b'B:16"T:15.75"S:15.25"51VIVITROL (naltrexone for extended-release injectable suspension) Intramuscular administration. Healthcare professionals should ensure that the VIVITROL injection issuicidal ideation, suicide attempt) were reported by 5% of opioid-dependent patientsUSE IN SPECIFIC POPULATIONS: Pregnancy: Risk Summary: The available data from BRIEF SUMMARY See package insert for full prescribing information given correctly, and should consider alternate treatment for those patients whose bodytreated with VIVITROL 380 mg (n=101) and 10% of opioid-dependent patients treatedpublished case series with VIVITROL use in pregnant women are insufficient to identify (rev. March 2021). habitus precludes an intramuscular gluteal injection with one of the provided needles.with oral naltrexone (n=20). In the 24-week, placebo-controlled pivotal trial that wasa drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal INDICATIONS AND USAGE: VIVITROL contains naltrexone, an opioid antagonist, and isPatients should be informed that any concerning injection site reactions should beconducted in Russia in 250 opioid-dependent patients, adverse events involvingoutcomes. There are clinical considerations (see Clinical Considerations). Reproduction indicated for the treatment of alcohol dependence in patients who are able to abstain frombrought to the attention of the healthcare professional. Patients exhibiting signs ofdepressed mood or suicidal thinking were not reported by any patient in either treatmentand developmental animal studies have not been conducted for VIVITROL. Daily oral alcohol in an outpatient setting prior to initiation of treatment with VIVITROL. Patientsabscess, cellulitis, necrosis, or extensive swelling should be evaluated by a physician togroup (VIVITROL 380 mg or placebo). When Reversal of VIVITROL Blockade Isadministration of naltrexone to female rats and rabbits increased the incidence of early should not be actively drinking at the time of initial VIVITROL administration. In addition,determine if referral to a surgeon is warranted. Precipitation of Opioid Withdrawal:Required for Pain Management: In an emergency situation in patients receivingfetal loss at exposures 11 times and 2 times the human exposure, respectively. Daily oral VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioidThe symptoms of spontaneous opioid withdrawal (which are associated with theVIVITROL, suggestions for pain management include regional analgesia or use of non- administration of naltrexone to pregnant rats and rabbits during the period of organogenesis detoxification. VIVITROL should be part of a comprehensive management program thatdiscontinuation of opioid in a dependent individual) are uncomfortable, but they are notopioid analgesics. If opioid therapy is required as part of anesthesia or analgesia,did not induce malformation at exposures up to 175 times and 14 times the human includes psychosocial support.generally believed to be severe or necessitate hospitalization. However, when withdrawalpatients should be continuously monitored in an anesthesia care setting by persons notexposure, respectively (see Data). The estimated background risk of major birth defects and is precipitated abruptly by the administration of an opioid antagonist to an opioid- involved in the conduct of the surgical or diagnostic procedure. The opioid therapy mustmiscarriage for the indicated population is unknown. All pregnancies have a background CONTRAINDICATIONS:VIVITROLiscontraindicatedin:patientsreceivingopioiddependent patient, the resulting withdrawal syndrome can be severe enough to requirebe provided by individuals specifically trained in the use of anesthetic drugs and therisk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the analgesics, patients with current physiologic opioid dependence, patients in acute opioidhospitalization. Review of postmarketing cases of precipitated opioid withdrawal inmanagement of the respiratory effects of potent opioids, specifically the establishmentestimated background risk of major birth defects and miscarriage in clinically recognized withdrawal, any individual who has failed the naloxone challenge test or has a positiveassociation with naltrexone treatment has identified cases with symptoms of withdrawaland maintenance of a patent airway and assisted ventilation. Irrespective of the drugpregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations: Disease-urine screen for opioids, and patients who have previously exhibited hypersensitivitysevere enough to require hospital admission, and in some cases, management in thechosen to reverse VIVITROL blockade, the patient should be monitored closely byassociated maternal and embryo-fetal risk: Untreated opioid addiction in pregnancy is tonaltrexone,polylactide-co-glycolide(PLG),carboxymethylcellulose,oranyotherintensivecareunit.Topreventoccurrenceofprecipitatedwithdrawalinpatientsappropriately trained personnel in a setting equipped and staffed for cardiopulmonaryassociated with adverse obstetrical outcomes such as low birth weight, preterm birth, components of the diluent. dependent on opioids, or exacerbation of a pre-existing subclinical withdrawal syndrome,resuscitation. Eosinophilic Pneumonia: In clinical trials with VIVITROL, there was oneand fetal death. In addition, untreated opioid addiction often results in continued or WARNINGSANDPRECAUTIONS:VulnerabilitytoOpioidOverdose:Afteropioidopioid-dependent patients, including those being treated for alcohol dependence, shoulddiagnosed case and one suspected case of eosinophilic pneumonia. Both casesrelapsing illicit opioid use. Published studies have demonstrated that alcohol is associated detoxification, patients are likely to have reduced tolerance to opioids. VIVITROL blocks thebe opioid-free (including tramadol) before starting VIVITROL treatment. An opioid-freerequired hospitalization, and resolved after treatment with antibiotics and corticosteroids.with fetal harm including growth restriction, facial abnormalities, central nervous system effects of exogenous opioids for approximately 28 days after administration. However, asinterval of a minimum of 710 days is recommended for patients previously dependentSimilar cases have been reported in postmarketing use. Should a person receivingabnormalities, behavioral disorders, and impaired intellectual development. Data: Animal the blockade wanes and eventually dissipates completely, patients who have been treatedon short-acting opioids. Patients transitioning from buprenorphine or methadone may beVIVITROL develop progressive dyspnea and hypoxemia, the diagnosis of eosinophilicData: Reproduction and developmental studies have not been conducted for VIVITROL. with VIVITROL may respond to lower doses of opioids than previously used, just as theyvulnerable to precipitation of withdrawal symptoms for as long as two weeks. If a morepneumonia should be considered. Patients should be warned of the risk of eosinophilicStudies with naltrexone administered via the oral route have been conducted in pregnant would have shortly after completing detoxification. This could result in potentially liferapid transition from agonist to antagonist therapy is deemed necessary and appropriatepneumonia, and advised to seek medical attention should they develop symptoms ofrats and rabbits. Daily oral administration of naltrexone has been shown to increase the threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse,by the healthcare provider, monitor the patient closely in an appropriate medical settingpneumonia. Clinicians should consider the possibility of eosinophilic pneumonia inincidence of early fetal loss when given to rats at doses 30 mg/kg/day (11 times the etc.) if the patient uses previously tolerated doses of opioids. Cases of opioid overdose withwhere precipitated withdrawal can be managed. In every case, healthcare providerspatients who do not respond to antibiotics. Hypersensitivity Reactions Includinghuman exposure based on an AUC (0-28d)comparison) and to rabbits at oral doses 60 fatal outcomes have been reported in patients who used opioids at the end of a dosingshould always be prepared to manage withdrawal symptomatically with non-opioidAnaphylaxis: Cases of urticaria, angioedema, and anaphylaxis have been observedmg/kg/ day (2 times the human exposure based on an AUC (0-28d)comparison). Daily oral interval, after missing a scheduled dose, or after discontinuing treatment. Patients shouldmedications because there is no completely reliable method for determining whether awith use of VIVITROL in the clinical trial setting and in postmarketing use. Patientsadministration of naltrexone to rats and rabbits during the period of organogenesis did be alerted that they may be more sensitive to opioids, even at lower doses, after VIVITROLpatient has had an adequate opioid-free period. A naloxone challenge test may be helpful;should be warned of the risk of hypersensitivity reactions, including anaphylaxis. In thenot induce malformations at doses up to 200 mg/kg/day (175- and 14-times the human treatment is discontinued, especially at the end of a dosing interval (i.e., near the end ofhowever, a few case reports have indicated that patients may experience precipitatedevent of a hypersensitivity reaction, patients should be advised to seek immediateexposure based on an AUC (0-28d)comparison, respectively). Lactation: Risk Summary: the month that VIVITROL was administered), or after a dose of VIVITROL is missed. It iswithdrawal despite having a negative urine toxicology screen or tolerating a naloxonemedical attention in a healthcare setting prepared to treat anaphylaxis. The patientNaltrexone and its major metabolite, 6-naltrexone, are present in human milk. There important that patients inform family members and the people closest to the patient of thischallenge test (usually in the setting of transitioning from buprenorphine treatment).should not receive any further treatment with VIVITROL. Intramuscular Injections: Asare no data on the effects on the breastfed infant or the effects on milk production. The increased sensitivity to opioids and the risk of overdose. There is also the possibility that aPatients should be made aware of the risks associated with precipitated withdrawal andwith any intramuscular injection, VIVITROL should be administered with caution todevelopmental health benefits of breastfeeding should be considered along with the patient who is treated with VIVITROL could overcome the opioid blockade effect ofencouraged to give an accurate account of last opioid use. Patients treated for alcoholpatients with thrombocytopenia or any coagulation disorder (eg, hemophilia and severemothers clinical need for naltrexone and any potential adverse effects on the breastfedS:10.25" T:10.75" B:11"VIVITROL. Although VIVITROL is a potent antagonist with a prolonged pharmacologicaldependence with VIVITROL should also be assessed for underlying opioid dependencehepatic failure). Alcohol Withdrawal: Use of VIVITROL does not eliminate nor diminishinfant from naltrexone or the mothers underlying maternal condition. Pediatric Use: The effect, the blockade produced by VIVITROL is surmountable. The plasma concentration ofand for any recent use of opioids prior to initiation of treatment with VIVITROL. Precipitatedalcohol withdrawal symptoms. Interference with Laboratory Tests: VIVITROL may besafety and efficacy of VIVITROL have not been established in the pediatric population. exogenous opioids attained immediately following their acute administration may beopioid withdrawal has been observed in alcohol-dependent patients in circumstancescross-reactive with certain immunoassay methods for the detection of drugs of abuseThe pharmacokinetics of VIVITROL have not been evaluated in a pediatric population. sufficient to overcome the competitive receptor blockade. This poses a potential risk towhere the prescriber had been unaware of the additional use of opioids or co-dependence(specificallyopioids)inurine.Forfurtherinformation,referencetothespecificGeriatric Use: In trials of alcohol-dependent subjects, 2.6% (n=26) of subjects were 65 individuals who attempt, on their own, to overcome the blockade by administering largeon opioids. Hepatotoxicity: Cases of hepatitis and clinically significant liver dysfunctionimmunoassay instructions is recommended. years of age, and one patient was 75 years of age. Clinical studies of VIVITROL did not amounts of exogenous opioids. Any attempt by a patient to overcome the antagonism bywere observed in association with VIVITROL exposure during the clinical developmentADVERSE REACTIONS: Clinical Trials Experience: Because clinical trials are conductedinclude sufficient numbers of subjects age 65 and over to determine whether they respond taking opioids is especially dangerous and may lead to life-threatening opioid intoxicationprogram and in the postmarketing period. Transient, asymptomatic hepatic transaminaseunder widely varying conditions, adverse reaction rates observed in the clinical trialsdifferently from younger subjects. No subjects over age 65 were included in studies of or fatal overdose. Patients should be told of the serious consequences of trying toelevations were also observed in the clinical trials and postmarketing period. Althoughof a drug cannot be directly compared to rates in the clinical trials of another drugopioid-dependent subjects. The pharmacokinetics of VIVITROL have not been evaluated in overcome the opioid blockade. Patient Access to Naloxone for the Emergency Treatmentpatients with clinically significant liver disease were not systematically studied, clinicaland may not reflect the rates observed in practice. In all controlled and uncontrolledthe geriatric population. This drug is known to be substantially excreted by the kidney, and of Opioid Overdose: Discuss the availability of naloxone for the emergency treatment oftrials did include patients with asymptomatic viral hepatitis infections. When patientstrials during the premarketing development of VIVITROL, more than 1100 patients withthe risk of adverse reactions to this drug may be greater in patients with impaired renal opioid overdose with the patient and caregiver, at the initial VIVITROL injection and withpresented with elevated transaminases, there were often other potential causative oralcohol and/or opioid dependence have been treated with VIVITROL. Approximately 700function. Because elderly patients are more likely to have decreased renal function, it each subsequent injection. Because of the risks for opioid overdose described above,contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitispatients have been treated for 6 months or more, and more than 400 for 1 year ormay be useful to monitor renal function. Renal Impairment: Pharmacokinetics of discuss with the patient and caregiver the importance of having access to naloxone for theB and/or C infection, and concomitant usage of other potentially hepatotoxic drugs.longer. Adverse Events Leading to Discontinuation of Treatment: Alcohol Dependence:VIVITROL are not altered in subjects with mild renal insufficiency (creatinine clearance of emergency treatment of opioid overdose. Inform patients and caregivers of the options forAlthoughclinicallysignificantliverdysfunctionisnottypicallyrecognizedasaIn controlled trials of 6 months or less in alcohol-dependent patients, 9% of alcohol- 50-80 mL/min). Dose adjustment is not required in patients with mild renal impairment. obtaining naloxone as permitted by individual state naloxone dispensing and prescribingmanifestation of opioid withdrawal, opioid withdrawal that is precipitated abruptly maydependent patients treated with VIVITROL discontinued treatment due to an adverseVIVITROL pharmacokinetics have not been evaluated in subjects with moderate and requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part oflead to systemic sequelae including acute liver injury. Patients should be warned of theevent, as compared to 7% of the alcohol-dependent patients treated with placebo.severe renal insufficiency. Because naltrexone and its primary metabolite are excreted a community-based program). Strongly consider prescribing naloxone for the emergencyrisk of hepatic injury and advised to seek medical attention if they experience symptomsAdverse events in the VIVITROL 380-mg group that led to more dropouts than in theprimarily in the urine, caution is recommended in administering VIVITROL to patients with treatment of opioid overdose. Educate patients and caregivers on how to recognize theof acute hepatitis. Use of VIVITROL should be discontinued in the event of symptoms and/ placebo-treated group were injection site reactions (3%), nausea (2%), pregnancymoderate to severe renal impairment. Hepatic Impairment: The pharmacokinetics of signs and symptoms of an opioid overdose and, if naloxone is prescribed, how to treat withor signs of acute hepatitis. Depression and Suicidality: Alcohol- and opioid-dependent(1%), headache (1%), and suicide-related events (0.3%). In the placebo group, 1% ofVIVITROL are not altered in subjects with mild to moderate hepatic impairment (Groups A naloxone. Emphasize the importance of calling 911 or getting emergency medical help inpatients, including those taking VIVITROL, should be monitored for the development ofpatients withdrew due to injection site reactions, and 0% of patients withdrew dueand B of the Child-Pugh classification). Dose adjustment is not required in subjects with all cases of known or suspected opioid overdose, even if naloxone is administered.depression or suicidal thinking. Families and caregivers of patients being treated withto the other adverse events. Opioid Dependence: In a controlled trial of 6 months, 2%mild or moderate hepatic impairment. VIVITROL pharmacokinetics were not evaluated in Injection Site Reactions: VIVITROL must be prepared and administered by a healthcareVIVITROL should be alerted to the need to monitor patients for the emergence ofof opioid-dependent patients treated with VIVITROL discontinued treatment due tosubjects with severe hepatic impairment.provider. VIVITROL injections may be followed by pain, tenderness, induration, swelling,symptoms of depression or suicidality, and to report such symptoms to the patientsan adverse event, as compared to 2% of the opioid-dependent patients treated withOVERDOSAGE: There is limited experience with overdose of VIVITROL. Single doses up to erythema, bruising, or pruritus; however, in some cases injection site reactions may behealthcareprovider.AlcoholDependence:IncontrolledclinicaltrialsofVIVITROLplacebo. Common Adverse Reactions: Alcohol Dependence: The adverse events seen784 mg were administered to 5 healthy subjects. There were no serious or severe adverse very severe. In the clinical trials, one patient developed an area of induration that continuedadministered to adults with alcohol dependence, adverse events of asuicidal naturemost frequently in association with VIVITROL therapy for alcohol dependence (ie, thoseevents. The most common effects were injection site reactions, nausea, abdominal pain, to enlarge after 4 weeks, with subsequent development of necrotic tissue that required(suicidal ideation, suicide attempts, completed suicides) were infrequent overall, but wereoccurring in 5% and at least twice as frequently with VIVITROL than placebo) includesomnolence, and dizziness. There were no significant increases in hepatic enzymes. In surgical excision. In the post marketing period, additional cases of injection site reactionmore common in patients treated with VIVITROL than in patients treated with placebonausea, vomiting, injection site reactions (including induration, pruritus, nodules andthe event of an overdose, appropriate supportive treatment should be initiated.with features including induration, cellulitis, hematoma, abscess, sterile abscess, and(1% vs 0%). In some cases, the suicidal thoughts or behavior occurred after studyswelling), arthralgia, arthritis, or joint stiffness, muscle cramps, dizziness or syncope,This brief summary is based on VIVITROL Full Prescribing Information (rev. March 2021).necrosis, have been reported. Some cases required surgical intervention, includingdiscontinuation, but were in the context of an episode of depression that began while thesomnolence or sedation, anorexia, decreased appetite or other appetite disorders. debridement of necrotic tissue. Some cases resulted in significant scarring. The reportedpatient was on study drug. Two completed suicides occurred, both involving patientsOpioid Dependence: The adverse events seen most frequently in association with cases occurred primarily in female patients. VIVITROL is administered as an intramusculartreatedwithVIVITROL.Depression-relatedeventsassociatedwithprematureVIVITROL therapy in opioid dependent patients (ie, those occurring in 2% and at least gluteal injection, and inadvertent subcutaneous injection of VIVITROL may increase thediscontinuation of study drug were also more common in patients treated with VIVITROLtwice as frequently with VIVITROL than placebo) were hepatic enzyme abnormalities, likelihood of severe injection site reactions. The needles provided in the carton are(~1%) than in placebo-treated patients (0%). In the 24-week, placebo-controlled pivotalinjection site pain, nasopharyngitis, insomnia, and toothache.customized needles. VIVITROL must not be injected using any other needle. The needletrial in 624 alcohol-dependent patients, adverse events involving depressed mood wereDRUG INTERACTIONS: Patients taking VIVITROL may not benefit from opioid-containingALKERMES and VIVITROL are registered trademarks of Alkermes, Inc.lengths (either 1 1/2 or 2 inches) may not be adequate in every patient because of bodyreported by 10% of patients treated with VIVITROL 380 mg, as compared to 5% ofmedicines. Naltrexone antagonizes the effects of opioid-containing medicines, such asManufactured and marketed by Alkermes, Inc.habitus. Body habitus should be assessed prior to each injection for each patient to assurepatients treated with placebo injections. Opioid Dependence: In an open-label, long-termcough and cold remedies, antidiarrheal preparations and opioid analgesics. 2021 Alkermes, Inc.All rights reservedVIV-006061Printed in U.S.A. that the proper needle is selected and that the needle length is adequate for intramuscularsafety study conducted in the US, adverse events of a suicidal nature (depressed mood, FS:7.125" FS:7.125"F:7.875" F:7.875"11552134_VIV005849_VA_AdSpread_Resize_M3FR.indd 2 12/6/21 1:38 PMPREPARED BY 11552134 VIV005849_VA_AdSpread_Print_15.75x10.75 M3FRJob info Images FontsSpecial InstructionsDate: 12-6-2021 1:38 PM 11552134_VIVITROL Brief Summa- None NoneClient: ALKERMES ry-HCP-Mar-2021_r1b.pdf (87%; 122KB)Product: ALKERMES VIVITROLClient Code: VIV005849 Additional InformationWF Issue # 10659621 NoneReleasing as: PDFx1AFinal Size: 15.75 (w) x 10.75 (h) - InchesFinishing: Trim Gutter: .5" each side Inks Additional Comments for SizingColors: 4CBlack NoneTeamProducer: Miles Cornman, Jarrett NewmanAD: Suzanne ElwardAE: Tanisha Makker Scale: 1"= 1"QC: LW Bleed 16" w x 11" h 16" w x 11" hProduction: Michael Patrissi, Bryant Santana Trim/Flat 15.75" w x 10.75" h 15.75" w x 10.75" hDigital Artist: Agosto, Victor (NYC-FCB) Live/Safety 15.25" w x 10.25" h 15.25" w x 10.25" h FR Spellcheck:NonePath: PrePress:Alkermes:ALKERMES_VIVITROL:11552134:11552134_VIV005849_VA_AdSpread_Resize_M3FR.inddPDFX1A _'