BDSI want to thank the Division of Anesthesia, Analgesia and Addiction Products at FDA for working with us in an expeditious and collaborative fashion to help allow patients benefiting from BUNAVAIL treatment to maintain uninterrupted availability," said Dr. Mark A. Sirgo, President and Chief Executive Officer. "We also want to thank all of the patients, physicians and other health providers, including pharmacists, for their patience and support during this period of inconvenience."

BDSI announces FDA approval of BUNAVAIL sNDA for manufacturing specification change

New drug multiplies analgesic effect of opioids without increasing constipation

Systemic (subcutaneous) or local (intraplantar) treatment of wild-type mice with the selective σ₁ antagonists BD-1063 [1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride] or S1RA [4-[2-[[5-methyl-1-(2-naphthalenyl)1H-pyrazol-3-yl]oxy]ethyl] morpholine hydrochloride] potentiated μ-opioid antinociception; these effects were fully reversed by the σ₁agonist PRE-084 [2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate) hydrochloride], showing the selectivity of the pharmacological approach. The μ-opioid antinociception potentiated by σ₁ inhibition (by σ₁-receptor knockout orσ₁-pharmacological antagonism) was more sensitive to the peripherally restricted opioid antagonist naloxone methiodide than opioid antinociception under normal conditions, indicating a key role for peripheral opioid receptors in the enhanced antinociception. Direct interaction between the opioid drugs and σ₁ receptor cannot account for our results, since the former lacked affinity for σ₁ receptors (labeled with [³H](+)-pentazocine). A peripheral role for σ₁ receptors was also supported by their higher density (Western blot results) in peripheral nervous tissue (dorsal root ganglia) than in several central areas involved in opioid antinociception (dorsal spinal cord, basolateral amygdala, periaqueductal gray, and rostroventral medulla). In contrast to its effects on nociception, σ₁-receptor inhibition did not alter fentanyl- or loperamide-induced constipation, a peripherally mediated nonanalgesic opioid effect. Therefore, σ₁-receptor inhibition may be used as a systemic or local adjuvant to enhance peripheral μ-opioid analgesia without affecting opioid-induced constipation.

Ref : http://jpet.aspetjournals.org/content/348/1/32.abstract?sid=60aaa64d-fb66-459c-aded-4e971ab39aac


New drug multiplies analgesic effect of opioids without increasing constipation

Drug May Help Women Who Quit Smoking Avoid Weight Gain - Drugs.com MedNews

In continuation of my update on Naltrexone

We know that, Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloridesalt, naltrexone hydrochloride, and marketed under the trade names Revia andDepade. In some countries including the United States, a once-monthly extended-release injectable formulation is marketed under the trade name Vivitrol. Also in the US, Methylnaltrexone Bromide, a closely related drug, is marketed as Relistor, for the treatment of opioid induced constipation.

Naltrexone should not be confused with naloxone (which is used in emergency cases of overdose rather than for longer-term dependence control) nor nalorphine. Using naloxone in place of naltrexone can cause far worse withdrawal symptoms; conversely, using naltrexone in place of naloxone in an overdose can lead to insufficient opiate antagonism and fail to reverse the overdose.

Drug May Help Women Who Quit Smoking Avoid Weight Gain - Drugs.com MedNews