b'B:16"T:15.75"S:14.75"VIVITROL (naltrexone for extended-release injectable suspension) Intramuscular individual) are uncomfortable, but they are not generally believed to be severe orreported by any patient in either treatment group (VIVITROL 380 mg or placebo).insufficient to identify a drug-associated risk of major birth defects, miscarriage BRIEF SUMMARY See package insert for full prescribing information necessitate hospitalization. However, when withdrawal is precipitated abruptly by theWhenReversalofVIVITROLBlockadeIsRequiredforPainManagement:oradversematernalorfetaloutcomes.Thereareclinicalconsiderations(see (rev. July 2020). administration of an opioid antagonist to an opioid-dependent patient, the resultingIn an emergency situation in patients receiving VIVITROL, suggestions for painClinicalConsiderations).Reproductionanddevelopmentalanimalstudieshave withdrawal syndrome can be severe enough to require hospitalization. Review ofmanagement include regional analgesia or use of non-opioid analgesics. If opioidnot been conducted for VIVITROL. Daily oral administration of naltrexone to female INDICATIONS AND USAGE: VIVITROL contains naltrexone, an opioid antagonist, andpostmarketing cases of precipitated opioid withdrawal in association with naltrexonetherapy is required as part of anesthesia or analgesia, patients should be continuouslyrats and rabbits increased the incidence of early fetal loss at exposures11 times and is indicated for the treatment of alcohol dependence in patients who are able totreatment has identified cases with symptoms of withdrawal severe enough tomonitored in an anesthesia care setting by persons not involved in the conduct of the 2 times the human exposure, respectively. Daily oral administration of naltrexone abstain from alcohol in an outpatient setting prior to initiation of treatment withrequire hospital admission, and in some cases, management in the intensive caresurgical or diagnostic procedure. The opioid therapy must be provided by individualsto pregnant rats and rabbits during the period of organogenesis did not induce VIVITROL. Patients should not be actively drinking at the time of initial VIVITROLunit. To prevent occurrence of precipitated withdrawal in patients dependent onspecifically trained in the use of anesthetic drugs and the management of themalformation at exposures up to 175 times and 14 times the human exposure, administration. In addition, VIVITROL is indicated for the prevention of relapse toopioids, or exacerbation of a pre-existing subclinical withdrawal syndrome, opioid- respiratory effects of potent opioids, specifically the establishment and maintenancerespectively(seeData).Theestimatedbackgroundriskofmajorbirthdefects opioid dependence, following opioid detoxification. VIVITROL should be part of adependent patients, including those being treated for alcohol dependence, shouldof a patent airway and assisted ventilation. Irrespective of the drug chosen to reverseand miscarriage for the indicated population is unknown. All pregnancies have a comprehensive management program that includes psychosocial support. be opioid-free (including tramadol) before starting VIVITROL treatment. An opioid- VIVITROL blockade, the patient should be monitored closely by appropriately trainedbackground risk of birth defect, loss, or other adverse outcomes. In the U.S. general free interval of a minimum of 710days is recommended for patients previouslypersonnel in a setting equipped and staffed for cardiopulmonary resuscitation.population, the estimated background risk of major birth defects and miscarriage in CONTRAINDICATIONS: VIVITROL is contraindicated in: patients receiving opioiddependentonshort-actingopioids.PatientstransitioningfrombuprenorphineEosinophilic Pneumonia: In clinical trials with VIVITROL, there was one diagnosedclinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical analgesics, patients with current physiologic opioid dependence, patients in acuteor methadone may be vulnerable to precipitation of withdrawal symptoms for ascase and one suspected case of eosinophilic pneumonia. Both cases requiredConsiderations: Disease-associated maternal and embryo-fetal risk: Untreated opioid opioid withdrawal, any individual who has failed the naloxone challenge test orlong as two weeks. If a more rapid transition from agonist to antagonist therapy ishospitalization, and resolved after treatment with antibiotics and corticosteroids.addiction in pregnancy is associated with adverse obstetrical outcomes such as low has a positive urine screen for opioids, and patients who have previously exhibiteddeemed necessary and appropriate by the healthcare provider, monitor the patientSimilar cases have been reported in postmarketing use. Should a person receivingbirth weight, preterm birth, and fetal death. In addition, untreated opioid addiction hypersensitivity to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose,closely in an appropriate medical setting where precipitated withdrawal can beVIVITROL develop progressive dyspnea and hypoxemia, the diagnosis of eosinophilicoften results in continued or relapsing illicit opioid use. Published studies have or any other components of the diluent. managed. In every case, healthcare providers should always be prepared to managepneumonia should be considered. Patients should be warned of the risk of eosinophilicdemonstrated that alcohol is associated with fetal harm including growth restriction, WARNINGS AND PRECAUTIONS: Vulnerability to Opioid Overdose: After opioidwithdrawalsymptomaticallywithnon-opioidmedicationsbecausethereisnopneumonia, and advised to seek medical attention should they develop symptoms offacialabnormalities,centralnervoussystemabnormalities,behavioraldisorders, detoxification, patients are likely to have reduced tolerance to opioids. VIVITROL blockscompletely reliable method for determining whether a patient has had an adequatepneumonia. Clinicians should consider the possibility of eosinophilic pneumonia inandimpairedintellectualdevelopment.Data:AnimalData:Reproductionand the effects of exogenous opioids for approximately 28 days after administration.opioid-free period. A naloxone challenge test may be helpful; however, a few casepatients who do not respond to antibiotics. Hypersensitivity Reactions Includingdevelopmental studies have not been conducted for VIVITROL. Studies with naltrexone However, as the blockade wanes and eventually dissipates completely, patientsreports have indicated that patients may experience precipitated withdrawal despiteAnaphylaxis: Cases of urticaria, angioedema, and anaphylaxis have been observedadministered via the oral route have been conducted in pregnant rats and rabbits. who have been treated with VIVITROL may respond to lower doses of opioids thanhaving a negative urine toxicology screen or tolerating a naloxone challenge testwith use of VIVITROL in the clinical trial setting and in postmarketing use. PatientsDaily oral administration of naltrexone has been shown to increase the incidence of previously used, just as they would have shortly after completing detoxification.(usually in the setting of transitioning from buprenorphine treatment). Patientsshould be warned of the risk of hypersensitivity reactions, including anaphylaxis. Inearly fetal loss when given to rats at doses 30 mg/kg/day (11 times the human Thiscouldresultinpotentiallylifethreateningopioidintoxication(respiratoryshould be made aware of the risks associated with precipitated withdrawal andthe event of a hypersensitivity reaction, patients should be advised to seek immediateexposure based on an AUC (0-28d)comparison) and to rabbits at oral doses 60 mg/kg/ compromise or arrest, circulatory collapse, etc.) if the patient uses previouslyencouraged to give an accurate account of last opioid use. Patients treated formedical attention in a healthcare setting prepared to treat anaphylaxis. The patientday (2 times the human exposure based on an AUC (0-28d)comparison). Daily oral tolerated doses of opioids. Cases of opioid overdose with fatal outcomes have beenalcohol dependence with VIVITROL should also be assessed for underlying opioidshould not receive any further treatment with VIVITROL. Intramuscular Injections:administration of naltrexone to rats and rabbits during the period of organogenesis reported in patients who used opioids at the end of a dosing interval, after missingdependence and for any recent use of opioids prior to initiation of treatment withAs with any intramuscular injection, VIVITROL should be administered with cautiondid not induce malformations at doses up to 200 mg/kg/day (175- and 14-times the a scheduled dose, or after discontinuing treatment. Patients should be alertedhuman exposure based on an AUC (0-28d)comparison, respectively). Lactation: Risk that they may be more sensitive to opioids, even at lower doses, after VIVITROLVIVITROL. Precipitated opioid withdrawal has been observed in alcohol-dependentto patients with thrombocytopenia or any coagulation disorder (eg, hemophilia andSummary: Naltrexone and its major metabolite, 6-naltrexone, are present in human treatment is discontinued, especially at the end of a dosing interval (i.e., near thepatients in circumstances where the prescriber had been unaware of the additionalsevere hepatic failure). Alcohol Withdrawal: Use of VIVITROL does not eliminatemilk. There are no data on the effects on the breastfed infant or the effects on milk end of the month that VIVITROL was administered), or after a dose of VIVITROL isuse of opioids or co-dependence on opioids. Hepatotoxicity: Cases of hepatitis andnor diminish alcohol withdrawal symptoms. Interference with Laboratory Tests:production. The developmental health benefits of breastfeeding should be considered missed. It is important that patients inform family members and the people closestclinically significant liver dysfunction were observed in association with VIVITROLVIVITROL may be cross-reactive with certain immunoassay methods for the detectionalong with the mothers clinical need for naltrexone and any potential adverse effects to the patient of this increased sensitivity to opioids and the risk of overdose. Thereexposure during the clinical development program and in the postmarketing period.of drugs of abuse (specifically opioids) in urine. For further information, reference toon the breastfed infant from naltrexone or the mothers underlying maternal condition. is also the possibility that a patient who is treated with VIVITROL could overcomeTransient, asymptomatic hepatic transaminase elevations were also observed in thethe specific immunoassay instructions is recommended. Pediatric Use: The safety and efficacy of VIVITROL have not been established in theS:9.75" T:10.75" B:11"the opioid blockade effect of VIVITROL. Although VIVITROL is a potent antagonistclinical trials and postmarketing period. Although patients with clinically significantADVERSEREACTIONS:ClinicalTrialsExperience:Becauseclinicaltrialsarepediatric population. The pharmacokinetics of VIVITROL have not been evaluated in with a prolonged pharmacological effect, the blockade produced by VIVITROL isliver disease were not systematically studied, clinical trials did include patients withconducted under widely varying conditions, adverse reaction rates observed in thea pediatric population. Geriatric Use: In trials of alcohol-dependent subjects, 2.6% surmountable. The plasma concentration of exogenous opioids attained immediatelyasymptomatic viral hepatitis infections. When patients presented with elevatedclinical trials of a drug cannot be directly compared to rates in the clinical trials of(n=26) of subjects were 65years of age, and one patient was 75years of age. following their acute administration may be sufficient to overcome the competitivetransaminases, there were often other potential causative or contributory etiologiesanother drug and may not reflect the rates observed in practice. In all controlledClinicalstudiesof VIVITROLdidnotincludesufficientnumbersofsubjectsage receptor blockade. This poses a potential risk to individuals who attempt, on theiridentified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection,and uncontrolled trials during the premarketing development of VIVITROL, more than65and over to determine whether they respond differently from younger subjects. own, to overcome the blockade by administering large amounts of exogenousand concomitant usage of other potentially hepatotoxic drugs. Although clinically1100patients with alcohol and/or opioid dependence have been treated with VIVITROL.No subjects over age 65were included in studies of opioid-dependent subjects. The opioids. Any attempt by a patient to overcome the antagonism by taking opioidssignificant liver dysfunction is not typically recognized as a manifestation of opioidApproximately 700patients have been treated for 6months or more, and more thanpharmacokinetics of VIVITROL have not been evaluated in the geriatric population. is especially dangerous and may lead to life-threatening opioid intoxication or fatalwithdrawal, opioid withdrawal that is precipitated abruptly may lead to systemic400for 1year or longer. Adverse Events Leading to Discontinuation of Treatment:This drug is known to be substantially excreted by the kidney, and the risk of adverse overdose. Patients should be told of the serious consequences of trying to overcomesequelae including acute liver injury. Patients should be warned of the risk of hepaticAlcohol Dependence: In controlled trials of 6months or less in alcohol-dependentreactions to this drug may be greater in patients with impaired renal function. Because the opioid blockade. Injection Site Reactions: VIVITROL must be prepared andinjury and advised to seek medical attention if they experience symptoms of acutepatients, 9% of alcohol-dependent patients treated with VIVITROL discontinuedelderly patients are more likely to have decreased renal function, it may be useful administered by a healthcare provider. VIVITROL injections may be followed byhepatitis. Use of VIVITROL should be discontinued in the event of symptoms and/ortreatment due to an adverse event, as compared to 7% of the alcohol-dependentto monitor renal function. Renal Impairment: Pharmacokinetics of VIVITROL are not pain, tenderness, induration, swelling, erythema, bruising, or pruritus; however, insigns of acute hepatitis. Depression and Suicidality: Alcohol- and opioid-dependentpatients treated with placebo. Adverse events in the VIVITROL 380-mg group thataltered in subjects with mild renal insufficiency (creatinine clearance of 50-80mL/some cases injection site reactions may be very severe. In the clinical trials, onepatients, including those taking VIVITROL, should be monitored for the developmentled to more dropouts than in the placebo-treated group were injection site reactionsmin). Dose adjustment is not required in patients with mild renal impairment. VIVITROL patient developed an area of induration that continued to enlarge after 4 weeks, withof depression or suicidal thinking. Families and caregivers of patients being treated(3%), nausea (2%), pregnancy (1%), headache (1%), and suicide-related eventspharmacokinetics have not been evaluated in subjects with moderate and severe renal subsequent development of necrotic tissue that required surgical excision. In the with VIVITROL should be alerted to the need to monitor patients for the emergence of(0.3%). In the placebo group, 1% of patients withdrew due to injection site reactions,insufficiency. Because naltrexone and its primary metabolite are excreted primarily post marketing period, additional cases of injection site reaction with featuressymptoms of depression or suicidality, and to report such symptoms to the patientsand 0% of patients withdrew due to the other adverse events. Opioid Dependence: Inin the urine, caution is recommended in administering VIVITROL to patients with including induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis,healthcare provider. Alcohol Dependence: In controlled clinical trials of VIVITROLa controlled trial of 6 months, 2% of opioid-dependent patients treated with VIVITROLmoderate to severe renal impairment. Hepatic Impairment: The pharmacokinetics have been reported. Some cases required surgical intervention, including debridementadministered to adults with alcohol dependence, adverse events of asuicidal naturediscontinued treatment due to an adverse event, as compared to 2% of the opioid- of VIVITROL are not altered in subjects with mild to moderate hepatic impairment of necrotic tissue. Some cases resulted in significant scarring. The reported cases(suicidal ideation, suicide attempts, completed suicides) were infrequent overall, butdependent patients treated with placebo.Common Adverse Reactions: Alcohol(Groups A and B of the Child-Pugh classification). Dose adjustment is not required in occurred primarily in female patients. VIVITROL is administered as an intramuscularwere more common in patients treated with VIVITROL than in patients treated withDependence: The adverse events seen most frequently in association with VIVITROLsubjects with mild or moderate hepatic impairment. VIVITROL pharmacokinetics were gluteal injection, and inadvertent subcutaneous injection of VIVITROL may increaseplacebo (1% vs 0%). In some cases, the suicidal thoughts or behavior occurredtherapy for alcohol dependence (ie, those occurring in 5% and at least twice asnot evaluated in subjects with severe hepatic impairment.the likelihood of severe injection site reactions. The needles provided in the cartonafter study discontinuation, but were in the context of an episode of depression that are customized needles. VIVITROL must not be injected using any other needle.began while the patient was on study drug. Two completed suicides occurred, bothfrequently with VIVITROL than placebo) include nausea, vomiting, injection siteOVERDOSAGE: There is limited experience with overdose of VIVITROL. Single doses up The needle lengths (either 1 1/2 or 2 inches) may not be adequate in every patientinvolving patients treated with VIVITROL. Depression-related events associated withreactions (including induration, pruritus, nodules and swelling), arthralgia, arthritis,to 784mg were administered to 5healthy subjects. There were no serious or severe because of body habitus. Body habitus should be assessed prior to each injection forpremature discontinuation of study drug were also more common in patients treatedor joint stiffness, muscle cramps, dizziness or syncope, somnolence or sedation,adverse events. The most common effects were injection site reactions, nausea, each patient to assure that the proper needle is selected and that the needle length iswith VIVITROL (~1%) than in placebo-treated patients (0%). In the 24-week, placebo- anorexia, decreased appetite or other appetite disorders. Opioid Dependence: Theabdominal pain, somnolence, and dizziness. There were no significant increases in adequate for intramuscular administration. Healthcare professionals should ensurecontrolled pivotal trial in 624 alcohol-dependent patients, adverse events involvingadverse events seen most frequently in association with VIVITROL therapy in opioidhepatic enzymes. In the event of an overdose, appropriate supportive treatment should that the VIVITROL injection is given correctly, and should consider alternate treatmentdepressed mood were reported by 10% of patients treated with VIVITROL 380mg,dependent patients (ie, those occurring in 2% and at least twice as frequentlybe initiated.for those patients whose body habitus precludes an intramuscular gluteal injectionas compared to 5% of patients treated with placebo injections. Opioid Dependence:with VIVITROL than placebo) were hepatic enzyme abnormalities, injection site pain, with one of the provided needles. Patients should be informed that any concerningIn an open-label, long-term safety study conducted in the US, adverse events of anasopharyngitis, insomnia, and toothache. ThisbriefsummaryisbasedonVIVITROLFullPrescribingInformation injection site reactions should be brought to the attention of the healthcare professional.suicidal nature (depressed mood, suicidal ideation, suicide attempt) were reportedDRUGINTERACTIONS: Patients taking VIVITROL may not benefit from opioid-(rev. July 2020).Patients exhibiting signs of abscess, cellulitis, necrosis, or extensive swelling shouldby 5% of opioid-dependent patients treated with VIVITROL 380mg (n=101) and 10%containingmedicines.Naltrexoneantagonizestheeffectsofopioid-containing be evaluated by a physician to determine if referral to a surgeon is warranted. of opioid-dependent patients treated with oral naltrexone (n=20). In the 24-week,medicines,suchascoughandcoldremedies,antidiarrhealpreparationsand PrecipitationofOpioidWithdrawal:Thesymptomsofspontaneousopioidplacebo-controlled pivotal trial that was conducted in Russia in 250 opioid-dependentopioid analgesics.withdrawal (which are associated with the discontinuation of opioid in a dependentpatients, adverse events involving depressed mood or suicidal thinking were notALKERMES and VIVITROL are registered trademarks of Alkermes, Inc. USEINSPECIFICPOPULATIONS:Pregnancy:RiskSummary:TheavailableManufactured and marketed by Alkermes, Inc. datafrompublishedcaseserieswithVIVITROLuseinpregnantwomenare2020 Alkermes, Inc.All rights reservedVIV-005538 Printed in U.S.A. FS:7.125" FS:7.125"F:7.875" F:7.875"11508764_VIV_VA_HOSP_US_MED_AD_M1.indd 2 1/12/21 2:20 PMPREPARED BY 11508764 Ad for compendium of US Medicine M1Job info Images FontsSpecial InstructionsDate: 1-12-2021 2:20 PM VIVITROL Brief Summary (HCP) (August 2020)None NoneClient: ALKERMES (1).pdf (88.71%; 131KB)Product: ALKERMES VIVITROLClient Code: VIV-005589 Additional InformationWF Issue # 8016332 NoneReleasing as: PDFx1AFinal Size: 15.75"w x 10.75"hFinishing: TrimGutter: Gutter clearance = .5" across Inks Additional Comments for SizingColors: 4/C spread + B&W Brief SummaryBlack NoneTeamProducer: Denzyl AmankwahAD: Kristine SoAE: Denzyl Amankwah Scale: 1"= 1"QC: Lynwood Bleed 16" w x 11" h 16" w x 11" hProduction: Emily O\'Loane Trim/Flat 15.75" w x 10.75" h 15.75" w x 10.75" hDigital Artist: Pitagorsky, Tracy (NYC-FCB) Live/Safety 14.75" w x 9.75" h 14.75" w x 9.75" h FR Spellcheck:NonePath: PrePress:Alkermes:Vivitrol:11508764:11508764_VIV_VA_HOSP_US_MED_AD_M1.indd_ _'