Document: Bivalirudin Reig Jofre powder for concentrate for solution for injection or infusion ENG PL change

• Bivalirudin Reig Jofre Powder for concentrate for solution for injection or infusion PL
• Bivalirudin Reig Jofre powder for concentrate for solution for injection or infusion ENG PL

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Package leaflet: Information for the user

Bivalirudin Reig Jofre 250 mg powder for concentrate for solution for injection or infusion

Bivalirudin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

- Keep this leaflet. You may need to read it again.

- If you have further questions, ask your doctor.

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Bivalirudin Reig Jofre is and what it is used for

2. What you need to know before you use Bivalirudin Reig Jofre

3. How to use Bivalirudin Reig Jofre

4. Possible side effects

5. How to store Bivalirudin Reig Jofre

6. Contents of the pack and other information

Bivalirudin Reig Jofre contains a substance called bivalirudin which is an antithrombotic medicine. Antithrombotics are medicines which prevent the formation of blood clots (thrombosis).

Bivalirudin Reig Jofre is used to treat patients:

• with chest pain due to heart disease (acute coronary syndrome - ACS)

• who are having surgery to treat blockages in their blood vessels (angioplasty and/or percutaneous coronary intervention - PCI).

Do not use Bivalirudin Reig Jofre

• if you are allergic to bivalirudin or any of the other ingredients of this medicine (listed in section 6) or hirudins (other blood thinning medicines).

• if you have, or have recently had, any bleeding from your stomach, intestines, bladder or other organs, for example, if you have noticed abnormal blood in your stools or urine (except from menstrual bleeding).

• if you have, or have had, difficulty with your blood clotting (a low platelet count).

• if you have severe high blood pressure.

• if you have an infection of the heart tissue.

• if you have severe kidney problems or if you need kidney dialysis.

Check with the doctor if you are unsure.

Warnings and precautions

Talk to your doctor before using Bivalirudin Reig Jofre.

• if bleeding occurs (if this happens, treatment with Bivalirudin Reig Jofre will be stopped). Throughout your treatment, the doctor will check you for any signs of bleeding.

• if you have been treated before with medicines similar to Bivalirudin Reig Jofre (e.g. lepirudin).

• before the start of the injection or infusion, the doctor will tell you about the signs of allergic reaction. Such a reaction is uncommon (affects 1 to 10 users in 1,000).

• if you are having radiation treatment in the vessels that supply blood to the heart (treatment called beta or gamma brachytherapy).

After being treated with Bivalirudin Reig Jofre for a cardiac event, you should stay in the hospital for at least 24 hours and you should be monitored for any symptoms or signs similar to the ones that remind you of your cardiac event and resulted in your hospitalization.

Children and adolescents

• if you are a child (less than 18 years of age), this medicine is not appropriate for you.

Other medicines and Bivalirudin Reig Jofre

Tell your doctor

• if you are taking, have recently taken, or might take any other medicines.

• if you are taking blood thinners or medicines to prevent blood clots(anticoagulants or antithrombotics,e.g. warfarin, dabigatran, apixaban, rivaroxaban, acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor).

These medicines may increase the risk of side effects such as bleeding when given at the same time as Bivalirudin Reig Jofre. Your warfarin blood test result (INR test) may be affected by Bivalirudin Reig Jofre.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Bivalirudin Reig Jofre should not be used during pregnancy, unless clearly necessary. Your doctor will decide whether or not this treatment is appropriate for you. If you are breast-feeding, the doctor will decide whether Bivalirudin Reig Jofre should be used.

Driving and using machines

The effects of this medicine are known to be short-term. Bivalirudin Reig Jofre is only given when a patient is in hospital. It is, therefore, unlikely to affect your ability to drive or to use machines.

Bivalirudin Reig Jofrecontains sodium

This medicine contains less than 23 mg of sodium per vial, which means that it is essentially “sodium free”.

Your treatment with Bivalirudin Reig Jofre will be supervised by a doctor. The doctor will decide how much Bivalirudin Reig Jofre you receive, and will prepare the medicine.

The dose given depends on your weight and on the kind of treatment you are being given.

Dosage

For patients with acute coronary syndrome (ACS) who are treated medically the recommended starting dose is:

• 0.1 mg/kgbody weight as an intravenous injection, followed by an infusion (drip) into vein of 0.25 mg/kgbody weight per hour for up to 72 hours.

If, after this, youthen need percutaneous coronary intervention (PCI) treatment, the dosage will be increased to:

• 0.5 mg/kgbody weight for the intravenous injection, followed by an infusion into vein of 1.75 mg/kgbody weight, per hour for at least the duration of the PCI. This intravenous infusion may continue for up to 4 hours.

• When this treatment is finished, the infusion may go back to 0.25 mg/kg body weight per hour.

If you need to have a coronary artery bypass graft operation, treatment with bivalirudin will either be stopped one hour before the operation or an additional dose of 0.5 mg/kg body weight will be given by injection followed by an infusion of 1.75 mg/kg body weight per hour.

For patients starting with percutaneous coronary intervention (PCI) the recommended dose is:

• 0.75 mg/kg body weight as an injection, followed immediately by an infusion of 1.75 mg/kg body weight, per hour (the intravenous infusion may continue for up to 4 hours).

If you have kidney problems, the dose of Bivalirudin Reig Jofre may need to be reduced.

In older people, if their kidney function is decreased, the dose may need to be reduced.

The doctor will decide for how long you should be treated.

Bivalirudin Reig Jofre is for injection, followed by infusion (drip), into a vein (never into a muscle). This is administered and supervised by a doctor experienced in caring for patients with heart disease.

If you receive more of this medicine than you should

Your doctor will decide how to treat you, including stopping the drug and monitoring for signs of ill effects.

If you have any further questions on the use of this medicine, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you get any of the following, potentially serious, side effects:

• while you are in hospital: tell the doctor or nurse immediately

• after you’ve left hospital: contact your doctor directly or go immediately to the Emergency Department of your nearest hospital

The most common, (may affect up to 1 in 10 people) serious side effect of treatment with Bivalirudin Reig Jofre is major bleeding, which could occur anywhere inside the body (e.g. stomach, digestive system (including vomiting blood or passing blood with the stools), abdomen, lungs, groin, bladder, heart, eye, ear, nose or brain). This may, rarely, result in a stroke or be fatal. Swelling or pain in the groin or the arm, back pain, bruising, headache, coughing blood, pink or red urine, sweating, feeling faint or sick or dizzy due to low blood pressure may be signs of internal bleeding. Bleeding is more likely to occur when Bivalirudin Reig Jofre is used in combination with other anticoagulant or antithrombotic medicines (see section 2 ‘Taking other medicines’).

If you get any of the following, (potentially less serious), side effects:

• while you are in hospital: tell the doctor or nurse

• after you’ve left hospital: first seek advice from your doctor. If you cannot get access to your doctor, go immediately to the Emergency Department of your nearest hospital

Verycommon side effects (may affect more than 1 in 10 people):

Common side effects (may affect up to 1 in 10 people):

• Anaemia (a low blood cell count)

• Haematoma (bruising)

Uncommon side effects (may affect up to 1 in 100 people):

- Nausea (feeling sick) and/or vomiting (being sick)

Rare side effects (may affect up to 1 in 1000 people):

• INR test (warfarin blood test result) increased (see Section 2, Other medicines and Bivalirudin Reig Jofre)

• Angina or chest pain

• Slow heartbeat

• Rapid heartbeat

• Shortness of breath

• Reperfusion injury (no or slow reflow): impaired flow in the heart arteries after they have been reopened

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V.

By reporting side effects you can help provide more information on the safety of this medicine.

AsBivalirudin Reig Jofre isa hospitalonly medicine,storageofBivalirudin Reig Jofre istheresponsibilityof healthcareprofessionals.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after ‘EXP’. The expiry date refers to the last day of that month.

Freeze-dried powder: This medicinal product does not require any special storage conditions

Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8ºC. Store in a refrigerator (2ºC-8ºC). Do not freeze.

Diluted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25ºC. Do not store above 25ºC. Do not freeze.

‘From a microbiological point of view, unless the method of opening/ reconstitution/ dilution precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of user.’

The solution should be a clear to slightly opalescent, colourless to slightly yellow solution.

The doctor will check the solution and will discard it, if it contains particles or is discoloured.

What Bivalirudin Reig Jofre contains

• The active substance is bivalirudin.

• Each vial contains 250 mg bivalirudin.

• After reconstitution (addition of 5 ml water for injections to the vial to dissolve the powder), 1 ml contains 50 mg bivalirudin.

• After dilution (mixing 5 ml of the reconstituted solution into an infusion bag [total volume of 50 ml] of glucose solution or sodium chloride solution), 1 ml contains 5 mg bivalirudin. The other ingredients are mannitol and sodium hydroxide (for pH adjustment).

What Bivalirudin Reig Jofre looks like and contents of the pack

Bivalirudin Reig Jofre is a powder for concentrate for solution for injection or infusion (powder for concentrate).

Bivalirudin Reig Jofre is a white to off-white powder in a glass vial.

Bivalirudin Reig Jofre is available in cartons containing 2 or 10 vials.

Marketing Authorisation Holder and Manufacturer

[to be completed nationally]

Marketing Authorisation Holder

[to be completed nationally]

Manufacturer

[to be completed nationally]

Forany information aboutthis medicine, pleasecontactthe localrepresentative ofthe MarketingAuthorisation Holder:

[to be completed nationally]

This leaflet was last revised in 12 January 2016

Detailed information on this medicinal product is available on the website of {name of MS/Agency}

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The followinginformationis intendedfor healthcare professionals only:

Healthcare professionalsshouldreferto the Summary of ProductCharacteristics forfullprescribinginformation.

Bivalirudin Reig Jofre isindicated as an anticoagulantin adultpatients undergoingpercutaneouscoronaryintervention(PCI), includingpatients with ST-segmentelevation myocardialinfarction (STEMI)undergoingprimaryPCI.

Bivalirudin Reig Jofre is alsoindicatedforthe treatmentofadultpatients with unstable angina/non-STsegmentelevation myocardialinfarction(UA/NSTEMI)planned forurgentorearlyintervention.

Bivalirudin Reig Jofre should beadministered withacetylsalicylicacidand clopidogrel.

Instructionsfor preparation

Aseptic procedures shouldbe used forthe preparationand administration ofBivalirudin Reig Jofre.

Add 5 mlsterile waterfor injectionsto one vialofBivalirudin Reig Jofre and swirlgentlyuntilcompletelydissolvedand the solutionis clear.

Withdraw 5 mlfrom the vial, and furtherdilute ina totalvolume of5%50 mlof glucose solution forinjection,or sodiumchloride 9 mg/ml(0.9%) solutionfor injectionto give a finalbivalirudinconcentration of5 mg/ml.

The reconstituted/diluted solution should be inspectedvisuallyfor particulate matteranddiscolouration. Solutionscontainingparticulate mattershould notbe used.

The reconstituted/diluted solution willbe a clearto slightlyopalescent, colourlessto slightlyyellow solution.

Anyunused productor waste materialshould be disposed ofin accordance withlocalrequirements.

Incompatibilities

The followingmedicinalproducts should not be administered inthe same intravenous lineas bivalirudin sincetheyresultin hazeformation, micro-particulateformation orgross precipitation;alteplase,amiodarone HCl,amphotericin B,chlorpromazine hydrochloride(HCl),diazepam,prochlorperazine edisylate,reteplase,streptokinase andvancomycin HCl.

The followingsix medicinalproducts show dose-concentration incompatibilities with bivalirudin. See section6.2 forthe summaryof compatible and incompatible concentrations ofthese compounds. Themedicinalproductsincompatible withbivalirudinat higherconcentrations are:dobutaminehydrochloride, famotidine,haloperidollactate,labetalolhydrochloride,lorazepamand promethazineHCl.

Contraindications

Bivalirudin Reig Jofre is contraindicatedin patients with:

• a known hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or to hirudins

• active bleeding or increased risk of bleeding because of haemostasis disorders and/or irreversible coagulation disorders

• severe uncontrolled hypertension

• subacute bacterial endocarditis

• severe renal impairment (GFR<30 ml/min) and in dialysis-dependent patients. (See section 4.3 of SmPC).

Posology

PatientsundergoingPCI,includingprimaryPCI

The recommended dose ofbivalirudin forpatients undergoingPCI is an intravenous bolus of

0.75 mg/kgbody weightfollowedimmediatelyby an intravenous infusionat a rateof 1.75 mg/kgbody weight/hourforatleastthe duration of theprocedure.The infusionof 1.75mg/kgbody

weight/hourmaybe continued forup to 4 hours post-PCIas clinicallywarrantedand furthercontinuedat areducedinfusion doseof 0.25 mg/kg/h for 4-12hours as clinicallynecessary.

Patients shouldbe carefullymonitoredfollowingprimaryPCI forsigns and symptoms consistentwith myocardialischaemia.

Patientswithunstableangina/non-ST segmentelevatedmyocardialinfarction(UA/NSTEMI)

The recommended startingdose ofbivalirudin forpatients withacute coronarysyndrome (ACS)is anintravenousbolus of0.1 mg/kgfollowed by aninfusion of0.25 mg/kg/h. Patientswho areto bemedicallymanaged maycontinue theinfusion of0.25mg/kg/h forup to 72 hours.

Ifthe patientproceeds to PCI, an additionalbolus of0.5 mg/kgof bivalirudin should beadministeredbeforethe procedure andthe infusionincreased to 1.75 mg/kg/h for the durationof the procedure.

FollowingPCI, the reducedinfusion dose of 0.25 mg/kg/h maybe resumed for4 to 12 hours asclinicallynecessary.

Forpatients who proceed tocoronaryarterybypass graft(CABG)surgeryoffpump, theintravenousinfusion ofbivalirudin should be continued untilthetime of surgery. Just priorto surgery, a 0.5 mg/kgbolus doseshould be administered followed by a 1.75mg/kg/h intravenous infusion forthe duration ofthe surgery.

Forpatients who proceed toCABG surgeryon pump, the intravenous infusionof bivalirudin shouldbe continueduntil1 hourpriorto surgeryafterwhichthe infusion should be discontinued and thepatient treated with unfractionatedheparin(UFH).

Toensure appropriate administration ofbivalirudin,the completelydissolved, reconstitutedand dilutedproductshould be thoroughlymixed priorto administration(see section 6.6).The bolus dose should be administered bya rapidintravenouspush toensure thatthe entire bolusreachesthe patientbeforethe startof the procedure.

Intravenous infusion lines should be primed with bivalirudinto ensure continuityofdrug infusion afterdeliveryofthe bolus.

The infusion doseshould be initiatedimmediatelyafterthe bolus doseis administered,ensuringdeliveryto the patientpriorto the procedure, and continued uninterruptedfor theduration ofthe procedure.The safetyand efficacyof a bolus dose ofbivalirudin withoutthe subsequentinfusion has not been evaluated andis notrecommended even ifa shortPCIprocedureis planned.

An increase in the activatedclottingtime (ACT)maybe usedas an indicationthata patienthasreceived bivalirudin.

Renalinsufficiency

Bivalirudin Reig Jofre is contraindicatedin patients withsevererenalinsufficiency(GFR<30 ml/min)and alsoin dialysis-dependentpatients(see section 4.3).

In patients with mild ormoderaterenalinsufficiency, the ACS dose(0.1 mg/kgbolus/0.25 mg/kg/hinfusion)should notbe adjusted.

Patients with moderate renalimpairment(GFR 30-59 ml/min)undergoingPCI(whether beingtreatedwith bivalirudin forACS ornot) shouldreceive a lowerinfusion rateof 1.4 mg/kg/h. The bolus doseshould notbe changed fromthe posologydescribed underACS orPCIabove.

Hepaticimpairment

No dose adjustmentis needed.

(Forfullinformation on posologysee section 4.2of SmPC)

Shelflife

30 months

Reconstituted solution:Chemicaland physicalin-use stabilityhas been demonstrated for24 hoursat 2-8ºC. Store in arefrigerator (2ºC –8ºC). Do not freeze.

Diluted solution:Chemicaland physicalin-use stabilityhas been demonstratedfor24 hoursat 25ºC.Do notstore above 25ºC. Do notfreeze.

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in use storage times and conditions are the responsibility of user.