Malignant Pleural Mesothelioma (MPM) treatment with ALIMTA therapy

Transcription

1 YOUR LIFE. Mlignnt Pleurl Mesotheliom (MPM) tretment with ALIMTA therpy ALIMTA is tretment for mlignnt pleurl mesotheliom (MPM), which is cncer tht ffects the inside lining of the chest cvity. ALIMTA is given with cispltin, nother nticncer medicine (chemotherpy), when surgery is not n option. ALIMTA cn suppress one mrrow function, which my cuse low lood cell counts. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll You re encourged to report negtive side effects of prescription drugs to the FDA. Visit or cll -8-FDA-88.

2 Tle of Contents Introduction 2 Wht is ALIMTA (pemetrexed for injection)? 4 Your tretment pln 5 Mlignnt pleurl mesotheliom therpy 7 How is your tretment given? 8 Side effects Frequently sked questions 8 Your helthcre tem 9 Importnt Sfety Informtion for ALIMTA 2 Resources 2 ALIMTA (pemetrexed for injection) cn suppress one mrrow function, which my cuse low lood cell counts. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll You re encourged to report negtive side effects of prescription drugs to the FDA. Visit or cll -8-FDA

3 Introduction Receiving the dignosis of mlignnt pleurl mesotheliom (MPM) is not esy. Like mny people living with cncer, you re proly deling with issues you hve never fced efore. And it is lright if you re worried out the new chllenge tht lies hed. Your doctor hs prescried ALIMTA (pemetrexed for injection) sed on your specific dignosis. As you egin to understnd the type of cncer you hve, know tht your helthcre tem is there for you. By working together with them sking questions, tlking out side effects you might e experiencing, nd understnding your options you cn help your tem understnd how your tretment is going. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

4 Wht is ALIMTA (pemetrexed for injection)? ALIMTA (lso known s pemetrexed) is n injectle chemotherpy or nticncer drug. Chemotherpy consists of tretment with one or more nticncer drugs tht re intended to kill cncer cells. ALIMTA is used to tret certin kind of cncer known s mlignnt pleurl mesotheliom (MPM). ALIMTA ppers to work y interfering with very importnt process tht llows cncer cells to reproduce nd spred. ALIMTA is tretment for mlignnt pleurl mesotheliom (MPM), which is cncer tht ffects the inside lining of the chest cvity. ALIMTA is given with cispltin, nother nticncer medicine (chemotherpy), when surgery is not n option. ALIMTA cn suppress one mrrow function, which my cuse low lood cell counts. Your tretment pln Wht do you need to know? You re receiving ALIMTA for the tretment of your specific type of cncer. Before you egin therpy, it is importnt for you to do some things to help get you redy for your tretment. If you re unsure out ny of the following sfety informtion, e sure to sk your helthcre tem. Working with your tem is very importnt during your course of therpy. If you know you re llergic to ALIMTA, tell your doctor ecuse you should not receive it. If you think you re pregnnt, re plnning to ecome pregnnt, or re nursing, plese tell your helthcre tem. ALIMTA my hrm your unorn or nursing y. Your physicin my tell you to use contrception (irth control) to prevent pregnncy while you re eing treted with ALIMTA. Beginning 7 dys efore you strt tking ALIMTA, you will need to tke folic cid pill ( type of B vitmin) once per dy to lower your risk of certin hrmful side effects. Your helthcre tem will tell you exctly wht to tke; the recommended mount is etween 4 nd mcg ech dy. You will continue to tke folic cid pill every dy until 2 dys fter your lst dose of ALIMTA. (continues on next pge) For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

5 Your tretment pln Wht do you need to know? (continued) Your helthcre tem will give you shot (into muscle) of vitmin B 2 one week efore you strt ALIMTA (pemetrexed for injection) to lower your risk of certin hrmful side effects. Your helthcre tem will then give you shot pproximtely every 9 weeks, most likely on the sme dy tht you receive your ALIMTA chemotherpy, for the rest of your tretment cycles. To help your helthcre tem effectively oversee your tretment, mke sure you tell them out ll of your medicl conditions. If you hve liver or kidney prolems, e sure to tell this to your helthcre tem. Your dose of ALIMTA my hve to e chnged, or ALIMTA my not e right for you. Tell your helthcre tem if you re tking other medicines, including prescription nd nonprescription medicines, vitmins, nd herl supplements. ALIMTA nd other medictions my ffect ech other, cusing serious side effects. If you re tking nonsteroidl nti-inflmmtory drug (n NSAID, like iuprofen, or other drugs used to tret pin nd rthritis conditions), you should mke sure to tell your helthcre tem. Depending on your sitution, you my e sked to stop tking these for period of time. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll You will e given n orl steroid mediction clled corticosteroid to lower the risk of skin-relted side effects (like rsh). Be sure to tke this drug twice dily on the dy efore, the dy of, nd the dy fter tretment, unless your helthcre tem gives you different instructions. This ooklet contins dditionl importnt informtion on the sfety profile nd side effects of ALIMTA therpy tht you must e wre of. Plese see the Importnt Sfety Informtion for ALIMTA nd Side effects sections in this ooklet. Mlignnt pleurl mesotheliom therpy Mlignnt pleurl mesotheliom (MPM) is cncer tht develops in the soft tissue tht surrounds the lungs clled the pleur. If you hve this type of cncer, your doctor my prescrie ALIMTA in comintion with cispltin ( pltinum-contining chemotherpy drug) to tret your cncer. Tlk to your doctor if you hve ny questions out your tretment. A clinicl tril demonstrted tht when compred with cispltin lone, ALIMTA plus cispltin showed improved medin survivl for ptients with MPM. (continues on next pge) Select Importnt Sfety Informtion If you know you re llergic to ALIMTA (pemetrexed for injection), tell your doctor immeditely ecuse you should not receive it. References. ALIMTA (pemetrexed for injection) [pckge insert]. Indinpolis, IN: Eli Lilly nd Compny; Vogelzng NJ, et l. J Clin Oncol. 23;2(4):

6 Mlignnt pleurl mesotheliom therpy (continued) The following sections will give you informtion on how mlignnt pleurl mesotheliom (MPM) therpy with ALIMTA (pemetrexed for injection) plus cispltin is given nd the possile side effects you my experience. How is your tretment given? ALIMTA should e given to you only y qulified helthcre professionl. Your helthcre tem will prepre ALIMTA y mixing it into solution nd giving it to you through needle into vein this is clled n intrvenous ALIMTA(IV) infusion. Cispltin ALIMTA will lso e given to you through n IV. Strt Initil Tretment Pltinum Agent For the Cispltin tretment of MPM, ALIMTA plus cispltin will e given usully once every 2 dys (3 weeks equls tretment cycle). Mintennce Discussion Mintennce Eligiility* ALIMTA Plus Cispltin Tretment Administrtion ALIMTA will e given to you s -minute IV infusion. 3 For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll After these two infusions, you will not e given ny more chemotherpy for the next 2 dys. These rest dys re norml prt of your tretment with ALIMTA. As prt of your tretment, you will lso receive dditionl medictions (including vitmin B 2, folic cid, nd corticosteroids) to help reduce hrmful side effects, which will e discussed in the next section. You will hve regulr lood tests efore nd during your tretment with ALIMTA. Your doctor my djust your dose of ALIMTA or dely tretment sed on the results of your lood tests nd on your generl condition, including ny side effects tht you my hve hd. Your helthcre tem my sk you to come ck for follow-up visits fter you receive ALIMTA therpy so they cn check on how you re doing. It s importnt to tlk out how you re feeling nd out ny side effects you might e experiencing. Your helthcre tem needs this informtion from you so tht they cn monitor how your tretment is going. If you hve questions out how ALIMTA is given, plese e sure to discuss them with your helthcre tem ent ility* e minute rek Cispltin will e given to you s 2-hour IV infusion.

7 Side effects Wht should you expect? Chemotherpy Side effects from chemotherpy re different depending on the type of cncer you hve nd the comintion of drugs you re given. Side effects my lso e different from ptient to ptient nd from tretment to tretment. This section discusses the most common or most serious side effects tht ptients experienced in the clinicl tril tht studied ALIMTA (pemetrexed for injection) plus cispltin for mlignnt pleurl mesotheliom (MPM). Side effects from chemotherpy should e wtched crefully oth y you nd your helthcre tem. Ftigue (tiredness), nuse, nd vomiting re few exmples. Another group of side effects, such s those tht chnge your lood cell counts, re monitored through regulr lood tests, ut they cn lso e identified through signs nd symptoms you might notice. We will discuss some of these in the following pges. Side effects cn e serious, ut most cn e treted. Though few side effects cn e permnent, mny lst only for short time nd go wy fter the tretment dose is lowered or stopped. ALIMTA (pemetrexed for injection) in comintion with cispltin Most ptients tking ALIMTA plus cispltin will hve side effects. For the purpose of this ooklet, we will discuss some of the most common nd/or most serious side effects tht my hppen if you tke ALIMTA plus cispltin for the tretment of MPM. It is not lwys possile to tell whether ALIMTA, cispltin, nother mediction, or the cncer itself is cusing these side effects. You should lwys tell your helthcre tem if you re experiencing nything new. Cll your helthcre tem right wy if you hve fever, chills, dirrhe, or mouth sores. These symptoms could men you hve n infection, which my e severe nd could led to deth. For more informtion out ll of the side effects noted in the clinicl tril of ALIMTA plus cispltin for MPM, plese tlk with your helthcre tem, see the Ptient Prescriing Informtion nd Prescriing Informtion ccompnying this ooklet, visit or cll You re encourged to report negtive side effects of prescription drugs to the FDA. Visit medwtch, or cll -8-FDA-88. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

8 Side effects tht you nd your helthcre tem should wtch for Before nd during your tretment with ALIMTA (pemetrexed for injection) plus cispltin, you will hve regulr lood tests to llow your helthcre tem to wtch for low lood cell counts. You my lso hve dditionl symptoms tht you must tell your helthcre tem out. Some of these side effects nd symptoms re descried in the next sections. Low white lood cell count (neutropeni/leukopeni) White lood cells (leukocytes) help you fight infection. A low white lood cell count is clled leukopeni. Neutrophils re type of white lood cell, nd when your count is low, you hve neutropeni. During this time, you re more likely to develop n infection, nd you should void crowds nd those with colds. You should cll your helthcre tem right wy if you hve ny signs of infection, such s chills or temperture over.4ºf. In the clinicl tril, out 5 percent of ptients on ALIMTA plus cispltin experienced neutropeni nd 53 percent experienced leukopeni. Low red lood cell count (nemi) Red lood cells help crry oxygen from your lungs to the other prts of your ody. A low red lood cell count is clled nemi. If your red lood cell count is low, you my feel tired, get tired esily, pper ple, nd ecome short of reth. Anemi ws experienced y 2 percent of ptients who received ALIMTA plus cispltin in the clinicl tril. Low pltelet count (thromocytopeni) Pltelets help your lood to clot. A lowered pltelet count puts you t more risk for leeding. If your helthcre tem tells you tht you hve low pltelet count, you my e sked to tke some precutions, including voiding injury, voiding constiption, using soft-ristle toothrush, etc. It is importnt tht you cll your helthcre tem if you see ny signs of leeding, such s unexplined ruising or lood in your stool (lck, trry stools). Of the ptients who received ALIMTA plus cispltin, 23 percent hd lowered pltelet count. You re encourged to report negtive side effects of prescription drugs to the FDA. Visit medwtch, or cll -8-FDA-88. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

9 Additionl side effects you ll wnt to wtch for Tiredness (ftigue) Of the ptients who received ALIMTA (pemetrexed for injection) plus cispltin in the clinicl tril, 48 percent experienced some degree of ftigue. If you experience tiredness or ftigue, some ides to counterct it include lncing your periods of ctivity with rest, incresing your fluid intke, nd following well-lnced diet. Gstrointestinl (GI) upset Be sure to tlk with your helthcre tem if you notice ny of the following side effects or nything different out the wy you feel: Nuse nd/or vomiting Of the ptients who received ALIMTA plus cispltin, 82 percent experienced nuse, nd 57 percent experienced vomiting. It is importnt tht you tell your helthcre tem if you hve nuse or vomiting. There re medictions tht cn help prevent nd tret nuse nd vomiting. Loss of ppetite (norexi) Among ptients who received ALIMTA plus cispltin, 2 percent experienced loss of ppetite. If you experience loss of ppetite, plese e sure to tell your helthcre tem. Also, the Ntionl Cncer Institute (NCI) hs helpful ooklet titled Eting Hints, which you cn get y clling -8-4-CANCER ( ) or visiting the NCI wesite t Dirrhe Of the ptients who received ALIMTA plus cispltin, 7 percent experienced dirrhe. Tell your helthcre tem if you hve dirrhe. It is very importnt tht you tlk with them efore you tke ny over-the-counter dirrhe medicines. Constiption Of the ptients treted with ALIMTA plus cispltin, 2 percent hd constiption. Your helthcre tem cn help you tret your constiption. It is importnt tht you tlk with them efore you tke ny over-the-counter lxtives or stool softeners. Mouth, throt, lip, or food pipe sores (stomtitis/phryngitis/esophgitis) Among ptients who received ALIMTA plus cispltin, 23 percent experienced redness or sores in their mouth, throt, or on their lips. These symptoms my hppen few dys fter you get tretment with ALIMTA plus cispltin. You my lso feel pin or hve difficulty when drinking or swllowing food. Tlk with your helthcre tem out proper mouth, lip, nd throt cre if you hve ny of these symptoms. You re encourged to report negtive side effects of prescription drugs to the FDA. Visit medwtch, or cll -8-FDA-88. (continues on next pge) For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

10 Additionl side effects you ll wnt to wtch for (continued) Rsh Of the ptients who received ALIMTA (pemetrexed for injection) plus cispltin, percent developed rsh. You my get rsh or itching during tretment. These rections usully pper etween tretments with ALIMTA nd usully go wy efore the next tretment. Skin rections or rshes tht include listering or peeling my e severe nd could led to deth. Cll your doctor if you hve ny of these symptoms. Before strting ALIMTA, your helthcre tem will give you mediction ( steroid) to help reduce this side effect. Hir loss (lopeci) In the clinicl tril, percent of ptients who received ALIMTA plus cispltin experienced some degree of lopeci, or hir loss. Hir loss is rrely permnent. Tlk with your helthcre tem out ny hir loss tht my hppen. Nerve dmge (neuropthy) Among ptients who received ALIMTA plus cispltin, percent experienced some form of nerve dmge. Symptoms of neuropthy my include wekness, pin, tingling senstion, nd/or numness, especilly in the toes nd fingertips. Drug delys nd discontinution You will hve regulr lood tests efore nd during your tretment with ALIMTA plus cispltin. Your helthcre tem my chnge your dose of ALIMTA or stop tretment for period of time sed on the results of your lood tests or your generl condition. Side effects my or my not e cused y the drug tretment itself; some effects my e due to the disese or to other resons. Contct your helthcre tem right wy if you hve fever, chills, dirrhe, or mouth sores. These symptoms could men you hve n infection, which my e severe nd could led to deth. Tlk with your helthcre tem if you hve ny side effects tht other you or don t go wy. For more informtion out ll of the side effects noted in the clinicl tril of ALIMTA plus cispltin for mlignnt pleurl mesotheliom (MPM), plese tlk with your helthcre tem, see the Ptient Prescriing Informtion nd Prescriing Informtion ccompnying this ooklet, visit or cll You re encourged to report negtive side effects of prescription drugs to the FDA. Visit medwtch, or cll -8-FDA-88. For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

11 Your helthcre tem When should you cll them? Frequently sked questions Why re folic cid nd vitmin B 2 so importnt? It is very importnt to tke folic cid nd vitmin B 2 s prescried y your helthcre tem to lower your chnces of hrmful side effects. How do I get more informtion out side effects? For more informtion out ll of the side effects noted in the clinicl tril of ALIMTA (pemetrexed for injection) plus cispltin for mlignnt pleurl mesotheliom (MPM), plese tlk with your helthcre tem, see the Ptient Prescriing Informtion nd Prescriing Informtion ccompnying this ooklet, visit or cll You re proly in tune with chnges in your ody now more thn ever. You must never tke these chnges for grnted. As person living with cncer, you my feel well enough to continue tking on the chllenges in your dily life, ut you must lwys e wre of infection. If you suspect n infection of ny kind, cll your helthcre tem immeditely. You should lso cll your helthcre tem right wy if you notice ny other chnges in your ody or experience ny of the symptoms shown elow during your chemotherpy tretment. They will let you know wht to do or decide if you need to go to the emergency room. A one-time temperture ove F or temperture ove.4 F for more thn hour Confusion or chnge in mentl sttus, including hllucintions Difficulty rething A new rsh Troule swllowing, drooling, or fcil, neck, or tongue swelling Incresed pin Hedche Adominl pin Constiption or uncontrollle dirrhe Uncontrollle nuse nd/or vomiting Bleeding Swelling in legs or rms For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll Reference. Ntionl Comprehensive Cncer Network. When to go to the emergency room. emergency_room.spx. Accessed Ferury 4,

12 Importnt Sfety Informtion for ALIMTA (pemetrexed for injection) Wht is the most importnt informtion tht I should know out ALIMTA? ALIMTA cn suppress one mrrow function, which my cuse low lood cell counts. ALIMTA my not e pproprite for some ptients. If you re llergic to ALIMTA, tell your doctor ecuse you should not receive it. If you hve liver or kidney prolems, e sure to tell your doctor. Your dose of ALIMTA my hve to e chnged, or ALIMTA my not e right for you. It is very importnt to tke the following medictions prior to nd during your tretment with ALIMTA to lower your chnces of hrmful side effects: You must tke folic cid every dy y mouth eginning 7 dys efore your first dose of ALIMTA. You must keep tking folic cid every dy during the time you re eing treted with ALIMTA, nd every dy for 2 dys fter you receive your lst dose of ALIMTA. Your doctor will give you vitmin B 2 injections while you re getting tretment with ALIMTA. You will get your first vitmin B 2 injection one week efore your first dose of ALIMTA, nd then out every 9 weeks during tretment. Your doctor will prescrie medicine clled corticosteroid tht you must tke the dy efore, the dy of, nd the dy fter ech tretment with ALIMTA to reduce rsh. You will hve regulr lood tests efore nd during your tretment with ALIMTA. Your doctor my djust your dose of ALIMTA or dely your tretment sed on the results of your lood test nd on your generl condition. Wht should I tell my doctor efore receiving ALIMTA? If you think you re pregnnt, re plnning to ecome pregnnt, or re nursing, plese tell your helthcre tem. ALIMTA my hrm your unorn or nursing y. Your physicin my dvise you to use effective contrception (irth control) to prevent pregnncy while you re eing treted with ALIMTA. Tell your doctor if you re tking other medicines, including prescription nd nonprescription medicines, vitmins, nd herl supplements. ALIMTA nd other medicines my ffect ech other, cusing serious side effects. Especilly, tell your doctor if you re tking medicines clled nonsteroidl nti-inflmmtory drugs (NSAIDs) for pin or swelling. (continues on next pge) For more informtion out the sfety profile of ALIMTA, plese see the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

13 Importnt Sfety Informtion for ALIMTA (pemetrexed for injection) (continued) Wht re the possile side effects of ALIMTA? Most ptients tking ALIMTA will hve side effects. Sometimes it is not lwys possile to tell whether ALIMTA, nother medicine, or the cncer itself is cusing these side effects. Cll your doctor right wy if you hve fever, chills, dirrhe, or mouth sores. These symptoms could men you hve n infection, which my e severe nd could led to deth. The most common side effects of ALIMTA when given lone or in comintion with cispltin re: Stomch upset, including nuse, vomiting, dirrhe, or constiption. You cn otin medicines to help control some of these symptoms. Cll your doctor if you get ny of these symptoms. Low lood cell counts: Low red lood cells. Low red lood cells my mke you feel tired, get tired esily, pper ple, nd ecome short of reth. Low white lood cells. Low white lood cells my give you greter chnce for infection. If you hve fever (temperture ove.4 F) or other signs of infection, cll your doctor right wy. Low pltelets. Low pltelets give you greter chnce for leeding. Your doctor will do lood tests to check your lood counts efore nd during tretment with ALIMTA. Tiredness. You my feel tired or wek for few dys fter your ALIMTA tretments. If you hve severe wekness or tiredness, cll your doctor. Redness or sores in your mouth, throt, on your lips, or in the tue tht connects your throt nd stomch (esophgus). You my get redness or sores in your mouth, throt, on your lips, or in your esophgus (stomtitis, phryngitis, esophgitis) or you my feel pin or hve difficulty when drinking or swllowing food. These symptoms my hppen few dys fter ALIMTA tretment. Tlk with your doctor if you get ny of these symptoms. Loss of ppetite. You my lose your ppetite nd lose weight during your tretment. Tlk to your doctor if this is prolem for you. Rsh. You my get rsh or itching during tretment. These rections usully pper etween tretments with ALIMTA nd usully go wy efore the next tretment. Skin rections or rshes tht include listering or peeling my e severe nd could led to deth. Cll your doctor if you hve ny of these symptoms. (continues on next pge) For more informtion out the sfety profile of ALIMTA, plese see the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

14 Importnt Sfety Informtion for ALIMTA (pemetrexed for injection) (continued) Tlk with your doctor, nurse, or phrmcist out ny side effect tht others you or tht doesn t go wy. These re not ll the side effects of ALIMTA. For more informtion, sk your doctor, nurse, or phrmcist. How is ALIMTA given? ALIMTA is slowly infused (injected) into vein. The injection or infusion will lst out minutes. You will usully receive ALIMTA once every 2 dys (3 weeks). For more informtion out ll of the side effects of ALIMTA, plese tlk with your helthcre tem, see the Ptient Prescriing Informtion nd Prescriing Informtion ccompnying this ooklet, visit or cll You re encourged to report negtive side effects of prescription drugs to the FDA. Visit medwtch, or cll -8-FDA-88. PM_CON_ISI_All_7OCT22 For more informtion out the sfety profile of ALIMTA, plese see the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

15 Resources For more informtion out mlignnt pleurl mesotheliom (MPM), living with cncer, nd ptient nd fmily support groups, visit the wesites elow. These resources re independent from Lilly Oncology; Lilly does not control the content. Mlignnt Pleurl Mesotheliom-Specific Resource Mesotheliom Applied Reserch Foundtion The Mesotheliom Applied Reserch Foundtion is nonprofit orgniztion dedicted to finding cure for mesotheliom nd esing the suffering cused y this cncer. The Meso Foundtion provides ptient support services nd eduction, including one-on-one medicl consulttions, privte support groups, rodcsts of interviews with experts, nd conferences. This orgniztion funds peer-reviewed mesotheliom reserch to develop effective tretments for the disese. To dte, the Meso Foundtion hs wrded over $9 million to reserch. They lso ctively dvocte to increse federl funding for mesotheliom reserch. Generl Cncer Resources Americn Cncer Society Cncer Support Community Ptient Advocte Foundtion The LIVESTRONG Foundtion CncerCre For more informtion out the sfety profile of ALIMTA (pemetrexed for injection), plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll

16 Notes For more informtion out the sfety profile of ALIMTA, plese see the Importnt Sfety Informtion on pges 2-24, the ccompnying Ptient Prescriing Informtion nd Prescriing Informtion, visit or cll You re encourged to report negtive side effects of prescription drugs to the FDA. Visit or cll -8-FDA

17 YOUR LIFE. Your Guide to ALIMTA Therpy. Mlignnt pleurl mesotheliom (MPM) Know wht to expect during therpy Find nswers to your tretment questions Locte resources for informtion nd support ALIMTA cn suppress one mrrow function, which my cuse low lood cell counts PM9552 4/25 Lilly USA, LLC 25. All rights reserved. ALIMTA is registered trdemrk of Eli Lilly nd Compny nd is ville y prescription only.

18 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), for Intrvenous Use Initil U.S. Approvl: 24 RECENT MAJOR CHANGES Dosge nd Administrtion, Premediction Regimen nd Concurrent Medictions (2.3) /22 Wrnings nd Precutions, Requirement for Premediction nd Concomitnt Mediction to Reduce Toxicity (5.) /22 Wrnings nd Precutions, Required Lortory Monitoring (5.5) /22 INDICATIONS AND USAGE ALIMTA is folte nlog metolic inhiitor indicted for: Loclly Advnced or Metsttic Nonsqumous Non-Smll Cell Lung Cncer: Initil tretment in comintion with cispltin. (.) Mintennce tretment of ptients whose disese hs not progressed fter four cycles of pltinum-sed first-line chemotherpy. (.2) After prior chemotherpy s single-gent. (.3) Mesotheliom: in comintion with cispltin. (.4) Limittions of Use: ALIMTA is not indicted for the tretment of ptients with squmous cell non-smll cell lung cncer. (.5) DOSAGE AND ADMINISTRATION Comintion use in Non-Smll Cell Lung Cncer nd Mesotheliom: Recommended dose of ALIMTA is 5 mg/m 2 i.v. on Dy of ech 2-dy cycle in comintion with cispltin 75 mg/m 2 i.v. eginning 3 minutes fter ALIMTA dministrtion. (2.) Single-Agent use in Non-Smll Cell Lung Cncer: Recommended dose of ALIMTA is 5 mg/m 2 i.v. on Dy of ech 2-dy cycle. (2.2) Prior to inititing ALIMTA, initite supplementtion with orl folic cid nd intrmusculr vitmin B 2. Continue folic cid nd vitmin B 2 supplementtion throughout tretment. Administer corticosteroids the dy efore, the dy of, nd the dy fter ALIMTA dministrtion. (2.3) Dose Reductions: Dose reductions or discontinution my e needed sed on toxicities from the preceding cycle of therpy. (2.4) DOSAGE FORMS AND STRENGTHS mg vil for injection (3) 5 mg vil for injection (3) CONTRAINDICATIONS History of severe hypersensitivity rection to pemetrexed. (4) WARNINGS AND PRECAUTIONS Premediction regimen: Prior to tretment with ALIMTA, initite supplementtion with orl folic cid nd intrmusculr vitmin B 2 to reduce the severity of hemtologic nd gstrointestinl toxicity of ALIMTA. (5.) Bone mrrow suppression: Reduce doses for susequent cycles sed on hemtologic nd nonhemtologic toxicities. (5.2) Renl function: Do not dminister when CrCl <45 ml/min. (2.4, 5.3) NSAIDs with renl insufficiency: Use cution in ptients with mild to moderte renl insufficiency (CrCl ml/min). (5.4) L monitoring: Do not initite cycle unless ANC 5 cells/mm 3, pltelets, cells/mm 3, nd CrCl 45 ml/min. (5.5) Pregnncy: Fetl hrm cn occur when dministered to pregnnt womn. Women should e dvised to use effective contrception mesures to prevent pregnncy during tretment with ALIMTA. (5.) ADVERSE REACTIONS The most common dverse rections (incidence 2%) with single-gent use re ftigue, nuse, nd norexi. Additionl common dverse rections when used in comintion with cispltin include vomiting, neutropeni, leukopeni, nemi, stomtitis/phryngitis, thromocytopeni, nd constiption. (.) To report SUSPECTED ADVERSE REACTIONS, contct Eli Lilly nd Compny t -8-LillyRx ( ) or FDA t -8-FDA-88 or DRUG INTERACTIONS NSAIDs: Use cution with NSAIDs. (7.) Nephrotoxic drugs: Concomitnt use of these drugs nd/or sustnces which re tuulrly secreted my result in delyed clernce. (7.2) See 7 for PATIENT COUNSELING INFORMATION nd FDA-pproved ptient leling. Revised: 9/23 FULL PRESCRIBING INFORMATION: CONTENTS* INDICATIONS AND USAGE. Nonsqumous Non-Smll Cell Lung Cncer Comintion with Cispltin.2 Nonsqumous Non-Smll Cell Lung Cncer Mintennce.3 Nonsqumous Non-Smll Cell Lung Cncer After Prior Chemotherpy.4 Mesotheliom.5 Limittions of Use 2 DOSAGE AND ADMINISTRATION 2. Comintion Use with Cispltin for Nonsqumous Non-Smll Cell Lung Cncer or Mlignnt Pleurl Mesotheliom 2.2 Single-Agent Use s Mintennce Following First-Line Therpy, or s Second- Line Therpy 2.3 Premediction Regimen nd Concurrent Medictions 2.4 Lortory Monitoring nd Dose Reduction/Discontinution Recommendtions 2.5 Preprtion nd Administrtion Precutions 2. Preprtion for Intrvenous Infusion Administrtion 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5. Requirement for Premediction nd Concomitnt Mediction to Reduce Toxicity 5.2 Bone Mrrow Suppression 5.3 Decresed Renl Function 5.4 Use with Non-Steroidl Anti-Inflmmtory Drugs (NSAIDs) with Mild to Moderte Renl Insufficiency 5.5 Required Lortory Monitoring 5. Pregnncy Ctegory D ADVERSE REACTIONS. Clinicl Trils Experience.2 Postmrketing Experience 7 DRUG INTERACTIONS 7. Non-Steroidl Anti-Inflmmtory Drugs (NSAIDs) 7.2 Nephrotoxic Drugs 8 USE IN SPECIFIC POPULATIONS 8. Pregnncy 8.3 Nursing Mothers 8.4 Peditric Use 8.5 Geritric Use 8. Ptients with Heptic Impirment 8.7 Ptients with Renl Impirment 8.8 Gender 8.9 Rce OVERDOSAGE DESCRIPTION 2 CLINICAL PHARMACOLOGY 2. Mechnism of Action 2.2 Phrmcodynmics 2.3 Phrmcokinetics 3 NONCLINICAL TOXICOLOGY 3. Crcinogenesis, Mutgenesis, Impirment of Fertility 4 CLINICAL STUDIES 4. Non-Smll Cell Lung Cncer (NSCLC) Comintion with Cispltin 4.2 Non-Smll Cell Lung Cncer Mintennce 4.3 Non-Smll Cell Lung Cncer After Prior Chemotherpy 4.4 Mlignnt Pleurl Mesotheliom 5 REFERENCES HOW SUPPLIED/STORAGE AND HANDLING. How Supplied.2 Storge nd Hndling 7 PATIENT COUNSELING INFORMATION *Sections or susections omitted from the full prescriing informtion re not listed. ALIMTA (pemetrexed for injection), for Intrvenous Use PV 8927 AMP ALIMTA (pemetrexed for injection), for Intrvenous Use PV 8927 AMP ALIMTA PI PV8927AMP W/ PPI PX4AMP PRINTER VERSION OF

19 FULL PRESCRIBING INFORMATION INDICATIONS AND USAGE. Nonsqumous Non-Smll Cell Lung Cncer Comintion with Cispltin ALIMTA is indicted in comintion with cispltin therpy for the initil tretment of ptients with loclly dvnced or metsttic nonsqumous non-smll cell lung cncer..2 Nonsqumous Non-Smll Cell Lung Cncer Mintennce ALIMTA is indicted for the mintennce tretment of ptients with loclly dvnced or metsttic nonsqumous non-smll cell lung cncer whose disese hs not progressed fter four cycles of pltinum-sed first-line chemotherpy..3 Nonsqumous Non-Smll Cell Lung Cncer After Prior Chemotherpy ALIMTA is indicted s single-gent for the tretment of ptients with loclly dvnced or metsttic nonsqumous non-smll cell lung cncer fter prior chemotherpy..4 Mesotheliom ALIMTA in comintion with cispltin is indicted for the tretment of ptients with mlignnt pleurl mesotheliom whose disese is unresectle or who re otherwise not cndidtes for curtive surgery..5 Limittions of Use ALIMTA is not indicted for the tretment of ptients with squmous cell non-smll cell lung cncer. [see Clinicl Studies (4., 4.2, 4.3)] 2 DOSAGE AND ADMINISTRATION 2. Comintion Use with Cispltin for Nonsqumous Non-Smll Cell Lung Cncer or Mlignnt Pleurl Mesotheliom The recommended dose of ALIMTA is 5 mg/m 2 dministered s n intrvenous infusion over minutes on Dy of ech 2-dy cycle. The recommended dose of cispltin is 75 mg/m 2 infused over 2 hours eginning pproximtely 3 minutes fter the end of ALIMTA dministrtion. See cispltin pckge insert for more informtion. 2.2 Single-Agent Use s Mintennce Following First-Line Therpy, or s Second-Line Therpy The recommended dose of ALIMTA is 5 mg/m 2 dministered s n intrvenous infusion over minutes on Dy of ech 2-dy cycle. 2.3 Premediction Regimen nd Concurrent Medictions Vitmin Supplementtion Instruct ptients to initite folic cid 4 mcg to mcg orlly once dily eginning 7 dys efore the first dose of ALIMTA. Continue folic cid during the full course of therpy nd for 2 dys fter the lst dose of ALIMTA [see Wrnings nd Precutions (5.)]. Administer vitmin B 2 mg intrmusculrly week prior to the first dose of ALIMTA nd every 3 cycles therefter. Susequent vitmin B 2 injections my e given the sme dy s tretment with ALIMTA [see Wrnings nd Precutions (5.)]. Corticosteroids Administer dexmethsone 4 mg y mouth twice dily the dy efore, the dy of, nd the dy fter ALIMTA dministrtion [see Wrnings nd Precutions (5.)]. 2.4 Lortory Monitoring nd Dose Reduction/Discontinution Recommendtions Monitoring Complete lood cell counts, including pltelet counts, should e performed on ll ptients receiving ALIMTA. Ptients should e monitored for ndir nd recovery, which were tested in the clinicl study efore ech dose nd on dys 8 nd 5 of ech cycle. Ptients should not egin new cycle of tretment unless the ANC is 5 cells/mm 3, the pltelet count is, cells/mm 3, nd cretinine clernce is 45 ml/min. Periodic chemistry tests should e performed to evlute renl nd heptic function [see Wrnings nd Precutions (5.5)]. Dose Reduction Recommendtions Dose djustments t the strt of susequent cycle should e sed on ndir hemtologic counts or mximum nonhemtologic toxicity from the preceding cycle of therpy. Tretment my e delyed to llow sufficient time for recovery. Upon recovery, ptients should e retreted using the guidelines in Tles -3, which re suitle for using ALIMTA s single-gent or in comintion with cispltin. Ndir ANC <5/mm 3 nd ndir pltelets 5,/mm 3. Ndir pltelets <5,/mm 3 without leeding regrdless of ndir ANC. Ndir pltelets <5,/mm 3 with leeding, regrdless of ndir ANC. Tle : Dose Reduction for ALIMTA (single-gent or in comintion) nd Cispltin Hemtologic Toxicities 75% of previous dose (pemetrexed nd cispltin). 75% of previous dose (pemetrexed nd cispltin). 5% of previous dose (pemetrexed nd cispltin). These criteri meet the CTC version 2. (NCI 998) definition of CTC Grde 2 leeding. If ptients develop nonhemtologic toxicities (excluding neurotoxicity) Grde 3, tretment should e withheld until resolution to less thn or equl to the ptient s pre-therpy vlue. Tretment should e resumed ccording to guidelines in Tle 2. Tle 2: Dose Reduction for ALIMTA (single-gent or in comintion) nd Cispltin Nonhemtologic Toxicities, Dose of ALIMTA (mg/m 2 ) Dose of Cispltin (mg/m 2 ) Any Grde 3 or 4 toxicities except mucositis 75% of previous dose 75% of previous dose Any dirrhe requiring hospitliztion (irrespective of Grde) or Grde 3 or 4 dirrhe 75% of previous dose 75% of previous dose Grde 3 or 4 mucositis 5% of previous dose % of previous dose NCI Common Toxicity Criteri (CTC). Excluding neurotoxicity (see Tle 3). In the event of neurotoxicity, the recommended dose djustments for ALIMTA nd cispltin re descried in Tle 3. Ptients should discontinue therpy if Grde 3 or 4 neurotoxicity is experienced. Tle 3: Dose Reduction for ALIMTA (single-gent or in comintion) nd Cispltin Neurotoxicity ALIMTA (pemetrexed for injection), for Intrvenous Use PV 8927 AMP ALIMTA (pemetrexed for injection), for Intrvenous Use PV 8927 AMP CTC Grde Dose of ALIMTA (mg/m 2 ) Dose of Cispltin (mg/m 2 ) - % of previous dose % of previous dose 2 % of previous dose 5% of previous dose Discontinution Recommendtion ALIMTA therpy should e discontinued if ptient experiences ny hemtologic or nonhemtologic Grde 3 or 4 toxicity fter 2 dose reductions or immeditely if Grde 3 or 4 neurotoxicity is oserved. Renlly Impired Ptients In clinicl studies, ptients with cretinine clernce 45 ml/min required no dose djustments other thn those recommended for ll ptients. Insufficient numers of ptients with cretinine clernce elow 45 ml/min hve een treted to mke dosge recommendtions for this group of ptients [see Clinicl Phrmcology (2.3)]. Therefore, ALIMTA should not e dministered to ptients whose cretinine clernce is <45 ml/min using the stndrd Cockcroft nd Gult formul (elow) or GFR mesured y Tc99m-DTPA serum clernce method: [4 - Age in yers] Actul Body Weight (kg) Mles: = ml/min 72 Serum Cretinine (mg/dl) Femles: Estimted cretinine clernce for mles.85 Cution should e exercised when dministering ALIMTA concurrently with NSAIDs to ptients whose cretinine clernce is <8 ml/min [see Drug Interctions (7.)]. 2.5 Preprtion nd Administrtion Precutions As with other potentilly toxic nticncer gents, cre should e exercised in the hndling nd preprtion of infusion solutions of ALIMTA. The use of gloves is recommended. If solution of ALIMTA contcts the skin, wsh the skin immeditely nd thoroughly with sop nd wter. If ALIMTA contcts the mucous memrnes, flush thoroughly with wter. Severl pulished guidelines for hndling nd disposl of nticncer gents re ville [see References (5)]. ALIMTA is not vesicnt. There is no specific ntidote for extrvstion of ALIMTA. To dte, there hve een few reported cses of ALIMTA extrvstion, which were not ssessed s serious y the investigtor. ALIMTA extrvstion should e mnged with locl stndrd prctice for extrvstion s with other non-vesicnts. 2. Preprtion for Intrvenous Infusion Administrtion. Use septic technique during the reconstitution nd further dilution of ALIMTA for intrvenous infusion dministrtion. 2. Clculte the dose of ALIMTA nd determine the numer of vils needed. Vils contin either mg or 5 mg of ALIMTA. The vils contin n excess of ALIMTA to fcilitte delivery of lel mount. 3. Reconstitute ech -mg vil with 4.2 ml of.9% Sodium Chloride Injection (preservtive free). Reconstitute ech 5-mg vil with 2 ml of.9% Sodium Chloride Injection (preservtive free). Reconstitution of either size vil gives solution contining 25 mg/ml ALIMTA. Gently swirl ech vil until the powder is completely dissolved. The resulting solution is cler nd rnges in color from colorless to yellow or green-yellow without dversely ffecting product qulity. The ph of the reconstituted ALIMTA solution is etween. nd 7.8. FURTHER DILUTION IS REQUIRED. 4. Prenterl drug products should e inspected visully for prticulte mtter nd discolortion prior to dministrtion, whenever solution nd continer permit. If prticulte mtter is oserved, do not dminister. 5. An pproprite quntity of the reconstituted ALIMTA solution must e further diluted into solution of.9% Sodium Chloride Injection (preservtive free), so tht the totl volume of solution is ml. ALIMTA is dministered s n intrvenous infusion over minutes.. Chemicl nd physicl stility of reconstituted nd infusion solutions of ALIMTA were demonstrted for up to 24 hours following initil reconstitution, when stored refrigerted. When prepred s directed, reconstitution nd infusion solutions of ALIMTA contin no ntimicroil preservtives. Discrd ny unused portion. Reconstitution nd further dilution prior to intrvenous infusion is only recommended with.9% Sodium Chloride Injection (preservtive free). ALIMTA is physiclly incomptile with diluents contining clcium, including Lctted Ringer s Injection, USP nd Ringer s Injection, USP nd therefore these should not e used. Codministrtion of ALIMTA with other drugs nd diluents hs not een studied, nd therefore is not recommended. ALIMTA is comptile with stndrd polyvinyl chloride (PVC) dministrtion sets nd intrvenous solution gs. 3 DOSAGE FORMS AND STRENGTHS ALIMTA, pemetrexed for injection, is white to either light-yellow or green-yellow lyophilized powder ville in sterile single-use vils contining mg or 5 mg pemetrexed. 4 CONTRAINDICATIONS ALIMTA is contrindicted in ptients who hve history of severe hypersensitivity rection to pemetrexed. 5 WARNINGS AND PRECAUTIONS 5. Requirement for Premediction nd Concomitnt Mediction to Reduce Toxicity Vitmin Supplementtion Prior to tretment with ALIMTA, initite supplementtion with orl folic cid nd intrmusculr vitmin B 2 to reduce the severity of hemtologic nd gstrointestinl toxicity of ALIMTA [see Dosge nd Administrtion (2.3)]. Do not sustitute orl vitmin B 2 for intrmusculr vitmin B 2. In clinicl studies, the incidence of the following Grde 3-4 toxicities were higher in ptients with mesotheliom who were never supplemented s compred to ptients who were fully supplemented with folic cid nd vitmin B 2 prior to nd throughout ALIMTA tretment: neutropeni [38% versus 23%], thromocytopeni [9% versus 5%], ferile neutropeni [9% versus.%], nd infection with neutropeni [% versus. ]. Corticosteroids Administer dexmethsone the dy efore, the dy of, nd the dy fter ALIMTA dministrtion [see Dosge nd Administrtion (2.3)]. 5.2 Bone Mrrow Suppression ALIMTA cn suppress one mrrow function, s mnifested y neutropeni, thromocytopeni, nd nemi (or pncytopeni) [see Adverse Rections (.)]; myelosuppression is usully the dose-limiting toxicity. Dose reductions for susequent cycles re sed on ndir ANC, pltelet count, nd mximum nonhemtologic toxicity seen in the previous cycle [see Dosge nd Administrtion (2.4)]. 5.3 Decresed Renl Function ALIMTA is primrily eliminted unchnged y renl excretion. No dosge djustment is needed in ptients with cretinine clernce 45 ml/min. Insufficient numers of ptients hve een studied with cretinine clernce <45 ml/min to give dose recommendtion. Therefore, ALIMTA should not e dministered to ptients whose cretinine clernce is <45 ml/min [see Dosge nd Administrtion (2.4)]. ALIMTA PI PV8927AMP W/ PPI PX4AMP PRINTER VERSION 2 OF

20 One ptient with severe renl impirment (cretinine clernce 9 ml/min) who did not receive folic cid nd vitmin B 2 died of drug-relted toxicity following dministrtion of ALIMTA lone. 5.4 Use with Non-Steroidl Anti-Inflmmtory Drugs (NSAIDs) with Mild to Moderte Renl Insufficiency Cution should e used when dministering NSAIDs concurrently with ALIMTA to ptients with mild to moderte renl insufficiency (cretinine clernce from 45 to 79 ml/min) [see Drug Interctions (7.)]. 5.5 Required Lortory Monitoring Otin complete lood count nd renl function tests t the eginning of ech cycle nd s needed. Do not initite cycle of tretment unless the ANC is 5 cells/mm 3, the pltelet count is, cells/mm 3, nd cretinine clernce is 45 ml/min [see Dosge nd Administrtion (2.4)]. 5. Pregnncy Ctegory D Bsed on its mechnism of ction, ALIMTA cn cuse fetl hrm when dministered to pregnnt womn. Pemetrexed dministered intrperitonelly to mice during orgnogenesis ws emryotoxic, fetotoxic nd tertogenic in mice t greter thn /833rd the recommended humn dose. If ALIMTA is used during pregnncy, or if the ptient ecomes pregnnt while tking this drug, the ptient should e pprised of the potentil hzrd to the fetus. Women of childering potentil should e dvised to void ecoming pregnnt. Women should e dvised to use effective contrceptive mesures to prevent pregnncy during tretment with ALIMTA [see Use in Specific Popultions (8.)]. ADVERSE REACTIONS. Clinicl Trils Experience Becuse clinicl trils re conducted under widely vrying conditions, dverse rections rtes cnnot e directly compred to rtes in other clinicl trils nd my not reflect the rtes oserved in clinicl prctice. In clinicl trils, the most common dverse rections (incidence 2%) during therpy with ALIMTA s single-gent were ftigue, nuse, nd norexi. Additionl common dverse rections (incidence 2%) during therpy with ALIMTA when used in comintion with cispltin included vomiting, neutropeni, leukopeni, nemi, stomtitis/phryngitis, thromocytopeni, nd constiption. Non-Smll Cell Lung Cncer (NSCLC) ALIMTA in Comintion with Cispltin Tle 4 provides the frequency nd severity of dverse rections tht hve een reported in >5% of 839 ptients with NSCLC who were rndomized to study nd received ALIMTA plus cispltin nd 83 ptients with NSCLC who were rndomized to study nd received gemcitine plus cispltin. All ptients received study therpy s initil tretment for loclly dvnced or metsttic NSCLC nd ptients in oth tretment groups were fully supplemented with folic cid nd vitmin B 2. Rection Tle 4: Adverse Rections in Fully Supplemented Ptients Receiving ALIMTA plus Cispltin in NSCLC ALIMTA/cispltin (N=839) All Grdes Grde 3-4 Gemcitine/cispltin (N=83) All Grdes Grde 3-4 All Adverse Rections Lortory Hemtologic Anemi Neutropeni Leukopeni Thromocytopeni Renl Cretinine elevtion 7 Clinicl Constitutionl Symptoms Ftigue Gstrointestinl Nuse Vomiting Anorexi Constiption Stomtitis/Phryngitis Dirrhe Dyspepsi/Herturn Neurology Neuropthy-sensory Tste disturnce Dermtology/Skin Alopeci Rsh/Desqumtion c 2 9 For the purpose of this tle cut off of 5% ws used for inclusion of ll events where the reporter considered possile reltionship to ALIMTA. Refer to NCI CTC Criteri version 2. for ech Grde of toxicity. c According to NCI CTC Criteri version 2., this dverse event term should only e reported s Grde or 2. No cliniclly relevnt differences in dverse rections were seen in ptients sed on histology. In ddition to the lower incidence of hemtologic toxicity on the ALIMTA nd cispltin rm, use of trnsfusions (RBC nd pltelet) nd hemtopoietic growth fctors ws lower in the ALIMTA nd cispltin rm compred to the gemcitine nd cispltin rm. The following dditionl dverse rections were oserved in ptients with non-smll cell lung cncer rndomly ssigned to receive ALIMTA plus cispltin. Incidence % to 5% Body s Whole ferile neutropeni, infection, pyrexi Generl Disorders dehydrtion Metolism nd Nutrition incresed AST, incresed ALT Renl cretinine clernce decrese, renl filure Specil Senses conjunctivitis c c c Incidence Less thn % Crdiovsculr rrhythmi Generl Disorders chest pin Metolism nd Nutrition incresed GGT Neurology motor neuropthy Non-Smll Cell Lung Cncer (NSCLC) Mintennce ALIMTA Mintennce Following Non-ALIMTA Contining, Pltinum-Bsed Induction Therpy Tle 5 provides the frequency nd severity of dverse rections reported in >5% of the 438 ptients with NSCLC who received ALIMTA mintennce nd the 28 ptients with NSCLC who received plceo following pltinum-sed induction therpy. All ptients received study therpy immeditely following 4 cycles of pltinum-sed tretment for loclly dvnced or metsttic NSCLC. Ptients in oth study rms were fully supplemented with folic cid nd vitmin B 2. Tle 5: Adverse Rections in Ptients Receiving ALIMTA versus Plceo in NSCLC Following Pltinum-Bsed Induction Therpy Rection All Grdes ALIMTA (N=438) Grde 3-4 All Grdes Plceo (N=28) Grde 3-4 All Adverse Rections 37 4 Lortory Hemtologic Anemi Neutropeni Leukopeni Heptic Incresed ALT Incresed AST 5 8 Clinicl Constitutionl Symptoms Ftigue 25 5 Gstrointestinl Nuse Anorexi Vomiting Mucositis/stomtitis Dirrhe Infection Neurology Neuropthy-sensory 9 4 Dermtology/Skin Rsh/Desqumtion 3 For the purpose of this tle cut off of 5% ws used for inclusion of ll events where the reporter considered possile reltionship to ALIMTA. Refer to NCI CTCAE Criteri version 3. for ech Grde of toxicity. No cliniclly relevnt differences in Grde 3/4 dverse rections were seen in ptients sed on ge, gender, ethnic origin, or histology except higher incidence of Grde 3/4 ftigue for Cucsin ptients compred to non-cucsin ptients (.5% versus.%). Sfety ws ssessed y exposure for ptients who received t lest one dose of ALIMTA (N=438). The incidence of dverse rections ws evluted for ptients who received cycles of ALIMTA, nd compred to ptients who received > cycles of ALIMTA. Increses in dverse rections (ll grdes) were oserved with longer exposure; however no cliniclly relevnt differences in Grde 3/4 dverse rections were seen. Consistent with the higher incidence of nemi (ll grdes) on the ALIMTA rm, use of trnsfusions (minly RBC) nd erythropoiesis stimulting gents (ESAs; erythropoietin nd drepoetin) were higher in the ALIMTA rm compred to the plceo rm (trnsfusions 9.5% versus 3.2%, ESAs 5.9% versus.8%). The following dditionl dverse rections were oserved in ptients with non-smll cell lung cncer who received ALIMTA. Incidence % to 5% Dermtology/Skin lopeci, pruritis/itching Gstrointestinl constiption Generl Disorders edem, fever (in the sence of neutropeni) Hemtologic thromocytopeni Renl decresed cretinine clernce, incresed cretinine, decresed glomerulr filtrtion rte Specil Senses oculr surfce disese (including conjunctivitis), incresed lcrimtion Incidence Less thn % Crdiovsculr suprventriculr rrhythmi Dermtology/Skin erythem multiforme Generl Disorders ferile neutropeni, llergic rection/hypersensitivity Neurology motor neuropthy Renl renl filure Continution of ALIMTA s Mintennce Following ALIMTA Plus Pltinum Induction Therpy Tle provides the frequency nd severity of dverse rections reported in >5% of the 5 ptients with non-squmous NSCLC who received t lest one cycle of ALIMTA mintennce (n=333) or plceo (n=7) on the continution mintennce tril. The medin of mintennce cycles dministered to ptients receiving one or more doses of mintennce therpy ws 4 on oth the pemetrexed nd plceo rms. Dose reductions for dverse events occurred in 3.3% of ptients in the ALIMTA rm nd.% in the plceo rm. Dose delys for dverse events occurred in 22% of ptients in the ALIMTA rm nd % in the plceo rm. Ptients in oth study rms were supplemented with folic cid nd vitmin B ALIMTA (pemetrexed for injection), for Intrvenous Use PV 8927 AMP ALIMTA (pemetrexed for injection), for Intrvenous Use PV 8927 AMP ALIMTA PI PV8927AMP W/ PPI PX4AMP PRINTER VERSION 3 OF