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Adamis Pharmaceuticals updates comparative pharmacology model data supporting the higher 5 mg intramuscular dose of naloxone in Zimhi.

Read time: 2 mins
Last updated:20th Dec 2021
Published:2nd Dec 2021
Adamis Pharmaceuticals Corporation announced that additional data in a quantitative systems pharmacology model supports the dose of naloxone hydrochloride that is included in the company’s Zimhi (naloxone HCL Injection, USP) 5 mg/0.5 mL product.

The model data supports the dose of naloxone in Zimhi as being more likely to produce successful resuscitation of high concentration fentanyl overdoses.These results support the dose of naloxone in Zimhi as being appropriate for more likely successful resuscitation from fentanyl overdoses, thereby saving more lives. The company recently announced that the FDA has approved Zimhi 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. Fentanyl is approximately 100 times more potent than morphine.

According to statistics published by the Centers for Disease Control and Prevention (CDC), drug overdoses resulted in approximately 100,306 deaths in the United States during the 12-month period ending April 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. The deaths represent a new record high.

The company previously announced the publication of an article entitled “Higher naloxone dosing in a quantitative systems pharmacology model that predicts naloxone-fentanyl competition at the opioid mu receptor level” in the peer reviewed publication “PLOS ONE”. This study was done in collaboration with Rosa & Co. LLC (www.rosaandco.com). The new data expands the previous findings to include additional doses of naloxone, comparing the dose in Zimhi to the already approved higher intranasal (IN) dose, and higher levels of fentanyl exposure.

The previous manuscript described an opioid receptor quantitative systems pharmacology (QSP) model which was developed to predict the effects of different intramuscular (IM or the equivalent IN dose) doses of naloxone in response to different levels of fentanyl exposure (low, medium, high, and very high). The model defined a successful reversal as lowering the amount of opioid bound to the brain receptors to less than 50% within 10 minutes. For the lowest and middle levels of fentanyl exposure, the model predicted that the 2 mg IM (equivalent to 4 mg IN) naloxone resulted in successful resuscitations within ten minutes, but more rapid reversal was observed with the 5 mg IM dose. However, at high levels of fentanyl exposure, the model predicted that the 2 mg IM (4 mg IN) doses of naloxone did not result in a successful reversal. In contrast, the 5 mg IM doses of naloxone (Zimhi) successfully reversed opioid toxicity.

The new experiments examined the 4 mg IM (equivalent to 8 mg IN) dose in the model. The time to decreasing the amount of opioid (fentanyl) bound to the brain receptors to less than 50% was found to be earlier for the 5 mg IM dose (found in Zimhi) compared to the 4 mg IM dose (8 mg IN) at high level of fentanyl exposure. At the highest fentanyl concentration tested, the 5 mg IM, but not the 4 mg IM (8 mg IN), decreased fentanyl brain receptor occupancy to less than 50%. Thus, the 5 mg IM resulted in a successful resuscitation in this model, but the 4 mg IM (8 IN) did not.

Dr. Dennis J. Carlo, President and CEO of Adamis, stated, “We believe these additional data support the need for Zimhi’s higher IM dose of naloxone in the treatment of opioid overdoses, particularly those that involve fentanyl. The data generated predicts that Zimhi will result in more rapid and higher levels of naloxone when compared to the other available commercial products, including the recently approved higher IN dose. This should result in more successful resuscitations and more lives saved. We believe that our partners at US WorldMeds, who are leaders in the addiction treatment area, will leverage their commercial infrastructure to successfully launch Zimhi.”

Condition: Opioid Dependence/Overdose
Type: drug

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