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.”\

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  

Charleston Laboratories, Inc. and Daiichi Sankyo, Inc. Announce FDA Acceptance of New Drug Application (NDA) for CL-108

In continuation of my updates on hydrocodone, Promethazine & acetaminophen

Charleston Laboratories, Inc. and Daiichi Sankyo, Inc.  announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for CL-108   (is a novel bi-layered tablet containing 12.5mg of immediate release promethazine with a modified release of 7.5 mg of hydrocodone and 325mg of acetaminophen) for the relief of moderate to severe pain while preventing or reducing the associated opioid-induced nausea and vomiting (OINV). CL-108 is a fixed-dose, immediate-release bi-layered tablet with a rapid release layer containing 12.5 mg of promethazine and a second layer containing 7.5 mg of hydrocodone and 325 mg of acetaminophen. The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of January 31, 2017.

 promethazine

"With this NDA acceptance, patients are one step closer to being able to have an option for relieving pain while also preventing or minimizing the nausea and vomiting side effects of opioid treatment," said Paul Bosse, President and Chief Executive Officer of Charleston Laboratories, Inc. "At Charleston Laboratories, a key part of our mission is to develop and commercialize products that provide patients with novel solutions for improving their pain management. This acceptance represents an important contractual milestone under our relationship with Daiichi Sankyo."

"Daiichi Sankyo is dedicated to bringing innovative medicines to patients with unmet medical needs in the area of pain management," said Mahmoud Ghazzi, MD, PhD, President and Global Head of Development for Daiichi Sankyo. "We look forward to working closely with the FDA during the review process for CL-108 and support the Agency's efforts to foster the safe and responsible use of opioid medications."

The NDA for CL-108 is supported by two pivotal randomized, double-blind, placebo- and active-controlled Phase 3 clinical studies, one following oral surgery (molar removal) and the other after bunionectomy surgery (removal of bunions from the foot), as well as by an additional Phase 3 open-label, actual use safety study in patients with moderate-to-severe acute pain, or "flares," associated with osteoarthritis of the knee or hip. More than 1,000 patients have been enrolled in the CL-108 Phase 3 clinical trial program. A human abuse liability study has also been conducted.

Tris Pharma announces launch of generic TUSSIONEX

Tris Pharma, a specialty pharmaceutical company that develops innovative drug delivery technologies, announced the launch of Tris-labeled generic TUSSIONEX®, an extended-release suspension containing hydrocodone polistirex and chlorpheniramine polistirex.

Tussionex®, originally approved in the early 1980's, had no generic competition until 2010 when Tris Pharma's generic product entered the market under an exclusive distribution agreement with Par Pharmaceuticals. Under the terms of the distribution agreement, Par had the exclusive right to market Tris Pharma's hydrocodone polistirex and chlorpheniramine polistirex ER oral suspension for a five year period ending September 30, 2015. With the conclusion of the five year term, the rights have reverted back to Tris and as of October 1, 2015, hydrocodone polistirex and chlorpheniramine polistirex ER Suspension in 115ml and 473 ml bottles (compare to Tussionex®) will be marketed and distributed by Tris Pharma's generic business.

Tris Pharma announces launch of generic TUSSIONEX

FDA Approves 'Abuse-Resistant' Narcotic Painkiller

In continuation of my update on Hydrocodone

Seeking to make it tougher for people to misuse prescription painkillers, the U.S. Food and Drug Administration on Thursday approved a new hydrocodone tablet that's designed to help thwart abuse.

Hydrocodone -- best known by the brand name Vicodin (combination of Hydrocodone and Paracetamol) - is a powerful opioid painkiller that has been tied to a surge in dangerous addictions across the United States.

The FDA said that newly approved Hysingla ER (hydrocodone bitartrate) is an extended-release tablet to treat pain severe enough to require daily, round-the-clock, long-term opioid treatment that can't be eased by other pain medications.

The drug is not approved for "as-needed" pain relief, the agency said.

Hysingla has features that are expected to reduce, but not prevent, abuse of the drug. According to the FDA, the tablet is difficult to crush, break or dissolve, making it tougher for abusers to snort or inject it.

FDA Approves 'Abuse-Resistant' Narcotic Painkiller  

Phase 3 study: Tapentadol ER lowers incidence of gastrointestinal adverse events..

Tapentadol (see structure) is a new molecular entity that is structurally similar to tramadol (Ultram). It is a centrally-acting analgesic with a dual mode of action as an agonist at the μ-opioid receptor and as a norepinephrine reuptake inhibitor. While its action reflects aspects of tramadol and morphine its ability to kill pain is more on the order of hydrocodone and oxycodone. Interestingly it  has opioid and nonopioid acitivity in a single compound.  Tapentadol is FDA approved for the treatment of moderate to severe acute pain. Due to the dual mechanism of action as an opioid agonist and norepinephrine reuptake inhibitor is potential for off use in chronic pain.

Tapentadol was developed by Grünenthal in conjunction with Johnson & Johnson Pharmaceutical Research and Development. It is being marketed as immediate release oral tablets of 50 mg, 75 mg, and 100 mg under the brabd name Nucynta.

A Phase 3 open-label study (by Johnson & Johnson Pharmaceutical Research & Development, L.L.C), recently published online by Pain Practice, has compared tapentadol extended release (ER) tablets, an investigational pain medication, to an existing prescription pain medication, oxycodone controlled release (CR) tablets.

The study found tapentadol ER was associated with a lower overall incidence of gastrointestinal adverse events than oxycodone CR (tapentadol ER, 52.0 percent; oxycodone CR, 64.1 percent) in patients with chronic knee or hip osteoarthritis pain or chronic low back pain, including: Constipation (tapentadol ER, 22.6 percent; oxycodone CR, 38.6 percent); Nausea (tapentadol ER, 18.1 percent; oxycodone CR, 33.2 percent); and Vomiting (tapentadol ER, 7.0 percent; oxycodone CR, 13.5 percent).

The median duration of treatment was substantially longer with tapentadol ER (268 days) than with oxycodone CR (59 days), and the incidence of overall gastrointestinal treatment-emergent adverse events (TEAEs) leading to study discontinuation was approximately 2.5 times greater in the oxycodone CR group than in the tapentadol ER group (oxycodone CR, 21.5 percent; tapentadol ER, 8.6 percent). In addition, the incidence of constipation leading to study discontinuation was 4.5 times greater in the oxycodone CR group than in the tapentadol ER group (oxycodone CR, 7.2 percent; tapentadol ER, 1.6 percent).

The study also found tapentadol ER provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis pain or chronic low back pain for up to one year. At baseline, mean pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 and 7.6; at endpoint, they had decreased to 4.4 and 4.

"We are encouraged by these study results as they illustrate the tolerability of tapentadol ER compared with oxycodone CR, a standard chronic pain treatment," said Dr. Bruce Moskovitz, Therapeutic Area Leader for Pain, Ortho-McNeil Janssen Scientific Affairs, LLC. "We are pleased about the possibility of bringing this important investigational compound forward to patients in the future."

This study of tapentadol ER examined its long-term safety and tolerability compared to oxycodone CR and the primary objective of this study was to evaluate the safety of twice-daily doses of tapentadol ER (100 to 250 mg) over one year. Patients were randomized in a 4:1 ratio to receive controlled, adjustable, oral, twice-daily doses of tapentadol ER (100-250 mg) or oxycodone HCl CR (20-50 mg) in open-label treatment for up to one year. There were 1,117 patients in the study that received at least one dose of study medication (tapentadol).

Ref : http://www.jnjpharmarnd.com/jnjpharmarnd/news_release_02042010.html