Dotagraf 0.5 Mmol/Ml Solution For Injection
Package leaflet: Information for the user
Dotagraf 0.5 mmol/ml Solution for injection
Gadoteric acid
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 any further questions, ask your doctor or radiologist.
• If you get any side effects, talk to your doctor, radiologist or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet:
1. What Dotagraf is and what it is used for
2. What you need to know before Dotagraf is used
3. How Dotagraf is used
4. Possible side effects
5. How to store Dotagraf
6. Contents of the pack and other information
1. WHAT DOTAGRAF IS AND WHAT IT IS USED FOR
Dotagraf is a diagnostic agent. It belongs to the group of contrast agents used for magnetic resonance imaging (MRI).
Dotagraf is used to enhance the contrast of the images obtained during MRI examination techniques. This contrast enhancement improves the visualisation and delineation of:
• MRI of the CNS including defects (lesions) in brain, spinal cord and adjacent tissue;
• Whole body MRI including defects (lesions) in liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system;
• MR angiography including defects (lesions) and narrowing (stenosis) in arteries, except in coronary arteries.
This medicine is for diagnostic use only.
2. WHAT YOU NEED TO KNOW BEFORE DOTAGRAF IS USED
The information in this section should be read carefully.
The information given should be taken into consideration by you and your doctor or radiologist before you are given Dotagraf.
You should NOT be given Dotagraf
• if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to medicines containing gadolinium (like other contrast agents used for magnetic resonance imaging).
Warnings and precautions
Inform your doctor or radiologist if the following applies to you:
• you have previously reacted to a contrast agent during an examination
• you have asthma
• you have a history of allergy (such as seafood allergy, urticaria, hay fever)
• you are being treated with a beta-blocker (medicine for heart and blood pressure disorders, such as metoprolol)
• your kidneys do not work properly
• you have recently had, or soon expect to have, a liver transplant
• you have a disease affecting your heart or your blood vessels
• you have had convulsions or you are being treated for epilepsy.
In all these cases, your doctor or radiologist will assess the benefit-to-risk ratio and decide whether you should be given Dotagraf. If you are given Dotagraf, your doctor or radiologist will take the precautions necessary and the administration of Dotagraf will be carefully monitored.
Your doctor or radiologist may decide to take a blood test to check how well your kidneys are working before making the decision to use Dotagraf, especially if you are 65 years of age or older.
Neonates and infants
As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Dotagraf will only be used in these patients after careful consideration by the doctor.
Remove all metallic objects you may wear before the examination. Inform your doctor or radiologist if you have:
• a pacemaker
• a vascular clip
• an infusion pump
• a nerve stimulator
• a cochlear implant (implant in the inner ear)
• any suspected metallic foreign bodies, particularly in the eye.
This is important as these can result in serious problems, as magnetic resonance imaging devices use very strong magnetic fields.
Other medicines and Dotagraf
Tell your doctor or radiologist if you are taking or have recently taken any other medicines. In particular, please inform your doctor, radiologist or pharmacist if you are taking or have recently taken medicines for heart and blood pressure disorders such as beta-blocking agents (such as metoprolol), vasoactive substances (such as doxazosin), angiotensin-converting enzyme inhibitors (such as ramipril), angiontensin II receptor antagonists (such as valsartan).
Dotagraf with food, drink and alcohol
There are no known interactions between Dotagraf and food and drinks. However, please check with your doctor, radiologist or pharmacist if it is required not to eat or drink before the examination.
Pregnancy, breastfeeding and fertility
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or radiologist for advice before taking this medicine.
Pregnancy
Dotagraf should not be used during pregnancy unless strictly necessary.
Breastfeeding
Your doctor or radiologist will discuss whether you should continue breast-feeding or interrupt breast-feeding for a period of 24 hours after you receive Dotagraf.
Driving and using machines
No data are available on the effects of Dotagraf on the ability to drive. If you feel unwell after the examination, you should not drive or use machines.
3. HOW DOTAGRAF IS USED
Dotagraf will be administered to you by intravenous injection.
During the examination, you will be under the supervision of a doctor or radiologist. A needle will be left in your vein; this will allow the doctor or radiologist to inject you with appropriate emergency drugs if necessary. If you experience an allergic reaction, the administration of Dotagraf will be stopped.
Dotagraf can be administered by hand or by the mean of an automatic injector. In children, the product will only be administered by hand.
The procedure will be carried out in a hospital, clinic or private practice. The attending staff know what precautions have to be taken for the examination. They are also aware of the possible complications that can occur.
Dosage
Your doctor or radiologist will determine the dose you will receive and supervise the injection.
Dosage in special patient groups
The use of Dotagraf 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 Dotagraf during a scan and you should not receive a second injection for at least 7 days.
Neonates, infants, children and adolescents
As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Dotagraf will only be used in these patients after careful consideration by the doctor. Neonates and infants should only receive one dose of Dotagraf during a scan and should not receive a second injection for at least 7 days.
Use for angiography is not recommended in children less than 18 years of age.
Use for whole body MRI is not recommended in children less than 6 months of age.
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 too much Dotagraf has been administered to you
It is highly unlikely that you will be given an overdose. You will be given Dotagraf in a medical setting by a trained person. In the real case of overdose, Dotagraf can be removed from the body by haemodialysis (blood cleaning).
Additional information regarding the use and handling by the medical or healthcare professional is given at the end of this leaflet.
If you have any further questions on the use of this medicine, ask your doctor or radiologist.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody gets them.
After the administration, you will be kept under observation for at least half an hour. Most side effects occur immediately or sometimes delayed. Some effects can occur up to seven days after Dotagraf injection.
There is a small risk that you may have an allergic reaction to Dotagraf. Such reactions can be severe and result in shock (case of allergic reaction that could put your life in danger). The following symptoms may be the first signs of a shock. Inform immediately your doctor, radiologist or health professional if you feel any
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of them:
• swelling of the face, mouth or throat which may cause you difficulties in swallowing or breathing
• swelling of hands or feet
• lightheadedness (hypotension)
• breathing difficulties
• whistling respiration
• coughing
• itching
• runny nose
• sneezing
• eye irritation
• hives
• skin rash
Very common side effects (may affect more than 1 in 10 people)
• headaches
• tingling sensation
Common side effects (may affect up to 1 in 10 people)
• sensation of warmth or cold and/or pain at the injection site
• nausea (feeling sick)
• vomiting (being sick)
• redness of the skin, itching and rash
Uncommon side effects (may affect up to 1 in 100 people)
• allergic reactions
Rare side effects (may affect up to 1 in 1,000 people)
• unusual taste in the mouth
• hives, increased perspiration
Very rare side effects (may affect up to 1 in 10,000 people)
• agitation, anxiety
• coma, seizures, syncope (brief loss of consciousness), faintness (dizziness and feeling of imminent loss of consciousness), dizziness, disorder of smell (perception of often unpleasant odours), tremor
• conjunctivitis, red eye, blurred vision, increased tear secretion, eye swelling
• cardiac arrest, accelered or slow heart beat, irregular heart beat, palpitations, low or high blood pressure, vascular dilatation, pallor
• respiratory arrest, pulmonary oedema, breathing difficulties, feeling of tight throat, wheezing, stuffy nose, sneezing, cough, dry throat
• diarrhoea, stomach pain, increased saliva secretion
• eczema
• muscle contractures, muscle weakness, back pain
• malaise, chest pain, chest discomfort, fever, chills, swelling of the face, fatigue, injection site discomfort, injection site reaction, injection site swelling, diffusion of the product outside of blood vessels that can lead to inflammation (redness and local pain) or tissue dying off at the injection site, inflammation of a vein
• decrease in oxygen level in blood
There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may affect also soft tissue and internal organs), most of which were in patients who received Dotagraf together with other gadolinium-containing contrast agents. If, during the weeks following the MRI examination, you notice changes in the colour and/or thickness of your skin in any part of your body, inform the radiologist who performed the examination.
If you get any side effects, talk to your doctor or radiologist. This includes any side effects not listed in this leaflet.
Reporting of side effects
If you get any side effects, talk to your radiologist, pharmacist, doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Malta
ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal
5. HOW TO STORE DOTAGRAF
Keep this medicine out of the sight and reach of children.
This medicinal product does not require any special precaution for storage.
Chemical and physical in-use stability has been demonstrated 72 hours at room temperature. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer that 24 hours at 2 to 8°C, unless opening has taken place in controlled and validated aseptic conditions.
Do not use this medicine after the expiry date which is stated on the vial and on the carton, after the abbreviation “Exp”. The expiry date refers to the last day of that month.
6. CONTENTS OF THE PACK AND OTHER INFORMATION What Dotagraf contains
• The active substance is gadoteric acid. One millilitre of solution for injection contains 279.32 mg of gadoteric acid (as meglumine salt), equivalent to 0.5 mmol of gadoteric acid (as meglumine salt).
• The other ingredients are meglumine, DOTA and water for injection.
What Dotagraf looks like and contents of the pack
Dotagraf is a clear, colourless to yellow solution for intravenous injection.
The Dotagraf pack contains one or ten vials with 10, 15 and 20 ml of solution for injection.
Not all pack sizes may be marketed.
Marketing Authorisation Holder Austria Bayer Austria Ges.m.b.H.
HerbststraBe 6-10 1160 Vienna
Marketing Authorisation Holder Belgium
Bayer SA-NV
J.E. Mommaertslaan 14
B-1831 Diegem (Machelen)
Marketing Authorisation Holder France
Bayer HealthCare
220 Avenue de la recherche
59120 LOOS
Marketing Authorisation Holder Germany
Jenapharm GmbH & Co. KG Otto-Schott-StraBe 15 D-07745Jena
Marketing Authorisation Holder Italy
Bayer S.p.A.
Viale Certosa, 130 20156 Milano
Marketing Authorisation Holder Spain Bayer Hispania, S.L.
Avda. Baix Llobregat 3-5 08970 Sant Joan Despi (Barcelona)
Marketing Authorisation Holder United Kingdom
Bayer plc Bayer House Strawberry Hill Newbury Berkshire RG14 1JA
Manufacturer
Sanochemia Pharmazeutika AG
Landeggerstrasse 7
2491 Neufeld/Leitha, Austria
This medicinal product is authorised in the Member States of the EEA under the following name: Dotagraf 0,5 mmol/ml Injektionslosung (Austria)
Dotagraph 0,5 mmol/ml oplossing voor injectie / solution injectable / Injektionslosung (Belgium) Dotagraph 0,5 mmol/ml, solution injectable (France)
Dotagraf 0.5 mmol/ml Injektionslosung (Germany)
Dotagraf (Italy)
Dotagraf (Spain)
This leaflet was last revised in September 2016
The following information is intended for medical or healthcare professionals only:
Posology
• Brain and spinal MRI: In neurological examinations, the dose can vary from 0.1 to 0.3 mmol/kg BW, corresponding to 0.2 to 0.6 ml/kg BW. After administration of 0.1 mmol/kg BW to patients with brain tumours, the additional dose of 0.2 mmol/kg BW may improve tumour characterisation and facilitate therapeutic decision- making.
• MRI of other organs and Angiography: The recommended dose for intravenous injection is 0.1 mmol/kg (i.e. 0.2 ml/kg) to provide diagnostically adequate contrast.
• Angiography: In exceptional circumstances (e.g. failure to gain satisfactory images of an extensive vascular territory) administration of a second consecutive injection of 0.1 mmol/kg BW, equivalent to 0.2 ml/kg BW may be justified. However, if the use of 2 consecutive doses of Dotagraf is anticipated prior to commencing angiography, use of 0.05 mmol/kg BW, equivalent to 0.1ml/kg BW for each dose may be of benefit, depending on the imaging equipment available.
• Children: The 0.1 mmol/kg BW dose applies to all indications except angiography due to insufficient
data on efficacy and safety in this indication.
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Dotagraf should only be used in these patients after careful consideration at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Dotagraf injections should not be repeated unless the interval between injections is at least 7 days.
In neonates and infants the required dose should be administered by hand.
• Patients with renal impairment: The adult dose applies to patients with mild to moderate renal impairment (GFR > 30 ml/min/1.73m2). See also below “Impaired renal function”.
• Patients with hepatic impairment: The adult dose applies to these patients. Caution is recommended, especially in the case of perioperative liver transplantation period.
Method of administration
Dotagraf is indicated for intravenous administration only. Dotagraf must not be administered by subarachnoid (or epidural) injection.
Infusion rate: 3-5 ml/min (for angiographic procedures, higher infusion rates up to 120 ml/min, i.e. 2 ml/sec, may be used for angiographic procedures)
Optimal imaging: within 45 minutes after injection Optimal image sequence: T1-weighted
Intravascular administration of contrast media should, if possible, be done with the patient lying down. After the administration, the patient should be kept under observation for at least half an hour, since experience shows that the majority of undesirable effects occur within this time.
Prepare a syringe with a needle. Remove the plastic disk. After cleaning the stopper with a pad soaked in alcohol, puncture the stopper with the needle. Withdraw the quantity of product required for the examination and inject it intravenously.
For single use only, any unused solution should be discarded.
The solution for injection should be inspected visually prior to use. Only clear solutions free of visible particles should be used.
Impaired renal function
Prior to administration of Dotagraf, 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 < 30ml/min/1.73m2). 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 Dotagraf, it should therefore only be used in patients with severe renal impairment and in patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI. If it is necessary to use Dotagraf, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Dotagraf injections should not be repeated unless the interval between injections is at least 7 days. Haemodialysis shortly after Dotagraf administration may be useful at removing Dotagraf 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.
Elderly
As the renal clearance of gadoteric acid may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.
Neonates and infants
See under Posology, Children
Pregnancy and lactation
Dotagraf should not be used during pregnancy unless the clinical condition of the woman requires use of gadoteric acid.
Continuing or discontinuing breast feeding for a period of 24 hours after administration of Dotagraf, should be at the discretion of the doctor and lactating mother.
Instructions on handling
The peel-off tracking label 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. If electronic patient records are used, the name of the product, the batch number and the dose should be entered into the patient record.
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