NALOXONE HYDROCHLORIDE INJECTION, USP, AUTO-INJECTOR

NALOXONE HYDROCHLORIDE injection, USP, for intramuscular or subcutaneous use, is an opioid antagonist in a pre-filled, single-dose auto-injector containing 10 mg of naloxone HCl in 0.4 mL solution. NALOXONE HYDROCHLORIDE injection is not made with natural rubber latex. Chemically, naloxone HCl is the hydrochloride salt of 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride with the following structure: C 19 H 21 NO 4 HC1 M.W.363.84 Naloxone HCl occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform. Each 0.4 mL of NALOXONE HYDROCHLORIDE injection contains 10 mg of naloxone HCl (equivalent to 9.0 mg naloxone base), 3.34 mg of sodium chloride, hydrochloric acid to adjust pH, and water for injection. The pH range is 3.0 to 4.5. chemical structure

NALOXONE HYDROCHLORIDE injection is indicated for use by military personnel and chemical incident responders for: Emergency treatment of patients 12 years of age and older where use of high-potency opioids such as fentanyl analogues as a chemical weapon is suspected. Temporary prophylaxis of respiratory and/or central nervous system depression in military personnel and chemical incident responders entering an area contaminated with high-potency opioids such as fentanyl analogues. NALOXONE HYDROCHLORIDE injection is an opioid antagonist indicated for use by military personnel and chemical incident responders for: Emergency treatment of patients 12 years of age and older where use of high-potency opioids such as fentanyl analogues as a chemical weapon is suspected. ( 1 ) Temporary prophylaxis of respiratory and/or central nervous system depression in military personnel and chemical incident responders entering an area contaminated with high-potency opioids such as fentanyl analogues. ( 1 )

Administer NALOXONE HYDROCHLORIDE injection according to the INSTRUCTIONS FOR USE. ( 2.1 ) Administer as soon as possible after known or suspected opioid exposure and seek emergency medical assistance immediately after the first dose. ( 2.1 ) Administer into the anterolateral aspect of the thigh, through clothing if necessary. ( 2.2 ) If the patient relapses into respiratory or central nervous system depression after the first dose, administer additional naloxone HCl, as necessary, until emergency medical assistance becomes available. ( 2.2 ) Keep the patient under continued surveillance until medical care is available. ( 2.2 ) 2.1 Important Administration Instructions Read the Instructions for Use at the time of receiving a single-dose, pre-filled NALOXONE HYDROCHLORIDE injection auto-injector. Administer NALOXONE HYDROCHLORIDE injection as soon as possible after known or suspected opioid exposure because prolonged respiratory depression may result in damage to the central nervous system or death. NALOXONE HYDROCHLORIDE injection contains 10 mg/0.4 mL naloxone HCl in a single-dose, pre-filled auto-injector for intramuscular or subcutaneous use only. Do not attempt to reuse the NALOXONE HYDROCHLORIDE injection auto-injector. Periodically visually inspect NALOXONE HYDROCHLORIDE injection through the viewing window for particulate matter. Request a replacement if the solution is cloudy or contains particles, or if the glass container is damaged. Once the red safety guard is removed, NALOXONE HYDROCHLORIDE injection auto-injector must be used immediately or disposed of properly. Do not attempt to replace the red safety guard once it is removed. 2.2 Dosing in Adults and Pediatric Patients at Least 12 Years Old Inject NALOXONE HYDROCHLORIDE injection into the anterolateral aspect of the thigh according to the Instructions for Use and the printed instructions on the device label. In summary, Ensure that the injection site is free of other materials (e.g., equipment or other obstructions), except for clothing. Pull the auto-injector from the outer case. When ready to use, firmly pull off the red safety guard. Do not touch the black base of the auto-injector, which is where the needle comes out. Place the black end of the auto-injector against the anterolateral aspect of the thigh, through clothing, if needed. Press firmly until you hear a click and hiss sound and then hold in place for 5 seconds. Upon actuation, the auto-injector automatically inserts the needle intramuscularly or subcutaneously, delivers the naloxone HCl injection, and retracts the needle into the device. The needle will not be visible before, during, or after the injection. Post-injection, the black base locks in place and a red indicator appears in the drug viewing window. NALOXONE HYDROCHLORIDE injection can be injected through clothing or MOPP4 PPE. NALOXONE HYDROCHLORIDE injection can be self- or buddy-administered. Emergency treatment of patients 12 years of age and older where use of high-potency opioids such as fentanyl analogues as a chemical weapon is suspected. Seek immediate emergency medical assistance immediately after administration of the first dose of NALOXONE HYDROCHLORIDE injection. Keep the patient under continued surveillance until medical care is available. If the patient relapses into respiratory and/or central nervous system depression after the first dose of NALOXONE HYDROCHLORIDE injection, administer additional naloxone HCl, as necessary, until emergency medical assistance becomes available. If the patient does not show some improvement after administering the dose of NALOXONE HYDROCHLORIDE injection, consider if the respiratory depression is due to a non-opioid etiology. Temporary prophylaxis of respiratory and/or central nervous system depression in military personnel and chemical incident responders entering an area contaminated with high-potency opioids such as fentanyl analogues. Administer immediately prior to entering an area believed to be contaminated with high-potency opioids. Each pre-filled NALOXONE HYDROCHLORIDE injection can only be used one time. NALOXONE HYDROCHLORIDE injection provides temporary protection. If exposure to high potency opioids is prolonged, additional doses may be necessary.

NALOXONE HYDROCHLORIDE injection is contraindicated in individuals known to be hypersensitive to naloxone HCl or to any of the other ingredients. Hypersensitivity to naloxone hydrochloride or to any of the other ingredients in NALOXONE HYDROCHLORIDE injection. ( 4 )

The following serious adverse reactions are discussed elsewhere in the labeling: Precipitation of Severe Opioid Withdrawal [see Warnings and Precautions (5.1) ] Recurrent Respiratory and Central Nervous System Depression [see Warnings and Precautions (5.2) ] The following adverse reactions were observed in more than one subject in clinical studies evaluating NALOXONE HYDROCHLORIDE injection: dizziness, feeling hot, headache, and injection site erythema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact kaleo, Inc. at 1-877-341-5330 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. In three pharmacokinetic studies with a total of 78 healthy adult subjects exposed to NALOXONE HYDROCHLORIDE injection 0.4 mg auto-injector, two NALOXONE HYDROCHLORIDE injection 0.4 mg (0.8 mg naloxone HCl total) auto-injectors, NALOXONE HYDROCHLORIDE injection 2 mg auto-injector, or NALOXONE HYDROCHLORIDE injection 10 mg auto-injector, adverse reactions occurring in more than one subject were dizziness, feeling hot, headache, and injection site erythema. 6.2 Postmarketing Experience The following adverse reactions have been identified during the use of naloxone HCl to reverse the effects of opioids. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: aggression, anger, anxiety, back pain, bradycardia, cardiac arrest, confusion, depression, disorientation, dyspnea, hypertension, hypotension, loss of consciousness, malaise, miosis, pain, pulmonary edema, somnolence, unresponsiveness to stimuli, and ventricular tachycardia and fibrillation. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone HCl have resulted in significant reversal of analgesia and have caused agitation [see Warnings and Precautions (5.1) ] .

16.2 Storage and Handling Storage and Shipping Store at controlled room temperature 15°C - 25°C (59°F - 77°F); excursions permitted between 4°C and 40°C (39°F and 104°F). Do not freeze. Protect from heat. Use and Handling Store the NALOXONE HYDROCHLORIDE injection auto-injector in the outer case provided. If NALOXONE HYDROCHLORIDE injection is frozen and is needed in an emergency, do NOT wait for NALOXONE HYDROCHLORIDE injection to thaw; get emergency medical help right away. Once thawed, NALOXONE HYDROCHLORIDE injection may be used. Manufactured for: Kaleo, Inc. Richmond, VA 23219 This product may be covered by one or more U.S. patents or pending patent applications. See www.kaleopharma.com/pat for details.