`International Medication Systems, Limited
`----------
`NALOXONE HYDROCHLORIDE
`INJECTION, USP
`Opioid Antagonist
`Rx Only
`
`DESCRIPTION
`Naloxone hydrochloride, an opioid antagonist, is a synthetic congener of oxymorphone. In structure it
`differs from oxymorphone in that the methyl group on the nitrogen atom is replaced by an allyl group.
`NALOXONE HYDROCHLORIDE
`(-)-17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride
`
`Naloxone hydrochloride 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.
`Naloxone Hydrochloride Injection is available as a sterile solution for intravenous, intramuscular and
`subcutaneous administration in 1 mg/mL concentration. pH is adjusted to 3.5 ± 0.5 with hydrochloric
`acid. Each mL also contains 8.35 mg of sodium chloride. Naloxone Hydrochloride Injection is
`preservative-free.
`
`CLINICAL PHARMACOLOGY
`Complete or Partial Reversal of Opioid Depression
`Naloxone hydrochloride prevents or reverses the effects of opioids including respiratory depression,
`sedation, and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-
`antagonist such as pentazocine.
`Naloxone hydrochloride is an essentially pure opioid antagonist, i.e., it does not possess the
`“agonistic” or morphine-like properties characteristic of other opioid antagonists. When administered
`in usual doses and in the absence of opioids or agonistic effects of other opioid antagonists, it exhibits
`essentially no pharmacologic activity.
`Naloxone hydrochloride has not been shown to produce tolerance or cause physical or psychological
`dependence. In the presence of physical dependence on opioids, naloxone hydrochloride will produce
`withdrawal symptoms. However, in the presence of opioid dependence, opiate withdrawal symptoms
`may appear within minutes of naloxone hydrochloride administration and subside in about 2 hours. The
`severity and duration of the withdrawal syndrome are related to the dose of naloxone hydrochloride and
`to the degree and type of opioid dependence.
`While the mechanism of action of naloxone hydrochloride is not fully understood, in vitro evidence
`suggests that naloxone hydrochloride antagonizes opioid effects by competing for the μ, κ and σ opiate
`receptor sites in the CNS, with the greatest affinity for the μ receptor.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 1
`
`
`
`When naloxone hydrochloride is administered intravenously (I.V.), the onset of action is generally
`apparent within two minutes. The onset of action is slightly less rapid when it is administered
`subcutaneously (S.C.) or intramuscularly (I.M.). The duration of action is dependent upon the dose and
`route of administration of naloxone hydrochloride. Intramuscular administration produces a more
`prolonged effect than intravenous administration. Since the duration of action of naloxone
`hydrochloride may be shorter than that of some opiates, the effect of the opiate may return as the effects
`of naloxone hydrochloride dissipates. The requirement for repeat doses of naloxone hydrochloride
`will also be dependent upon the amount, type and route of administration of the opioid being
`antagonized.
`Adjunctive Use in Septic Shock
`Naloxone hydrochloride has been shown in some cases of septic shock to produce a rise in blood
`pressure that may last up to several hours; however, this pressor response has not been demonstrated to
`improve patient survival. In some studies, treatment with naloxone hydrochloride in the setting of septic
`shock has been associated with adverse effects, including agitation, nausea and vomiting, pulmonary
`edema, hypotension, cardiac arrhythmias, and seizures. The decision to use naloxone hydrochloride in
`septic shock should be exercised with caution, particularly in patients who may have underlying pain or
`have previously received opioid therapy and may have developed opioid tolerance.
`Because of the limited number of patients who have been treated, optimal dosage and treatment regimens
`have not been established.
`
`PHARMACOKINETICS
`Distribution
`Following parenteral administration, naloxone hydrochloride is rapidly distributed in the body and
`readily crosses the placenta. Plasma protein binding occurs but is relatively weak. Plasma albumin is the
`major binding constituent but significant binding of naloxone also occurs to plasma constituents other
`than albumin. It is not known whether naloxone is excreted into human milk.
`Metabolism and Elimination
`Naloxone hydrochloride is metabolized in the liver, primarily by glucuronide conjugation with
`naloxone-3-glucoronide as the major metabolite. In one study the serum half-life in adults ranged from
`30 to 81 minutes (mean 64 ± 12 minutes). In a neonatal study the mean plasma half-life was observed to
`be 3.1 ± 0.5 hours. After an oral or intravenous dose, about 25-40% of the drug is excreted as
`metabolites in urine within 6 hours, about 50% in 24 hours, and 60-70% in 72 hours.
`
`INDICATIONS AND USAGE
`Naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid
`depression, including respiratory depression, induced by natural and synthetic opioids including,
`propoxyphene, methadone and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine and
`butorphanol and cyclazocine. Naloxone hydrochloride is also indicated for the diagnosis of suspected
`or known acute opioid overdosage.
`Naloxone hydrochloride injection may be useful as an adjunctive agent to increase blood pressure in the
`management of septic shock. (see CLINICAL PHARMACOLOGY; Adjunctive Use in Septic Shock).
`
`CONTRAINDICATIONS
`Naloxone hydrochloride injection is contraindicated in patients known to be hypersensitive to it or to
`any of the other ingredients in naloxone hydrochloride.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 2
`
`
`
`WARNINGS
`Drug Dependence
`Naloxone hydrochloride should be administered cautiously to persons including newborns of mothers
`who are known or suspected to be physically dependent on opioids. In such cases an abrupt and
`complete reversal of opioid effects may precipitate an acute withdrawal syndrome.
`The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include,
`but are not limited to, the following: body aches, diarrhea, tachycardia, fever, runny nose, sneezing,
`piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering
`or trembling, abdominal cramps, weakness, and increased blood pressure. In the neonate, opioid
`withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes.
`Repeat Administration
`The patient who has satisfactorily responded to naloxone hydrochloride should be kept under continued
`surveillance and repeated doses of naloxone hydrochloride should be administered, as necessary, since
`the duration of action of some opioids may exceed that of naloxone hydrochloride.
`Respiratory Depression due to Other Drugs
`Naloxone hydrochloride is not effective against respiratory depression due to non-opioid drugs and in
`the management of acute toxicity caused by levopropoxyphene. Reversal of respiratory depression by
`partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete
`or require higher doses of naloxone. If an incomplete response occurs, respirations should be
`mechanically assisted as clinically indicated.
`
`PRECAUTIONS
`
`General
`In addition to naloxone hydrochloride, other resuscitative measures such as maintenance of a free
`airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed
`when necessary to counteract acute opioid poisoning.
`Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating,
`tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation,
`pulmonary edema, and cardiac arrest which may result in death. Excessive doses of naloxone
`hydrochloride in postoperative patients may result in significant reversal of analgesia and may cause
`agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-
`Postoperative Opioid Depression).
`Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary
`edema, and cardiac arrest have been reported in postoperative patients. Death, coma, and encephalopathy
`have been reported as sequelae of these events. These have occurred in patients most of whom had
`preexisting cardiovascular disorders or received other drugs which may have similar adverse
`cardiovascular effects. Although a direct cause and effect relationship has not been established,
`naloxone hydrochloride should be used with caution in patients with preexisting cardiac disease or
`patients who have received medications with potential adverse cardiovascular effects, such as
`hypotension, ventricular tachycardia or fibrillation, and pulmonary edema. It has been suggested that the
`pathogenesis of pulmonary edema associated with the use of naloxone hydrochloride is similar to
`neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a
`dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic
`pressures.
`
`Drug Interactions
`Large doses of naloxone are required to antagonize buprenorphine since the latter has a long duration
`of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 3
`
`
`
`Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased
`duration of action of the normally prolonged respiratory depression. The barbiturate methohexital
`appears to block the acute onset of withdrawal symptoms induced by naloxone in opiate addicts.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`Studies in animals to assess the carcinogenic potential of naloxone hydrochloride have not been
`conducted. Naloxone hydrochloride was weakly positive in the Ames mutagenicity and in the in vitro
`human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79
`cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study.
`Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of
`2
`a 50 kg human given 10 mg/day (when based on surface area or mg/m ), demonstrated no embryotoxic or
`teratogenic effects due to naloxone hydrochloride.
`
`Use in Pregnancy
`Teratogenic Effects: Pregnancy Category C: Teratology studies conducted in mice and rats at doses
`4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface
`2
`area or mg/m ), demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride.
`There are, however, no adequate and well-controlled studies in pregnant women. Because animal
`reproduction studies are not always predictive of human response, naloxone hydrochloride should be
`used during pregnancy only if clearly needed.
`Non-teratogenic Effects: Risk-benefit must be considered before naloxone hydrochloride is
`administered to a pregnant woman who is known or suspected to be opioid-dependent since maternal
`dependence may often be accompanied by fetal dependence. Naloxone crosses the placenta, and may
`precipitate withdrawal in the fetus as well as in the mother. Patients with mild to moderate hypertension
`who receive naloxone during labor should be carefully monitored as severe hypertension may occur.
`
`Use in Labor and Delivery
`It is not known if naloxone hydrochloride affects the duration of labor and/or delivery. However,
`published reports indicated that administration of naloxone during labor did not adversely affect
`maternal or neonatal status.
`Nursing Mothers: It is not known whether naloxone is excreted in human milk. Because many drugs are
`excreted in human milk, caution should be exercised when naloxone is administered to a nursing woman.
`
`Pediatric Use
`Naloxone hydrochloride injection, USP may be administered intravenously, intramuscularly or
`subcutaneously in children and neonates to reverse the effects of opiates. The American Academy of
`Pediatrics, however, does not endorse subcutaneous or intramuscular administration in opiate
`intoxication since absorption may be erratic or delayed. Although the opiate-intoxicated child responds
`dramatically to naloxone hydrochloride, he/she must be carefully monitored for at least 24 hours as a
`relapse may occur as naloxone is metabolized.
`When naloxone hydrochloride is given to the mother shortly before delivery, the duration of its effect
`lasts only for the first two hours of neonatal life. It is preferable to administer naloxone hydrochloride
`directly to the neonate if needed after delivery. Naloxone hydrochloride has no apparent benefit as an
`additional method of resuscitation in the newly born infant with intrauterine asphyxia which is not
`related to opioid use.
`Usage in Pediatric Patients and Neonates for Septic Shock: The safety and effectiveness of naloxone
`hydrochloride in the treatment of hypotension in pediatric patients and neonates with septic shock have
`not been established. One study of two neonates in septic shock reported a positive pressor response;
`however, one patient subsequently died after intractable seizures.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 4
`
`
`
`Geriatric Use
`Clinical studies of naloxone hydrochloride did not include sufficient numbers of subjects aged 65 and
`over to determine whether they respond differently from younger subjects. Other reported clinical
`experience has not identified differences in responses between the elderly and younger patients. In
`general, dose selection for an elderly patient should be cautious, usually starting at the low end of the
`dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of
`concomitant disease or other drug therapy.
`Renal Insufficiency/Failure
`The safety and effectiveness of naloxone hydrochloride in patients with renal insufficiency/failure have
`not been established in well-controlled clinical trials. Caution should be exercised when naloxone
`hydrochloride is administered to this patient population.
`Liver Disease
`The safety and effectiveness of naloxone hydrochloride in patients with liver disease have not been
`established in well-controlled clinical trials. Caution should be exercised when naloxone
`hydrochloride is administered to patients with liver disease.
`
`ADVERSE REACTIONS
`Postoperative
`The following adverse events have been associated with the use of naloxone hydrochloride in
`postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea,
`pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae
`of these events. Excessive doses of naloxone hydrochloride in postoperative patients may result in
`significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND
`ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression).
`Opioid Depression
`Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased
`blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and
`cardiac arrest which may result in death (see PRECAUTIONS).
`Opioid Dependence
`Abrupt reversal of opioid effects in persons who are physically dependent on opioids may precipitate
`an acute withdrawal syndrome which may include, but is not limited to, the following signs and
`symptoms: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness,
`shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal
`cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal may also include:
`convulsions; excessive crying; hyperactive reflexes (see WARNINGS).
`Adverse events associated with the postoperative use of naloxone hydrochloride are listed by organ
`system and in decreasing order of frequency as follows:
`Cardiac Disorders: pulmonary edema, cardiac arrest or failure, tachycardia, ventricular fibrillation, and
`ventricular tachycardia. Death, coma, and encephalopathy have been reported as sequelae of these
`events.
`Gastrointestinal Disorders:vomiting, nausea
`Nervous System Disorders: convulsions, paraesthesia, grand mal convulsion
`Psychiatric Disorders: agitation, hallucination, tremulousness
`Respiratory, Thoracic and Mediastinal Disorders:dyspnea, respiratory depression, hypoxia
`Skin and Subcutaneous Tissue Disorders:nonspecific injection site reactions, sweating
`Vascular Disorders: hypertension, hypotension, hot flushes or flushing.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 5
`
`
`
`See also PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults; Postoperative
`Opioid Depression.
`
`DRUG ABUSE AND DEPENDENCE
`Naloxone hydrochloride is an opioid antagonist. Physical dependence associated with the use of
`naloxone hydrochloride has not been reported. Tolerance to the opioid antagonist effect of naloxone
`hydrochloride is not known to occur.
`
`OVERDOSAGE
`There is limited clinical experience with naloxone hydrochloride overdosage in humans.
`Adult Patients
`In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity. In another study,
`2
`36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m /min) of naloxone
`hydrochloride followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced
`adverse events associated with naloxone use, and naloxone was discontinued in seven patients because
`of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension
`(1), and hypotension and/or bradycardia (3).
`At doses of 2 mg/kg in normal subjects, cognitive impairment and behavioral symptoms, including
`irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, and lack of appetite have
`been reported. In addition, somatic symptoms, including dizziness, heaviness, sweating, nausea, and
`stomachaches were also reported. Although complete information is not available, behavioral symptoms
`were reported to often persist for 2-3 days.
`Pediatric Patients
`Up to 11 doses of 0.2 mg of naloxone (2.2 mg) have been administered to children following overdose
`of diphenoxylate hydrochloride with atropine sulfate. Pediatric reports include a 2-1/2 year-old child
`who inadvertently received a dose of 20 mg of naloxone for treatment of respiratory depression
`following overdose with diphenoxylate hydrochloride with atropine sulfate. The child responded well
`and recovered without adverse sequelae. There is also a report of a 4-1/2 year-old child who received
`11 doses during a 12-hour period, with no adverse sequelae.
`Patient Management
`Patients who experience a naloxone hydrochloride overdose should be treated symptomatically in a
`closely supervised environment.
`Physicians should contact a poison control center for the most up-to-date patient management
`information.
`
`DOSAGE AND ADMINISTRATION
`Naloxone hydrochloride injection may be administered intravenously, intramuscularly, or
`subcutaneously. The most rapid onset of action is achieved by intravenous administration, which is
`recommended in emergency situations.
`Since the duration of action of some opioids may exceed that of naloxone, the patient should be kept
`under continued surveillance. Repeated doses of naloxone should be administered, as necessary.
`Intravenous Infusion
`Naloxone hydrochloride injection may be diluted for intravenous infusion in normal saline or 5%
`dextrose solutions. The addition of 2 mg of naloxone in 500 mL of either solution provides a
`concentration of 0.004 mg/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 6
`
`
`
`unused mixture must be discarded. The rate of administration should be titrated in accordance with the
`patient’s response.
`Naloxone hydrochloride injection should not be mixed with preparations containing bisulfite,
`metabisulfite, long-chain or high molecular weight anions, or any solution having an alkaline pH. No
`drug or chemical agent should be added to naloxone hydrochloride injection unless its effect on the
`chemical and physical stability of the solution has first been established.
`General
`Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
`administration whenever solution and container permit.
`Usage in Adults
`Opioid Overdose—Known or Suspected: An initial dose of 0.4 mg to 2 mg of naloxone
`hydrochloride may be administered intravenously. If the desired degree of counteraction and
`improvement in respiratory functions are not obtained, it may be repeated at two-to-three-minute
`intervals. If no response is observed after 10 mg of naloxone hydrochloride have been administered, the
`diagnosis of opioid-induced or partial opioid-induced toxicity should be questioned. Intramuscular or
`subcutaneous administration may be necessary if the intravenous route is not available.
`Postoperative Opioid Depression: For the partial reversal of opioid depression following the use of
`opioids during surgery, smaller doses of naloxone hydrochloride are usually sufficient. The dose of
`naloxone hydrochloride should be titrated according to the patient’s response. For the initial reversal of
`respiratory depression, naloxone hydrochloride should be injected in increments of 0.1 to 0.2 mg
`intravenously at two-to three-minute intervals to the desired degree of reversal—i.e., adequate
`ventilationand alertness without significant pain or discomfort. Larger than necessary dosage of
`naloxone may result in significant reversal of analgesia and increase in blood pressure. Similarly, too
`rapid reversal may induce nausea, vomiting, sweating, or circulatory stress.
`Repeat doses of naloxone may be required within one- to two-hour intervals depending upon the
`amount, type (i.e., short or long acting) and time interval since last administration of opioid.
`Supplemental intramuscular doses have been shown to produce a longer lasting effect.
`Septic Shock:The optimal dosage of naloxone hydrochloride or duration of therapy for the treatment of
`hypotension in septic shock patients has not been established (see CLINICAL PHARMACOLOGY).
`Usage in Children
`Opioid Overdose—Known or Suspected:The usual initial dose in children is 0.01 mg/kg body weight
`given I.V. If this dose does not result in the desired degree of clinical improvement, a subsequent dose
`of 0.1 mg/kg body weight may be administered. If an l.V. route of administration is not available,
`naloxone may be administered I.M. or S.C. in divided doses. If necessary, naloxone hydrochloride
`injection can be diluted with sterile water for injection.
`Postoperative Opioid Depression: Follow the recommendations and cautions under Adult
`Postoperative Depression. For the initial reversal of respiratory depression naloxone hydrochloride
`should be injected in increments of 0.005 mg to 0.01 mg intravenously at two- to three-minute intervals
`to the desired degree of reversal.
`Usage in Neonates
`Opioid-lnduced Depression: The usual initial dose is 0.01 mg/kg body weight administered I.V., I.M., or
`S.C. This dose may be repeated in accordance with adult administration guidelines for postoperative
`opioid depression.
`
`HOW SUPPLIED
`1 mg/mL naloxone hydrochloride injection USP, for intravenous, intramuscular and subcutaneous
`administration.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 7
`
`
`
`Available as follows:
`1 mg/mL
`®
`2 mL single dose disposable prefilled syringes, in the MIN-I-JET system with 21 G. x 11/2” needle.
`Shrink Wrapped Packages of 10.
` NDC 76329-1469-1 Stock No. 1469 (contains no preservative)
`2 mL single dose disposable Luer-JetTM Luer-Lock Prefilled Syringe. Shrink Wrapped Packages of
`10.
` NDC 76329-3369-1 Stock No. 3369 (contains no preservative)
`Syringe Assembly Directions:
`®
`The MIN-I-JET syringe with needle, illustrated below, is the basic unit upon which all the other
`syringe systems are built; slight adaptations and/ or additional auxiliary parts create the other syringe
`systems. Assembly directions remain essentially the same.
`USE ASEPTIC TECHNIQUE
`Do not assemble until ready to use.
`
`*CAUTION: IMPROPER ENGAGING MAY CAUSE GLASS BREAKAGE AND SUBSEQUENT
`INJURY.
`Store at 25˚C (77˚F); excursions permitted to 15˚-30˚C (59˚-86˚F). [See USP Controlled Room
`Temperature.]
`Protect from light.
`Store in carton until contents have been used.
`INTERNATIONAL MEDICATION SYSTEMS, LIMITED
`SO. EL MONTE, CA 91733, U.S.A. REV. 11-13
`An Amphastar Pharmaceuticals Company
`© INTERNATIONAL MEDICATION SYSTEMS, LIMITED 2013
`
`PRINCIPLE DISPLAY PANEL: Vial Label (Stock No. 1469)
`IMS, LIMITED
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 8
`
`
`
`So. El Monte, CA 91733, U.S.A.
`7614690K 1-15
`2 mL 2 mg 1 mg / mL
`NALOXONE HYDROCHLORIDE INJECTION, USP
`FOR I.M., I.V. OR
`S.C. USE / SINGLE DOSE
`SEE INSERT
`Rx Only
`Approx. 0 0.5 1 1.5
`mg mL 0 0.5 1 1.5
`
`PRINCIPLE DISPLAY PANEL: Carton (Stock No. 1469)
`®
`MIN-I-JET
`Prefilled Syringe
`Rx Only
`NDC 76329-1469-1
`STOCK NO. 1469
`NALOXONE HYDROCHLORIDE INJ., USP
`(1 mg/mL)
`2 mg per 2 mL
`FOR INTRAVENOUS, INTRAMUSCULAR
`OR SUBCUTANEOUS USE / AN OPIOID ANTAGONIST
`®
`MIN-I-JET
`21 G. X 1-1/2" NEEDLE
`2 mL single dose disposable prefilled syringe
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 9
`
`
`
`Single use, do not reuse or resterilize.
`
`PRINCIPLE DISPLAY PANEL: Vial Label (Stock No. 3369)
`IMS, LIMITED
`So. El Monte, CA 91733, U.S.A.
`7633690B 8-11
`2 mL 2 mg 1 mg / mL
`NALOXONE HYDROCHLORIDE INJECTION, USP
`FOR I.M., I.V. OR
`S.C. USE / SINGLE DOSE
`SEE INSERT
`Rx Only
`Approx. 0 0.5 1 1.5
`mg mL 0 0.5 1 1.5
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 10
`
`
`
`PRINCIPLE DISPLAY PANEL: Carton (Stock No. 3369)
`Luer-Lock Prefilled Syringe
`Rx Only
`NDC 76329-3369-1
`STOCK NO. 3369
`NALOXONE HYDROCHLORIDE INJ., USP
`(1 mg/mL)
`2 mg per 2 mL
`FOR INTRAVENOUS, INTRAMUSCULAR
`OR SUBCUTANEOUS USE
`AS AN OPIOID ANTAGONIST
`TM
`LUER-JET
` LUER-LOCK PREFILLED SYRINGE
`2 mL single dose disposable prefilled syringe
`Single use, do not reuse or resterilize.
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 11
`
`
`
`NALOXONE HYDROCHLORIDE
`naloxone hydrochloride injection
`
`Product Information
`Product T ype
`
`Route of Administration
`
`HUMAN PRESCRIPTION DRUG
`
`Ite m Code (Source )
`
`NDC:76 329 -146 9
`
`PARENTERAL
`
`Active Ingredient/Active Moiety
`Ingredient Name
`Na lo xo ne Hydro chlo ride (UNII: F8 50 56 9 PQR) (Nalo xo ne - UNII:36 B8 2AMQ7N)
`
`Basis of Strength
`Nalo xo ne Hydro chlo ride
`
`Strength
`1 mg in 1 mL
`
`Packaging
`
`# Item Code
`
`1 NDC:76 329 -
`146 9 -1
`
`1
`
`Package Description
`
`Marketing Start
`Date
`
`Marketing End
`Date
`
`10 in 1 BOX
`
`0 4/0 1/19 9 8
`
`2 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System
`(syringe, patch, etc.)
`
`Marketing Information
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 12
`
`
`
`Marke ting Cate gory
`ANDA
`
`Application Numbe r or Monograph Citation Marke ting Start Date Marke ting End Date
`ANDA0 720 76
`0 4/0 1/19 8 8
`
`NALOXONE HYDROCHLORIDE
`naloxone hydrochloride injection
`
`Product Information
`Product T ype
`
`Route of Administration
`
`HUMAN PRESCRIPTION DRUG
`
`Ite m Code (Source )
`
`NDC:76 329 -336 9
`
`PARENTERAL
`
`Active Ingredient/Active Moiety
`Ingredient Name
`Na lo xo ne Hydro chlo ride (UNII: F8 50 56 9 PQR) (Nalo xo ne - UNII:36 B8 2AMQ7N)
`
`Basis of Strength
`Nalo xo ne Hydro chlo ride
`
`Strength
`1 mg in 1 mL
`
`Packaging
`
`#
`
`Item Code
`
`1 NDC:76 329 -
`336 9 -1
`
`1
`
`Package Description
`
`Marketing Start
`Date
`
`Marketing End
`Date
`
`10 in 1 BOX
`
`0 6 /0 1/20 0 1
`
`2 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System
`(syringe, patch, etc.)
`
`Marketing Information
`Marke ting Cate gory
`Application Numbe r or Monograph Citation Marke ting Start Date Marke ting End Date
`ANDA
`ANDA0 720 76
`0 6 /0 1/20 0 1
`
`Labeler - International Medication Systems, Limited (055750020)
`
`Establishment
`Name
`Internatio nal Medicatio n
`Systems, Limited
`
`Revised: 11/2016
`
`
`
`Addre ss
`
`Busine ss Ope rations
`ID/FEI
`0 55750 0 20 analysis(76 329 -146 9 , 76 329 -336 9 ) , manufacture(76 329 -146 9 , 76 329 -336 9 ) ,
`label(76 329 -146 9 , 76 329 -336 9 )
`
`International Medication Systems, Limited
`
`Opiant Exhibit 2083
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 13
`
`