PACKAGE LEAFLET: INFORMATION FOR TIE USER

HEPARIN SODIUM 1,0001.U./ml solution for injection or concenlraAe for soluljon for illusion

Read al of this leaflet careMly before you start taking thtamedciie.

-    Keepthis leafleL\t>u mayneedto read itagain.

-    Ifyouhaveanyfurtherquestions, pleaseaskyourdoctor or nurse.

-    Unis medicjne has been prescribed foryou. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

The name of yoir medicine is heparin sodium 1,000I.U/ml solutionlbrinjecAionorconcentiHlBltrsolLitionlbrinfiJSion. In the rest of this leaflet it is called heparti injection.

ki this leaflet

1.    What heparti injection is and what it is used for

2.    Before you am given heparin injection

3.    How heparin injection is given

4.    Possible side effects

5.    Howto store heparin injection

6.    Further information

Taking other meddnes

It is very important that you inform your doctor if you are taking, or have recently taken, any other medicines, including those medicines obtained without a prescription, as some medicines may affect the way heparin injection works. Taking some medicines at the same time as heparin may mean you may be likely to bleed more.

In particular, tell you^- doctor if you are taking any of the following:

•    aspirin or other non-steroidal anti-infiammatbry drugs (e.g diclofenac or ibuprofen)

•    dexbran solutions (used to treat shod^

•    medidneswhichmayinterierewiththeproperctotbngofthe blood (e.g. dpyridamole, epoprostenol, dopidogrel or streptokinase)

•    cephalosporns, used to treat infections

•    medicines called ACE inhibitors used for h|gh blood pressure and heart failure (e.g. captopril, enalapril, lisinopril or ramapril)

•    medicines that may increase the potassium level in you^-blood (e.g. amiloride, triamterene, eplerenone or spironolactone

•    glyceryl trinitrate given into a vein (for coronary heart disuse)

•    aminoglycoside antibiotics (e.g. gentamicin, amikacin, neomycin or tobramycin)

•    probenecid, used inthetreatmentof gout

1.WHAT ffiVRIN ELECTION IS AID WHAT TTB USB) FOR

Heparin betongstoagraup of drugs that are called anti-coagulants. These help to stop blood dotting. Heparin injection is used in concftions where blood vessels may become blocked by blood dots. It is therefore used to treat

•    blood dots in leg veins (deep vein thrombosis)

•    blooddotsinthelLiig(pulmonaryembdism)aswellasfor

•    thetreatmentofchestpainsresultiigffomdiseaseofthe heart arteries (irstable angina pectoris)

•    the treatment of severe blockages affecting arteries in the legs (acute peripheral arterial ocduskm)

It is also used during heart and lung operations and during kktoey dialysis.

If you need one of the above medidnes your doctor may dedde to alter the dose of heparin injection or the other medication. If you have any doubts about whether this medidne should be administered then discuss things more tolly with yar doctor or nurse before it is given.

Tobacco smoke can also interfere with the working of heparin injection. Vbu should inform your doctor if you smoke.

The presence of heparin in the blood can affect the results of some blood tests such as thyroid tests and the levels of caldum or some antibiotics (e.g. gentamicin) in the blood.

Pregnancy and breast-feeding

Vbu should let your doctor or nurse know before you are given heparin injection if you are pregiant or wish to become pregnant

2 BBDRE YOU ARE GIVEN HEPARIN INJECTION

Heparin tojedton should not be gven if you:

•    are allergic to heparin or any of the other ingredients in your medidne, (see "What heparin injection contains’ section 6)

•    dink large amomts of alcohol

•    are cnrently bleeding from anywhere in the body, (apartfrom your normal periods which does not stop you being given heparin injection)

•    havehaemophiliafageneticdisorderwhichmaycauseyou to bleed excessively) or any other bleeding problem

•    have or have ever had thrombocytopenia (a serious blood disorder which prevents blood Horn dotting property

•    bruise easily (fragile capillaries) or have lots of purple spots that look like bruises (pupua)

•    have very high blood pressure

•    are suffering from tuberculosis (IB)

•    have had severe skin problems resulting from previous heparin treatment

•    areabouttohavesugeryofthebrain,spineoreye,alumbar puncture or local anaesthetic nerve block, or some cither procedure where bleeding could be a problem

•    have recently had an operation

•    sufferfrom severe liver problems which can lead to bleeding into the oesophagus (guile?

•    have bleeding into the brain.

If you are being given heparin injection bleeding may be a problem during pregnancy or after delivery. Vbur bones may get thinner if you receive heparin tor a long time during pregnancy.

Askyour doctor or nurse tor advice if you wish to breast-feed.

Driving and usiig machines

Heparin injection has not been reported to affect ability to drive or operate machines.

a HOW HERARIN INJECTION SHOULD BE GIVEN

Vbur doctor or nurse will inject your dose of heparin into a vein either all at once or over a longer period of time (usually via a drip).

Vbu may need to have blood tests if you are receiving higher doses of heparin or if you are pregnantto check on the effects of your heparin treatment

Vbu may require a lower dose if you have kidney or liver disease.

To TTEAT blood dots in leg veins (deep vein thrombosis), blood dots in the ling, (pdmonary embolism), chest pains (instable angtoa pectoris) and severe blood dots to the arteries (acute pertoheral arterial ocdusion)

Speak to yar doctor before heparin injection is given If you:

•    areover60yearsofage

•    have any condition which makes you Ikely to bleed more easily (tor example a stomach ulcer, hiatus hernia, inflammation of the heart, problems in the back of your eye, haemorrhoids (piles), aslroke, cancer or threatened miscarriage). Ifyouareunsure,askyourdoctorornurse.

•    suffer from dabetes

•    sufferfrom excess acid or high levels of potassium in your blood or are taking a medicine that may hcrease the potassium level in your blood (e.g. amiloride, triamterene, eplerenone or spironolactone). Ifanyaftheseappiyyoumay need to have a blood test before the start of you^- heparin treatment If you are unsue, ask your doctor or nurse

•    have kidney or liver disease. Vbur doctor may decide that a lower dose is necessary

•    sufferfrom allergies or have previously had an allergic reaction to low molecular weight (LMW) heparin. Asmall test dose of heparin sodium injection rrcy be given first

Vbur doctor will check your blood if you receive treatment tor

longer than five days and may do other blood tests if you have

major surgery.

Vbur doctor will take particular care if:

•    youhaveanepiduralorananaeslheticgivenintothespine.

Addts

The usual dose in adults is 5,000 units injected into a vein. This is followed by:

•    1,000-2,000 units/hour injected slowly into a vein

or

•    5,000-10,000 units 4 hourly injected all at once into a vein Bderty

Lower doses may be used in the elderly Small adults and chicken

Small adults and children will be given 50mits/kg body weight injected into a vein followed by:

•    15-25 units/kg body weight/hour injected slowiy into a vein

or

•    100 units/kg body weight 4 honly injected all at once into a vein

Vbu will have blood tests every day to check the effects of your heparin

Divhg heart and luig sugery (AtUts)

Initially you will be given 300 units per kg body weight This will be chaiged according to the results of your blood tests.

Duiig kkhey dialysis (Adtals)

Initially you will be given 1 -5,000 inits per hcnr. Thiswill be changed according to the results of your blood tests.

ti you think you have been cjven too much heparin injection

Vbur doctor will decide which dose is best for you. Toomuch heparin can cause bleeding. Slight bleeding can be stopped by stopping your heparin treatment However if you have more severe bleeding you may need blood tests and an rijection of a medicine called protamine sulphate. Ifyouthinktoomuch medicine has been given toyou contact you^- doctor or nurse.

4 POSSIBLE SIDE BFECTS

Like all medcres, heparin injection may cause side effects in some patients although not everybody gets them. These are most likely to occur when treatment is first started. Vbu should inform your doctor or nurse immediately if you feel unwell.

tmportant side effects to look out for

•    Severe alergic reactions

Heparin can cause a severe allergic reaction with wheezing, difficulty breathing, a blue tinge to the I ps, swelling of the eyes and lips or shock

If you thinkyou are havtag a severe allergic reaction (see symptoms above) you must tel yoir doctor or nuse immedately

•    BleerSngandBnising

Heparin injection can reduce the number of cells that help your blood dot (thrombocytopenia) and so can cause bleeding and bruising. This is most likely to occur within the first tew days of treatment but may occur later too. The risk of bleeding is increased in the elderly (particularly elderly women).

Signs that you are bleeding more easily indude:

•    unusual bruising or purple spots on your skin

•    unusual bleeding from your gums

•    unusual nose bleeds

•    blood inyariiinefwhichmaycauselhistogodari^

•    blacktarry looking stools

•    bleedingthatwillnotstopfromanyoperationsiteor other injuy

If you are concerned about musual WeetSig you must tell yar doctor or nuse immedately as you may need to stop you heparin.

Other side effects hdude:

Rare side effects (affects 1 to 10 users in 10,000):

•    raised levels of potassium in the blood, particularly in patients with kidney failure or diabetes. If affected you mayfeel fired and weak

•    allergc reactions incfuding an itchy skri rash, eye irritation, ninny nose, wheezing, rapid breathing, a blue tinge to the lips, fever, chills, swelling of the eyes and lips, and shock

•    irritation orstougfriingof skin mayoccuraroindthe injection site.

Side effects with mknown frequency:

•    loss of hair (alopecia) if heparin sodium rijection is given over many months

•    weakening of the bones (osteoporosis) if heparin sodium injection is given over many months

•    persistent erection of the penis (priapism)

•    abnormal liver tests

•    the amomt of a hormone called aldosterone may be lower than normal. Vbur doctor can explain this more.

•    high lipid levels on stopping heparin

If any of the side effects gels serious or you notice any side effects not listed in this leaflet, please tell you doctor, or nurse.

Medicines should not be disposed of via wastewater or household waste. Askyour pharmacist howto dispose of medcines no longer requrelThese measures will help to protect the environment

What heparin injection contains

The active substance is heparin sodium.

1 ml of solution of heparin sodium injection 1,000I.U/ml contains 1,000 international units of the active ingredient

Other ingredients include water tor injections, hydrochloric acid and sodium hydroxide.

Presentations avalabie to the UK

Heparin injection is available in ampoules contatoing 1,0001.U. in 1 ml of solution, 5,0001.U. in 5ml of solution, 10,0001.U. in 10ml of solution and 20,0001.U. in 20ml of solution.

Presentations avalabie to beland

Heparin injection is available in ampoules contaiiing 5,0001.U. in 5ml of solution and 10,0001.U. in 10ml of solution.

What heparin injection looks Ike and contents of the pack

Heparin injection is a colourless or straw-ooloured liquid.

Each carton contains 10 glass ampoules.

Other formats

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge:

06001965000 (UK Only)

Please be ready to give the following information:

This is a service provided by the Royal National Institute of Blind People.

Marketing Authorisation Hokler and Manufactuer

Marketing Authorisation Holder Vffackhardt UK Lid, Ash Road North, Wrexham, LL13 9UE UK.

Manufacturer CP Pharmaceuticals Lid, Ash Road North, Wrexham, 1113 9UFi UK

This leaflet was revised April 2006.

5l HOW TO STORE mARVI INJECTION

Keepthis medicine out of the reach and sight of children.

Vbur doctor or nurse will usually be responsible ter storing and preparing heparin injection before use and tor checking that the vials have not passed their expiry date stated on the carton and the label. The medicine must not be used afterthe expiry date which is slated on the carton and the labeLThe expiry date refers to the last day of the month.

Heparin tojectionshodd not be given if it shows signs of deterioration such as dscoiouration.

Do not store above 25°C. Store in the original packaging in order to protectthe product from light

After opening, heparin ampoules must be used immediately. Any porfionofthecontentsnotusedatonceshouldbediscarded.

'7WOCKHARDT

1. NAIVE OF THE MEDICINAL PRODUCT

Heparin sodium 1,0001.UAnl Solution tor injection or concentrate tor solution for infusion

2 QUALITATIVE AND QUANTTTAT1VE COM>OSmON

Heparin sodium 1,0001.U./ml

(5,0001.U. in 5ml, 10,0001.U in 10ml) (UKand Ireland)

(1,000 LUTml in 1 ml, 20,0001.U in 20ml) (UK only)

For a toll list of excipients, see section 6.1.

2 PHARMACEUTICAL FORM Solution for injection or concentrate for solution tor infusion A colourless or straw-coloured liqiid, free from turbidity and from matter that deposits onstancfng.

4. CUfACAL PARTICULARS 4.1 Therapeutic indications

Treatment of deep vein thrombosis, pulmonary embolism, unstable angina pectoris and acute perphetBl arterial occlusion.

In extracorporeal circulation and haemodialysis.

an actual or potential bleeding site eg. hiatus hernia, peptic ulcer, neoplasm, bacterial endocaidtis, retinopathy, bleeding haemorrhoids, suspected intracranial haemorrhage, cerebral thrombosis or threatened abortion.

Menstruation is not a conba-indication.

44 Special warnings and precautions for use

Platelet counts should be measured in patients receivfog heparin treatment for longer than 5 d^s and the treatment should be stopped immediately in those who develop thrombocytopenia In patients with advanced renal or hepadc disease, a reduction in dosage may be necessary. The risk of bleeding[is increased with severe renal impairment and in the elderly (particularly elderly women).

Although heparin hypersensitivity is rare, it is advisable to gve atrial dose of 1,0001.U. in patients with a history of allergy. Caution should be exercised in patients with known hypersensitivity to low molecular weigfrTt heparins.

42Posotogyand method of actonstration

Route of administration

By continuous totravenous infusion in 5% glucose or 0.9% sodum chloride or by intermittent intravenous injection.

As the effects of heparin are short-lived, administration by intravenous infusion is preferable to intermittent intravenous injections.

Recommended dosage

Treatment of deep vein thrombosis, pulmonary embolism, unstable angina pectoris, acute peripheral arterial occlusion:

AMs:

Loading dose:    5,000 unite intravenously (10,000 mits

may be required in severe pulmonary embolism)

Maintenance:    1,000-2,000 mits/hour by

intravenous illusion, or 5,000-10,000 mits 4-houly by intravenous rijection.

Bderty.

Dosage reduction may be advisable.

Chilcken and small adults:

Loading dose:    50units/kg ritravenously

Maintenance:    15-25 mits/kg/hoir by intravenous

infusion, or 100 unils/kg 4-honly by intravenous rijection

Daily laboratory monitoring (ideally at the same time each day, storting 4-6 hours after initiation of treatment) is essential during fiJI-dose heparti treatment with arfiustment of dosage to maintain an AFTT value 1.5-2.5 x midpoint of normal range or control value.

In extracorporeal crculation and haemodialysis AMs:

Cardiopulmonary bypass: Initially 300 units/kg intravenously, adjusted thereafter to maintain the activated dottaig time (ACT) in the range 400-500 seconds.

Haemodialysis

and haemofiltration:    Initially 1-5,000 unite,

Maintenance:    1-2,000 mits/hour, adjusted to

maintain clotting time >40 minutes.

Heparii resistance

Patients with altered heparti responsiveness or heparin resistance may require disproportionately higher doses of heparin to achieve the desired effect Also refertosectfon 4.4, Special wamhgs and precautions for use.

43 Contra ideations

Patients who consume large amourils of alcohol, who are sensitive to the drug, who are actively bieedtog or who have haemophilia or other bleeding disorders, severe liver disease (including oesophageal varices), pupua, severe hypertension, active tuberculosis or increased capillary permeability.

Merits with prepit or previous thrombocytopenia The rare occurrence of skh necrosis in patients receiving heparin contra-indicates the ftrther use of heparii either by subculaneous or intravenous routes because of the risk of thrombocytopenia.

Because of the special hazard of post-operative haemorrhage heparii is contra-iicfcated during surgery of the brain, spinal cord and eye, in procedures at sites where there is a risk of bleedng, ii patients that have had recent surgery, and in patients undergoing lumbar pmetue or regional anaesthetic block

The relative risks and benefits of heparin should be carefully assessed in patients with a bleeding tendency or those patients with

In most patients, the recommended low-dose regimen produces no alteration ii clotting time. However, paOents show an individual response to heparin, and it is therefore essential that the effect of theiapy on coagulation time should be monitored in patients mdergoing major surgery.

Caution is recommended in spinal or epidural anaesthesia (risk of spinal haematoma).

Heparii can sippress arterial secretion of aldosterone leading to hyperkalemia, particularty in patientssuchasthosewithciabetBS meilitus, chronic renal foilne, preexisting metabolic acidosis, a raised plasma potassium, ortaking potassium sparing drags. The risk of hyperkalemia appears to increase with diration of therapy but is usually reversible. Plasma potassium should be measured in paOents at risk before sterling heparin therapy and to all patients treated for more than 7 days.

Heparin res&ance

There is considerable variation in individual antfooagJant responses to heparto.

Heparti resistance, defined as an inadequate response to heparin at a standard dose for achieving a therapeutic goal occus in approximately 5 to 30% of paOents.

Factors predisposing to the development of heparin resistance, include:

■    Antithrombin III activity less than 60% of normal (antithrombin Ill-dependent heparin resistance):

Reduced antithrombin III activity may be heredtary or more commonly, acquired (secondary to preoperadve heparin therapy to the main, chronic liver disease, nephrotic syndrome, cardio-pdmonary bypass, low grade disseminated intravascular coagulation or drag induced, e.g. by aprotinin, oestrogen or possibly nitroglycerin)

■    (Merits with normal or stpranormal antithrombin III levels (antithrombin ll-todependent heparin resistance)

■    Thromboembolic disorders

■    Increased heparin clearance

■    Bevated levels of heparin binding proteins, foctorVII, von Willebrand factor, fibrinogen, platelet factor 4 or histidine-rich glycoprotein

■    Active infection (sepsis or endocarditis)

■    Preoperadve intra-aortic balloon counterpulsation •Thrombocytopenia

■Thrombocytosis ■Advanced age

■    Plasma albumin concentration < 35g/d

■    Relative hypovolaemia

Heparto resistance is also often encountered to acutely ill patients, to patients with malignancy and during pregnancy or the post-partum period.

45 Interaction with other medciial products and other forms of toteraefion

Analgesics: Drags that toterfere with platelet aggregation eg. aspirin and other NSAIDs, should be used with care. Increased risk of haemorrhage with ketorolac (avoid concomitant use even with low-dose heparin).

AnticoagiJants, platelet inhibitors, etc: Increased risk of bieedtog with oral anticoagulants, epoprostenol, dopidogrel, fidopidne, streptokinase, dipyridamole, dexlran solutions, or any other drag which may interfere with coagulation.

Cephalosporins:$ame cephalosporins, e.g. cefaclor, cefixime and ceftriaxone, can affect the coagulation process and may therefore increase the risk of haemorrhage when used conccrrently with heparin.

ACEiiiiitDrs:

Hyperkalaemia may occir with concomitant use.

Nitrates:

Reduced activity of heparin has been reported with simultaneous intravenous glyceryl trtoitrale infusion.

Probenecid:

May increase the anticoagulant effects of heparin.

Tobacco smoke: Nicotine may partially counteract the anticoagulant effect of heparto. tocreased heparto dosage may be requred in smokers.

Interference with diagnostic teste may be associated with pseudo-hypocatcaemia fin haemodialysis patients), artefoctual increases in total thyroxine and tritoddhyrorine, simulated metabolic acidosis and inhibition of the chromogenic lysate assay for endotoxin. Heparin may toterfere with the determination of aminoglycosides by immunoassays.

46    Pregnancy and lactation

Heparin is not contraindicated in pregnancy. Heparin does not cress the placenta or appear in breast milk The decision to use heparin to pregnancy should be taken after evaluation of the risk/benefit to any particular circumstances.

Reduced bone density has been reported with prelonged heparin treatment during pregnancy

Haemorrhage may be a problem during pregnancy or after delivery.

47    Effects on ability to rfrive and use machines None stated.

48    UndesteaHe effects

Haemorrhage (see also Special Warnings and Precautions and Overdosage Information).

Adrenal insufficiency secondary to adrenal haemorrhage has been associated with heparto (rarely).

Thrombocytopenia has been observed occasionally (see also Special Precautions and Wamtogs). Two types of heparin-induced thrombocytopenia have been defined. Type I is frequent mild (usually >50 x 10⁹/l) and transient, occurring within 1-5 days of heparin administration. Type II is less frequent but often associated with severe thrombocytopenia (usually <50 x10⁹A). It is immune-mediatedandoccureafteraweekormore (earlier in patients previously exposed to heparin). It is associated with the production of a platelet-aggregating antibody and thromboembolic complications which may precede the onset of thrombocytopenia Heparin should be discontinued immediately.

There is some evidence that prolonged dosing with heparin fie. over many months) may cause alopecia and osteojxxosis. Significant bone demineralisation has been reported in women taktog more than 10,0001.U. per day of heparin for at least 6 months.

Heparin products can cause hypoaldosteronism which may result in an increase to plasma potassium. Rarely, dtoically significant hyperkalemia may occur particularly in pkierte with chronic renal failure and diabetes meilitus (see Wamtogs and Precautions).

Hypersensitivity reactions to heparin are rare. They include urticaria, conjunctivitis, rhinitis, asthma, cyanosis, fachypnoea, feeling of oppression, fever, chills, angioneurotic oedema and anaphylactic shock

Local toftation and skin necrosis may occur but are rare.

Priapism has been reported, tocreased serum transaminase values may occir but usually resolve on discontinuation of heparin. Heparin administration is associated with release of Ipoprotein lipase toto the plasma; rebound hyperlipidaemia may follow heparin withdrawal.

49    Overdose

A potential hazard of heparin therapy is haemorrhage, but this is usually due to overdosage and the risk is minimised by strict laboratory control, Slkfit haemorrhage can usually be treated by withdrawing the drug. If bleeding is more severe, dotting time and platelet count should be determined. Prolonged dotting time will indicate the presence of an excessive anticoagulant effect requiitog neutralisation by intravenous prolamine sulphate, at a dosage of t mg for every 1001.U. of heparin to be neutralised. The bolus dose of prolamine sulphate shodd be given slowly over about 10 minutes and not exceed 50 mg. If more than 15 minutes have elapsed since the injection of heparin, lower doses of prolamine will be necessary.

5. PHARMACOLOGICAL PR0PBTT1ES 5.1 Pharmacodynamic properties

Heparin is an anticoagulant and acts by inhbiting thrombin and by potentiating the naturally occurring inhibitors of activated Factor X ptafi.

52 Phamiacokfoetic properties

As heparin is not absorbed from the gastrohtestinal tract and sublingual sites it is admtoislered by injection. After injection heparin

extensively binds to plasma proteins.

Heparin is metabolised in the liver and the inactive metabolic products are excreted in the nine.

The half life of heparin is dependent on the dose.

53 PrecHcal safely dab

There are no pre-dinical data of relevance to the prescriber which are additional to those already included to other sections.

6.    PHARMACEUTICAL PARTICULARS 6.1 Ustof excipients

Vtfeler for injections Sodium hyctodde solution 3M Hydrochloric add 3M 62hGompaH)ilities

Heparin is incompattole with many injectable preparations eg. some antibiotics, opioid analgesics and antihistamines.

The following (tugs are incompatible with heparin;

Alteplase, amkadn sulphate, amiodarone hycfrochtoride, ampidllin sodium, aprotinin, benzylpenidllto potassium or sodium, cefolotin sodium, chtorpromaztoe hydrochloride, dproftoxadn lactate, dsafracnium hesitate, cyfarabine, dacaibazine, dainorabidn hydrochloride, diazepam, daxorubidn hydrochloride, draperidd, eiythromydn lactobionate, gentamicin sulphate, hatoperidol lactate, hyaluronidase, hydrocortisone sodium suednate, kanamydn sulphate, labetelot hydrochloride, metidllin sodum, methotrimepra-ztoe, netilmicin sdphate, nicardipine hydochloride, axytetracydine hydrochloride, pethidine hydrochloride, polymyxin B sulphate, promethazine hydrochloride, streptomycin sdphate, tobramycin sulphate, triflupromazine hydochloride, vancomydn hydrochloride and vinblastine sulphate.

Dobutamine hydrochloride and heparto should not be mixed or tofosed throudi the same intravenous line, as this causes precipitation.

Heparin and reteplase are incompatible when combined in solution.

If reteplase and heparto are to be given through the same line this, together with any Y-lines, must be thoroughly flushed with a 0.9% saline or a 5% glucose sdution prior to and following the reteplase tojedton.

63    Shelf life

Unopened-36 months

Horn a microbiological pant of view, unless the method of opening predudes 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 the user.

64    Special precautions far storage

Do not store above 25°C Store in the original package

65    Natue and contents of container

Neutral glass ampodes (Type I Ph Eui) of 1 ml or 2ml, 5ml, 10ml and 20ml capacity containing 1 ml, 5ml, 10ml and 20ml of solution respectively. Cartons contain 10 ampoules. (UK only)

Neutral glass ampodes (Type I Ph an) of 5ml capacity contaiiing 5ml of sdution and 10ml capacity conlaintog 10ml of sdution. Cartons contain 10 ampoules, (island only)

66    Special precautions for disposal Not applicable

7.    MARKETUG AUTHORISATION HOLDB1

WockhandtUKLtd Ash Road North Wrexham LL139UF UK

6    MARKETING AUTHORISATION NUMBB1(S)

PL 29831/0105 R41339(9/3 (5ml ampoules)

RA1339/9/4 (10 ml ampoules)

MA 1544)2001

a DATE OF FIRST AUIHORBATTON/RBIIEWAL OF THE AUTH0RBAT10N

Date of first authorisation:

7    September 2007 (UK)

16 November2007 (teeland)

1a DSIEOFRBflSIONOFUETEXr

May2009

WOCKHARDT