b'B:16"T:15.75"S:14.75"VIVITROL (naltrexone for extended-release injectable suspension) Intramuscular proper needle is selected and that the needle length is adequate for intramuscularsuicidal 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 informationadministration. Healthcare professionals should ensure that the VIVITROL injection istreated 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. September 2022). given correctly, and should consider alternate treatment for those patients whose bodywith 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 ishabitus precludes an intramuscular gluteal injection with one of the provided needles.conducted in Russia in 250 opioid-dependent patients, adverse events involving depressedoutcomes. There are clinical considerations (see Clinical Considerations). Reproduction indicated for the treatment of alcohol dependence in patients who are able to abstain fromPatients should be informed that any concerning injection site reactions should be broughtmood or suicidal thinking were not reported by any patient in either treatment groupand developmental animal studies have not been conducted for VIVITROL. Daily oral alcohol in an outpatient setting prior to initiation of treatment with VIVITROL. Patientsto the attention of the healthcare professional. Patients exhibiting signs of abscess,(VIVITROL 380 mg or placebo). When Reversal of VIVITROL Blockade Is Required foradministration 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,cellulitis, necrosis, or extensive swelling should be evaluated by a physician to determinePain Management: In an emergency situation in patients receiving VIVITROL, suggestions fetal loss at exposures 11 times and 2 times the human exposure, respectively. VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioidif referral to a surgeon is warranted. Precipitation of Opioid Withdrawal: The symptomsfor pain management include regional analgesia or use of non-opioid analgesics. If opioidDaily oral administration of naltrexone to pregnant rats and rabbits during the period of detoxification. VIVITROL should be part of a comprehensive management program thatof spontaneous opioid withdrawal (which are associated with the discontinuation of opioidtherapy is required as part of anesthesia or analgesia, patients should be continuouslyorganogenesis did not induce malformation at exposures up to 175 times and 14 times the includes psychosocial support.in a dependent individual) are uncomfortable, but they are not generally believed to bemonitored in an anesthesia care setting by persons not involved in the conduct of thehuman exposure, respectively (see Data). The estimated background risk of major birth severe or necessitate hospitalization. However, when withdrawal is precipitated abruptlysurgical or diagnostic procedure. The opioid therapy must be provided by individualsdefects and miscarriage for the indicated population is unknown. All pregnancies have CONTRAINDICATIONS:VIVITROLiscontraindicatedin:patientsreceivingopioidby the administration of an opioid antagonist to an opioid-dependent patient, the resultingspecifically trained in the use of anesthetic drugs and the management of the respiratorya background risk of birth defect, loss, or other adverse outcomes. In the U.S. general analgesics, patients with current physiologic opioid dependence, patients in acute opioidwithdrawal syndrome can be severe enough to require hospitalization. Review ofeffects of potent opioids, specifically the establishment and maintenance of a patentpopulation, the estimated background risk of major birth defects and miscarriage in withdrawal, any individual who has failed the naloxone challenge test or has a positivepostmarketing cases of precipitated opioid withdrawal in association with naltrexoneairway and assisted ventilation. Irrespective of the drug chosen to reverse VIVITROLclinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical urine screen for opioids, and patients who have previously exhibited hypersensitivity treatment has identified cases with symptoms of withdrawal severe enough to requireblockade, the patient should be monitored closely by appropriately trained personnel in aConsiderations: Disease-associated maternal and embryo-fetal risk: Untreated opioid to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose, or any otherhospital admission, and in some cases, management in the intensive care unit. To preventsetting equipped and staffed for cardiopulmonary resuscitation.E osinophilic Pneumonia:addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth components of the diluent. occurrence of precipitated withdrawal in patients dependent on opioids, or exacerbationIn clinical trials with VIVITROL, there was one diagnosed case and one suspected case ofweight, preterm birth, and fetal death. In addition, untreated opioid addiction often results WARNINGS AND PRECAUTIONS: Vulnerability to Opioid Overdose: After opioidof a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, includingeosinophilic pneumonia. Both cases required hospitalization, and resolved after treatmentin continued or relapsing illicit opioid use. Published studies have demonstrated that alcohol detoxification, patients are likely to have reduced tolerance to opioids. VIVITROL blocks thethose being treated for alcohol dependence, should be opioid-free (including tramadol)with antibiotics and corticosteroids. Similar cases have been reported in postmarketingis associated with fetal harm including growth restriction, facial abnormalities, central effects of exogenous opioids for approximately 28 days after administration. However, asbefore starting VIVITROL treatment. An opioid-free interval of a minimum of 710 days isuse. Should a person receiving VIVITROL develop progressive dyspnea and hypoxemia,nervous system abnormalities, behavioral disorders, and impaired intellectual development. the blockade wanes and eventually dissipates completely, patients who have been treatedrecommendedforpatientspreviouslydependentonshort-actingopioids.Patientsthe diagnosis of eosinophilic pneumonia should be considered. Patients should be warnedData: Animal Data: Reproduction and developmental studies have not been conducted for with VIVITROL may respond to lower doses of opioids than previously used, just as theytransitioning from buprenorphine or methadone may be vulnerable to precipitation ofof the risk of eosinophilic pneumonia, and advised to seek medical attention should theyVIVITROL. Studies with naltrexone administered via the oral route have been conducted would have shortly after completing detoxification. This could result in potentially life-withdrawal symptoms for as long as two weeks. If a more rapid transition from agonist todevelop symptoms of pneumonia. Clinicians should consider the possibility of eosinophilicin pregnant rats and rabbits. Daily oral administration of naltrexone has been shownthreatening opioid intoxication (respiratory compromise or arrest, circulatory collapse,antagonist therapy is deemed necessary and appropriate by the healthcare provider,pneumonia in patients who do not respond to antibiotics. Hypersensitivity Reactionsto increase the incidence of early fetal loss when given to rats at doses 30 mg/kg/dayetc.) if the patient uses previously tolerated doses of opioids. Cases of opioid overdose withmonitor the patient closely in an appropriate medical setting where precipitated withdrawalIncluding Anaphylaxis: Cases of urticaria, angioedema, and anaphylaxis have been(11 times the human exposure based on an AUCcomparison) and to rabbits at oral (0-28d)fatal outcomes have been reported in patients who used opioids at the end of a dosingcan be managed. In every case, healthcare providers should always be prepared toobserved with use of VIVITROL in the clinical trial setting and in postmarketing use.doses 60 mg/kg/ day (2 times the human exposure based on an AUCcomparison). (0-28d)interval, after missing a scheduled dose, or after discontinuing treatment. Patients shouldmanage withdrawal symptomatically with non-opioid medications because there is noPatients should be warned of the risk of hypersensitivity reactions, including anaphylaxis.Daily oral administration of naltrexone to rats and rabbits during the period of organogenesis be alerted that they may be more sensitive to opioids, even at lower doses, after VIVITROLcompletely reliable method for determining whether a patient has had an adequate opioid- In the event of a hypersensitivity reaction, patients should be advised to seek immediatedid not 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 offree period. A naloxone challenge test may be helpful; however, a few case reports havemedical attention in a healthcare setting prepared to treat anaphylaxis. The patient shouldexposure 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 isindicated that patients may experience precipitated withdrawal despite having a negativenot receive any further treatment with VIVITROL. Intramuscular Injections: As with anyNaltrexone 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 thisurine toxicology screen or tolerating a naloxone challenge test (usually in the setting ofintramuscular injection, VIVITROL should be administered with caution to patients withare no data on the effects on the breastfed infant or the effects on milk production. increased sensitivity to opioids and the risk of overdose. There is also the possibility that atransitioning from buprenorphine treatment). Patients should be made aware of the risksthrombocytopenia or any coagulation disorder (eg, hemophilia and severe hepatic failure).The developmental health benefits of breastfeeding should be considered along withpatient who is treated with VIVITROL could overcome the opioid blockade effect ofassociated with precipitated withdrawal and encouraged to give an accurate account ofAlcohol Withdrawal: Use of VIVITROL does not eliminate nor diminish alcohol withdrawalthe mothers clinical need for naltrexone and any potential adverse effects on the breastfed VIVITROL. Although VIVITROL is a potent antagonist with a prolonged pharmacologicallast opioid use. Patients treated for alcohol dependence with VIVITROL should also besymptoms. Interference with Laboratory Tests: VIVITROL may be cross-reactive withinfant from naltrexone or the mothers underlying maternal condition. Pediatric Use:S:9.75" T:10.75" B:11"effect, the blockade produced by VIVITROL is surmountable. The plasma concentration ofassessed for underlying opioid dependence and for any recent use of opioids prior tocertain immunoassay methods for the detection of drugs of abuse (specifically opioids) ThesafetyandefficacyofVIVITROLhavenotbeenestablishedinthepediatricexogenous opioids attained immediately following their acute administration may beinitiation of treatment with VIVITROL. Precipitated opioid withdrawal has been observed inin urine. For further information, reference to the specific immunoassay instructions population. The pharmacokinetics of VIVITROL have not been evaluated in a pediatric sufficient to overcome the competitive receptor blockade. This poses a potential risk toalcohol-dependent patients in circumstances where the prescriber had been unaware ofis recommended. population. Geriatric Use: In trials of alcohol-dependent subjects, 2.6% (n=26) of subjects individuals who attempt, on their own, to overcome the blockade by administering largethe additional use of opioids or co-dependence on opioids. Hepatotoxicity: Cases ofADVERSE REACTIONS: In all controlled and uncontrolled trials during the premarketingwere 65 years of age, and one patient was 75 years of age. Clinical studies of VIVITROL amounts of exogenous opioids. Any attempt by a patient to overcome the antagonism byhepatitis and clinically significant liver dysfunction were observed in association withdevelopment of VIVITROL, more than 1100 patients with alcohol and/or opioid dependencedid not include sufficient numbers of subjects age 65 and over to determine whether they taking opioids is especially dangerous and may lead to life-threatening opioid intoxicationVIVITROL exposure during the clinical development program and in the postmarketinghave been treated with VIVITROL. Approximately 700 patients have been treated for respond differently from younger subjects. No subjects over age 65 were included in studies or fatal overdose. Patients should be told of the serious consequences of trying toperiod. Transient, asymptomatic hepatic transaminase elevations were also observed in6 months or more, and more than 400 for 1 year or longer. Adverse Events Leading toof opioid-dependent subjects. The pharmacokinetics of VIVITROL have not been evaluated overcome the opioid blockade. Patient Access to Naloxone for the Emergency Treatmentthe clinical trials and postmarketing period. Although patients with clinically significantDiscontinuation of Treatment: Alcohol Dependence: In controlled trials of 6 months or lessin the geriatric population. This drug is known to be substantially excreted by the kidney, of Opioid Overdose: Discuss the availability of naloxone for the emergency treatment ofliver disease were not systematically studied, clinical trials did include patients within alcohol-dependent patients, 9% of alcohol-dependent patients treated with VIVITROLand the risk of adverse reactions to this drug may be greater in patients with impaired opioid overdose with the patient and caregiver, at the initial VIVITROL injection and withasymptomaticviralhepatitisinfections.Whenpatientspresentedwithelevateddiscontinued treatment due to an adverse event, as compared to 7% of the alcohol- renal function. Because elderly patients are more likely to have decreased renal function, each subsequent injection. Because of the risks for opioid overdose described above,transaminases, there were often other potential causative or contributory etiologiesdependent patients treated with placebo. Adverse events in the VIVITROL 380-mg groupit may be useful to monitor renal function. Renal Impairment: Pharmacokinetics of discuss with the patient and caregiver the importance of having access to naloxone for theidentified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, andthat led to more dropouts than in the placebo-treated group were injection site reactionsVIVITROL are not altered in subjects with mild renal insufficiency (creatinine clearanceemergency treatment of opioid overdose. Inform patients and caregivers of the options forconcomitant usage of other potentially hepatotoxic drugs. Although clinically significant(3%), nausea (2%), pregnancy (1%), headache (1%), and suicide-related events (0.3%).of 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 prescribingliver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioidIn the placebo group, 1% of patients withdrew due to injection site reactions, and 0% ofVIVITROL pharmacokinetics have not been evaluated in subjects with moderate and requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part ofwithdrawal that is precipitated abruptly may lead to systemic sequelae including acutepatients withdrew due to the other adverse events. Opioid Dependence: In a controlledsevere renal insufficiency. Because naltrexone and its primary metabolite are excreted a community-based program). Strongly consider prescribing naloxone for the emergencyliver injury. Patients should be warned of the risk of hepatic injury and advised to seektrial of 6 months, 2% of opioid-dependent patients treated with VIVITROL discontinuedprimarily in the urine, caution is recommended in administering VIVITROL to patients with treatment of opioid overdose. Educate patients and caregivers on how to recognize themedical attention if they experience symptoms of acute hepatitis. Use of VIVITROL shouldtreatment due to an adverse event, as compared to 2% of the opioid-dependent patientsmoderate to severe renal impairment. Hepatic Impairment: The pharmacokinetics of signs and symptoms of an opioid overdose and, if naloxone is prescribed, how to treat withbe discontinued in the event of symptoms and/or signs of acute hepatitis. Depressiontreated with placebo. Common Adverse Reactions: Alcohol Dependence: The adverseVIVITROL 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 inand Suicidality: Alcohol- and opioid-dependent patients, including those taking events seen most frequently in association with VIVITROL therapy for alcohol dependenceand 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.VIVITROL, should be monitored for the development of depression or suicidal thinking.(ie,thoseoccurringin5%andatleasttwiceasfrequentlywithVIVITROLthanmild or moderate hepatic impairment. VIVITROL pharmacokinetics were not evaluated in Injection Site Reactions: VIVITROL must be prepared and administered by a healthcareFamilies and caregivers of patients being treated with VIVITROL should be alerted to theplacebo) include nausea, vomiting, injection site reactions (including induration, pruritus,subjects with severe hepatic impairment.provider. VIVITROL must ONLY be administered as a deep intramuscular gluteal injection.need to monitor patients for the emergence of symptoms of depression or suicidality, andnodules and swelling), arthralgia, arthritis, or joint stiffness, muscle cramps, dizzinessOVERDOSAGE: There is limited experience with overdose of VIVITROL. Single doses up to VIVITROL injections may be followed by pain, tenderness, induration, swelling, erythema,to report such symptoms to the patients healthcare provider. Alcohol Dependence: Inor syncope, somnolence or sedation, anorexia, decreased appetite or other appetite784 mg were administered to 5 healthy subjects. There were no serious or severe adverse bruising, or pruritus; however, in some cases injection site reactions may be very severe.controlled clinical trials of VIVITROL administered to adults with alcohol dependence,disorders. Opioid Dependence: In the open-label, long-term safety study conducted inevents. The most common effects were injection site reactions, nausea, abdominal pain, In the clinical trials, one patient developed an area of induration that continued to enlargeadverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides )the US, the commonly reported adverse reactions among the opioid-dependent patientssomnolence, and dizziness. There were no significant increases in hepatic enzymes. In after 4 weeks, with subsequent development of necrotic tissue that required surgicalwere infrequent overall, but were more common in patients treated with VIVITROL than inin the study were similar to those commonly observed events in the alcohol-dependentthe event of an overdose, appropriate supportive treatment should be initiated.excision. In the postmarketing period, additional cases of injection site reaction withpatients treated with placebo (1% vs 0%). In some cases, the suicidal thoughts or behaviorpopulations in VIVITROL clinical trials. Injection site reactions of all types, nausea andThis brief summary is based on VIVITROL Full Prescribing Information (rev. September 2022).features including induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis,occurred after study discontinuation, but were in the context of an episode of depressiondiarrhea occurred in more than 5% of patients on VIVITROL in the open-label study. In have been reported. Some cases required surgical intervention, including debridement ofthat began while the patient was on study drug. Two completed suicides occurred, bothcontrast, 48% percent, of the opioid-dependent patients had at least one adverse event necrotic tissue. Some cases resulted in significant scarring. The reported cases occurredinvolving patients treated with VIVITROL. Depression-related events associated within the Infections and Infestations Body System. Adverse Reactions/Preferred Terms of primarily in female patients. VIVITROL is administered as a deep intramuscular glutealpremature discontinuation of study drug were also more common in patients treated withnasopharyngitis, upper respiratory tract infection, urinary tract infection, and sinusitis injection, and inadvertent subcutaneous injection of VIVITROL may increase the likelihoodVIVITROL (~1%) than in placebo-treated patients (0%). In the 24-week, placebo-controlledwere most commonly reported.of severe injection site reactions. The needles provided in the carton are customizedpivotal trial in 624 alcohol-dependent patients, adverse events involving depressed moodDRUG INTERACTIONS: Patients taking VIVITROL may not benefit from opioid-containing ALKERMES and VIVITROL are registered trademarks of Alkermes, Inc. needles. VIVITROL must not be injected using any other needle. The needle lengths (eitherwere reported 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. 1 1/2 or 2 inches) may not be adequate in every patient because of body habitus. Bodypatients treated with placebo injections. Opioid Dependence: In an open-label, long-termcough and cold remedies, antidiarrheal preparations and opioid analgesics. 2023 Alkermes, Inc.All rights reservedVIV-006522Printed in U.S.A. habitus should be assessed prior to each injection for each patient to assure that thesafety study conducted in the US, adverse events of a suicidal nature (depressed mood, F:7.875" F:7.875"12037252_VIV_2023_VA_CFU_JA_US_Med_Dir_M2FR.indd 2 11/20/23 11:27 AMPREPARED BY 12037252-vc12042827 VIV 2023 VA CFU JA - US Medicine_Directory Edition M2FRJob info Images FontsSpecial InstructionsDate: 11-20-2023 11:27 AM VIVITROL Brief Summary (HCP)_SeptemberNone Rename: VIV-006991_Vivitrol 2023 VA CFU Client: Alkermes 2022 (1).pdf (86.12%, 86.47%; 115KB) Journal Ad_US Medicine_DirectoryProduct: VivitrolClient Code: VIV-006991 Additional InformationWF Issue # 9148612 NoneReleasing as: Native + PDFx1aFinal Size: 15.75" x 10.75"Finishing: TrimGutter: None Inks Additional Comments for SizingColors: 4C + 1/0 (K)Black NoneTeamProducer: Stacy WichnerAD: Suzanne ElwardAE: Bhavish Vora Scale: 1"= 1"QC: lp / dy Bleed 16" w x 11" h 16" w x 11" hProduction: Steve Bertuzzi Trim/Flat 15.75" w x 10.75" h 15.75" w x 10.75" hDigital Artist: YIP (NYC-SRX) Live/Safety 14.75" w x 9.75" h 14.75" w x 9.75" h Path: PrePress:Alkermes:Vivitrol:12037252:12037252_VIV_2023_VA_CFU_JA_US_Med_Dir_M2FR.inddPDFX1A _'