1181158

SCIENTIFIC LEAFLET

OMNISCAN™ 0.5 mmol/ml Solution for Injection

QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient	Content pr ml	Function
GADODIAMIDE (GdDTPA-BMA)	287 mg equiv. 0.5 mmol	MRI-contrast agent

OMNISCAN Solution for injection is a non-ionic paramagnetic contrast medium with the following physicochemical properties:

Osmolality (mOsm/kg H20) at 37°C	780
Viscosity (mPa»s) at 20°C	2.8
Viscosity (mPa»s) at 37°C	1.9
Density at 20°C (kg/l)	1.15
Molar relaxivity
r2 (mM'1 • s_1) at 20 MHz and 37°C	3.9
TjImM1 • s1) at 10 MHz and 37°C	4.6
r2 (mM1 • s1) at 10 MHz and 37°C	5.1
PH	6.0-7.0

Gadodiamide is freely soluble in water. Excipient(s) with known effect:

Omniscan also contains sodium 0.62mg/ml

For the full list of excipients, see list of excipients.

PHARMACEUTICAL FORM

Solution for injection, for intravenous use.

The product is a clear, colourless to slightly yellow aqueous solution.

CLINICAL PARTICULARS

Therapeutic indications

Contrast medium for cranial and spinal magnetic resonance imaging (MRI) and for general MRI of the body after intravenous administration.

The product provides contrast enhancement and facilitates visualisation of abnormal structures or lesions in various parts of the body including the CNS.

For cardiac MRI, the product is indicated for the evaluation of coronary artery disease (CAD) by myocardial perfusion imaging MRI (stress/rest and late enhancement examination) for the detection and localization of coronary artery disease (CAD) and differentiation between areas of ischaemia and infarction in subjects with known or suspected CAD.

Posology and method of administration

No special preparation of the patient is required. OMNISCAN should be drawn into the syringe immediately before use. Both the vial and the bottle are intended for one patient only. Contrast medium not used in one examination must be discarded.

For both adults and children the required dose should be administered as a single intravenous injection. To ensure complete injection of the contrast medium, the intravenous line may be flushed with sodium chloride injection 0.9%.

CNS

Dosage for adults and children

The recommended dosage is 0.1 mmol/kg body weight (equivalent to 0.2 ml/kg b.w.) up to 100 kg. Above 100 kg body weight 20 ml is usually sufficient to provide diagnostically adequate contrast.

Adults only

When brain metastases are suspected in patients with equivocal scans after administration of the

0.1 mmol/kg b.w. injection, a second bolus injection of 0.2 mmol/kg b.w. (equiv. to 0.4 ml/kg b.w.) up to 100 kg may be of additional diagnostic value when administered within 20 minutes of the first injection. Above 100 kg b.w. a second bolus injection of 40 ml should be sufficient to provide diagnostically adequate contrast.

Whole body

Dosage for adults and children from 2 years of age

The recommended dosage is 0.1 mmol/kg b.w.

(equiv. to 0.2 ml/kg b.w.) up to 100 kg.

Above 100 kg b.w. 20 ml is usually sufficient to provide diagnostically adequate contrast.

OMNISCAN has also been used in a limited number of children below 2 years of age.

CNS and Whole body only

Contrast-enhanced MRI should start shortly after administration of the contrast medium, depending on the pulse sequences used and the protocol for the examination. Optimal enhancement is observed within the first minutes after injection (time depending on type of lesion/tissue). Enhancement is generally lasting up to 45 minutes after contrast medium injection, ^-weighted scanning sequences are particularly suitable for contrast-enhanced examinations with OMNISCAN.

In the investigated range of field strengths, from 0.15 Tesla up to 1.5 Tesla, the relative image contrast was found to be independent of the applied field strength.

Angiography Dosage for adults

The recommended dosage is 0.1 mmol/kg body weight (equivalent to 0.2 ml/kg b.w.). The efficacy and safety of OMNISCAN for use in angiography in children under the age of 18 years has not been established.

Imaging should be performed during the first pass of the contrast agent, during and immediately after injection, depending on the MR equipment used, to obtain optimal contrast effect.

Mammography Dosage for adults

The recommended dosage is 0.1 - 0.2 mmol/kg body weight (equivalent to 0.2 - 0.4 ml/kg b.w.).

Above 100 kg b.w. 20 ml - 40 ml is usually sufficient to provide diagnostically adequate contrast.

Coronary Artery Disease (CAD)

Dosage for adults

The recommended dosage for evaluation of cardiac perfusion is 0.15 mmol/kg b.w.

(equiv. to 0.3 ml/kg b.w.) given as two separate doses of 0.075 mmol/kg b.w. (equiv. to 0.15 ml/kg b.w.) administered within an interval of >10 minutes; one at pharmacological stress followed by one at rest.

For the intravenous bolus injection in cardiac MRI, the use of a suitable injector is recommended at a rate of up to 8 ml/sec.

An adequate pharmacological stress agent should be administered via separate intravenous line. For the evaluation of late enhancement only, a total dose of 0.15 mmol/kg b.w. is recommended.

The CAD indication has not been studied in children.

Special Populations Renal impairment

Omniscan is contraindicated in patients with severe renal impairment (GFR < 30 ml/min/1.73m²) or acute kidney injury and in patients in the perioperative liver transplantation period (see contra-indications). Omniscan should only be used after careful risk/benefit evaluation in patients with moderate renal impairment (GFR 30-59 ml/min/1.73m²) at a dose not exceeding 0.1 mmol/kg body weight (see special warnings and precautions for use).

More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Omniscan injections should not be repeated unless the interval between injections is at least 7 days.

Neonates up to 4 weeks of age and infants up to 1 year of age

Omniscan is contraindicated in neonates up to 4 weeks of age (see contra-indications).

Due to immature renal function in infants up to 1 year of age, Omniscan 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, Omniscan injections should not be repeated unless the interval between injections is at least 7 days.

Elderly (aged 65 years and above)

No dosage adjustment is considered necessary. Caution should be exercised in elderly patients (see special warnings and precautions for use).

Contra-indications

OMNISCAN should not be used in patients known to have hypersensitivity to OMNISCAN or its constituents. Omniscan is contraindicated in patients with severe renal impairment (GFR <30ml/min/1.73m²) or acute kidney injury, in patients in the perioperative liver transplantation period and in neonates up to 4 weeks of age (see special warnings and precautions for use).

Special warnings and special precautions for use

The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid or cardiovascular reactions or other idiosyncratic reactions should always be considered, especially in those patients with a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders. A course of action should therefore be planned in advance, with necessary drugs and equipment available for immediate treatment should a serious reaction occur.

Transitory changes in serum iron (within the normal range in the majority of cases) have been observed in some patients after administration of OMNISCAN. The clinical significance of this, if any, is not known, but all patients in whom this effect was observed remained asymptomatic.

OMNISCAN interferes with serum calcium measurements with some colorimetric (complexometric) methods commonly used in hospitals. It may also interfere with determinations of other electrolytes (e.g. iron). Thus it is recommended not to use such methods for 12-24 hours after administration of OMNISCAN. If such measurements are necessary, the use of other methods is recommended.

Patients with impaired renal function Prior to administration of Omniscan, all patients should be screened for renal dysfuncion by obtaining laboratory tests.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of Omniscan and some other gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30 ml/min/1.73m²) and/or acute renal injury. Omniscan is contraindicated in these patients (see contra-indications).

Caution should be exercised in use and dose selection of OMNISCAN in patients with hepatorenal syndrome. Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. Therefore Omniscan must not be used in patients with severe renal impairment, in patients in the perioperative liver transplantation period and in neonates (see contra-indications).

In addition, the risk for development of NSF in patients with moderate renal impairment (GFR 30-59 ml/min/1.73 m²) is unknown, therefore, Omniscan should be only used after careful risk-benefit evaluation in patients with moderate renal impairment.

The elimination half-life of Omniscan is prolonged in patients with impaired renal function. Because of the lack of information on repeated administration to these patients, Omniscan injections should not be repeated unless the interval between injections is at least 7 days.

Haemodialysis shortly after Omniscan administration may be useful at removing Omniscan 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. Patient with central nervous system disorders In patients suffering from epilepsy or brain lesions the likelihood of convulsions during the examination may be increased. Precautions are necessary when examining these patients (e.g. monitoring of the patient) and the equipment and medicinal products needed for the rapid treatment of possible convulsions should be available.

Neonates and Infants:

Omniscan is contraindicated in neonates up to 4 weeks of age (see contra-indications). Due to immature renal function in infants up to 1 year of age, Omniscan should only be used in these patients after careful consideration.

Elderly

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

This medicinal product contains: 0.62 mg/ml of sodium. This needs to be taken into consideration for patients on a controlled sodium diet.

Interaction with other medicaments and other forms of interaction

None known.

Fertility, pregnancy and lactation Pregnancy

There are no data from the use of gadodiamide in pregnant women. Animal studies have shown reproductive toxicity at repeated high doses (see preclinical safety data). Omniscan should not be used during pregnancy unless the clinical condition of the woman requires use of gadodiamide. Breastfeeding

It is unknown whether gadodiamide is excreted in human milk. Available data in animals have shown excretion of gadodiamide in milk (for details see preclinical safety data). A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued for at least 24 hours after the administration of Omniscan.

Effects on ability to drive and use machines

None known.

Undesirable effects

Adverse reactions have been reported in approximately 6% of the patients in clinical trials. Most events have been transient and the majority of mild intensity. The most commonly reported spontaneous adverse effects after Omniscan are hypersensitivity reactions, nausea and vomiting. Cases of nephrogenic systemic fibrosis (NSF) have been reported with Omniscan (see Special warnings and precautions for use).

1181158

PACKAGE LEAFLET: INFORMATION FOR THE USER

Omniscan 0.5 mmol/ml solution for injection

Gadodiamide

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

•    If you get any side effects, talk to your doctor.

This includes any possible side effects not listed in this leaflet. See section 4.

In this leaflet:

1.    What Omniscan is and what it is used for

2.    What you need to know before you are given Omniscan

3.    How Omniscan is given

4.    Possible side effects

5.    How to store Omniscan

6.    Contents of the pack and other information

1.    What Omniscan is and what it is used for

This medicine is for diagnostic use only.

Omniscan is a contrast medium which is used in Magnetic Resonance Imaging (MRI) examinations of the brain, spine and for whole body examinations. Omniscan is used only for identifying (diagnosing) an illness. Omniscan is used when the brain, spine or whole body are examined with a MRI scanner. It can help the doctor see some medical conditions more clearly. This can increase the amount of information the doctor has to identify the illness (make a diagnosis).

2.    What you need to know before you are given Omniscan

Do not have Omniscan

•    if you are allergic (hypersensitive) to gadodiamide the active substance of Omniscan or to any of its other ingredients (listed in section 6)

•    If you suffer from severe kidney problems and/or acute kidney injury.

•    if you are a liver transplant patient.

as use of Omniscan in patients with these conditions has been associated with a disease called Nephrogenic systemic fibrosis (NSF). NSF is a disease which causes discolouration and thickening of the skin and may be painful and result in reduced joint mobility, muscle weakness or impairment of the function of the internal organs.

Warnings and precautions

Talk to you doctor before using Omniscan

•    if you have or have had any allergies

(e.g. allergies to seafood, hay fever, nettle rash).

•    if you have asthma or other breathing problems caused by an allergy.

•    if you have a history of epilepsy, brain lesions or if you have ever had fits or seizures.

•    if you have any kidney problems.

•    if you are going to have a blood test between 12-24 hours after having the Omniscan injection. This is because Omniscan may affect how accurately the blood test shows the level of iron or calcium (electrolytes) in your blood.

You should not be given Omniscan if you suffer from severe kidney problems, or if you are a patient who is about to have or has recently had a liver transplant, as use of Omniscan in patients with these conditions has been associated with a disease called nephrogenic systemic fibrosis (NSF). NSF is a disease involving thickening of the skin and connective tissues. NSF may result in severe joint immobility, muscle weakness or may affect the normal working of internal organs which may potentially be life threatening.

Omniscan should also not be given to newborn babies up to age of 4 weeks.

Before you receive Omniscan, you will need to have a blood test to check how well your kidneys are working.

Children and adolescents

Omniscan should not be used in newborn babies up to the age of 4 weeks. As kidney function is immature in infants up to 1 year of age, Omniscan will only be used in infants after careful consideration by the doctor.

Other medicines and Omniscan

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

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 you are given Omniscan, as Omniscan should not be used during pregnancy unless strictly necessary.

Tell your doctor if you are breast-feeding or about to start breast-feeding. Breast-feeding should be discontinued for at least 24 hours after you receive Omniscan.

Driving and using machines

No effects are known on the ability to drive and use machines.

This medicinal product contains 0.62mg/ml of sodium. To be taken into consideration if you are on a low sodium diet

3. How to use Omniscan

Dosage and administration

•    Omniscan will be given to you by injection into one of your veins. This is usually as a single injection before or during your MRI scan.

•    Sometimes a second injection of Omniscan is given to help the doctor identify (diagnose) the condition.

The amount injected will depend on your weight and what part of your body is being examined.

•    The usual amount is 0.2 ml for each kilogram of body weight.

•    Sometimes the amount given is up to 0.6 ml for each kilogram of body weight.

You will not normally receive more than 20 ml Omniscan, even if you weigh more than 100 kilograms. However, for identifying (diagnosing) some conditions you may need to have 60 ml Omniscan.

Dosage in special patient groups

You should not be given Omniscan if you suffer from severe kidney problems or if you are a patient who is about to have or has recently had a liver transplant. Omniscan should also not be used in newborn babies up to the age of 4 weeks.

If you have moderate kidney problems, you should only receive one dose of Omniscan during a scan and you should not receive a second injection for at least 7 days.

As kidney function is immature in infants up to 1 year of age, infants should only receive one dose of Omniscan during a scan and should not receive a second injection for at least 7 days.

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

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

4. Possible side effects

There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may affect also soft tissue and internal organs).

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

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

If you get any of the following during or after the examination:

•    Allergic reactions:

-    wheeziness, difficulty in breathing or tightness or pain in the chest.

-    skin rash, lumps or itchy spots.

•    A decrease in the amount or urine you pass, or a change in its colour.

•    Nephrogenic systemic fibrosis (NSF), which causes discolouration and thickening of the skin and may be painful and result in reduced joint mobility, muscle weakness or impairment of the function of the internal organs.

You should tell the doctor straight away.

This is a list of side effects which may occur during or after the examination:

Common (affects less than 1 in 10 people)

•    An uncomfortable feeling of warmth, coolness, pressure or pain may occur in the area around where injection is given. This lasts for only a short time.

•    Headache.

•    Nausea (feeling sick).

Uncommon (affects less than 1 in 100 people)

•    Allergic-like reactions of skin and mucous membrane (mouth and throat).

•    Feeling dizzy.

•    Tingling sensations.

•    Vomiting.

•    Diarrhoea.

•    Flushing.

•    Itching.

•    A momentary change in your sense of taste.

Rare (affects less than 1 in 1,000 people)

•    A momentary change in your sense of smell.

•    Fits or seizures.

•    Feeling drowsy.

•    Difficulty in breathing.

•    Pain in the joints.

•    Shaking or tremors.

•    Feeling anxious.

•    Disturbance of vision.

•    Chest pain.

•    Acute kidney failure

•    Coughing

•    Rash and hives

•    Swelling, including face swelling, mouth or throat.

•    Fever.

•    Shivering.

Unknown (the number of people affected is unknown)

•    Allergic (hypersensitive) reactions, including allergic shock, see "Allergic reactions" above for other signs.

•    Nephrogenic systemic fibrosis (NSF), which causes discolouration and thickening of the skin and may be painful and result in reduced joint mobility, muscle weakness or impairment of the function of the internal organs.

•    Very fast heart beat.

•    Irritation in the throat.

•    Sneezing.

•    Severe difficulty in breathing.

•    Increase in levels of creatinine in your blood, (creatinine level is used as a measure of how your kidneys are functioning)

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 Yellow Card Scheme,

Website: www.mhra.gov.uk/yellowcard

5.    Howto store Omniscan

•    Keep out of the sight and reach of children.

•    Store in the outer carton in order to protect from light.

•    Do not freeze.

•    Do not use Omniscan after the expiry date which is stated on the label.

•    If electronic patient records are used, the name of the product, the batch number and the dose should be entered into the patient record.

6.    Contents of the pack and other information

What Omniscan contains

•    The active substance is gadodiamide (287 mg of gadodiamide in each ml, equivalent to 0.5 mmol in each ml).

•    The other ingredients are caldiamide sodium and sodium hydroxide or hydrochloric acid (for pH adjustment) and water for injections.

What Omniscan looks like and contents of the pack

Omniscan is a solution for injection. It is a clear, watery (aqueous) solution, colourless to slightly yellow.

Omniscan is supplied as:

Glass vials of 5 ml, 10 ml, 15 ml and 20 ml Pre-filled syringe of 10ml, 15ml and 20ml Not all pack sizes may be marketed.

Marketing Authorisation Holder

GE Healthcare AS Nycoveien 1-2 P.O. Box 4220 Nydalen NO-0401 Oslo, Norway

Manufacturer

GE Healthcare AS Nycoveien 1-2 P.O. Box 4220 Nydalen NO-0401 Oslo, Norway Or

GE Healthcare Ireland IDA Business Park Carrigtohill Co. Cork, Ireland

Local Representative:

GE Healthcare Limited

Little Chalfont, Buckinghamshire HP7 9 NA

This leaflet was last approved in

June 2015

Omniscan is a trademark of GE Healthcare

GE and the GE monogram are trademarks of General

Electric Company.

Incompatibilities

OMNISCAN should not be directly mixed with other drugs. A separate syringe and needle should be used.

Shelf life

3 years

Special precautions for storage

OMNISCAN in glass vials should be stored below 30°C and protected from light and freezing. The vial is intended for one patient only. Any unused portions must be discarded.

Nature and content of containers

The product is filled in injection vials with a fill volume of 5 ml, 10 ml, 15 and 20 ml. The vials are made of colourless highly resistant borosilicate glass (Ph.Eur. Type I) and are closed with latex free rubber stoppers, sealed with complete tear off capsules of aluminium with coloured plastic "flip-off" tops.

The product is supplied as:

1 vial of 5 ml 10 vials of 5 ml 10 vials of 10 ml 10 vials of 15 ml 10 vials of 20 ml

Special precautions for disposal and other 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.

MARKETING AUTHORISATION HOLDER

GE Healthcare AS Nycoveien 1-2 P.O. Box 4220 Nydalen NO-0401 Oslo, Norway

Local representative

GE Healthcare Limited Amersham Place Little Chalfont Buckinghamshire HP7 9NA

Manufacturer

GE Healthcare AS    or

Nycoveien 1-2 P.O.Box 4220 Nydalen NO-0401 OSLO, NORWAY Telephone: +47 23 18 50 50 Telefax:    +47 23 18 60 00

Legal category

POM

MARKETING AUTHORISATION NUMBER

PL 00637/0015

DATE OF THE FIRST AUTHORISATION OR RENEWAL

25th September 1992 in UK / 10 June 2005

DATE OF REVISION OF THE TEXT

April 2015