b'B:16"T:15.75"S:14.75"VIVITROL (naltrexone for extended-release injectable suspension) for proper needle is selected and that the needle length is adequate for intramuscular suicidal ideation, suicide attempt) were reported by 5% of opioid-dependent patientsUSE IN SPECIFIC POPULATIONS: Pregnancy: Risk Summary: The available data from intramuscularuse administration. Healthcare professionals should ensure that the VIVITROL injection is treated 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 BRIEF SUMMARYSee package insert for full Prescribing Information. given correctly, and should consider alternate treatment for those patients whose body 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 is habitus 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 from Patients should be informed that any concerning injection site reactions should be brought mood 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. Patients to 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 determine Pain 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 opioid if referral to a surgeon is warranted. PrecipitationofOpioidWithdrawal: The symptoms for 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 that ofspontaneous opioid withdrawal (which areassociated with the discontinuation of opioid therapy 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 be monitored 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 abruptly surgical or diagnostic procedure. The opioid therapy must be provided by individualsdefects and miscarriage for the indicated population is unknown. All pregnancies have CONTRAINDICATIONS: VIVITROLiscontraindicatedin:patientsreceivingopioid by the administration of an opioid antagonist to an opioid-dependent patient, the resulting specifically 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 opioid withdrawal 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 positive postmarketing cases of precipitated opioid withdrawal in association with naltrexone airway 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 require blockade, 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 prevent setting 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. occurrenceofprecipitatedwithdrawalinpatientsdependentonopioids,orexacerbation In 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 opioid of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, including eosinophilic 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 the those 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, as before starting VIVITROL treatment. An opioid-freeinterval of a minimum of710 days is use. 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 treated recommended for patients previously dependent on short-acting opioids. Patients the 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 they transitioning from buprenorphine or methadone may be vulnerable to precipitation of of 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 to develop 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 with monitor the patient closely in an appropriate medical setting where precipitated withdrawal Including 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 dosing can be managed. In every case, healthcare providers should always be prepared to observed 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 should manage withdrawal symptomatically with non-opioid medications because there is no Patients 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 VIVITROL completely 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 of free period. A naloxone challenge test may be helpful; however, a few case reports have medical 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 is indicated that patients may experience precipitated withdrawal despite having a negative not 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 this urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of intramuscular 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 a transitioning from buprenorphine treatment). Patients should be made aware of the risks thrombocytopenia 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 of associated with precipitated withdrawal and encouraged to give an accurate account of Alcohol Withdrawal: Use of VIVITROL does not eliminate nor diminish alcohol withdrawalthe mothers clinical need for naltrexone and any potential adverse effects on the breastfedS:9.75" T:10.75" B:11"VIVITROL. Although VIVITROL is a potent antagonist with a prolonged pharmacological last opioid use. Patients treated for alcohol dependence with VIVITROL should also be symptoms. Interference with Laboratory Tests: VIVITROL may be cross-reactive withinfant from naltrexone or the mothers underlying maternal condition. Pediatric Use: effect, the blockade produced by VIVITROL is surmountable. The plasma concentration of assessed for underlying opioid dependence and for any recent use of opioids prior to certain immunoassay methods for the detection of drugs of abuse (specifically opioids) ThesafetyandefficacyofVIVITROLhavenotbeenestablishedinthepediatricexogenous opioids attained immediately following their acute administration may be initiation of treatment with VIVITROL. Precipitated opioid withdrawal has been observed in in 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 to alcohol-dependent patients in circumstances where the prescriber had been unaware of is 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 large the additional use of opioids or co-dependence on opioids. Hepatotoxicity: Cases of ADVERSE 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 by hepatitis and clinically significant liver dysfunction were observed in association with development 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 intoxication VIVITROL exposure during the clinical development program and in the postmarketing have 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 to period. Transient, asymptomatic hepatic transaminase elevations were also observed in 6 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 overcometheopioidblockade. Patient Access to Naloxone for the Emergency Treatment the clinical trials and postmarketing period. Although patients with clinically significant Discontinuation 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 of liver disease were not systematically studied, clinical trials did include patients with in 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 with asymptomaticviralhepatitisinfections.Whenpatientspresentedwithelevated discontinued 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 etiologies dependent 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 the identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and that 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 for concomitant 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 prescribing liver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioid In 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 of withdrawal that is precipitated abruptly may lead to systemic sequelae including acute patients 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 emergency liver injury. Patients should be warned of the risk of hepatic injury and advised to seek trial 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 the medical attention if they experience symptoms of acute hepatitis. Use of VIVITROL should treatment 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 with be discontinued in the event of symptoms and/or signs of acute hepatitis. Depression treated 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 in and Suicidality: Alcohol- and opioid-dependent patients, including those takingevents 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 InjectionSiteReactions: VIVITROL must be prepared and administered by a healthcare Families and caregivers of patients being treated with VIVITROL should be alerted to the placebo) 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, and nodules 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: In or 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 enlarge adverse 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 surgical were infrequent overall, but were more common in patients treated with VIVITROL than in in 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 with patients treated with placebo (1% vs 0%). In some cases, the suicidal thoughts or behavior populations in VIVITROL clinical trials. Injection site reactions of all types, nausea andThis brief summary is based on VIVITROL Full Prescribing Information (rev. January 2024). features including induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis, occurred after study discontinuation, but were in the context of an episode of depression diarrhea 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 of that began while the patient was on study drug. Two completed suicides occurred, both contrast, 48% percent, of the opioid-dependent patients had at least one adverse event necrotic tissue. Some cases resulted in significant scarring. The reported cases occurred involving patients treated with VIVITROL. Depression-related events associated with in the Infections and Infestations Body System. Adverse Reactions/Preferred Terms of primarily in female patients. VIVITROL is administered as a deep intramuscular gluteal premature discontinuation of study drug were also more common in patients treated with nasopharyngitis, upper respiratory tract infection, urinary tract infection, and sinusitis injection, and inadvertent subcutaneous injection of VIVITROL may increase the likelihood VIVITROL (~1%) than in placebo-treated patients (0%). In the 24-week, placebo-controlled were most commonly reported.of severe injection site reactions. The needles provided in the carton are customized pivotal trial in 624 alcohol-dependent patients, adverse events involving depressed mood DRUG INTERACTIONS: Patients taking VIVITROL may not benefit from opioid-containingneedles. VIVITROL must not be injected using any other needle. The needle lengths (either were reported by 10% of patients treated with VIVITROL 380 mg, as compared to 5% of medicines. Naltrexone antagonizes the effects of opioid-containing medicines, such asALKERMES and VIVITROL are registered trademarks of Alkermes, Inc. 1 1/2 or 2 inches) may not be adequate in every patient because of body habitus. Body patients treated with placebo injections. OpioidDependence:Inanopen-label,long-term cough and cold remedies, antidiarrheal preparations and opioid analgesics. 2024 Alkermes, Inc. All rights reserved VIV-007182 habitus should be assessed prior to each injection for each patient to assure that the safety study conducted in the US, adverse events of a suicidal nature (depressed mood,F:7.875" F:7.875"PREPARED BY12206949_VA_Journal_Ad_US_Medicine_M2FR.indd 2 12206949 vc12226236 VA Journal Ad U.S. Medicine M2FR 10/28/24 3:46 PMJob info Images FontsSpecial InstructionsDate: 10-28-2024 3:46 PM 12206949_VIVITROL Brief Summa- None NoneClient: Alkermes ry-HCP-Oct-2024_r1.pdf (86.5%, 86.5%; 103KB)Product: VivitrolClient Code: VIV-007210WF Issue # None Additional InformationReleasing as: PDFx1A NoneFinal Size: 15.75 x 10.75Finishing: NoneGutter: None InksColors: 4/0 & 1/0BlackRename upon VIV-007210_Vivitrol VA Journal Ad_US release: Medicine Additional Comments for SizingComponent NoneDescription: NoneTeamProject Mgr: Steve BertuzziAD: Suzanne ElwardAE: Bhavish Vora Scale: 1 = 1QC: LP/DY Bleed 16 w x 11 h 16 w x 11 hProduction: Stacy Wichner Trim/Flat 15.75 w x 10.75 h 15.75 w x 10.75 hDigital Artist: Pitagorsky, Tracy (NYC-SRX) Live/Safety 14.75 w x 9.75 h 14.75 w x 9.75 h Path: NYC-SRX:PRINT & DIGITAL:PREPRESS:Alkermes:ALKERMES_VIVITROL:12206949:12206949_VA_Journal_Ad_US_Medicine_M2FR.inddPDFX1A _'