Package leaflet: Information for the user

lopamigita 370 mg/ml solution for injection/infusion

Iodine (as lopamidol)

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 pharmacist.

•    This medicine has been prescribed foryou 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 yourdoctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What lopamigita is and what it is used for

2.    What you need to know before you use lopamigita

3.    How to use lopamigita

4.    Possible side effects

5.    How to store lopamigita

6.    Contents of the pack and other information

1. What lopamigita is and what it is used for

lopamigita is one of a group of medicines called X-ray contrast media.. This medicine is for diagnostic use only.

You will be given lopamigita before or during X-ray examination or other imaging techniques (CT-scan) . When it is injected into the body, it shows up very well on an X-ray (because iodine blocks X-rays) and is used to help doctors to decide what the problem is.

The following is a list of the most common uses of lopamigita:

•    Examinationsofthebloodvessels

•    Examinations of the heart and its blood vessels

•    Computerised tomography (CT) enhancement such as brain orwhole body scanning

2. What you need to know before you use lopamigita Do not use lopamigita

•    if you are allergic to Iodine (as lopamidol) or any of the other ingredients of this medicine (listed in section 6).

•    if you have overactivity of the thyroid gland (hyperthyroidism).

•    if you have a history of major immediate or delayed skin reaction (see section 4 " Possible side effects; Tell the radiologist orX-ray staff immediately ") to injection of iopamidol.

Warnings and precautions

Talk to yourdoctor or pharmacist before using lopamidol

•    ifyou have an overactive thyroid without symptoms (latent hyperthyroidism) and/orthyroid nodule(s) without signs of inflammation (euthyroid goitre)

•    if you have kidney or severe liver problems

•    if you have (a history of) severe heart or blood vessel (cardiovascular) disease

•    ifyou have bronchial asthma

•    ifyou have diabetes mellitus

•    ifyou have a seizure disorder

•    ifyou have advanced arteriosclerosis (hardening) of arteries supplying the brain

•    if you have had an acute stroke

•    during acute bleeding in the brain or in conditions accompanied by damage to the blood-brain barrier and swelling of the brain

•    if you are in poor overall health or have a fluid deficit (dehydration)

•    if you have an abnormality with the proteins or antibodies in your blood such as dysproteinaemia or paraproteinaemia (e.g. in multiple myeloma/plasmocytoma)

•    if you have high blood pressure due to a tumour near the kidney (phaeochromocytoma).

Precautions to be considered while using lopamigita

The patient should hydrate himself/herself sufficiently.

As with all iodine-containing contrast media, dose-independent allergic-like side effects may occur afteryou have been given lopamigita.

Usually these reactions result in minor symptoms. If such reactions happen, contact your doctor immediately.

Allergic reactions are more common in patients with allergies and/orasthma and also in patients with known allergy to contrast media. If you have a history of allergies or bronchial asthma, you may be given antihistamines and/or corticosteroids before the X-ray investigation.

Iodine-containing contrast media can effect thyroid function. This may induce overactivity of the thyroid gland or even thyreotoxic crisis (over active thyroid gland function) in patients with thyroid disease. If you are potentially at risk, then your thyroid function has to be assessed prior to the X-ray examination.

Patients with heart and circulation problems, especially those with cardiac weakness, severe coronary heart disease, unstable angina pectoris, diseases of the heart valves, previous heart attack, heart bypass and high blood pressure, are at higher risk for serious reactions of the heart. This is especially applicable following intracoronary, left and right ventricular application of the contrast media.

Patients with diseases of the brain vessels (cerebrovascular diseases), who have had a previous stroke or short term blood vessel constriction or blockage, brain tumour or a wasting or inflammation of the brain are at an increased risk of complications. The presence of brain tumours and epilepsy may lead to an increased risk of seizures. Short or long term alcoholism may cause contrast medium induced reactions of the central nervous system.

The symptoms of myasthenia gravis may be increased by iodinated contrast media.

Among patients with autoimmune diseases cases of serious inflammatory reactions of blood vessels or Stevens-Johnson-like syndromes (life-threatening conditions affecting the skin) were reported.

Catheter X-ray investigation with dyes is connected with the risk to induce sudden blocking of blood vessels or blood clots.

Excitation, anxiety or pain may increase the risk of undesirable effects. Patients with marked anxiety may receive calming treatment.

Contrast media may promote changes in red blood cells in individuals with sickle cell disease when injected intravenously and intra-arterially.

Beta-blockers, vasoactive substances (medicines causing constriction or dilation of blood vessels), angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptorantagonists (blood pressure lowering medicines).

These medicinal products reduce your body's ability to manage changes in blood pressure: the doctor must be informed before injection of the X-ray dye and resuscitation equipment must be at hand.

Children

Toddlers aged less than 1 year and new-born infants are especially susceptible to an imbalance of salts in the body and haemodynamic changes (blood changes). Caution is, therefore, advised with regard to dosage of the contrast medium, conducting the examination and the patient's condition. Premature new-born infants should be monitored very carefully as application of the contrast medium can result in temporary decline in the functioning of the thyroid gland.

Other medicines and lopamigita

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Iodine containing x-ray contrast media can reduce the ability of the thyroid gland to take up radioisotopes used in the diagnosis and treatment of thyroid disease for 2-6 weeks.

The application of X-ray contrast media may induce temporary kidney function impairment which may cause lactate acidosis in patients with diabetes mellitus treated with metformin. Therefore use of metformin must be stopped for a certain period of time before and after the examination. For safety precautions see Precautions to be considered while using lopamigita.

In patients taking beta-receptor blockers (for heart problems and high blood pressure), hypersensitivity reactions may occur more frequently and, above all, more intensely.

Medicines that reduce the seizure threshold (e.g. phenothiazine derivatives, analeptics, tricyclic antidepressants, monoamine oxidase inhibitors, antipsychotics) may facilitate seizures especially in patients with epilepsy or focal brain damage. If medically acceptable, treatment with such medicines should be suspended for48 hours before and up to 24 hours after cerebral angiography in such patients.

In patients who have been treated with interferons and interleukins, known contrast medium reactions such as skin redness, feverand/orflu-like symptoms may occur more frequently and, above all, with a time lag. No cause has been identified.

Arterial thrombosis has been reported when iopamidol was given following papaverine.

The administration of vasopressors strongly potentiates the neurological effect of the intra-arterial contrast media.

When renal scintigraphy using an injection of radiopharmaceutical secreted by the renal tubule is planned, it should preferably be performed before injection of the contrast agent.

Pregnancy and breast-feeding

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

Pregnancy

You must tell your doctor if you are pregnant.

Safe use of iopamidol in pregnantwomen has not been established. When a pregnantwoman has an x-ray examination, the child in her womb will also be exposed to radiation. For this reason alone, the benefit of any x-ray examination, with or without a contrast medium, must be carefully considered. Apart from trying to avoid foetal radiation exposure wherever possible, the benefit-risk assessment of the use of iodine containing contrast media should also take account of the iodine sensitivity of the foetal thyroid gland.

Breast feeding

Low amounts of iodinated contrast agents are secreted into the breast milk. Occasional administration to the mother is associated with a low risk of adverse effects for the infant.

However, as a precautionary measure, it is preferable to suspend breast feeding for 24 hours after administration of a iodinated contrast agent.

Driving and using machines

The effects on the ability to drive and use machines have not been investigated,

lopamigita contains sodium

This medicinal product contains approximately 0.059 mg of sodium per milliliter (ml). To be taken into consideration by patients on a controlled sodium diet.

3. How to use lopamigita

The medicine will be given to you by a doctor. You should check with yourdoctor or pharmacist if you are not clear about anything. Unless prescribed otherwise by yourdoctor, the dose will depend on the type of examination to be performed on you, your age, weight, heart function and general state of health, and the type of examination that is being used. Usually the same iodine concentrations and volumes are used as with other non-ionic iodine containing x-ray contrast media. The lowest dose necessary to obtain the desired diagnostic information should be used.

Iodine-containing contrast media should only be used under the precondition that treatment of emergencies is possible. This includes availability of the necessary technical and medicinal equipment. Following application, the patient shall be monitored for at least Vi hour, as from experience the majority of all serious incidents occur within this timeframe.

Intravenous orintraarterial use (injection orinfusion).

The contrast medium should be brought to body temperature before administration. Experience has shown that a warmed contrast medium is tolerated better.

Do not use lopamigita if you notice that the solution is not clear.

Contrast media should normally not be drawn up into a syringe until immediately before use. To minimise the risk of thrombo-embolism associated with the examination, the contact time between blood and contrast medium in syringes and catheters should be kept as short as possible.

Attention should also be paid to careful angiographic technique and frequent flushing of catheters with sodium chloride 9 mg/ml (0,9%) solution for injection (adding heparin if necessary). Contrast medium not completely used up during an examination must be discarded.

The contrast medium should be administered to the recumbent patient if at all possible. Immediate repositioning must be possible. To enable emergency management if necessary, a secured venous access should be in place before starting the examination. Like all iodine containing x-ray contrast media, lopamigita should be used with any diagnostic technique only if resuscitative equipment and emergency medication are available.

After the examination, patients should be monitored for at least 30 minutes because experience shows that most severe adverse reactions to contrast media occur during this time. All medical and nursing staff must be informed of adverse reactions as well as general and pharmacological emergency measures.

In patients with impaired renal function, cardio-circulatory insufficiency as well as bad general condition, the dosage of contrast media should be kept as low as possible. Kidney function should be monitored at least three days following the examination.

Pretesting using a low dose of contrast medium for hypersensitivity is not recommended, as this not meaningful and occasionally resulted in serious hypersensitivity reactions.

As the intravascular administration of iopamidol can lead to renal failure, metformin must be discontinued prior to, or at the time of the test and not be reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.

The dose recommendations given at the end of this leaflet are based on general experience with non-ionic x-ray contrast media as well as clinical studies performed with iopamidol. The total volume administered should not exceed 250 ml.

Unless indicated otherwise, the dosage for children depends on their age and body weight, and should be determined by the attending physician.

lopamigita is a diagnostic product forsingle injection in the intended indications. Multiple injections or repeated examinations are possible.

How to use lopamigita

You should have nothing to eat for 2 hours prior to the investigation, in order to reduce the risk of aspiration, as nausea and vomiting are known possible adverse reactions.

If you use more lopamigita than you should

In case of accidental overdose or significantly impaired kidney function, iopamidol can be removed from the body by dialysis.

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

4. Possible side effects

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

Side effects you may get after being given a contrast media like lopamigita are usually mild to moderate and do not last long.

However, as with similarcontrast media, severe reactions and life-threatening reactions can occur, that require rapid and effective emergency treatment.

If you notice:

•    swelling of the face or throat (angioedema)

•    itchy orwatery eyes (conjunctivitis); coughing; itching; runny or blocked nose; sneezing; nettle rash

•    a massive fall in blood pressure, increased heart rate (tachycardia)

•    difficulty in breathing, gagging, feeling of suffocation (anaphylactoid reactions)

•    agitation, blue lips, blue or pale skin, cold sweats, clouding or loss of consciousness,

•    headache, dizziness, feeling faint.

•    the fall in blood pressure may also be connected with decreased heart rate (bradycardia; vasovagal reaction), from which increased heart rate (tachycardia) usually develops over time.

Tell the radiologist or X-ray staff immediately as these may be the first signs of allergic reaction orshock. Yourinvestigation will need to be stopped, and you may need furthertreatment.

Apart from the symptoms listed above, these are the other side effects of lopamigita, starting with the more common ones:

Common (may affect uptolinlO people)

•    Temporary changes in breathing rate; shortness of breath; difficulty breathing as well as coughing

•    Nausea; vomiting; problems with your sense of taste

•    Swelling of the hands, ankles or feet (oedemas); flush; nettle rash; rash; itching; redness of skin Rare (may affect up to 1 in 1,000 people)

•    X-ray procedures of the brain and other procedures in which the contrast media enters the arterial blood in the brain in a high concentration: agitation; confusion; loss of memory; speech, sight and hearing disorders; epileptic fits; shaking; weakness causing loss of movement; paralyses; tingling or numbness of the hands or feet (pins and needles); increased sensitivity to light; temporary blindness; coma; drowsiness

•    Blockage of a blood vessel by a blood clot have been reported during catheter angiographic examinations, which resulted in heart attack

•    Difficulty in breathing or wheezing, swelling or spasm of the voice box (larynx).

•    Stomach complaints

•    Kidney function disorders extending to acute kidney failure, particularly in patients whose renal function was already impaired

•    Serious life-threatening reactions (including fatalities) that require emergency treatment and are associated with vital functions of the cardiovascular system, usually in connection with respiratory and central nervous reactions: Feeling warmth; changes in body temperature (fever); headache; feeling unwell; sweating; a cold feeling; fainting

Very rare (may affect uptol in10,000 people)

•    Clinically relevant disorders of: blood pressure; heart rate; fast, slow or irregular heartbeats; pain or tightness in the chest; heart failure; heart attack

•    Swelling or fluid in the lungs; stopped breathing (respiratory arrest)

•    Swelling of salivary glands in and around the mouth (iodide mumps)

•    Swelling of the face, skin, tongue, other mucous membranes (e.g. inside nose or mouth) or other parts of the body; severe skin disease (red, blistered, bleeding, painful skin, which may affect the lips, eyes, mouth, nose and genitals too).

•    Swelling and redness along a vain which is extremely tender when touched; blood clots of the veins

•    Injection site reactions: inflammation and soft tissue infections

Not known

Frequency cannot be estimated from the available data

•    Altered thyroid gland function or a severe form of overactive thyroid (thyrotoxic crisis)

•    Blockage of a blood vessel by a blood clot that results in a stroke

•    Temporary complications such as dizziness and headache

•    Injection site reactions: if the injection does not go directly into the blood vessel; local pain and swelling (oedemas)

Delayed reactions can occur, ifyou are concerned you should contactyourdoctor.

If you get any side effects, talk to your doctor or the X-ray department staff/radiologist. This

includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard

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

5.    How to store lopamigita

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 vial and carton after "EXP". The expiry date refers to the last day of that month.

Do not refrigerate or freeze.

Store in the original package in order to protect from light. Protect from x-rays.

Do not use this medicine if you notice that the solution is not clear.

Once opened:

Do not refrigerate or freeze.

Chemical and physical in-use stability has been demonstrated for24 hours at 25°C.

From a microbiological point of view, unless the method of opening 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.

Each vial is for single patient use only.

Discard any unused contents.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6.    Contents of the pack and other information

What lopamigita contains

The active substance is iopamidol.

1 ml solution contains 755.2 mg iopamidol, equivalent to 370 mg iodine.

One vial of 20 ml solution contains 15,104 mg Iopamidol, equivalent to 7,400 mg Iodine.

One vial of 50 ml solution contains 37,760 mg Iopamidol equivalent to 18,500 mg Iodine.

One vial of 75 ml solution contains 56,640 mg Iopamidol, equivalent to 27,750 mg Iodine. Onevial of 100 ml solution contains 75,520 mg Iopamidol equivalent to 37,000mg Iodine. Onevial of 200 ml solution contains 151,040 mg Iopamidol, equivalentto 74,000 mg Iodine.

The other ingredients are trometamol, edetate calcium disodium (dihydrate), hydrochloric acid 36 % (for pH adjustment) and water for injection

What lopamigita looks like and contents of the pack

lopamigita is a solution for injection and infusion. Clear, colourless or light yellow solution.

Your medicinal product comes in a clear glass vial with a rubber stopper and aluminium cap that is packed into a carton along with this patient information leaflet (package leaflet).

lopamigita 370 mg/ml is presented in the following packs:

10 vials with 20, 50, 75, 100 and 200 ml solution for injection/infusion 30 vials with 20, 50, 75 and 100 ml solution for injection/infusion 20 vials with 200 ml solution for injection/infusion

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Agfa HealthCare Imaging Agents GmbH Am Coloneum 4 50829 Koln Germany

Tel: +49 221 5717-660 Fax: + 49 221 5717-1051 E-mail: imagingagents@agfa.com

This leaflet was last revised in 06/2013

The patient must be kept sufficiently hydrated before and after the examination. Any fluid and electrolyte imbalance should be corrected. In patients with dysproteinaemia or paraproteinaemia (multiple myeloma/plasmacytoma), diabetes mellitus, polyuria or oliguria, gout, as well as in young children, old patients and patients in poorgeneral condition, fluid intake must neverbe restricted before administering the contrast medium. In patients at risk, the water and electrolyte balance should be monitored, watching for symptoms of decreasing serum calcium levels.

Reversible kidney failure can occur in rare cases. A history of or existing kidney disease, age over 60 years, fluid imbalance, advanced arteriosclerosis, decompensated heart insufficiency, high doses of contrast media and multiple injections, direct application of contrast media to the renal artery, exposition to further medicines which may damage the kidneys, severe and chronic high blood pressure, hyperuricaemia and paraproteinaemia (e. g. plasmocytoma, macroglubulinaemia) are predisposing factors.

In patients with impaired kidney function, the use of potentially kidney damaging medicines should, if at all possible, be avoided until excretion of the contrast medium is complete. Further contrast medium examinations should be postponed until kidney function has returned to baseline. Iodine-containing contrast media can be removed from the blood by dialysis.

In patients with phaeochromocytoma, it is recommended to administer alpha-adrenergic receptor blockers before the examination because severe high blood pressure crises may occur following intravascularadministration of non-ionic contrast media.

Contrast media may interfere with laboratory tests for bilirubin, proteins or inorganic substances (eg iron, copper, calcium, phosphate). These substances should not be assayed during the same day following the administration of contrast media.

Dosage adjustments in specific patient groups is required such as in patients with renal impairment and hepatic impairment.

Prior to use, the solution has to be inspected visually. Only solutions without visible signs of deterioration or particles may be used.

Neuroleptics must be absolutely avoided because they lower the seizure threshold. The same applies to analgesics, antiemetics, antihistamines and sedatives of the phenothiazine group. Whenever possible, treatment with such drugs should be discontinued at least 48 hours before administration of the contrast medium and not be resumed less than 24 hours after completion of the procedure.

Angiography should be avoided whenever possible in patients with homocystinuria due to an increased risk of thrombosis and embolism.

To avoid sickling in individuals who are homozygous for sickle cell disease appropriate hydration should be assured and the minimum effective volume should be used.

Contents not used in a patient during one single investigation must be discarded.

lodinated contrast media can react with metallic surfaces containing copper (e.g. Brass).

Therefore the use of equipment in which the product comes into direct contact with such surfaces, should be avoided.

What to do in the event of side effects

If an adverse reaction occurs, administration of the contrast medium must be stopped immediately. Treatment should be in response to the clinical picture. General resuscitative measures and the use of medicines may be necessary e.g. general treatment (antihistaminic, corticosteroids, oxygenotherapy),treatment of cardiovascular disorders (vasopressors, plasma, electrolytes),treatment of convulsions (diazepam), treatment of tetanic crisis (calcic gluconate), Renal function should be monitored at least the following 3 days after overdose.

It should be borne in mind that the effects of adrenaline and volume replacement are reduced in patients co-administered ^-receptor blockers.