PACKAGE LEAFLET: INFORMATION FOR THE USER

Ablavar 0.25 mmol/ml solution for injection

Gadofosveset

Read all of this leaflet carefully before you are given this medicine.

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

• If you have further questions, please ask the doctor giving you Ablavar (the radiologist) or the hospital/MRI-centre personnel

• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or radiologist.

  
  

  In this leaflet:

  1. What Ablavar is and what it is used for

  2. Before you are given Ablavar

  3. How to use Ablavar

  4. Possible side effects

  5. How to store Ablavar

  6. Further information

  
  

  1. WHAT ABLAVAR IS AND WHAT IT IS USED FOR

     
     

     Ablavar is an injectable contrast medium for making a diagnostic image of the body's blood vessels in the abdomen or limb clearer. It is for use in adults only.

     
     

     Medicinal product no longer authorised

     Ablavar is for diagnostic use only. It is used to help detect changes in the blood vessels which are known or suspected to be abnormal. The diagnosis can be made with greater accuracy than without using this medicine.

     
     

     This medicine, a contrast agent with magnetic properties, helps to visualise the passage of blood through the vessels by brightening the blood for an extended period. This medicine is used together with an imaging technique called magnetic resonance imaging (MRI).

     
     

     If you have any questions or are not sure about something, ask the doctor or MRI-centre personnel.

     
     

  2. BEFORE YOU ARE GIVEN ABLAVAR

     
     

     Do not use Ablavar

     You must not be given Ablavar if you are allergic (hypersensitive) to gadofosveset or any of the other ingredients of this medicine (see section 6 of this leaflet).

     
     

     Take special care with Ablavar

     You will need special medical attention if allergy-like reactions occur. Tell your doctor immediately if you notice itching, a feeling of mild swelling in your throat or tongue, which might be a first sign of some allergy-like reaction. Your doctor will be mindful of other signs as well.

     
     

     Tell your doctor if:

     • you have a cardiac pacemaker or any ferromagnetic implant or a metallic stent in your body

     • you suffer from allergy (e.g. hay fever, hives) or asthma

     • you had any reactions to previous injections of contrast media

     • your kidneys do not work properly

     • you have recently had, or soon expect to have, a liver transplant

     If any of these apply to you, your doctor will decide whether the intended examination is possible or not.

     
     

     Your doctor may decide to take a blood test to check how well your kidneys are working before making the decision to use this medicine, especially if you are 65 years of age or older.

     
     

     Children or adolescents under 18 years

     This medicine should not be used in children or adolescents under 18 year of age.

     
     

     Using other medicines

     Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

     Your doctor will advise you what to do.

     
     

     Pregnancy and breast-feeding

     Ask your doctor for advice before taking any medicine.

     You must tell your doctor if you think you are or might become pregnant.

     It has not been proven that this medicine is safe to use during pregnancy. Your doctor or radiologist will consider this with you. This medicine must not be used in pregnant women unless strictly necessary.

     Tell your doctor if you are breast-feeding or about to start breast-feeding. Your doctor will discuss whether you should continue breast-feeding or interrupt breast-feeding for a period of 24 hours after you receive this medicine.

     
     

     Driving and using machines

     There are no studies on the effects on the ability to drive and use machines.

     Medicinal product no longer authorised

     This medicine can uncommonly cause dizziness or vision problems. If you get these effects you should not drive or use machines

     
     

     Important information about some of the ingredients of Ablavar

     This medicine contains 6.3 mmol sodium (or 145 mg) per dose. To be taken into consideration by patients on a controlled sodium diet.

     
     

  3. HOW TO USE ABLAVAR

     
     

     You will be asked to lie down on the MRI scanning bed. Scanning may start immediately after the Ablavar injection. After the injection you will be observed in case there might be any initial side effects.

     
     

     The usual dose

     
     

     The dose of this medicine varies depending on your weight. The doctor will decide how much medicine is needed for your examination. The dose is: 0.12 ml/kg body weight (equivalent to

     0.03 mmol/kg of body weight).

     Further information regarding the administration and handling of this medicine is given at the end of the leaflet.

     
     

     Method of administration

     This medicine is given as a rapid injection into a vein by a medical professional only. The usual injection site is the back of your hand or just in front of your elbow.

     
     

     Dose in special patient groups

     The use of this medicine is not recommended in patients with severe kidney problems and patients who have recently had, or soon expect to have, a liver transplant. However if use is required you should only receive one dose of this medicine during a scan and you should not receive a second injection for at least 7 days.

     
     

     Elderly

     It is not necessary to adjust your dose if you are 65 years of age or older but you may have a blood test to check how well your kidneys are working.

     
     

     If you receive more Ablavar than you should have received:

     If you think you may have had an overdose talk to your doctor immediately. Your doctor will treat you should overdose occur. If necessary, this medicine can be removed from the body by haemodialysis using high-flux filters.

     
     

     If you have any further questions on the use of this medicine, please consult your doctor, the radiologist or MRI-centre personnel.

     
     

  4. POSSIBLE SIDE EFFECTS

     
     

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

     
     

     If you have any of the following symptoms you should tell a doctor immediately:

     
     

     Ablavar can be associated with allergy-like reactions (anaphylactoid / hypersensitivity reactions) characterised by:-

     • skin reactions, (cutaneous reactions)

       Medicinal product no longer authorised

     • breathing difficulties and/or heart/ pulse-rate/ blood pressure disturbances which may lead to consciousness disorders respiratory reactions, and /or cardiovascular manifestations which may lead to shock).

       
       

       Most of the side effects were mild to moderate in intensity. Most of the side effects (80%) occurred within 2 hours. Delayed effects (after hours to days) may occur.

       
       

       Below are listed the reported/experienced side effects by frequency): Very common: affects more than 1 user in 10

       Common: affects 1 to 10 users in 100

       Uncommon: affects 1 to 10 users in 1,000

       Rare: affects 1 to 10 users in 10,000 Very rare: affects less than 1 user in 10,000

       Not known: frequency cannot be estimated from the available data.

       The following is a list of side-effects observed in clinical trials: Common:

       Headache

       Tingling or numbness of the hands or feet Change of taste in mouth

       Burning sensation

       Warm feeling (vasodilatation) including flushing Nausea

       Itching Feeling cold.

       
       

       Uncommon:

       Runny nose Sore throat Feeling anxious Confusion

       Allergy-like reaction Impairment of taste Dizziness

       Shaking

       Decreased feeling or sensitivity (especially of the skin) Sense of smell distortion

       Involuntary muscle contractions Abnormal vision

       Tear secretion increased

       Disturbed nerve signals in the heart (first degree) Fast heart beat

       Problems with the electrical rhythm of the heart (long QT) High blood pressure

       Swelling and clotting in a vein

       Coldness in the fingers and toes

       Shortness of breath Cough

       Vomiting Attempting to vomit Diarrhoea

       Stomach discomfort Stomach pain

       Medicinal product no longer authorised

       Pain in the throat Indigestion

       Dry mouth Wind

       Decreased feeling or sensitivity of the lips Increased production of saliva

       Anal itching

       Hives

       Reddening of the skin Rash

       Sweating increased Muscle cramps Muscle spasms Neck pain

       Pain in arms or legs Genital itching

       Genital burning sensation Pain

       Chest pain Tiredness Feeling abnormal Groin pain Feeling hot

       Injection site pain Injection site coldness

       Reddening of skin at the injection site Blood in the urine

       Proteins in the urine Sugar in the urine

       High sugar levels in the blood

       Low calcium levels in the blood Unusual amount of salt in the body.

       
       

       Rare:

       Inflammation of the skin Urinary tract infection Abnormal dreams

       Seeing, feeling or hearing things that is not there

       Appetite decreased Eyesight disorders Abnormal eye sensation Ear pain

       Heartbeat irregularity/disturbed heart-chamber contractions (cardiac flutter, atrial fibrillation) problems with the electrical rhythm of the heart (ST segment/T wave abnormalities)

       Chest pain Slow heart beat Palpitations

       Thickening of the arteries due to cholesterol deposits Low blood pressure

       Shallow breathing Face swelling Sweatiness Muscle tightness

       Sensation of heaviness Urge to pass urine Kidney pain

       Medicinal product no longer authorised

       Passing urine frequently Lower abdominal pain Fever

       Shivering Weakness

       Chest pressure sensation Injection site blood clot Injection site bruising Injection site inflammation Injection site burning

       Fluid escaping from injection site into the surrounding tissue Injection site bleeding

       Injection site itching Sensation of pressure

       Phantom pain in the arms or legs

       Low or high potassium levels in the blood High sodium levels in the blood.

       
       

       There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may affect also soft tissue and internal organs) associated with use of other gadolinium-containing contrast agents.

       
       

       If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or radiologist.

       
       

  5. HOW TO STORE ABLAVAR

     
     

     Keep out of the reach and sight of children.

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

     
     

     Keep the injection vial in its outer carton in order to protect from light. After first opening, the medicine should be used immediately.

     Do not use this medicine if you notice severe discolouration, the occurrence of particulate matter or a defective container.

     
     

     Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

     
     

  6. FURTHER INFORMATION

  
  

  What Ablavar contains

  
  

• The active substance is gadofosveset. 1 ml contains 227 mg gadofosveset equivalent to 244 mg/ml (0.25 mmol/millilitre) gadofosveset trisodium.

  10 ml solution contains 2.27 g, 15 ml solution contains 3.41g and 20 ml solution contains 4.54 g of gadofosveset in a vial.

  
  

• The other ingredients are fosveset, sodium hydroxide, hydrochloric acid, and water for injections.

What Ablavar looks like and contents of the pack

Medicinal product no longer authorised

Ablavar is a clear, colourless to pale yellow liquid supplied in a rubber stoppered glass vial, with an aluminium seal, in individual cartons. The contents of the packs are:

1, 5 or 10 injection vials with 10 ml solution for injection (in 10-ml glass vial) 1, 5 or 10 injection vials with 15 ml solution for injection (in 20-ml glass vial) 1, 5 or 10 injection vials with 20 ml solution for injection (in 20-ml glass vial) Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

TMC Pharma Services Ltd., Finchampstead, Berkshire RG40 4LJ , UK Tel:01252 842255

This leaflet was last approved in

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The following information is intended for medical or healthcare professionals only:

Prior to administration of Ablavar it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR< 30 ml/min /1.73 m2). Patients undergoing liver transplantation are at particular risk since the

incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with Ablavar, it should therefore be avoided in patients with severe renal impairment and in patients in the perioperative liver transplantation period unless the diagnostic information is essential and not available with non-contrast enhanced MRI. If use of Ablavar cannot be avoided, the dose should not exceed 0.03 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Ablavar injections should not be repeated unless the interval between injections is at least 7 days.

As the renal clearance of gadofosveset may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.

Haemodialysis shortly after Ablavar administration may be useful at removing Ablavar from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.

Ablavar should not be used during pregnancy unless the clinical condition of the woman requires use of gadofosveset.

Continuing breast feeding or discontinuing Ablavar for a period of 24 hours after administration, should be at the discretion of the doctor and lactating mother.

The peel-off tracking label included on the vials should be stuck onto the patient record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.

Ablavar is supplied ready to use as a clear, colourless to pale yellow aqueous solution.

Medicinal product no longer authorised

Contrast media should not be used in case of severe discolouration, the occurrence of particulate matter, or defective container.

Vials containing Ablavar are not intended for the withdrawal of multiple doses. The rubber stopper should never be pierced more than once. After withdrawal of the solution from the vial, this medicinal product should be used immediately.

Any remaining solution not used in one examination must be discarded.