INVEGA SUSTENNA (paliperidone palmitate) extended-release injectable

Size: px
Start display at page:

Download "INVEGA SUSTENNA (paliperidone palmitate) extended-release injectable"

Transcription

1 (pliperidone plmitte) extended-relese injectble suspension, for intrmusculr use HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescribing informtion for. (pliperidone plmitte) extended-relese injectble suspension, for intrmusculr use Initil U.S. Approvl: 2006 WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing informtion for complete boxed wrning. Elderly ptients with dementi-relted psychosis treted with ntipsychotic drugs re t n incresed risk of deth. (5.1) is not pproved for use in ptients with dementirelted psychosis. (5.1) RECENT MAJOR CHANGES Dosge nd Administrtion (2.5) 06/2017 Wrnings nd Precutions (5.8) 02/2017 Wrnings nd Precutions (5.10) 06/ INDICATIONS AND USAGE is n typicl ntipsychotic indicted for Tretment of schizophreni. (1) Tretment of schizoffective disorder s monotherpy nd s n djunct to mood stbilizers or ntidepressnts. (1) DOSAGE AND ADMINISTRATION For intrmusculr injection only. (2.1) Ech injection must be dministered only by helth cre professionl. (2.1) For deltoid injection, use 1-inch 23G needle for ptients weighing less thn 90 kg or 1 ½-inch 22G needle for ptients weighing 90 kg or more. For glutel injection, use 1 ½-inch 22G needle regrdless of ptient weight. (2.1) Indiction Initition Dosing (deltoid) Dy 1 Dy 8 Monthly Mintennce Dose (deltoid or glutel) Mximum Monthly Dose Schizophreni (2.2) 234 mg 156 mg mg b 234 mg Schizoffective disorder (2.2) 234 mg 156 mg mg c 234 mg Administered 5 weeks fter the first injection. b The recommended mintennce dose for tretment of schizophreni is 117 mg. Some ptients my benefit from lower or higher mintennce doses within the dditionl vilble strengths (39 mg, 78 mg, 156 mg, nd 234 mg). c Adjust dose bsed on tolerbility nd/or efficcy using vilble strengths. The 39 mg strength ws not studied in the long-term schizoffective disorder study. For ptients nïve to orl pliperidone or orl or injectble risperidone, estblish tolerbility with orl pliperidone or orl risperidone prior to inititing tretment with. (2.2) Missed Doses: To mnge either missed second initition dose or missed monthly mintennce dose, refer to the Full Prescribing Informtion. (2.3) Moderte to severe renl impirment (cretinine clernce < 50 ml/min): is not recommended. (2.5) Mild renl impirment (cretinine clernce 50 ml/min to < 80 ml/min): Administer 156 mg on tretment dy 1 nd 117 mg one week lter, both dministered in the deltoid muscle. Follow with monthly injections of 78 mg in either the deltoid or glutel muscle. (2.5) DOSAGE FORMS AND STRENGTHS Extended-relese injectble suspension: 39 mg, 78 mg, 117 mg, 156 mg, or 234 mg (3) (pliperidone plmitte) CONTRAINDICATIONS Known hypersensitivity to pliperidone, risperidone, or to ny excipients in. (4) WARNINGS AND PRECAUTIONS Cerebrovsculr Adverse Rections, Including Stroke, in Elderly Ptients with Dementi-Relted Psychosis: Incresed incidence of cerebrovsculr dverse rections (e.g. stroke, trnsient ischemic ttck, including ftlities). is not pproved for use in ptients with dementi-relted psychosis (5.2) Neuroleptic Mlignnt Syndrome: Mnge with immedite discontinution of drug nd close monitoring (5.3) QT Prolongtion: Avoid use with drugs tht lso increse QT intervl nd in ptients with risk fctors for prolonged QT intervl (5.4) Trdive Dyskinesi: Discontinue drug if cliniclly pproprite (5.5) Metbolic Chnges: Atypicl ntipsychotic drugs hve been ssocited with metbolic chnges tht my increse crdiovsculr/cerebrovsculr risk. These metbolic chnges include: Hyperglycemi nd Dibetes Mellitus: Monitor for symptoms of hyperglycemi including polydipsi, polyuri, polyphgi, nd wekness. Monitor glucose regulrly in ptients with dibetes or t risk for dibetes. (5.6) Dyslipidemi: Undesirble ltertions hve been observed. (5.6) Weight Gin: Significnt weight gin hs been reported. Monitor weight gin. (5.6) Orthosttic Hypotension nd Syncope: Use with cution in ptients with known crdiovsculr or cerebrovsculr disese nd ptients predisposed to hypotension (5.7) Leukopeni, Neutropeni, nd Agrnulocytosis: Monitor complete blood count in ptients with history of cliniclly significnt low white blood cell count (WBC) or drug-induced leukopeni/neutropeni. Consider discontinution if cliniclly significnt decline in WBC in the bsence of other custive fctors (5.9) Hyperprolctinemi: Prolctin elevtions occur nd persist during chronic dministrtion (5.10) Potentil for Cognitive nd Motor Impirment: Use cution when operting mchinery (5.11) Seizures: Use cutiously in ptients with history of seizures or with conditions tht lower the seizure threshold (5.12) ADVERSE REACTIONS The most common dverse rections (incidence 5% nd occurring t lest twice s often s plcebo) were injection site rections, somnolence/sedtion, dizziness, kthisi, nd extrpyrmidl disorder. (6) To report SUSPECTED ADVERSE REACTIONS, contct Jnssen Phrmceuticls, Inc. t JANSSEN ( ) or FDA t FDA-1088 or DRUG INTERACTIONS Drugs tht my cuse orthosttic hypotension: An dditive effect my occur when co-dministered with. (7.1) Strong CYP3A4/P-glycoprotein (P-gp) inducers: Avoid using strong inducer of CYP3A4 nd/or P-gp (e.g., crbmzepine, rifmpin, St John s Wort) during dosing intervl for. If dministering strong inducer is necessry, consider mnging the ptient using pliperidone extended relese tblets. (2.5, 7.1, 12.3) USE IN SPECIFIC POPULATIONS Pregnncy: My cuse extrpyrmidl nd/or withdrwl symptoms in neontes with third trimester exposure. (8.1) See 17 for PATIENT COUNSELING INFORMATION nd FDA-pproved ptient lbeling. Revised: 06/2017 1

2 (pliperidone plmitte) FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Administrtion Instructions 2.2 Schizophreni nd Schizoffective Disorder 2.3 Missed Doses 2.4 Use with Risperidone or with Orl Pliperidone 2.5 Dosge Adjustments 2.6 Switching from Other Antipsychotics 2.7 Instructions for Use 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Incresed Mortlity in Elderly Ptients with Dementi-Relted Psychosis 5.2 Cerebrovsculr Adverse Rections, Including Stroke, in Elderly Ptients with Dementi-Relted Psychosis 5.3 Neuroleptic Mlignnt Syndrome 5.4 QT Prolongtion 5.5 Trdive Dyskinesi 5.6 Metbolic Chnges 5.7 Orthosttic Hypotension nd Syncope 5.8 Flls 5.9 Leukopeni, Neutropeni, nd Agrnulocytosis 5.10 Hyperprolctinemi 5.11 Potentil for Cognitive nd Motor Impirment 5.12 Seizures 5.13 Dysphgi 5.14 Pripism 5.15 Disruption of Body Temperture Regultion 6 ADVERSE REACTIONS 6.1 Clinicl Trils Experience 6.2 Postmrketing Experience (pliperidone plmitte) 7 DRUG INTERACTIONS 7.1 Drugs Hving Cliniclly Importnt Interctions with 7.2 Drugs Hving No Cliniclly Importnt Interctions with 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnncy 8.2 Lbor nd Delivery 8.3 Nursing Mothers 8.4 Peditric Use 8.5 Geritric Use 8.6 Renl Impirment 8.7 Heptic Impirment 8.8 Ptients with Prkinson s Disese or Lewy Body Dementi 9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substnce 9.2 Abuse 9.3 Dependence 10 OVERDOSAGE 10.1 Humn Experience 10.2 Mngement of Overdosge 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechnism of Action 12.2 Phrmcodynmics 12.3 Phrmcokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Crcinogenesis, Mutgenesis, Impirment of Fertility 14 CLINICAL STUDIES 14.1 Schizophreni 14.2 Schizoffective Disorder 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing informtion re not listed. FULL PRESCRIBING INFORMATION WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly ptients with dementi-relted psychosis treted with ntipsychotic drugs re t n incresed risk of deth [see Wrnings nd Precutions (5.1)]. is not pproved for use in ptients with dementirelted psychosis [see Wrnings nd Precutions (5.1)]. 1 INDICATIONS AND USAGE (pliperidone plmitte) is indicted for the tretment of: Schizophreni [see Clinicl Studies (14.1)]. Schizoffective disorder s monotherpy nd s n djunct to mood stbilizers or ntidepressnts [see Clinicl Studies (14.2)] 2 DOSAGE AND ADMINISTRATION 2.1 Administrtion Instructions Ech injection must be dministered only by helthcre professionl. Prenterl drug products should be inspected visully for foreign mtter nd discolortion prior to dministrtion, whenever product nd continer permit. is intended for intrmusculr use only. Do not dminister by ny other route. Avoid indvertent injection into blood vessel. Administer the dose in single injection; do not dminister the dose in divided injections. Inject slowly, deep into the deltoid or glutel muscle. must be dministered using only the needles tht re provided in the kit. The recommended needle size for dministrtion of into the deltoid muscle is determined by the ptient s weight: For ptients weighing less thn 90 kg, the 1-inch, 23 guge needle is recommended. For ptients weighing 90 kg or more, the 1 ½-inch, 22 guge needle is recommended. Deltoid injections should be lternted between the two deltoid muscles. The recommended needle size for dministrtion of into the glutel muscle is the 1 ½-inch, 22 guge needle regrdless of ptient weight. Administer into the upper-outer qudrnt of the glutel muscle. Glutel injections should be lternted between the two glutel muscles. 2.2 Schizophreni nd Schizoffective Disorder For ptients who hve never tken orl pliperidone or orl or injectble risperidone, it is recommended to estblish tolerbility with orl pliperidone or orl risperidone prior to inititing tretment with. The recommended dosing of for ech pproved indiction is displyed in Tble 1. The recommended initition of is with dose of 234 mg on tretment dy 1 nd 156 mg one week lter, both dministered in the deltoid muscle. Following the second initition dose, monthly mintennce doses cn be dministered in either the deltoid or glutel muscle. Tble 1: Recommended Dosing of for Adults with Schizophreni or Schizoffective Disorder Indiction Initition Dosing (deltoid) Dy 1 Dy 8 Monthly Mintennce Dose (deltoid or glutel) Mximum Monthly Dose Schizophreni 234 mg 156 mg mg b 234 mg Schizoffective 234 mg 156 mg mg disorder c 234 mg Administered 5 weeks fter the first injection. b The recommended mintennce dose for tretment of schizophreni is 117 mg. Some ptients my benefit from lower or higher mintennce doses within the dditionl vilble strengths (39 mg, 78 mg, 156 mg, nd 234 mg). c Adjust dose bsed on tolerbility nd/or efficcy using vilble strengths. The 39 mg strength ws not studied in the long-term schizoffective disorder study. Adjustment of the mintennce dose my be mde monthly. When mking dose djustments, the prolonged-relese chrcteristics of should be considered [see Clinicl Phrmcology (12.3)], s the full effect of the dose djustment my not be evident for severl months. 2.3 Missed Doses Avoiding Missed Doses It is recommended tht the second initition dose of be given one week fter the first dose. To void missed dose, ptients my be given the second dose 4 dys before or fter the one-week time point. Similrly, the third nd subsequent injections fter the initition regimen re recommended to be given monthly. To void missed monthly dose, ptients my be given the injection up to 7 dys before or fter the monthly time point. 2

3 (pliperidone plmitte) Mngement of Missed Second Initition Dose If the trget dte for the second injection (one week ± 4 dys) is missed, the recommended reinitition depends on the length of time which hs elpsed since the ptient s first injection. In cse of missed second initition dose follow the dosing instructions provided in Tble 2. Tble 2: Mngement of Missed Second Initition Dose TIMING OF MISSED DOSING SECOND INITIATION DOSE Less thn 4 weeks since first injection 4 to 7 weeks since first injection More thn 7 weeks since first injection Administer the second initition dose of 156 mg in the deltoid muscle s soon s possible. 1. It is recommended to dminister third injection of 117 mg in either the deltoid or glutel muscle 5 weeks fter the first injection (regrdless of the timing of the second injection). 2. Therefter, resume regulr monthly dosing in either the deltoid or glutel muscle. Resume dosing with two injections of 156 mg in the following mnner: 1. Administer deltoid injection s soon s possible. 2. Administer second deltoid injection 1 week lter. 3. Therefter, resume regulr monthly dosing in either the deltoid or glutel muscle. Restrt dosing with recommended initition (see Section 2.2, Tble 1): 1. Administer 234 mg deltoid injection on Dy Administer 156 mg deltoid injection 1 week lter. 3. Therefter, resume regulr monthly dosing in either the deltoid or glutel muscle. Mngement of Missed Mintennce Dose In cse of missed mintennce dose follow the dosing instructions provided in Tble 3. Tble 3: Mngement of Missed Mintennce Dose TIMING OF MISSED DOSING MAINTENANCE DOSE 4 to 6 weeks since lst injection More thn 6 weeks to 6 months since lst injection More thn 6 months since lst injection Resume regulr monthly dosing s soon s possible t the ptient s previously stbilized dose, followed by injections t monthly intervls. Resume the sme dose the ptient ws previously stbilized on (unless the ptient ws stbilized on dose of 234 mg, then the first 2 injections should ech be 156 mg) in the following mnner: 1. Administer deltoid injection s soon s possible. 2. Administer second deltoid injection 1 week lter t the sme dose. 3. Therefter, resume dministering the previously stbilized dose in the deltoid or glutel muscle 1 month fter the second injection. Restrt dosing with recommended initition (see Section 2.2, Tble 1): 1. Administer 234 mg deltoid injection on Dy Administer 156 mg deltoid injection 1 week lter. 3. Therefter, resume dministering the previously stbilized dose in the deltoid or glutel muscle 1 month fter the second injection. 2.4 Use with Risperidone or with Orl Pliperidone Since pliperidone is the mjor ctive metbolite of risperidone, cution should be exercised when is codministered with risperidone or with orl pliperidone for extended periods of time. Sfety dt involving concomitnt use of with other ntipsychotics is limited. 2.5 Dosge Adjustments Renl Impirment hs not been systemticlly studied in ptients with renl impirment [see Clinicl Phrmcology (12.3)]. For ptients with mild renl impirment (cretinine clernce 50 ml/min to < 80 ml/min [Cockcroft-Gult Formul]), initite with dose of 156 mg on tretment dy 1 nd 117 mg one week lter. Administer both doses in the deltoid muscle. Therefter, follow with monthly injections of 78 mg in either the deltoid or glutel muscle [see Use in Specific Popultions (8.6) nd Clinicl Phrmcology (12.3)]. is not recommended in ptients with moderte or severe renl impirment (cretinine clernce < 50 ml/min) [see Use in Specific Popultions (8.6) nd Clinicl Phrmcology (12.3)]. (pliperidone plmitte) Codministrtion with Strong CYP3A4/P-glycoprotein (P-gp) Inducers Avoid using strong inducer of CYP3A4 nd/or P-gp (e.g., crbmzepine, rifmpin, St John s Wort) during the 1-month dosing intervl for, if possible. If dministering strong inducer is necessry, consider mnging the ptient using pliperidone extended relese tblets [see Drug Interctions (7.1) nd Clinicl Phrmcology (12.3)]. 2.6 Switching from Other Antipsychotics There re no systemticlly collected dt to specificlly ddress switching ptients with schizophreni or schizoffective disorder from other ntipsychotics to, or concerning concomitnt dministrtion with other ntipsychotics. Switching from Orl Antipsychotics For ptients who hve never tken orl pliperidone or orl or injectble risperidone, tolerbility should be estblished with orl pliperidone or orl risperidone prior to inititing tretment with. Previous orl ntipsychotics cn be grdully discontinued t the time of initition of tretment with. Recommended initition of is with dose of 234 mg on tretment dy 1 nd 156 mg one week lter, both dministered in the deltoid muscle [see Dosge nd Administrtion (2.2)]. Ptients previously stbilized on different doses of INVEGA Extended-Relese tblets cn ttin similr pliperidone stedy-stte exposure during mintennce tretment with monthly doses s depicted in Tble 4. Tble 4: Doses of INVEGA nd Needed to Attin Similr Stedy-Stte Pliperidone Exposure During Mintennce Tretment Formultion INVEGA Extended-Relese Tblet Injection Dosing Frequency Once Dily Once every 4 weeks Dose (mg) Switching from Long-Acting Injectble Antipsychotics For ptients who hve never tken orl pliperidone or orl or injectble risperidone, tolerbility should be estblished with orl pliperidone or orl risperidone prior to inititing tretment with. When switching ptients currently t stedy-stte on long-cting injectble ntipsychotic, initite therpy in plce of the next scheduled injection. should then be continued t monthly intervls. The one-week initition dosing regimen s described in Section 2.2 is not required. See Tble 1 bove for recommended monthly mintennce dosing. Bsed on previous clinicl history of tolerbility nd/or efficcy, some ptients my benefit from lower or higher mintennce doses within the vilble strengths (39 mg, 78 mg, 117 mg, 156 mg, nd 234 mg). The 39 mg strength ws not studied in the long-term schizoffective disorder study. Monthly mintennce doses cn be dministered in either the deltoid or glutel muscle [see Dosge nd Administrtion (2.2)]. If is discontinued, its prolonged-relese chrcteristics must be considered. As recommended with other ntipsychotic medictions, the need for continuing existing extrpyrmidl symptoms (EPS) mediction should be re-evluted periodiclly. 2.7 Instructions for Use Ech injection must be dministered only by helthcre professionl. The kit contins prefilled syringe nd 2 sfety needles ( 1 ½-inch 22 guge needle nd 1-inch 23 guge needle) for intrmusculr injection. is for single use only. 3

4 (pliperidone plmitte). Shke the syringe vigorously for minimum of 10 seconds to ensure homogeneous suspension. (pliperidone plmitte) f. Bring the syringe with the ttched needle in upright position to de-erte. De-erte the syringe by moving the plunger rod crefully forwrd. b. Select the pproprite needle. For DELTOID injection: If the ptient weighs less thn 90 kg, use the 1-inch 23 guge needle (needle with blue colored hub). If the ptient weighs 90 kg or more, use the 1 ½-inch 22 guge needle (needle with gry colored hub). For GLUTEAL injection: Use the 1 ½-inch 22 guge needle (needle with gry colored hub) regrdless of ptient s weight. c. While holding the syringe upright, remove the rubber tip cp with n esy clockwise twisting motion. g. Inject the entire contents intrmusculrly slowly, deep into the selected deltoid or glutel muscle of the ptient. Do not dminister by ny other route. h. After the injection is complete, use either thumb or finger of one hnd (h1, h2) or flt surfce (h3) to ctivte the needle protection system. The needle protection system is fully ctivted when click is herd. Discrd the syringe with needle ppropritely. h1 h2 d. Peel the sfety needle pouch hlf wy open. Grsp the needle sheth using the plstic peel pouch. Attch the sfety needle to the luer connection of the syringe with n esy clockwise twisting motion. h3 e. Pull the needle sheth wy from the needle with stright pull. Do not twist the sheth s the needle my be loosened from the syringe. 3 DOSAGE FORMS AND STRENGTHS is vilble s white to off-white queous extendedrelese injectble suspension for intrmusculr injection in dose strengths of 39 mg, 78 mg, 117 mg, 156 mg, nd 234 mg pliperidone plmitte. 4 CONTRAINDICATIONS is contrindicted in ptients with known hypersensitivity to either pliperidone or risperidone, or to ny of the excipients in the formultion. Hypersensitivity rections, including nphylctic rections nd ngioedem, hve been reported in ptients treted with risperidone nd in ptients treted with pliperidone. Pliperidone plmitte is converted to pliperidone, which is metbolite of risperidone. 5 WARNINGS AND PRECAUTIONS 5.1 Incresed Mortlity in Elderly Ptients with Dementi-Relted Psychosis Elderly ptients with dementi-relted psychosis treted with ntipsychotic drugs re t n incresed risk of deth. Anlyses of 17 plcebo-controlled trils (modl durtion of 10 weeks), lrgely in ptients tking typicl ntipsychotic drugs, reveled risk of deth in drug-treted ptients of between 1.6 to 1.7 times the risk of deth in plcebo-treted ptients. Over the course of typicl 10-week controlled tril, the rte of deth in drug-treted ptients ws bout 4.5%, compred to rte of bout 2.6% in the plcebo group. Although the cuses of deth were vried, most of the deths ppered to be either crdiovsculr (e.g., hert filure, sudden deth) or infectious (e.g., pneumoni) in nture. Observtionl studies suggest tht, similr to typicl ntipsychotic drugs, tretment with conventionl ntipsychotic drugs my increse mortlity. The extent to which the findings of incresed mortlity in observtionl studies my be ttributed to the ntipsychotic drug s opposed to some chrcteristic(s) of the ptients is not cler. is not pproved for the tretment of ptients with dementi-relted psychosis [see Boxed Wrning nd Wrnings nd Precutions (5.2)]. 5.2 Cerebrovsculr Adverse Rections, Including Stroke, in Elderly Ptients with Dementi-Relted Psychosis In plcebo-controlled trils with risperidone, ripiprzole, nd olnzpine in elderly subjects with dementi, there ws higher incidence of cerebrovsculr dverse 4

5 (pliperidone plmitte) rections (cerebrovsculr ccidents nd trnsient ischemic ttcks) including ftlities compred to plcebo-treted subjects. No studies hve been conducted with orl pliperidone,, or the 3-month pliperidone plmitte extended-relese injectble suspension in elderly ptients with dementi. These medicines re not pproved for the tretment of ptients with dementi-relted psychosis [see Boxed Wrning nd Wrnings nd Precutions (5.1)]. 5.3 Neuroleptic Mlignnt Syndrome A potentilly ftl symptom complex sometimes referred to s Neuroleptic Mlignnt Syndrome (NMS) hs been reported in ssocition with ntipsychotic drugs, including pliperidone. Clinicl mnifesttions of NMS re hyperpyrexi, muscle rigidity, ltered mentl sttus, nd evidence of utonomic instbility (irregulr pulse or blood pressure, tchycrdi, diphoresis, nd crdic dysrhythmi). Additionl signs my include elevted cretine phosphokinse, myoglobinuri (rhbdomyolysis), nd cute renl filure. The dignostic evlution of ptients with this syndrome is complicted. In rriving t dignosis, it is importnt to identify cses in which the clinicl presenttion includes both serious medicl illness (e.g., pneumoni, systemic infection, etc.) nd untreted or indequtely treted extrpyrmidl signs nd symptoms (EPS). Other importnt considertions in the differentil dignosis include centrl nticholinergic toxicity, het stroke, drug fever, nd primry centrl nervous system pthology. The mngement of NMS should include: (1) immedite discontinution of ntipsychotic drugs nd other drugs not essentil to concurrent therpy; (2) intensive symptomtic tretment nd medicl monitoring; nd (3) tretment of ny concomitnt serious medicl problems for which specific tretments re vilble. There is no generl greement bout specific phrmcologicl tretment regimens for uncomplicted NMS. If ptient ppers to require ntipsychotic drug tretment fter recovery from NMS, reintroduction of drug therpy should be closely monitored, since recurrences of NMS hve been reported. 5.4 QT Prolongtion Pliperidone cuses modest increse in the corrected QT (QTc) intervl. The use of pliperidone should be voided in combintion with other drugs tht re known to prolong QTc including Clss 1A (e.g., quinidine, procinmide) or Clss III (e.g., miodrone, sotlol) ntirrhythmic medictions, ntipsychotic medictions (e.g., chlorpromzine, thioridzine), ntibiotics (e.g., gtifloxcin, moxifloxcin), or ny other clss of medictions known to prolong the QTc intervl. Pliperidone should lso be voided in ptients with congenitl long QT syndrome nd in ptients with history of crdic rrhythmis. Certin circumstnces my increse the risk of the occurrence of Torsdes de pointes nd/or sudden deth in ssocition with the use of drugs tht prolong the QTc intervl, including (1) brdycrdi; (2) hypoklemi or hypomgnesemi; (3) concomitnt use of other drugs tht prolong the QTc intervl; nd (4) presence of congenitl prolongtion of the QT intervl. The effects of orl pliperidone on the QT intervl were evluted in doubleblind, ctive-controlled (moxifloxcin 400 mg single dose), multicenter QT study in dults with schizophreni nd schizoffective disorder, nd in three plcebo- nd ctive-controlled 6-week, fixed-dose efficcy trils in dults with schizophreni. In the QT study (n=141), the 8 mg dose of immedite-relese orl pliperidone (n=50) showed men plcebo-subtrcted increse from in QTcLD of 12.3 msec (90% CI: 8.9; 15.6) on dy 8 t 1.5 hours post-dose. The men stedystte pek plsm concentrtion for this 8 mg dose of pliperidone immedite relese (C mx ss = 113 ng/ml) ws more thn 2-fold the exposure observed with the mximum recommended 234 mg dose of dministered in the deltoid muscle (predicted medin C mx ss = 50 ng/ml). In this sme study, 4 mg dose of the immedite-relese orl formultion of pliperidone, for which C mx ss = 35 ng/ml, showed n incresed plcebo-subtrcted QTcLD of 6.8 msec (90% CI: 3.6; 10.1) on dy 2 t 1.5 hours post-dose. In the three fixed-dose efficcy studies of orl pliperidone extended relese in subjects with schizophreni, electrocrdiogrm (ECG) mesurements tken t vrious time points showed only one subject in the orl pliperidone 12 mg group hd chnge exceeding 60 msec t one time-point on Dy 6 (increse of 62 msec). In the four fixed-dose efficcy studies of in subjects with schizophreni nd in the long-term study in subjects with schizoffective disorder, no subject experienced chnge in QTcLD exceeding 60 msec nd no subject hd QTcLD vlue of > 500 msec t ny time point. In the mintennce study in subjects with schizophreni, no subject hd QTcLD chnge > 60 msec, nd one subject hd QTcLD vlue of 507 msec (Bzett s QT corrected intervl [QTcB] vlue of 483 msec); this ltter subject lso hd hert rte of 45 bets per minute. 5.5 Trdive Dyskinesi A syndrome of potentilly irreversible, involuntry, dyskinetic movements my develop in ptients treted with ntipsychotic drugs. Although the prevlence of the syndrome ppers to be highest mong the elderly, especilly elderly women, it is impossible to predict which ptients will develop the syndrome. Whether ntipsychotic drug products differ in their potentil to cuse trdive dyskinesi is unknown. The risk of developing trdive dyskinesi nd the likelihood tht it will become irreversible pper to increse s the durtion of tretment nd the totl cumultive dose of ntipsychotic drugs dministered to the ptient increse, but the syndrome cn develop fter reltively brief tretment periods t low doses, lthough this is uncommon. (pliperidone plmitte) There is no known tretment for estblished trdive dyskinesi, lthough the syndrome my remit, prtilly or completely, if ntipsychotic tretment is withdrwn. Antipsychotic tretment itself my suppress (or prtilly suppress) the signs nd symptoms of the syndrome nd my thus msk the underlying process. The effect of symptomtic suppression on the long-term course of the syndrome is unknown. Given these considertions, should be prescribed in mnner tht is most likely to minimize the occurrence of trdive dyskinesi. Chronic ntipsychotic tretment should generlly be reserved for ptients who suffer from chronic illness tht is known to respond to ntipsychotic drugs. In ptients who do require chronic tretment, the smllest dose nd the shortest durtion of tretment producing stisfctory clinicl response should be sought. The need for continued tretment should be ressessed periodiclly. If signs nd symptoms of trdive dyskinesi pper in ptient treted with, drug discontinution should be considered. However, some ptients my require tretment with despite the presence of the syndrome. 5.6 Metbolic Chnges Atypicl ntipsychotic drugs hve been ssocited with metbolic chnges tht my increse crdiovsculr/cerebrovsculr risk. These metbolic chnges include hyperglycemi, dyslipidemi, nd body weight gin. While ll of the drugs in the clss hve been shown to produce some metbolic chnges, ech drug hs its own specific risk profile. Hyperglycemi nd Dibetes Mellitus Hyperglycemi nd dibetes mellitus, in some cses extreme nd ssocited with ketocidosis or hyperosmolr com or deth, hve been reported in ptients treted with ll typicl ntipsychotics. These cses were, for the most prt, seen in post-mrketing clinicl use nd epidemiologic studies, not in clinicl trils. Hyperglycemi nd dibetes hve been reported in tril subjects treted with. Assessment of the reltionship between typicl ntipsychotic use nd glucose bnormlities is complicted by the possibility of n incresed bckground risk of dibetes mellitus in ptients with schizophreni nd the incresing incidence of dibetes mellitus in the generl popultion. Given these confounders, the reltionship between typicl ntipsychotic use nd hyperglycemi-relted dverse events is not completely understood. However, epidemiologicl studies suggest n incresed risk of hyperglycemi-relted dverse rections in ptients treted with the typicl ntipsychotics. Ptients with n estblished dignosis of dibetes mellitus who re strted on typicl ntipsychotics should be monitored regulrly for worsening of glucose control. Ptients with risk fctors for dibetes mellitus (e.g., obesity, fmily history of dibetes) who re strting tretment with typicl ntipsychotics should undergo fsting blood glucose testing t the beginning of tretment nd periodiclly during tretment. Any ptient treted with typicl ntipsychotics should be monitored for symptoms of hyperglycemi including polydipsi, polyuri, polyphgi, nd wekness. Ptients who develop symptoms of hyperglycemi during tretment with typicl ntipsychotics should undergo fsting blood glucose testing. In some cses, hyperglycemi hs resolved when the typicl ntipsychotic ws discontinued; however, some ptients required continution of nti-dibetic tretment despite discontinution of the suspect drug. Pooled dt from the four plcebo-controlled (one 9-week nd three 13-week), fixed-dose studies in subjects with schizophreni re presented in Tble 5. Tble 5: Chnge in Fsting Glucose from Four Plcebo-Controlled, 9- to 13-Week, Fixed-Dose Studies in Subjects with Schizophreni Plcebo 39 mg 78 mg 156 mg 234/39 mg 234/156 mg 234/234 mg Men chnge from (mg/dl) n=367 n=86 n=244 n=238 n=110 n=126 n=115 Serum Glucose Proportion of Ptients with Shifts Serum Glucose Norml to High (<100 mg/dl to 126 mg/dl) 4.6% (11/241) 6.3% (4/64) 6.4% (11/173) 3.9% (6/154) 2.5% (2/79) 7.0% (6/86) 6.6% (5/76) Initil deltoid injection of 234 mg followed by either 39 mg, 156 mg, or 234 mg every 4 weeks by deltoid or glutel injection. Other dose groups (39 mg, 78 mg, nd 156 mg) re from studies involving only glutel injection. [see Clinicl Studies (14.1)]. In long-term open-lbel phrmcokinetic nd sfety study in subjects with schizophreni in which the highest dose vilble (234 mg) ws evluted, ws ssocited with men chnge in glucose of -0.4 mg/dl t Week 29 (n=109) nd +6.8 mg/dl t Week 53 (n=100). During the initil 25-week open-lbel period of long-term study in subjects with schizoffective disorder, ws ssocited with men chnge in glucose of +5.3 mg/dl (n=518). At the endpoint of the subsequent 15-month double-blind period of the study, ws ssocited with men chnge in glucose of +0.3 mg/dl (n=131) compred with men chnge of +4.0 mg/dl in the plcebo group (n=120). 5

6 (pliperidone plmitte) Dyslipidemi Undesirble ltertions in lipids hve been observed in ptients treted with typicl ntipsychotics. Pooled dt from the four plcebo-controlled (one 9-week nd three 13-week), fixed-dose studies in subjects with schizophreni re presented in Tble 6. Tble 6: Chnge in Fsting Lipids from Four Plcebo-Controlled, 9- to 13-Week, Fixed-Dose Studies in Subjects with Schizophreni Plcebo 39 mg 78 mg 156 mg 234/39 mg 234/156 mg 234/234 mg Men chnge from (mg/dl) Cholesterol LDL HDL Triglycerides Cholesterol Norml to High (<200 mg/dl to 240 mg/dl) LDL Norml to High (<100 mg/dl to 160 mg/dl) HDL Norml to Low ( 40 mg/dl to <40 mg/dl) Triglycerides Norml to High (<150 mg/dl to 200 mg/dl) n= n= n= n= % (7/222) 1.1% (1/95) 13.8% (28/203) 3.6% (8/221) n= n= n= n= % (1/51) 0% (0/29) 14.8% (9/61) 6.1% (3/49) n= n= n= n= n= n= n= n= n= n= n= n= Proportion of Ptients with Shifts 2.0% (3/147) 0% (0/67) 9.6% (11/115) 9.2% (14/153) 2.1% (3/141) 0% (0/46) 14.2% (15/106) 7.2% (10/139) 0% (0/69) 0% (0/41) 12.7% (9/71) 1.3% (1/79) n= n= n= n= % (2/65) 0% (0/37) 10.5% (8/76) 3.7% (3/82) n= n= n= n= % (6/84) 0% (0/44) 16.0% (13/81) 10.7% (9/84) Initil deltoid injection of 234 mg followed by either 39 mg, 156 mg, or 234 mg every 4 weeks by deltoid or glutel injection. Other dose groups (39 mg, 78 mg, nd 156 mg) re from studies involving only glutel injection. [see Clinicl Studies (14.1)]. In long-term open-lbel phrmcokinetic nd sfety study in subjects with schizophreni in which the highest dose vilble (234 mg) ws evluted, the men chnges from in lipid vlues re presented in Tble 7. Tble 7: Chnge in Fsting Lipids from Long-term Open-lbel Phrmcokinetic nd Sfety Study in Subjects with Schizophreni 234 mg Week 29 Week 53 Men chnge from (mg/dl) Cholesterol n=112 n= LDL n=107 n= HDL n=112 n= Triglycerides n=112 n= The men chnges from in lipid vlues during the initil 25-week openlbel period nd t the endpoint of the subsequent 15-month double-blind period in long-term study in subjects with schizoffective disorder re presented in Tble 8. (pliperidone plmitte) Tble 8: Chnge in Fsting Lipids from n Open-Lbel nd Double-Blind Periods of Long-Term Study in Subjects with Schizoffective Disorder Open-Lbel Period Double-Blind Period Plcebo Men chnge from (mg/dl) Cholesterol n=198 n=119 n= LDL n=198 n=117 n= HDL n=198 n=119 n= Triglycerides n=198 n=119 n= Weight Gin Weight gin hs been observed with typicl ntipsychotic use. Clinicl monitoring of weight is recommended. Dt on men chnges in body weight nd the proportion of subjects meeting weight gin criterion of 7% of body weight from the four plcebo-controlled (one 9-week nd three 13-week), fixed-dose studies in subjects with schizophreni re presented in Tble 9. Tble 9: Men Chnge in Body Weight (kg) nd the Proportion of Subjects with 7% Gin in Body Weight from Four Plcebo-Controlled, 9- to 13-Week, Fixed-Dose Studies in Subjects with Schizophreni Plcebo 39 mg 78 mg 156 mg 234/39 mg 234/156 mg 234/234 mg n=451 n=116 n=280 n=267 n=137 n=144 n=145 Weight (kg) Weight Gin 7% increse from 3.3% 6.0% 8.9% 9.0% 5.8% 8.3% 13.1% Initil deltoid injection of 234 mg followed by either 39 mg, 156 mg, or 234 mg every 4 weeks by deltoid or glutel injection. Other dose groups (39 mg, 78 mg, nd 156 mg) re from studies involving only glutel injection. [see Clinicl Studies (14.1)]. In long-term open-lbel phrmcokinetic nd sfety study in which the highest dose vilble (234 mg) ws evluted, ws ssocited with men chnge in weight of +2.4 kg t Week 29 (n=134) nd +4.3 kg t Week 53 (n=113). During the initil 25-week open-lbel period of long-term study in subjects with schizoffective disorder, ws ssocited with men chnge in weight of +2.2 kg nd 18.4% of subjects hd n increse in body weight of 7% (n=653). At the endpoint of the subsequent 15-month double-blind period of the study, ws ssocited with men chnge in weight of -0.2 kg nd 13.0% of subjects hd n increse in body weight of 7% (n=161); the plcebo group hd men chnge in weight of -0.8 kg nd 6.0% of subjects hd n increse in body weight of 7% (n=168). 5.7 Orthosttic Hypotension nd Syncope Pliperidone cn induce orthosttic hypotension nd syncope in some ptients becuse of its lph-drenergic blocking ctivity. Syncope ws reported in < 1% (4/1293) of subjects treted with in the recommended dose rnge of 39 mg to 234 mg in the four fixed-dose, double-blind, plcebo-controlled trils compred with 0% (0/510) of subjects treted with plcebo. In the four fixeddose efficcy studies in subjects with schizophreni, orthosttic hypotension ws reported s n dverse event by < 1% (2/1293) of - treted subjects compred to 0% (0/510) with plcebo. Incidences of orthosttic hypotension nd syncope in the long-term studies in subjects with schizophreni nd schizoffective disorder were similr to those observed in the short-term studies. should be used with cution in ptients with known crdiovsculr disese (e.g., hert filure, history of myocrdil infrction or ischemi, conduction bnormlities), cerebrovsculr disese, or conditions tht predispose the ptient to hypotension (e.g., dehydrtion, hypovolemi, nd tretment with ntihypertensive medictions). Monitoring of orthosttic vitl signs should be considered in ptients who re vulnerble to hypotension. 6

7 (pliperidone plmitte) 5.8 Flls Somnolence, posturl hypotension, motor nd sensory instbility hve been reported with the use of ntipsychotics, including, which my led to flls nd, consequently, frctures or other fll-relted injuries. For ptients, prticulrly the elderly, with diseses, conditions, or medictions tht could excerbte these effects, ssess the risk of flls when inititing ntipsychotic tretment nd recurrently for ptients on long-term ntipsychotic therpy. 5.9 Leukopeni, Neutropeni, nd Agrnulocytosis In clinicl tril nd/or postmrketing experience, events of leukopeni nd neutropeni hve been reported temporlly relted to ntipsychotic gents, including. Agrnulocytosis hs lso been reported. Possible risk fctors for leukopeni/neutropeni include pre-existing low white blood cell count (WBC)/bsolute neutrophil count (ANC) nd history of drug-induced leukopeni/neutropeni. In ptients with history of cliniclly significnt low WBC/ANC or drug-induced leukopeni/neutropeni, perform complete blood count (CBC) frequently during the first few months of therpy. In such ptients, consider discontinution of t the first sign of cliniclly significnt decline in WBC in the bsence of other custive fctors. Monitor ptients with cliniclly significnt neutropeni for fever or other symptoms or signs of infection nd tret promptly if such symptoms or signs occur. Discontinue in ptients with severe neutropeni (bsolute neutrophil count < 1000/mm 3 ) nd follow their WBC until recovery Hyperprolctinemi Like other drugs tht ntgonize dopmine D 2 receptors, pliperidone elevtes prolctin levels nd the elevtion persists during chronic dministrtion. Pliperidone hs prolctin-elevting effect similr to tht seen with risperidone, drug tht is ssocited with higher levels of prolctin thn other ntipsychotic drugs. Hyperprolctinemi, regrdless of etiology, my suppress hypothlmic GnRH, resulting in reduced pituitry gondotrophin secretion. This, in turn, my inhibit reproductive function by impiring gondl steroidogenesis in both femle nd mle ptients. Glctorrhe, menorrhe, gynecomsti, nd impotence hve been reported in ptients receiving prolctin-elevting compounds. Long-stnding hyperprolctinemi when ssocited with hypogondism my led to decresed bone density in both femle nd mle subjects. Tissue culture experiments indicte tht pproximtely one-third of humn brest cncers re prolctin dependent in vitro, fctor of potentil importnce if the prescription of these drugs is considered in ptient with previously detected brest cncer. An increse in the incidence of pituitry glnd, mmmry glnd, nd pncretic islet cell neoplsi (mmmry denocrcinoms, pituitry nd pncretic denoms) ws observed in the risperidone crcinogenicity studies conducted in mice nd rts [see Nonclinicl Toxicology (13.1)]. Neither clinicl studies nor epidemiologic studies conducted to dte hve shown n ssocition between chronic dministrtion of this clss of drugs nd tumorigenesis in humns, but the vilble evidence is too limited to be conclusive. Prolctin dt from two long-term, double-blind, plcebo-controlled studies with re presented below; one study ws in popultion of ptients with schizophreni; the second study ws in ptients with schizoffective disorder. Schizophreni In long-term mintennce tril of in schizophreni ptients (Study PSY-3001), see Clinicl Studies (14.1), elevtions of prolctin to bove the reference rnge (> 18 ng/ml in mles nd > 30 ng/ml in femles) reltive to open-lbel t ny time during the double-blind phse were noted in higher percentge of the ptients in the group thn those in the plcebo group in mles (51.9% vs. 29.0%) nd in femles (50.5% vs. 42.9%). During the double-blind phse, 4 femles (4.2%) in the group experienced potentilly prolctin-relted dverse rections (menorrhe N=2; glctorrhe N=1; menstrution irregulr N=1), while 2 femles (2.2%) in the plcebo group experienced potentilly prolctin-relted dverse rections (menorrhe N=1; brest pin N=1). One mle (0.9%) in the group experienced erectile dysfunction nd 1 mle (0.9%) in plcebo group experienced gynecomsti. Prior to the double-blind phse (during the 33-week open-lbel phse of the longterm mintennce tril), the men (SD) serum prolctin vlues t were 14.9 (22.3) ng/ml in mles (N=490) nd 35.2 (39.6) ng/ml in femles (N=358). At the end of the open-lbel phse, men (SD) prolctin vlues were 24.7 (22.5) ng/ml in mles (N=470) nd 59.5 (38.1) ng/ml in femles (N=333). During the open-lbel phses 49.2% of femles nd 47.7% of mles experienced elevtions of prolctin bove the reference rnge reltive to, nd higher proportion of femles experienced potentilly prolctin-relted dverse rections compred to mles (5.3% vs. 1.8%). Amenorrhe (2.5%) in femles nd no single potentilly prolctinrelted dverse rection in mles were observed with rte greter thn 2%. Schizoffective Disorder In long-term mintennce tril of in ptients with schizoffective disorder (Study SCA-3004) see Clinicl Studies (14.2), elevtions of prolctin to bove the reference rnge (> ng/ml in mles nd > ng/ml in femles) reltive to open-lbel t ny time during the 15-month double-blind phse were noted in higher percentge of ptients in the group thn those in the plcebo group in mles (55.6% vs. 23.2%) nd in femles (44.3% vs. 25.0%). During the 15-month double-blind 7 (pliperidone plmitte) phse, 11 femles (13.9%) in the group hd 14 potentilly prolctin-relted dverse rections (hyperprolctinemi N=3; blood prolctin incresed N=4; libido decresed N=1; menorrhe N=3; glctorrhe N=3), while 5 femles (5.8%) in the plcebo group hd 6 potentilly prolctin-relted dverse rections (hyperprolctinemi N=2; blood prolctin incresed N=1; menorrhe N=2; glctorrhe N=1). Six mles (7.1%) in the group experienced 6 potentilly prolctin-relted dverse rections (hyperprolctinemi N=4; libido decresed N=1; erectile dysfunction N=1), while 1 mle (1.2%) in the plcebo group experienced dverse rection of blood prolctin incresed. Prior to the 15-month double-blind phse (during the 25-week open-lbel phse of the long-term mintennce tril), the men (SD) serum prolctin vlues t were 14.6 (14.0) ng/ml in mles (N=352) nd 39.1 (44.6) ng/ml in femles (N=302). At the end of the open-lbel phse, men (SD) prolctin vlues were 32.8 (17.2) ng/ml in mles (N=275) nd 72.4 (46.5) ng/ml in femles (N=239). During the open-lbel phse, 48.9% of femles nd 53.3% of mles experienced elevtions of prolctin bove the reference rnge reltive to, nd higher proportion of femles experienced potentilly prolctin-relted dverse rections compred to mles (10.0% vs. 9.0%). Amenorrhe (5.8%) nd glctorrhe (2.9%) in femles nd libido decrese (2.8%) nd erectile dysfunction (2.5%) in mles were observed with rte greter thn 2% Potentil for Cognitive nd Motor Impirment Somnolence, sedtion, nd dizziness were reported s dverse rections in subjects treted with [see Adverse Rections (6.1)]. Antipsychotics, including, hve the potentil to impir judgment, thinking, or motor skills. Ptients should be cutioned bout performing ctivities requiring mentl lertness, such s operting hzrdous mchinery or operting motor vehicle, until they re resonbly certin tht pliperidone therpy does not dversely ffect them Seizures In the four fixed-dose double-blind plcebo-controlled studies in subjects with schizophreni, <1% (1/1293) of subjects treted with in the recommended dose rnge of 39 mg to 234 mg experienced n dverse event of convulsion compred with <1% (1/510) of plcebo-treted subjects who experienced n dverse event of grnd ml convulsion. Like other ntipsychotic drugs, should be used cutiously in ptients with history of seizures or other conditions tht potentilly lower the seizure threshold. Conditions tht lower the seizure threshold my be more prevlent in ptients 65 yers or older Dysphgi Esophgel dysmotility nd spirtion hve been ssocited with ntipsychotic drug use. nd other ntipsychotic drugs should be used cutiously in ptients t risk for spirtion pneumoni Pripism Drugs with lph-drenergic blocking effects hve been reported to induce pripism. Although no cses of pripism hve been reported in clinicl trils with, pripism hs been reported with orl pliperidone during postmrketing surveillnce. Severe pripism my require surgicl intervention Disruption of Body Temperture Regultion Disruption of the body s bility to reduce core body temperture hs been ttributed to ntipsychotic gents. Approprite cre is dvised when prescribing to ptients who will be experiencing conditions which my contribute to n elevtion in core body temperture, e.g., exercising strenuously, exposure to extreme het, receiving concomitnt mediction with nticholinergic ctivity, or being subject to dehydrtion. 6 ADVERSE REACTIONS The following re discussed in more detil in other sections of the lbeling: Incresed mortlity in elderly ptients with dementi-relted psychosis [see Boxed Wrning nd Wrnings nd Precutions (5.1)] Cerebrovsculr dverse rections, including stroke, in elderly ptients with dementi-relted psychosis [see Wrnings nd Precutions (5.2)] Neuroleptic mlignnt syndrome [see Wrnings nd Precutions (5.3)] QT prolongtion [see Wrnings nd Precutions (5.4)] Trdive dyskinesi [see Wrnings nd Precutions (5.5)] Metbolic chnges [see Wrnings nd Precutions (5.6)] Orthosttic hypotension nd syncope [see Wrnings nd Precutions (5.7)] Flls [see Wrnings nd Precutions (5.8)] Leukopeni, neutropeni, nd grnulocytosis [see Wrnings nd Precutions (5.9)] Hyperprolctinemi [see Wrnings nd Precutions (5.10)] Potentil for cognitive nd motor impirment [see Wrnings nd Precutions (5.11)] Seizures [see Wrnings nd Precutions (5.12)] Dysphgi [see Wrnings nd Precutions (5.13)] Pripism [see Wrnings nd Precutions (5.14)] Disruption of body temperture regultion [see Wrnings nd Precutions (5.15)] 6.1 Clinicl Trils Experience Becuse clinicl trils re conducted under widely vrying conditions, dverse rection rtes observed in the clinicl trils of drug cnnot be directly compred to rtes in the clinicl trils of nother drug nd my not reflect the rtes observed in clinicl prctice.

8 (pliperidone plmitte) Ptient Exposure The dt described in this section re derived from clinicl tril dtbse consisting of totl of 3817 subjects (pproximtely 1705 ptient-yers exposure) with schizophreni who received t lest one dose of in the recommended dose rnge of 39 mg to 234 mg nd totl of 510 subjects with schizophreni who received plcebo. Among the treted subjects, 1293 received in four fixed-dose, doubleblind, plcebo-controlled trils (one 9-week nd three 13-week studies), 849 received in the mintennce tril (medin exposure 229 dys during the initil 33-week open-lbel phse of this study, of whom 205 continued to receive during the double-blind plcebo-controlled phse of this study [medin exposure 171 dys]), nd 1675 received in five non-plcebo controlled trils (three noninferiority ctive-comprtor trils, one long-term open-lbel phrmcokinetic nd sfety study, nd n injection site [deltoid-glutel] cross-over tril). One of the 13-week studies included 234 mg initition dose followed by tretment with either 39 mg, 156 mg, or 234 mg every 4 weeks. The sfety of ws lso evluted in long-term study in dult subjects with schizoffective disorder. A totl of 667 subjects received during the initil 25-week open-lbel period of this study (medin exposure 147 dys); 164 subjects continued to receive during the 15-month double-blind plcebo-controlled period of this study (medin exposure 446 dys). Adverse rections tht occurred more frequently in the thn the plcebo group ( 2% difference or more between groups) were weight incresed, nsophryngitis, hedche, hyperprolctinemi, nd pyrexi. Adverse Rections in Double-Blind, Plcebo-Controlled Clinicl Trils Commonly Observed Adverse Rections: The most common (t lest 5% in ny group) nd likely drug-relted (dverse events for which the drug rte is t lest twice the plcebo rte) dverse rections from the doubleblind, plcebo-controlled trils in subjects with schizophreni were injection site rections, somnolence/sedtion, dizziness, kthisi, nd extrpyrmidl disorder. No occurrences of dverse events reched this threshold in the long-term doubleblind, plcebo-controlled study in subjects with schizoffective disorder. Discontinution of Tretment Due to Adverse Events: The percentge of subjects who discontinued due to dverse events in the four fixed-dose, double-blind, plcebo-controlled schizophreni trils were similr for - nd plcebo-treted subjects. The percentge of subjects who discontinued due to dverse events in the openlbel period of the long-term study in subjects with schizoffective disorder ws 7.5%. During the double-blind, plcebo-controlled period of tht study, the percentges of subjects who discontinued due to dverse events were 5.5% nd 1.8% in - nd plcebo-treted subjects, respectively. Dose-Relted Adverse Rections: Bsed on the pooled dt from the four fixeddose, double-blind, plcebo-controlled trils in subjects with schizophreni, mong the dverse rections tht occurred with 2% incidence in the subjects treted with, only kthisi incresed with dose. Hyperprolctinemi lso exhibited dose reltionship, but did not occur t 2% incidence in -treted subjects from the four fixed-dose studies. Adverse Rections Occurring t n Incidence of 2% or More in - Treted Ptients: Tble 10 lists the dverse rections reported in 2% or more of -treted subjects nd t greter proportion thn in the plcebo group with schizophreni in the four fixed-dose, double-blind, plcebocontrolled trils. (pliperidone plmitte) Tble 10: Incidences of Adverse Rections 2% or More of - Treted Ptients (nd Greter thn Plcebo) with Schizophreni in Four Fixed-Dose, Double-Blind, Plcebo-Controlled Trils System Orgn Clss Adverse Rections Totl percentge of subjects with dverse rections Plcebo (N=510) 39 mg (N=130) 78 mg (N=302) 156 mg (N=312) 234/39 mg b (N=160) 234/156 mg b (N=165) 234/234 mg b (N=163) Gstrointestinl disorders Abdominl discomfort/ bdominl pin upper Dirrhe Dry mouth Nuse Toothche Vomiting Generl disorders nd dministrtion site conditions Astheni < Ftigue Injection site rections Infections nd infesttions Nsophryngitis Upper respirtory trct infection Urinry trct < infection Investigtions Weight incresed Musculoskeletl nd connective tissue disorders Bck pin Musculoskeletl 1 1 <1 < stiffness Mylgi < Pin in extremity Nervous system disorders Akthisi Dizziness Extrpyrmidl disorder Hedche Somnolence/ sedtion Psychitric disorders Agittion Anxiety Nightmre < Respirtory, thorcic nd medistinl disorders Cough Vsculr disorders Hypertension Percentges re rounded to whole numbers. Tble includes dverse rections tht were reported in 2% or more of subjects in ny of the dose groups nd which occurred t greter incidence thn in the plcebo group. Plcebo group is pooled from ll studies nd included either deltoid or glutel injection depending on study design. b Initil deltoid injection of 234 mg followed by either 39 mg, 156 mg, or 234 mg every 4 weeks by deltoid or glutel injection. Other dose groups (39 mg, 78 mg, nd 156 mg) re from studies involving only glutel injection. [see Clinicl Studies (14.1)] Adverse rections for which the incidence ws equl to or less thn plcebo re not listed in the tble, but included the following: dyspepsi, psychotic disorder, schizophreni, nd tremor. The following terms were combined: somnolence/sedtion, brest tenderness/brest pin, bdominl discomfort/ bdominl pin upper/stomch discomfort, nd tchycrdi/sinus tchycrdi/ hert rte incresed. All injection site rection-relted dverse rections were collpsed nd re grouped under Injection site rections. 8

INVEGA SUSTENNA (paliperidone palmitate) extended-release injectable

INVEGA SUSTENNA (paliperidone palmitate) extended-release injectable (pliperidone plmitte) extended-relese injectble suspension, for intrmusculr use HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively.

More information

Target: 10 mg/day within several days Schizophrenia in adolescents (2.1)

Target: 10 mg/day within several days Schizophrenia in adolescents (2.1) HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ZYPREXA sfely nd effectively. See full prescribing informtion for ZYPREXA. ZYPREXA (olnzpine) Tblet

More information

10-15 mg/day 15 mg/day 30 mg/day. 2-5 mg/day 5-10 mg/day 15 mg/day. 2 mg/day 5-10 mg/day 15 mg/day. 30 mg/day injected IM

10-15 mg/day 15 mg/day 30 mg/day. 2-5 mg/day 5-10 mg/day 15 mg/day. 2 mg/day 5-10 mg/day 15 mg/day. 30 mg/day injected IM HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ABILIFY sfely nd effectively. See full prescribing informtion for ABILIFY. Tblets ABILIFY DISCMELT

More information

Start ORKAMBI today. INDICATIONS AND USAGE IMPORTANT SAFETY INFORMATION. Sydney Age 4

Start ORKAMBI today. INDICATIONS AND USAGE IMPORTANT SAFETY INFORMATION. Sydney Age 4 F O R H E A L T H C A R E P R O F E S S I O N A L S For ptients ge 2 yers nd older who re homozygous for the F508del muttion 1,2 Modify the course. Strt tody. Sydney Age 4 F508del/F508del INDICATIONS AND

More information

PNEUMOVAX 23 is recommended by the CDC for all your appropriate adult patients at increased risk for pneumococcal disease 1,2 :

PNEUMOVAX 23 is recommended by the CDC for all your appropriate adult patients at increased risk for pneumococcal disease 1,2 : PNEUMOVAX 23 is recommended y the CDC for ll your pproprite dult ptients t incresed risk for pneumococcl disese 1,2 : Adults ged

More information

Clinical Study Report Synopsis Drug Substance Naloxegol Study Code D3820C00018 Edition Number 1 Date 01 February 2013 EudraCT Number

Clinical Study Report Synopsis Drug Substance Naloxegol Study Code D3820C00018 Edition Number 1 Date 01 February 2013 EudraCT Number EudrCT Number 2012-001531-31 A Phse I, Rndomised, Open-lbel, 3-wy Cross-over Study in Helthy Volunteers to Demonstrte the Bioequivlence of the Nloxegol 25 mg Commercil nd Phse III Formultions nd to Assess

More information

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling. Revised: 6/2016 FULL PRESCRIBING INFORMATION: CONTENTS*

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling. Revised: 6/2016 FULL PRESCRIBING INFORMATION: CONTENTS* 1 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use BASAGLAR sfely nd effectively. See full prescribing informtion for BASAGLAR BASAGLAR (insulin glrgine

More information

Dosing & Administration

Dosing & Administration Dosing & Administration REAL LIFE. REAL RESULTS. INDICATION INVEGA SUSTENNA (paliperidone palmitate) is indicated for the treatment of: Schizophrenia. Schizoaffective disorder as monotherapy and as an

More information

Safety and Tolerability of Subcutaneous Sarilumab and Intravenous Tocilizumab in Patients With RA

Safety and Tolerability of Subcutaneous Sarilumab and Intravenous Tocilizumab in Patients With RA Sfety nd Tolerbility of Subcutneous Srilumb nd Intrvenous Tocilizumb in Ptients With RA Pul Emery, 1 Jun Rondon, 2 Anju Grg, 3 Hubert vn Hoogstrten, 3 Neil M.H. Grhm, 4 Ming Liu, 4 Nncy Liu, 3 Jnie Prrino,

More information

INSTRUCTIONS FOR USE Please read complete instructions prior to use

INSTRUCTIONS FOR USE Please read complete instructions prior to use INSTRUCTIONS FOR USE Please read complete instructions prior to use For deltoid or gluteal intramuscular injection only 3 MONTHS Administer every 3 months 1 With the syringe tip pointing up, shake syringe

More information

The RUTHERFORD-2 trial in heterozygous FH: Results and implications

The RUTHERFORD-2 trial in heterozygous FH: Results and implications The RUTHERFORD-2 tril in heterozygous FH: Results nd implictions Slide deck kindly supplied s n eductionl resource by Professor Derick Rl MD PhD Crbohydrte & Lipid Metbolism Reserch Unit University of

More information

2.3. with type 1 diabetes <3 years of age. (8.4)

2.3. with type 1 diabetes <3 years of age. (8.4) 1 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use HUMALOG sfely nd effectively. See full prescribing informtion for HUMALOG. HUMALOG (insulin lispro

More information

Addendum to the Evidence Review Group Report on Aripiprazole for the treatment of schizophrenia in adolescents (aged years)

Addendum to the Evidence Review Group Report on Aripiprazole for the treatment of schizophrenia in adolescents (aged years) Addendum to the Evidence Review Group Report on Aripiprzole for the tretment of schizophreni in dolescents (ged 15-17 yers) Produced by Authors Correspondence to Southmpton Helth Technology Assessments

More information

XALKORI (crizotinib) Is Available Through Specialty Pharmacies

XALKORI (crizotinib) Is Available Through Specialty Pharmacies XALKORI (crizotinib) Is Avilble Through Specilty Phrmcies Specilty Phrmcy Ordering Process The Provider s Office Submits XALKORI prescriptions to the specilty phrmcy vi: Phone Fx Internet Submits ny supporting

More information

See 17 for PATIENT COUNSELING INFORMATION. Revised: 02/2011 FULL PRESCRIBING INFORMATION: CONTENTS*

See 17 for PATIENT COUNSELING INFORMATION. Revised: 02/2011 FULL PRESCRIBING INFORMATION: CONTENTS* HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use GEMZAR sfely nd effectively. See full prescribing informtion for GEMZAR. GEMZAR (gemcitbine for injection)

More information

Short-term therapy with lasting relief 2

Short-term therapy with lasting relief 2 # 1 PRESCRIBED MEDICATION APPROVED FOR IBS-D 1 * Short-term therpy with lsting relief 2 provided up to 6 months of symptom relief with 2-week tretment 2 Rnge of 6 to 24 weeks; medin of 10 weeks. Convenient

More information

ULTOMIRIS is administered once every 8 weeks a

ULTOMIRIS is administered once every 8 weeks a (rvulizumb-cwvz) for the tretment of dult ptients with proxysml nocturnl hemoglobinuri (PNH) is dministered once every 8 weeks PATIENTS STARTING WITH NO PRIOR TREATMENT FOR PNH THE RECOMMENDED DOSING REGIMEN

More information

Supplementary Online Content

Supplementary Online Content Supplementry Online Content Zulmn DM, Pl Chee C, Ezeji-Okoye SC, et l. Effect of n intensive outptient progrm to ugment primry cre for high-need Veterns Affirs ptients: rndomized clinicl tril. JAMA Intern

More information

DOSAGE FORMS AND STRENGTHS. Injection: 6 mg single-dose vial. (3)

DOSAGE FORMS AND STRENGTHS. Injection: 6 mg single-dose vial. (3) HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use SUMATRIPTAN SUCCINATE INJECTION sfely nd effectively. See full prescribing informtion for SUMATRIPTAN

More information

58 % 50 % REDUCTION IN RISK OF OVERT HE RECURRENCE 1

58 % 50 % REDUCTION IN RISK OF OVERT HE RECURRENCE 1 FOR ADULT PATIENTS WITH OVERT HEPATIC ENCEPHALOPATHY (HE) significntly reduced the risk of overt HE recurrence nd HE-relted hospitliztions 1 58 % 50 % REDUCTION IN RISK OF OVERT HE RECURRENCE 1 REDUCTION

More information

DOSAGE FORMS AND STRENGTHS HIGHLIGHTS OF PRESCRIBING INFORMATION

DOSAGE FORMS AND STRENGTHS HIGHLIGHTS OF PRESCRIBING INFORMATION HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ALIMTA sfely nd effectively. See full prescribing informtion for ALIMTA. ALIMTA (pemetrexed disodium)

More information

If Eligible, Get EFFEXOR XR Co-Pay Card Savings on Your Branded Prescription*

If Eligible, Get EFFEXOR XR Co-Pay Card Savings on Your Branded Prescription* If Eligible, Get EFFEXOR XR Co-Py Crd Svings on Your Brnded Prescription* REMEMBER: You must be prescribed brnd-nme EFFEXOR XR to receive the monthly svings tht come with your Co-Py Crd. *Terms nd conditions

More information

Weight-Based Dosage Regimen: (2.1) Body Weight Range (kg) Loading Dose (mg) Maintenance Dose (mg) greater or equal to 40 to less than 60 2,400 3,000

Weight-Based Dosage Regimen: (2.1) Body Weight Range (kg) Loading Dose (mg) Maintenance Dose (mg) greater or equal to 40 to less than 60 2,400 3,000 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescribing informtion for. (rvulizumb-cwvz) injection, for intrvenous

More information

T max (hr) 1.5 ± ± ± 0.6 AUC (0-10) (ng hr/ml)

T max (hr) 1.5 ± ± ± 0.6 AUC (0-10) (ng hr/ml) Progesterone Cpsules (progesterone, USP), 100 mg nd 200 mg WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER nd PROBABLE DEMENTIA FOR ESTROGEN PLUS PROGESTIN THERAPY Crdiovsculr Disorders nd Probble Dementi

More information

XII. HIV/AIDS. Knowledge about HIV Transmission and Misconceptions about HIV

XII. HIV/AIDS. Knowledge about HIV Transmission and Misconceptions about HIV XII. HIV/AIDS Knowledge bout HIV Trnsmission nd Misconceptions bout HIV One of the most importnt prerequisites for reducing the rte of HIV infection is ccurte knowledge of how HIV is trnsmitted nd strtegies

More information

WARNING: RISK OF THYROID C CELL TUMORS

WARNING: RISK OF THYROID C CELL TUMORS HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use VICTOZA sfely nd effectively. See full prescriing informtion for VICTOZA. VICTOZA (lirglutide) injection,

More information

Adverse Events Grading Card

Adverse Events Grading Card Adverse Events Grding Crd Common Terminology Criteri for Adverse Events* In clinicl studies, 2 of the most common dverse events reported with ALAVEN were peripherl neuropthy nd neutropeni. 1 With this

More information

Larry Alphs 1*, Cynthia A Bossie 1, Jennifer K Sliwa 1, Yi-Wen Ma 2 and Norris Turner 1. Abstract

Larry Alphs 1*, Cynthia A Bossie 1, Jennifer K Sliwa 1, Yi-Wen Ma 2 and Norris Turner 1. Abstract PRIMARY RESEARCH Open Access Onset of efficcy with cute long-cting injectble pliperidone plmitte tretment in mrkedly to severely ill ptients with schizophreni: post hoc nlysis of rndomized, double-blind

More information

Dosing & Administration

Dosing & Administration Dosing & Administration REAL LIFE. REAL RESULTS. INDICATION is indicated for the treatment of: Schizophrenia. Schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants.

More information

PRODUCT MONOGRAPH. Levofloxacin Tablets. 250 mg, 500 mg and 750 mg Levofloxacin (anhydrous) as Levofloxacin Hemihydrate. Antibacterial Agent

PRODUCT MONOGRAPH. Levofloxacin Tablets. 250 mg, 500 mg and 750 mg Levofloxacin (anhydrous) as Levofloxacin Hemihydrate. Antibacterial Agent PRODUCT MONOGRAPH Pr SANDOZ LEVOFLOXACIN Tblets 250 mg, 500 mg nd 750 mg (nhydrous) s Hemihydrte Antibcteril Agent Sndoz Cnd Inc. Dte of Revision: June 25, 2014 145 Jules-Léger Boucherville, QC, Cnd J4B

More information

STEPS SIMPLE TO INTRODUCE ONCE-DAILY THERAPY TO YOUR ADULT PATIENTS WITH TYPE 2 DIABETES START THE CONVERSATION WITH LOOK INSIDE TO FIND OUT HOW

STEPS SIMPLE TO INTRODUCE ONCE-DAILY THERAPY TO YOUR ADULT PATIENTS WITH TYPE 2 DIABETES START THE CONVERSATION WITH LOOK INSIDE TO FIND OUT HOW START THE CONVERSATION WITH SIMPLE STEPS TO INTRODUCE ONCE-DAILY THERAPY TO YOUR ADULT PATIENTS WITH TYPE 2 DIABETES LOOK INSIDE TO FIND OUT HOW Indiction nd Limittions of Use Victoz (lirglutide) injection

More information

Sponsor / Company: Sanofi Drug substance(s): AVE0005 (aflibercept)

Sponsor / Company: Sanofi Drug substance(s): AVE0005 (aflibercept) These results re supplied for informtionl purposes only. Prescribing decisions should be mde bsed on the pproved pckge insert in the country of prescription. Sponsor / Compny: Snofi Drug substnce(s): AVE0005

More information

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 10/2017

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 10/2017 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescribing informtion for. (ipilimumb) injection, for intrvenous use

More information

SYNOPSIS Final Abbreviated Clinical Study Report for Study CA ABBREVIATED REPORT

SYNOPSIS Final Abbreviated Clinical Study Report for Study CA ABBREVIATED REPORT Finl Arevited Clinicl Study Report Nme of Sponsor/Compny: Bristol-Myers Squi Ipilimum Individul Study Tle Referring to the Dossier (For Ntionl Authority Use Only) Nme of Finished Product: Yervoy Nme of

More information

Supplementary Online Content

Supplementary Online Content Supplementry Online Content Rieckmnn N, Kronish IM, Shpiro PA, Whng W, Dvidson KW. Serotonin reuptke inhibitor use, depression, nd long-term outcomes fter n cute coronry : prospective cohort study. JAMA

More information

CheckMate 153: Randomized Results of Continuous vs 1-Year Fixed-Duration Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer

CheckMate 153: Randomized Results of Continuous vs 1-Year Fixed-Duration Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer CheckMte 53: Rndomized Results of Continuous vs -Yer Fixed-Durtion Nivolumb in Ptients With Advnced Non-Smll Cell Lung Cncer Abstrct 297O Spigel DR, McCleod M, Hussein MA, Wterhouse DM, Einhorn L, Horn

More information

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ALIMTA sfely nd effectively. See full prescribing informtion for ALIMTA. ALIMTA (pemetrexed for injection),

More information

DOSING AND ADMINISTRATION SUMMARY

DOSING AND ADMINISTRATION SUMMARY Transitioning patients to INVEGA TRINZA DOSING AND ADMINISTRATION SUMMARY IMPORTANT SAFETY INFORMATION and INDICATIONS for INVEGA TRINZA and INVEGA SUSTENNA INVEGA TRINZA (paliperidone palmitate) a 3-month

More information

Recommended Dosage Regimen for AVYCAZ (ceftazidime and avibactam) b. AVYCAZ 1.25 grams (ceftazidime 1 gram and avibactam 0.25 grams) every 8 hours

Recommended Dosage Regimen for AVYCAZ (ceftazidime and avibactam) b. AVYCAZ 1.25 grams (ceftazidime 1 gram and avibactam 0.25 grams) every 8 hours HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use AVYCAZ sfely nd effectively. See full prescribing informtion for AVYCAZ. AVYCAZ (ceftzidime nd vibctm)

More information

Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis

Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis Sfety of Ocrelizumb in Multiple Sclerosis: Updted Anlysis in Ptients With Relpsing nd Primry Progressive Multiple Sclerosis SL Huser, L Kppos, X Montlbn, H Koendgen, C Chognot, C Li, C Mrcillt, A Prdhn,

More information

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved. Revised: 01/2019

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved. Revised: 01/2019 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ALIMTA sfely nd effectively. See full prescribing informtion for ALIMTA. ALIMTA (pemetrexed for injection),

More information

For Adults With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC)

For Adults With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) For Adults With Previously Treted Advnced Non-Smll Cell Lung Cncer (NSCLC) individuls depicted re models used for illustrtive purposes only. It cn be overwhelming to lern tht your previously treted dvnced

More information

Revised: 6/2018 History of severe hypersensitivity reaction to pemetrexed. (4)

Revised: 6/2018 History of severe hypersensitivity reaction to pemetrexed. (4) HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------ WARNINGS AND PRECAUTIONS ----------------------- These highlights do not include ll the informtion needed to use ALIMTA sfely nd effectively.

More information

Product Monograph INDICATIONS AND USAGE IMPORTANT RISK INFORMATION WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY

Product Monograph INDICATIONS AND USAGE IMPORTANT RISK INFORMATION WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY Product Monogrph INDICATIONS AND USAGE OFIRMEV (cetminophen) injection is indicted for the mngement of mild to moderte pin, mngement of moderte to severe pin with djunctive opioid nlgesics, nd reduction

More information

Gemmis Injection 38 mg/ml

Gemmis Injection 38 mg/ml Gemmis Injection 8 mg/ml Gemcitbine (Gemcitbine HCl) is nucleoside nlogue tht exhibits nti-tumor ctivity. The empiricl formul for Gemcitbine HCl is C 9H 11F 2N O.HCl. It hs moleculr weight of 299.66. Gemcitbine

More information

HIGHLIGHTS OF PRESCRIBING INFORMATION

HIGHLIGHTS OF PRESCRIBING INFORMATION HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ALIMTA sfely nd effectively. See full prescriing informtion for ALIMTA. ALIMTA (pemetrexed for injection)

More information

YERVOY (ipilimumab) injection, for intravenous use Initial U.S. Approval: 2011

YERVOY (ipilimumab) injection, for intravenous use Initial U.S. Approval: 2011 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescribing informtion for. (ipilimumb) injection, for intrvenous use

More information

HERCEPTIN (trastuzumab) Intravenous Infusion Initial U.S. Approval: 1998

HERCEPTIN (trastuzumab) Intravenous Infusion Initial U.S. Approval: 1998 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescriing informtion for. HERCEPTIN (trstuzum) Intrvenous Infusion

More information

of comorbid conditions, interventions Diagnosis and treatment, treatment reduction of risk factors for CVD to slow disease progression,

of comorbid conditions, interventions Diagnosis and treatment, treatment reduction of risk factors for CVD to slow disease progression, Tble 5.1. NKF Clssifiction of Chronic Kidney Disese nd Clinicl Fetures Stge Description GFR (ml/ min/1.73 m 2 ) U.S. Prevlence, b # Affected (%) Clinicl Fetures Action Pln c At incresed risk for CKD >60

More information

First-line and Maintenance Treatment with ALIMTA therapy for advanced nonsquamous non-small cell lung cancer (NSCLC)

First-line and Maintenance Treatment with ALIMTA therapy for advanced nonsquamous non-small cell lung cancer (NSCLC) YOUR LIFE. First-line nd Mintennce Tretment with ALIMTA therpy for dvnced nonsqumous non-smll cell lung cncer (NSCLC) ALIMTA is pproved by the FDA in combintion with cispltin (nother chemotherpy drug)

More information

Efficacy of Pembrolizumab in Patients With Advanced Melanoma With Stable Brain Metastases at Baseline: A Pooled Retrospective Analysis

Efficacy of Pembrolizumab in Patients With Advanced Melanoma With Stable Brain Metastases at Baseline: A Pooled Retrospective Analysis Efficcy of Pembrolizumb in Ptients With Advnced Melnom With Stble Brin Metstses t Bseline: A Pooled Retrospective Anlysis Abstrct 1248PD Hmid O, Ribs A, Dud A, Butler MO, Crlino MS, Hwu WJ, Long GV, Ancell

More information

FULL PRESCRIBING INFORMATION

FULL PRESCRIBING INFORMATION HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use Herceptin sfely nd effectively. See full prescriing informtion for Herceptin. HERCEPTIN (trstuzum)

More information

Submitting a Statement of Medical Necessity (SMN) for Humatrope (somatropin for injection)

Submitting a Statement of Medical Necessity (SMN) for Humatrope (somatropin for injection) Sumitting Sttement of Medicl Necessity (SMN) for Humtrope (somtropin for injection) INFORMATION NEEDED FOR FULL SMN FORM SUBMISSION PATIENT INFORMATION: Plese provide Ptient Nme nd Dte of Birth. PRIMARY

More information

Results. Table 1: Demographic and Baseline Characteristics, Open-Label Safety Population Prior Double-Blind OC/APAP ER (n=77)

Results. Table 1: Demographic and Baseline Characteristics, Open-Label Safety Population Prior Double-Blind OC/APAP ER (n=77) Open-Lbel Extension of Rndomized, Double-Blind, Plcebo-Controlled, Phse 3 Study of the Sfety nd Anlgesic Efficcy of MNK-795 Oxycodone/Acetminophen Extended-Relese (OC/APAP ER) Tblets in n Acute Pin Model

More information

Antiviral Therapy 2015; 20: (doi: /IMP2920)

Antiviral Therapy 2015; 20: (doi: /IMP2920) Antivirl Therpy 2015; 20:397 405 (doi: 10.3851/IMP2920) Originl rticle Sfety, tolerbility nd phrmcokinetics of dorvirine, novel HIV non-nucleoside reverse trnscriptse inhibitor, fter single nd multiple

More information

Management and Outcomes of Binge-Eating Disorder in Adults: Current State of the Evidence

Management and Outcomes of Binge-Eating Disorder in Adults: Current State of the Evidence Clinicin Summry Mentl Helth Eting Disorders Mngement nd Outcomes of Binge-Eting Disorder in Adults: Current Stte of the Evidence Focus of This Summry This is summry of systemtic review evluting the evidence

More information

Abstract. Background. Aim. Patients and Methods. Patients. Study Design

Abstract. Background. Aim. Patients and Methods. Patients. Study Design Impct of the Use of Drugs nd Substitution Tretments on the Antivirl Tretment of Chronic Heptitis C: Anlysis of Complince, Virologicl Response nd Qulity of Life (CHEOBS). Melin, 1 J.-. Lng, D. Ouzn, 3 M.

More information

TRULICITY TRU-0003-USPI _TRU-0002-MG , 8 X 10.5 PRINTER VERSION 1 OF 8

TRULICITY TRU-0003-USPI _TRU-0002-MG , 8 X 10.5 PRINTER VERSION 1 OF 8 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescriing informtion for. (dulglutide) injection, for sucutneous use

More information

INVEGA TRINZA (paliperidone palmitate)

INVEGA TRINZA (paliperidone palmitate) INVEGA TRINZA (paliperidone palmitate) extended-release injectable suspension, for intramuscular use HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to

More information

Community. Profile Big Horn County. Public Health and Safety Division

Community. Profile Big Horn County. Public Health and Safety Division Community Helth Profile 2015 Big Horn County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl

More information

SEIZURES AND EPILEPSY

SEIZURES AND EPILEPSY SEIZURES AND EPILEPSY CONTENT CREATED BY Lern more t www.helth.hrvrd.edu TALK WITH YOUR DOCTOR Tble of Contents WHAT IS A SEIZURE? 4 WHAT IS EPILEPSY? 6 TESTING 7 TREATMENT OPTIONS 9 ANTI-SEIZURE MEDICATION

More information

Community. Profile Powell County. Public Health and Safety Division

Community. Profile Powell County. Public Health and Safety Division Community Helth Profile 2015 Powell County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl Risk

More information

Community. Profile Lewis & Clark County. Public Health and Safety Division

Community. Profile Lewis & Clark County. Public Health and Safety Division Community Helth Profile 2015 Lewis & Clrk County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl

More information

Effect on Glycemic, Blood Pressure, and Lipid Control according to Education Types

Effect on Glycemic, Blood Pressure, and Lipid Control according to Education Types Originl Article http://dx.doi.org/10.4093/dmj.2011.35.6.580 pissn 2233-6079 eissn 2233-6087 D I A B E T E S & M E T A B O L I S M J O U R N A L Effect on Glycemic, Blood Pressure, nd Lipid Control ccording

More information

Original Article. T Akter 1, N Islam 2, MA Hoque 3, S Khanam 4, HA khan 5, BK Saha 6. Abstract:

Original Article. T Akter 1, N Islam 2, MA Hoque 3, S Khanam 4, HA khan 5, BK Saha 6. Abstract: Fridpur Med. Coll. J. 214;9(2):61-67 Originl Article Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus Norml Sline) in Acute

More information

Community. Profile Yellowstone County. Public Health and Safety Division

Community. Profile Yellowstone County. Public Health and Safety Division Community Helth Profile 2015 Yellowstone County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl

More information

1 Indications and Usage

1 Indications and Usage HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ERBITUX sfely nd effectively. See full prescriing informtion for ERBITUX. ERBITUX (cetuxim) injection,

More information

Community. Profile Missoula County. Public Health and Safety Division

Community. Profile Missoula County. Public Health and Safety Division Community Helth Profile 2015 Missoul County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl Risk

More information

Community. Profile Anaconda- Deer Lodge County. Public Health and Safety Division

Community. Profile Anaconda- Deer Lodge County. Public Health and Safety Division Community Helth Profile 2015 Ancond- Deer Lodge County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12

More information

Patient Monitoring Checklist

Patient Monitoring Checklist Ptient Monitoring Checklist Ptient nme Dte This checklist is intended for nurses or other helthcre professionls (HCPs) to use prior to dosing ech ptient nd t ny follow-up visits or clls with the ptient

More information

Emerging Options for Thromboprophylaxis After Orthopedic Surgery: A Review of Clinical Data

Emerging Options for Thromboprophylaxis After Orthopedic Surgery: A Review of Clinical Data Emerging Options for Thromboprophylxis After Orthopedic Surgery: A Review of Clinicl Dt Bob L. Lobo, Phrm.D. In four rndomized, controlled studies of ptients undergoing orthopedic surgery, the ntithrombotic

More information

Bright Futures Medical Screening Reference Table 2 to 5 Day (First Week) Visit

Bright Futures Medical Screening Reference Table 2 to 5 Day (First Week) Visit Bright Futures Medicl Reference Tle 2 to 5 Dy (First Week) Visit Universl Action Metolic nd Verify documenttion of neworn metolic screening results, pproprite rescreening, nd needed follow-up. Document

More information

Trends in antihypertensive and lipidlowering therapy in subjects with type II diabetes: clinical effectiveness or clinical discretion?

Trends in antihypertensive and lipidlowering therapy in subjects with type II diabetes: clinical effectiveness or clinical discretion? ORIGINAL ARTICLE Trends in ntihypertensive nd lipidlowering therpy in subjects with type II dibetes: clinicl effectiveness or clinicl discretion? MC Gulliford, J Chrlton nd R Ltinovic Deprtment of Public

More information

EFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE

EFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE Swine Dy 22 Contents EFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE B. J. Johnson, J. P. Kyser, J. D. Dunn, A. T. Wyln, S. S. Dritz 1, J.

More information

Chorea is characterized by continuous, random, Comprehensive treatment of Huntington disease and other choreic disorders ABSTRACT

Chorea is characterized by continuous, random, Comprehensive treatment of Huntington disease and other choreic disorders ABSTRACT CARLOS SINGER, MD Professor of Neurology, Chief, Center for Prkinson s Disese nd Movement Disorders, Leonrd M. Miller School of Medicine, University of Mimi, Mimi, FL Comprehensive tretment of Huntington

More information

Seasonal influenza vaccination programme country profile: Ireland

Seasonal influenza vaccination programme country profile: Ireland Sesonl influenz vccintion progrmme country profile: Irelnd 2012 13 Seson Bckground informtion Influenz immunistion policy nd generl fcts bout Irelnd Volume indices of GDP per cpit in 2011 nd 2013 (EU-

More information

These highlights do not include all the information needed to use ADVATE safely and effectively. See full prescribing information for ADVATE.

These highlights do not include all the information needed to use ADVATE safely and effectively. See full prescribing information for ADVATE. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use ADVATE sfely nd effectively. See full prescribing informtion for ADVATE. ADVATE [Antihemophilic Fctor

More information

PROFILE OF A PATIENT WITH mbc with visceral metastases

PROFILE OF A PATIENT WITH mbc with visceral metastases Ptient P.V. PRFILE F A PATIENT WIT mbc with viscerl metstses Indiction Metsttic Brest Cncer ALAVEN (eribulin mesylte) Injection is indicted for the tretment of ptients with metsttic brest cncer (mbc) who

More information

Product Monograph. Published by

Product Monograph. Published by Product Monogrph Pulished y INDICATION AND LIMITATION OF USE JARDIANCE is indicted s n djunct to diet nd exercise to improve glycemic control in dults with type 2 dietes mellitus. JARDIANCE is not recommended

More information

IMMUNOSUPPRESSION IN RAPID METABOLIZERS OF TACROLIMUS Considerations for a Clinically Relevant Subgroup

IMMUNOSUPPRESSION IN RAPID METABOLIZERS OF TACROLIMUS Considerations for a Clinically Relevant Subgroup Join us for n engging discussion out IMMUNOSUPPRESSION IN RAPID METABOLIZERS OF TACROLIMUS Considertions for Cliniclly Relevnt Sugroup Presented y TARIQ SHAH, MD, ASSOCIATE DIRECTOR MULTI ORGAN TRANSPLANT

More information

IMPORTANT Reminders for Patients. IMPORTANT Information for Doctors/Nurses

IMPORTANT Reminders for Patients. IMPORTANT Information for Doctors/Nurses Monitor Your Signs nd Symptoms (nivolum) is prescription medicine used in comintion with YERVOY (ipilimum) to tret type of skin cncer clled melnom tht hs spred or cnnot e removed y surgery (dvnced melnom).

More information

Assessment of Depression in Multiple Sclerosis. Validity of Including Somatic Items on the Beck Depression Inventory II

Assessment of Depression in Multiple Sclerosis. Validity of Including Somatic Items on the Beck Depression Inventory II Assessment of Depression in Multiple Sclerosis Vlidity of Including Somtic Items on the Beck Depression Inventory II Peggy Crwford, PhD; Noh J. Webster, MA Signs nd symptoms of multiple sclerosis (MS)

More information

Impact of Pharmacist Intervention on Diabetes Patients in an Ambulatory Setting

Impact of Pharmacist Intervention on Diabetes Patients in an Ambulatory Setting Impct of Phrmcist Intervention on Dibetes Ptients in n Ambultory Setting Julie Stding, PhrmD, CDE, Jmie Herrmnn, PhrmD, Ryn Wlters, MS, Chris Destche, PhrmD, nd Aln Chock, PhrmD Dibetes is the seventh-leding

More information

Community. Profile Carter County. Public Health and Safety Division

Community. Profile Carter County. Public Health and Safety Division Community Helth Profile 2015 Crter County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl Risk

More information

See 17 for PATIENT COUNSELING INFORMATION. Revised: 01/2018 FULL PRESCRIBING INFORMATION: CONTENTS*

See 17 for PATIENT COUNSELING INFORMATION. Revised: 01/2018 FULL PRESCRIBING INFORMATION: CONTENTS* HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescriing informtion for. (rifximin) tlets, for orl use Initil U.S.

More information

See 17 for PATIENT COUNSELING INFORMATION. Revised: 09/2017 FULL PRESCRIBING INFORMATION: CONTENTS*

See 17 for PATIENT COUNSELING INFORMATION. Revised: 09/2017 FULL PRESCRIBING INFORMATION: CONTENTS* HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use Gemzr sfely nd effectively. See full prescriing informtion for Gemzr. GEMZAR (gemcitine for injection),

More information

For Adults with Metastatic Melanoma

For Adults with Metastatic Melanoma For Adults with Metsttic Melnom The + YERVOY Regimen ws shown to reduce the risk of disese progression by nerly 60% compred to YERVOY lone. Hlf of the ptients on + YERVOY were live t 11.5 months without

More information

Mecadox. Improves pig performance in a wide range of health and growing conditions. (Carbadox) Talk With a Phibro Expert:

Mecadox. Improves pig performance in a wide range of health and growing conditions. (Carbadox) Talk With a Phibro Expert: SWINE (Crbdox) Improves pig performnce in wide rnge of helth nd growing conditions The Advntge Over the yers, medicted feed dditive hs proven to be cost-effective mngement tool for improving pig performnce

More information

Summary of Package Insert 1

Summary of Package Insert 1 Summry of Pckge Insert 1 For Sttes with Non-Published Policies Indictions Non-infected prtil nd full-thickness skin ulcers due to VSU 2 of greter thn 1 month durtion nd which hve not dequtely responded

More information

Isoetharinewith PhenylephrineAerosol in Asthma

Isoetharinewith PhenylephrineAerosol in Asthma J Clin Phrmcol. 1983; 23:82-88. Comprison of Fenoterol,Isoproterenol,od Isoethrineith PhenylephrineAerosol in Asthm GEORGE G. SPELLMAN, JR., M.D.,* BARBARA J. GRUEBEL, M.D., JOEL D. EPSTEIN, M.D., HAROLD

More information

BOTOX Billing and Coding for Chronic Migraine

BOTOX Billing and Coding for Chronic Migraine S T R E A M L I N E Billing nd Coding for Chronic Migrine Indiction Chronic Migrine for injection is indicted for the prophylxis of hedches in dult ptients with chronic migrine ( 15 dys per month with

More information

Presented at the 75 th Annual Meeting of the American Academy of Dermatology, Orlando, FL, March 3-7, 2017 METHODS INTRODUCTION OBJECTIVE

Presented at the 75 th Annual Meeting of the American Academy of Dermatology, Orlando, FL, March 3-7, 2017 METHODS INTRODUCTION OBJECTIVE Seven-Yer Interim Results from the ESPRIT 10-Yer Postmrketing Surveillnce Registry of Adlimumb for Moderte to Severe Psorisis Frncisco Kerdel, 1 Aln Menter, 2 Jshin J. Wu, 3 Mreike Bereswill, 4 Dilek Arikn,

More information

7Disconnect the syringe from the. 9Reconnect the syringe to the ADVATE

7Disconnect the syringe from the. 9Reconnect the syringe to the ADVATE TROUBLESHOOTING GUIDE The following instructions will guide you through recovering ADVATE if the initil reconstitution procedure does not work. Some steps my need to be repeted from this initil reconstitution

More information

In the treatment of cardiovascular disease (CVD), national

In the treatment of cardiovascular disease (CVD), national n report n Beyond LDL Cholesterol: The Role of Elevted Triglycerides nd Low HDL Cholesterol in Residul CVD Risk Remining After Sttin Therpy Peter Algon Jr, MD, FACC In the tretment of crdiovsculr disese

More information

A review of the patterns of docetaxel use for hormone-resistant prostate cancer at the Princess Margaret Hospital

A review of the patterns of docetaxel use for hormone-resistant prostate cancer at the Princess Margaret Hospital MEDICAL ONCOLOGY A review of the ptterns of docetxel use for hormone-resistnt prostte cncer t the Princess Mrgret Hospitl S.N. Chin MD,* L. Wng MSc, M. Moore MD,* nd S.S. Sridhr MD MSc* ABSTRACT Bckground

More information

UNLOCKING SELF-POTENTIAL

UNLOCKING SELF-POTENTIAL ADVATE is FDA pproved for prophylxis in both dults & children (0-16 yers) 1 UNLOCKING SELF-POTENTIAL Setting Gols Worksheet Plese see pge 3 for ADVATE Indictions nd Detiled Importnt Risk Informtion. Plese

More information

Immune-Mediated Adverse Reactions Management Guide

Immune-Mediated Adverse Reactions Management Guide Immune-Medited Adverse Rections Mngement Guide INDICATIONS AND USAGE YERVOY (ipilimumb) is indicted for: Tretment of unresectble or metsttic melnom in dults nd peditric ptients (12 yers nd older) Adjuvnt

More information

The potential future of targeted radionuclide therapy: implications for occupational exposure? P. Covens

The potential future of targeted radionuclide therapy: implications for occupational exposure? P. Covens The potentil future of trgeted rdionuclide therpy: implictions for occuptionl exposure? Introduction: Trgeted Rdionuclide Therpy (TRT) Systemic tretment Molecule lbelled with rdionuclide delivers toxic

More information