Pemetrexed Sigillata

Package leaflet: Information for the user

Pemetrexed Sigillata 100 mg powder for concentrate for solution for infusion

/…/ 500 mg powder for concentrate for solution for infusion

/…/ 1000 mg powder for concentrate for solution for infusion

pemetrexed

Read allofthisleafletcarefully beforeyou startreceiving thismedicinebecauseitcontains importantinformationforyou.

- Keep thisleaflet. You may needto readitagain.

- Ifyou haveany furtherquestions, ask yourdoctororpharmacist.

- Ifyou getany sideeffects, talkto yourdoctoror nurse or pharmacist.Thisincludesany possibleside effectsnotlistedinthisleaflet.See section 4.

What isinthisleaflet:

1. What Pemetrexed Sigillata isand whatitisusedfor

2. What you need to knowbeforeyou use Pemetrexed Sigillata

3. Howto usePemetrexed Sigillata

4. Possiblesideeffects

5. Howto storePemetrexed Sigillata

6. Contentsofthepackand otherinformation

1. WhatPemetrexed Sigillata is andwhatit isusedfor

Pemetrexed Sigillata isa medicine used inthetreatmentofcancer. It contains the active substance pemetrexed. Pemetrexed belongs to a group of medicines known as folic acid analogues and disrupts processes that are essential for cell replication.

Pemetrexed Sigillata isgiven in combination with cisplatin, anotheranti-cancermedicine, astreatmentfor malignantpleuralmesothelioma, a formof cancerthataffectstheliningof thelung,to patientswho havenot received priorchemotherapy.

Pemetrexed Sigillata isalso given in combination with cisplatinfor theinitialtreatmentofpatientswith advanced stageof lungcancer.

Pemetrexed Sigillatacan beprescribedtoyou ifyou havelung cancerat an advanced stageifyourdiseasehas respondedtotreatmentoritremainslargelyunchanged afterinitialchemotherapy.

Pemetrexed Sigillata isalso atreatmentforpatientswith advancedstageof lungcancerwhosediseasehas progressed afterotherinitialchemotherapyhas beenused.

2. Whatyouneed toknow beforeyouuse Pemetrexed Sigillata

Do notusePemetrexed Sigillata

- ifyou areallergicto pemetrexed or anyof theotheringredientsof this medicine (listed in section 6).

- ifyou arebreast-feeding;you mustdiscontinuebreast-feedingduringtreatmentwith Pemetrexed Sigillata.

- ifyou haverecentlyreceived or areabouttoreceivea vaccineagainstyellowfever.

Warningsandprecautions

Talk toyourdoctoror hospital pharmacist beforereceivingPemetrexed Sigillata.

Ifyou currentlyhaveor havepreviouslyhad problemswith yourkidneys, talktoyour doctoror hospitalpharmacistas youmaynot beableto receivePemetrexed Sigillata.

Beforeeach infusion you willhavesamplesof yourblood taken to evaluateifyou havesufficientkidneyand liverfunction and to checkthatyou haveenough blood cellsto receivePemetrexed Sigillata. Your doctormaydecideto changethe doseor delaytreatingyou dependingon yourgeneralconditionand if yourbloodcellcountsaretoo low. Ifyou arealsoreceivingcisplatin, yourdoctorwillmakesurethat you areproperlyhydrated and receiveappropriatetreatmentbeforeand afterreceivingcisplatinto preventvomiting.

Ifyou havehad or aregoingto haveradiationtherapy, pleasetellyourdoctor, astheremaybe an early or lateradiation reaction with Pemetrexed Sigillata.

Ifyou havebeen recentlyvaccinated, pleasetellyourdoctor, as thiscan possiblycause bad effects with Pemetrexed Sigillata.

Ifyou haveheartdiseaseor ahistoryof heartdisease,pleasetellyourdoctor.

Ifyou havean accumulation of fluid around yourlungs, yourdoctormaydecideto removethe fluid beforegivingyou Pemetrexed Sigillata.

Children and adolescents

Thereisno relevantuse ofPemetrexed Sigillata inthepaediatricpopulation.

Othermedicinesand Pemetrexed Sigillata

Please tell your doctor if you are taking any medicines forpain orinflammation (swelling), such asmedicinescalled “nonsteroidalanti-inflammatorydrugs”(NSAIDs), includingmedicinespurchased withouta doctor’sprescription (suchas ibuprofen).Therearemanysortsof NSAIDswith different durationsofactivity. Basedon theplanneddateof yourinfusion ofPemetrexed Sigillata and/oron thestatusof yourkidneyfunction, yourdoctorneedsto adviseyou on which medicinesyou can takeand when you can takethem. Ifyou areunsure, ask yourdoctoror pharmacistifany ofyourmedicinesareNSAIDs.

Like other chemotherapy medicines /…/ is not recommended with live attenuated vaccines. Inactive vaccines should be used where possible.

Tell your doctor or hospital pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Pregnancy, breast-feedingandfertility

Pregnancy

Ifyou arepregnant, think you may be pregnant or are planning to have a baby,tellyourdoctor and ask for advice before taking this medicine.The useof Pemetrexed Sigillata should be avoided duringpregnancy. Yourdoctorwilldiscusswith you thepotentialriskof taking Pemetrexed Sigillata duringpregnancy. Women mustuse effectivecontraception duringtreatmentwith Pemetrexed Sigillata.

Breast-feeding

Ifyou arebreast-feeding, tellyourdoctor.

Breast-feedingmustbe discontinued duringPemetrexed Sigillata treatment.

Fertility

Men areadvised notto fathera child duringand up to6 monthsfollowingtreatmentwith Pemetrexed Sigillata and shouldthereforeuse effectivecontraceptionduringtreatmentwith Pemetrexed Sigillata and forup to 6 monthsafterwards. Ifyou would liketo fathera childduringthetreatmentor inthe6 months followingreceiptoftreatment, seekadvicefromyourdoctoror pharmacist.Youmaywantto seek counsellingon spermstoragebeforestartingyour therapy.

Driving and usingmachines

Pemetrexed Sigillata may makeyou feeltired. Becarefulwhendrivinga carorusingmachines.

Pemetrexed Sigillata containssodium

One vial of 100 mgcontainsapproximately11.29 mgsodiumper vial.

One vial of 500 mg contains approximately 53.77 mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

One vial of 1000 mg contains approximately 107.54 mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

3. How tousePemetrexed Sigillata

/…/ powder for concentrate for solution for infusion will always be given to you by a healthcare professional.The doseof Pemetrexed Sigillata is500 milligramsfor everysquaremetreofyourbody’ssurfacearea. Your heightand weightaremeasuredto workout thesurfaceareaofyourbody. Yourdoctorwillusethis body surfaceareato workout therightdoseforyou.Thisdosemaybe adjusted, ortreatmentmaybe delayed dependingon yourbloodcellcountsand on yourgeneralcondition. A hospitalpharmacist, nurseor doctorwillhavemixedthePemetrexed Sigillata powderwith 9 mg/ml(0.9 %)sodiumchloridesolution forinjectionbeforeitis given to you.

You willalwaysreceivePemetrexed Sigillata byinfusion into oneof yourveins.Theinfusion willlast approximately10 minutes.

When usingPemetrexed Sigillata in combination withcisplatin:

Thedoctoror hospitalpharmacistwillworkout thedoseyou need based on yourheightand weight. Cisplatinisalso given by infusion intoone ofyourveins, and isgiven approximately30 minutesafter theinfusion of Pemetrexed Sigillata hasfinished.Theinfusionof cisplatin willlastapproximately2 hours.

You should usually receive your infusion once every 3 weeks.

Additional medicines:

Corticosteriods: your doctor will prescribe you steroid tablets (equivalent to 4 milligram of dexamethasone twice a day) that you will need to take on the day before, on the day of, and the day after Pemetrexed Sigillata treatment. This medicine is given to you to reduce the frequency and severity of skin reactions that you may experience during your anticancer treatment.

Vitamin supplementation:yourdoctorwillprescribeyou oralfolicacid(vitamin)or amultivitamin containingfolicacid (350 to 1000 micrograms)thatyou must takeonce aday whileyou aretaking Pemetrexed Sigillata. You musttakeat least5 dosesduringtheseven daysbeforethefirstdoseof Pemetrexed Sigillata. You mustcontinuetakingthefolicacid for21 daysafterthelastdoseofPemetrexed Sigillata. You willalsoreceive an injection ofvitamin B₁₂(1000 micrograms)in theweekbeforeadministration ofPemetrexed Sigillata and then approximatelyevery9 weeks(correspondingto3 coursesofPemetrexed Sigillata treatment).Vitamin B₁₂and folicacidaregiven to you to reducethepossibletoxiceffectsof theanticancertreatment.

Your condition will be closely monitored during treatment. This routinely involves blood tests, including checks on your liver and kidney function. Your dose may be changed or treatment delayed depending on results from these tests.

Ifyou haveany furtherquestionson theuse ofthismedicine, askyour doctororpharmacist.

4. Possiblesideeffects

Likeallmedicines,thismedicine can causesideeffects, although noteverybodygetsthem.

You mustcontactyourdoctorimmediatelyifyou noticeany ofthefollowing:

^Fe^v^er ^or ⁱⁿ^f^ec^tⁱ^on ⁽^co^mm^oⁿ⁾^: ⁱ^f ^y^{ou ha}^v^e ^a ^t^e^m^pe^r^a^t^u^r^e ^of ³⁸^º^C ^o^r ^g^r^ea^t^e^r^, ^s^w^e^a^tⁱ^ng ^or ^o^t^h^e^r signs of infection(since you might have less white blood cells than normal which is very common). Infection (sepsis) may be severe and could lead to death.
If you start feeling chest pain (common) or having a fast heart rate (uncommon).
If you have pain, redness, swelling or sores in your mouth (very common).
Allergic reaction: if you develop skin rash (very common) / burning or prickling sensation (common), or fever (common). Rarely, skin reactions may be severe and could lead to death. Contact your doctor if you get a severe rash, or itching, or blistering (Stevens-Johnson Syndrome or Toxic epidermal necrolysis).
If you experience tiredness, feeling faint, becoming easily breathless or if you look pale (since you might have less haemoglobin than normal which is very common).
If you experience bleeding from the gums, nose or mouth or any bleeding that would not stop, reddish or pinkish urine, unexpected bruising (since you might have less platelets than normal which is very common).
If you experience sudden breathlessness, intense chest pain or cough with bloody sputum (uncommon)(may indicate a blood clot in the blood vessels of the lungs)

Other sideeffectswith Pemetrexed Sigillatamayinclude:

Verycommon(may affect more than 1 in 10 people)

Lowwhiteblood cells

Lowhaemoglobin level(anaemia)

Lowplateletcount

Diarrhoea

Vomiting

Pain,redness,swellingorsoresin yourmouth

Nausea

Lossofappetite

Fatigue(tiredness)

Skin rash, peeling of the skin

Hairloss

Constipation

Lossofsensation

Kidney:abnormalblood tests

Common(may affect up to 1 in 10 people)

Allergicreaction:skinrash/burningorpricklingsensation

Infectionincludingsepsis

Fever

Dehydration

Kidneyfailure

Irritation oftheskinanditching

Hives

Chestpain

Muscleweakness

Conjunctivitis(inflamed eye)

Upsetstomach

Painin theabdomen

Tastechange

Liver:abnormalbloodtests

Wateryeyes

Dizziness

Uncommon (may affect up to 1 in 100 people)

Acuterenalfailure

Fastor irregular heartrate

Inflammation oftheliningoftheoesophagus(gullet)hasbeen experienced with Pemetrexed Sigillata/radiation therapy

Colitis(inflammation oftheliningofthelargebowel,which maybeaccompaniedbyintestinalor rectalbleeding)

Interstitialpneumonitis(scarringoftheairsacsofthelung)

Oedema(excess fluid in bodytissue, causingswelling)

Somepatientshaveexperienced aheart attack, strokeor“mini-stroke”whilereceivingPemetrexed Sigillata usuallyin combinationwith another anticancertherapy

Pancytopenia-combined lowcountsofwhitecells, redcellsand platelets

Radiation pneumonitis(scarringoftheairsacsofthelungassociated withradiation therapy)may occurin patientswhoarealso treated withradiation eitherbefore, duringoraftertheirPemetrexed Sigillata therapy.

Extremitypain, lowtemperatureand discolouration havebeen reported.

Blood clotsin thelungblood vessels(pulmonaryembolism)

Rare (may affect up to 1 in 1,000 people)

Radiation recall(askinrash likeseveresunburn)which can occuron skinthathaspreviouslybeen exposed toradiotherapy, fromdaysto yearsaftertheradiation.

Bullousconditions(blisteringskin diseases)-includingStevens-Johnson syndromeandToxic epidermalnecrolysis

Immune mediated haemolyticanaemia(antibody-mediated destruction ofred bloodcells)

Hepatitis(inflammation oftheliver)

Anaphylacticshock(severeallergicreaction)

Reporting of side effects

Ifyou getanysideeffects, talkto yourdoctororpharmacist.Thisincludesanypossiblesideeffects notlistedintheleaflet. You can also report side effects directly via <[To be completed nationally]>. By reporting side effects you can help provide more information on the safety of this medicine.

5. How tostorePemetrexed Sigillata

Keep this medicine outofthesight and reach ofchildren.

Do notusethis medicine aftertheexpirydatewhich is stated on the label and carton after ‘EXP’. The expiry date refers to the last day of that month.

Keep the vial in the outer carton in order to protect from light.

This medicinal product does not require any special temperature storage conditions.

Reconstituted and infusionsolutions

When prepared as directed,reconstituted and infusionsolutionsofPemetrexed Sigillata contain no antimicrobial preservatives. Chemical and physical in-use stability of reconstituted and infusion solutions of pemetrexed were demonstrated for 3 days at room temperature at normal lighting conditions and 14 days at refrigerated temperature (2-8°C). Froma microbiologicalpoint of view, theproductshouldbe used immediately. Ifnot used immediately, in-usestoragetimesand conditionspriorto usearetheresponsibilityof theuserand would notbe longerthan 24 hoursat 2°C to 8°C, unless reconstitution / dilution has taken place in controlled and validated aseptic conditions.

/…/ should not been used if there are any signs of particles.

Thismedicineisforsingleuseonly;anyunused solution mustbedisposed ofinaccordancewith local requirement.

6. Contents of thepackandotherinformation

What Pemetrexed Sigillata contains

Theactivesubstanceispemetrexed.

/…/ 100 mg: Each vialcontains100 milligramsofpemetrexed(aspemetrexed disodium hemipentahydrate).

/…/ 500 mg: Each vialcontains500 milligramsofpemetrexed(aspemetrexed disodium hemipentahydrate).

/…/ 1000 mg: Each vialcontains1000 milligramofpemetrexed(aspemetrexed disodium hemipentahydrate).

After reconstitution, the solution contains 25 mg/ml of pemetrexed. Furtherdilution byahealthcare providerisrequired priortoadministration.

Theotheringredientsaremannitol,hydrochloricacid and sodiumhydroxide.

WhatPemetrexed Sigillata lookslikeand contentsofthepack

Pemetrexed Sigillata isapowderforconcentrateforsolutionforinfusionin avial. Itisawhiteto eitheryellow or greenish-yellow lyophilisate powder.

/…/ is in colourless glass vials (type I) with type I rubber (bromobutyl) lyo-stopper and an aluminium cap with polypropylene disk. <Vials are sheathed in protective sleeve.>

Each packofPemetrexed Sigillata consistsofonePemetrexed Sigillata vial.

Not all pack sizes may be marketed.

MarketingAuthorisationHolder

[To be completed nationally]

{Name and address}

<{tel}>

<{fax}>

<{e-mail}>

Manufacturer

S.C. SINDAN-PHARMA S.R.L.

11^thIon Mihalache Boulevard

011171, Bucharest 1

Romania

This medicinal product is authorised in the Member States of the EEA under the following names:

[To be completed nationally]

This leaflet was last revised in

15 March 2016

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_I_ns_tr_uc_t_i_ons_f_or_use,_han_d_l_i_ng_and
d_i_sp_o_s_a_l_.

1. Useaseptictechniquesduringthereconstitutionandfurtherdilution ofpemetrexed for intravenousinfusion administration.

2. Calculate the dose and the number of Pemetrexed Sigillata vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the label amount.

3. Reconstitute 100 mg vials with 4.2 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed.

Reconstitute 500 mg vials with 20 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed.

Reconstitute 1000 mg vials with 40 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed.

Gentlyswirleach vialuntilthepowderiscompletelydissolved.Theresultingsolution isclear and rangesincolourfromcolourlessto yelloworgreen-yellowwithoutadverselyaffecting productquality.ThepHofthereconstituted solutionisbetween 6.6and 7.8.Furtherdilutionis required.

4. The appropriate volume of reconstituted pemetrexed solution must be further diluted to 100 ml with 9 mg/ml (0.9 %) sodium chloride solution for injection, without preservative, and administered as an intravenous infusion over 10 minutes.

5. Pemetrexed infusion solutions prepared as directed above are compatible with polyvinyl chloride and polyolefin lined administration sets and infusion bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer’s Injection and Ringer’s Injection.

6. Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, do not administer.

7. Pemetrexed solutions are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

Preparationand administration precautions: Aswith otherpotentiallytoxicanticanceragents, careshould beexercised inthehandlingand preparation ofpemetrexedinfusion solutions.Theuseof glovesisrecommended. Ifapemetrexed solutioncontactstheskin, wash theskinimmediatelyand thoroughlywith soap andwater. Ifpemetrexed solutionscontactthemucousmembranes, flush thoroughlywith water. Pemetrexedisnotavesicant.Thereisnotaspecificantidoteforextravasation ofpemetrexed.Therehavebeen afewreported casesofpemetrexed extravasation,which werenot assessedasseriousbytheinvestigator. Extravasation should bemanaged bylocalstandardpracticeas with othernon-vesicants.