Optimark 500 micromol/ml solution for injection in a pre-filledsyringe

Optimark is an injectable contrast medium. It is used to make clearer diagnostic images of the brain, spine and of the liver, in adults and children. As a result, it helps to clearly show abnormalities in the brain and spine, and in the liver.
This medicine is for diagnostic use only.

Do not use Optimark
if you are allergic (hypersensitive)

• to the active substance gadoversetamide or
• to any of the other ingredients of Optimark, or
• to other gadolinium contrast agents

You should not be given Optimark if you suffer from severe kidney impairment, or if you are a patient who is about to have or has had a liver transplant as use of Optimark 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 debilitating joint immobility, muscle weakness or may affect the normal working of internal organs which may potentially be life threatening.

Optimark should not be used in new born babies up to the age of 4 weeks.

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

Take special care with Optimark

Diagnostic procedures involving the use of contrast agents should be conducted under supervision of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed. Tell your doctor, if:

• you suffer from allergies (e.g. medicinal products, seafood, hay fever, hives) or asthma
• you had any reactions to previous injections of a contrast agent, including a previous history of reaction to iodine-based contrast agents
• your kidneys do not work properly
• you have recently had, or soon expect to have, a liver transplant
• Optimark is planned to be used in your child who is below the age of two years

Tell your doctor, if:

• you are feeling thirsty and/or if you have only had small quantities or nothing to drink before the examination
• you have a cardiac pacemaker or any ferromagnetic implant (vascular clips, etc.) or a metallic stent in your body
• you are taking a special kind of antihypertensive medicine, i.e. a beta-blocker
• you have heart disease
• you suffer from epilepsy or brain lesions
• you are or your child is on a controlled sodium diet If any of these apply to you, your doctor will decide whether the intended examination is possible or not.

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

Pregnancy and breast-feeding

Ask you doctor for advice before taking any medicine.

Pregancy

You must tell your doctor if you are or might become pregnant as Optimark should not be used during pregnancy unless strictly necessary.

Breast-feeding

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 Optimark.

Driving and using machines

If you are an ambulant patient and plan to drive or use tools or machines, take into acount that dizziness may incidentally occur after you undergo a procedure involving the injection of Optimark.

Important information about some of the ingredients of Optimark

This medicine contains less than 1 mmol sodium (23 mg) per dose of up to 17 ml, i.e. essentially ?sodium- free?. Higher doses contain 1 mmol of sodium or more, which have to be taken into consideration if you are or your child is on a controlled sodium diet.

The usual dose

The usual dose is about 14 ml injected over about 7 -14 seconds into a vein, usually a vein in an arm. The injection is then flushed through with a saline injection to make sure none is left in the needle or tube used for the injection. A second dose may be given within 30 minutes of the first injection. Certain questions regarding treatment of a brain disease may require the injection of three times the usual dose in one injection. The doctor will decide how much Optimark is needed for your examination. You must tell the doctor or nurse/technologist immediately if you feel pain around the area where the needle is placed.

Dosage in special patient groups
You should not be given Optimark if you suffer from severe kidney problems or if you are a patient who is about to have or has had a liver transplant. Optimark should also not be used in newborn babies up to the age of 4 weeks.
In patients with moderate kidney problems, more than one dose of Optimark should not be used during a scan. Optimark injections should not be repeated unless the interval between injections is 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 are given more Optimark than you should have been

If too much Optimark was injected it is unlikely that it will do you much harm, as much higher doses did not lead to any problems when some people received them. If your kidneys are working normally it is unlikely you will have any problems. Optimark can be removed using dialysis. If you think you have been injected with too much Optimark, tell the doctor or nurse/technologist immediately.

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

Like all medicinal products, Optimark can cause side effects, although not everybody gets them. Most of the undesirable effects observed after the use of Optimark were of mild to moderate intensity and transient in nature. The most common undesirable effects were a strange taste in the mouth, feeling hot, headache and dizziness.
Immediately tell the doctor or nurse/technologist who is giving you the injection, if you feel unwell, especially if you feel any tightness, pain or discomfort in your chest, face or throat, or you have difficulty breathing. Possible side effects are described in greater detail below.

The majority of adverse reactions observed after the use of Optimark were found to be adverse reactions of the nervous system, followed by general adverse reactions, digestive tract disorders/skin disorders.

The frequencies below and the following symptoms are based on clinical trials, and on the experience in using Optimark after it was on the market:

very common In more than 1 of 10 treated patients common In less than 1 of 10, but more than 1 of 100 treated patients uncommon In less than 1 of 100, but more than 1 of 1,000 treated patients rare In less than 1 of 1,000, but more than 1 of 10,000 treated patients very rare In 1 case or less of 10,000 treated patients including isolated reports

Frequency Possible side effects common dizziness, headache, strange taste in the mouth, feeling hot uncommon allergichypersensitivity reaction, tingling sensation, numbness, reduced sense of smell, skin red and warm, nasal congestion, sore throat, nausea, diarrhoea, hives, itching, rash, chest discomfort, feeling cold, administration site reactions rare decreased appetite, feeling anxious, sleep disorder, fainting, shaking, drowsy feeling, burning sensation, ringing in the ears, eyelid redness, eye pain, vision blurred, fast heart beat, awareness of the heartbeat, irregular heartbeats, extra heartbeats, low blood pressure, high blood pressure, shortness of breath, hoarseness, cough, runny nose, throat constriction, mouth watering, vomiting, abdominal pain, constipation, dry mouth, cold sweat, redness, sweating, higher blood level of a substance creatinine usually eliminated by the kidneys, blood in urine, chest pain, face swollen, fatigue,

fever, swelling in limbs, pain, cold feeling in extremities, liver enzyme increased, urine analysis abnormal, mineral values in urine increased, heart and muscle enzyme increased, decreased haemoglobin, changes in blood calcium levels very rare Feeling confused, convulsion, bloodshot eyes, heart beat irregularities, tightening of the airways, swollen throat or vocal cords, raw throat, itchy nose, sneezing, swelling around the eyes, flu-like symptoms, feeling unwell, problems with the electrical rhythm of the heart long QT

There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may affect also soft tissue and internal organs).
When Optimark was used in children aged 2 or older they had similar side effects as in adults.

You must report any of the following symptoms immediately to the doctor or nurse/technologist, and get immediate treatment as they can be or can become very serious: side effects affecting the heart (fainting, extra heart beats, chest pain) or the respiratory system (shortness of breath, tightening of the airways, swollen or tight throat, itchy or runny nose, sneezing).

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 pharmacist.

Keep out of the reach and sight of children.
Do not use Optimark after the expiry date which is stated on the label. Keep the syringe in the outer carton in order to protect from light.

Do not refrigerate or freeze.

Medicinal products 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.

What Optimark contains

• The active substance is gadoversetamide. 1 ml contains 330.9 mg gadoversetamide, equivalent to 500 micromol.
• The other ingredients are: versetamide, calcium hydroxide, calcium chloride dihydrate, sodium hydroxide and/or hydrochloric acid, water for injections.

What Optimark looks like and contents of the pack

Optimark syringes contain a clear, colourless to pale yellow solution.
Optimark is supplied in pre-filled syringes made of polypropylene. Syringe tip cap and piston are made of bromobutyl rubber.

Optimark pre-filled syringes are supplied in the following package sizes 1 x 10 ml 1 x 15 ml 1 x 20 ml 1 x 30 ml 10 x 10 ml 10 x 15 ml 10 x 20 ml 10 x 30 ml Not all package sizes may be marketed. Optimark is also available in glass vials of 10 ml, 15 ml and 20 ml.

Do not use the solution if it is discoloured or particulate matter is present.

Marketing Authorisation Holder

For any information about this medicine, please contact the Marketing Authorisation Holder: Covidien Deutschland GmbH
Gewerbepark 1
93333 Neustadt/Donau
Germany

Manufacturer
Mallinckrodt Medical Imaging Ireland
Damastown
Mulhuddart, Dublin 15
Ireland

This leaflet was last approved in:

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

Optimark is indicated for use with magnetic resonance imaging (MRI) of the central nervous system (CNS) and liver. It provides contrast enhancement and facilitates visualization and helps with characterization of focal lesions and abnormal structures in the CNS and liver in patients with known or highly suspected pathology.

Special warnings and precautions for use

As with any paramagnetic contrast agent, enhancement of MRI with Optimark may impair the visualization of existing lesions. Some of these lesions may be seen on unenhanced, non-contrast MRI. Therefore, caution should be exercised when contrast enhanced scan interpretation is made in the absence of a companion unenhanced MRI.
Before the examination, care must be taken that patients are sufficiently hydrated. The usual contraindications of MR examinations must be applied, such as exclusion of patients with infusion pumps, pacemakers, ferro-magnetic clips etc.

• Hypersensitivity Allergoid and other idiosyncratic reactions may occur with all contrast media for intravenous application, also with gadoversetamide, which could become manifest in form of cardiovascular, respiratory and skin reactions. Most of these reactions occur within half an hour after administering the contrast medium. As with all other contrast media of the same class, late reactions may occur (after hours or days) in rare cases; however, none were reported in the completed clinical trials. If hypersensitivity reactions occur, the administration of the contrast medium must be discontinued immediately and intravenous treatment initiated, if necessary. During the examination, supervision by a physician is necessary and insertion of a flexible in-dwelling catheter is recommended. To enable immediate action in emergencies, the necessary medicinal products (e.g. epinephrine/adrenaline, theophylline, antihistamines, corticosteroids and atropines), endotracheal tube and ventilator must be immediately available. The risk of hypersensitivity reactions is increased in the following cases:
• patients with allergic predisposition
• patients with bronchial asthma; in these patients it is especially the risk of bronchospasm which is increased
• patients with a history of reactions to contrast agents, including a previous history of reaction to iodine-based contrast agents

Before the injection of contrast media, patients should be asked whether they have any allergies (e.g. allergies to seafood or medicinal products, hay fever, urticaria), whether they are hypersensitive to contrast media and whether they have bronchial asthma. Premedication with antihistamines and/or glucocorticoids may be considered.

• Patients taking beta-blockers It should be noted that patients using beta-blockers do not necessarily respond to the beta-agonists usually used for the treatment of hypersensitivity reactions.
• Patients with cardiovascular disease In this group of patients hypersensitivity reactions may be severe. Especially in patients with serious heart diseases (e.g. severe heart failure, coronary artery disease) cardiovascular reactions may deteriorate. However, these were not evident from clinical trials with Optimark.
• 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.
• Renal impairment and liver transplant patients Prior to administration of Optimark, all patients should be screened for renal dysfunction by obtaining laboratory tests. There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of Optimark and some other gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR 2). Patients who have had or are undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. Therefore, Optimark must not be used in patients with severe renal impairment, in patients who have had or are undergoing liver transplantation. The risk for development of NSF in patients with moderate renal impairment (GFR 30?59 ml/min/1.73 m 2) is unknown, therefore, Optimark should be only used after careful risk-benefit evaluation in patients with moderate renal impairment at a dose not exceeding 100 micromol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Optimark injections should not be repeated unless the interval between injections is at least 7 days. Gadoversetamide is dialysable. Haemodialysis shortly after Optimark administration may be useful at removing Optimark 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.
• Children Optimark must not be administered with an autoinjector. The required dose should be administered by hand to children to avoid overdosage by mistake.
• Neonates and infants Optimark should not be given to newborn babies up to the age of 4 weeks and to children below the age of two years. Safety and efficacy have not been studied in this age group.
• Elderly As the renal clearance of gadoversetamide may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.
• Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per dose of up to 17 ml, i.e. essentially ?sodium- free?. Higher doses contain 1 mmol of sodium or more, which should be taken into consideration for patients on a controlled sodium diet.
• Serum iron and zinc Caution should be exercised because transient decreases in serum iron and zinc parameters have been observed in clinical trials. The clinical significance of this is unknown.

Pregnancy and Lactation

Optimark should not be used during pregnancy unless the clinical condition of the women requires the use of gadoversetamide.

Breast-feeding should be discontinued for at least 24 hours after administration of Optimark.

Posology and method of administration

The agent should be administered as a bolus peripheral intravenous injection at a dose of 0.2 ml/kg (0.1 mmol/kg) body weight. To ensure complete injection of the contrast medium, the injection should be followed by a 5 ml flush of sodium chloride 9 mg/ml (0.9 %) injection. The imaging procedure should be completed within 1 hour of administration of the contrast medium.

In cranial MRI, if a strong clinical suspicion of a lesion persists despite a single dose contrast-enhanced MRI or when more accurate information on the number, size or extent of lesions might influence management or therapy of the patient, in subjects with normal renal function, a second bolus injection of 0.1 mmol/kg may be administered within 30 minutes of the first injection as it may increase the diagnostic yield of the examination. The safety of repeat doses has not been established in children and adolescents, in patients with impaired renal function, or the elderly.

Limited data with other gadolinium contrast agents suggests that for the exclusion of additional cranial metastases in a patient with a known solitary resectable metastasis, an MR exam with the injection of 0.3 mmol/kg body weight of Optimark may lead to higher diagnostic confidence.

Optimark is not recommended for use in children below the age of two years because the safety, efficacy, and impact of immature kidney function have not been studied in this age group. Optimark has been studied in children of 2 years and older with a similar safety profile as shown in the adult population.

Insertion of a flexible in-dwelling venous catheter is recommended.

Interaction with other medicinal products and other forms of interaction
No formal interaction studies have been performed.
Gadoversetamide has been shown to cause interference in the measurement of serum calcium using the ortho-cresolphthalein complexone (OCP) colorimetric method. However, the administration of gadoversetamide does not cause a true decrease in serum calcium. In the presence of gadoversetamide, the OCP technique produces an erroneous, low value for plasma calcium. The magnitude of this measurement artefact is proportional to the concentration of gadoversetamide in the blood, and in patients with normal renal clearance accurate values can be obtained approximately 90 minutes following injection. In patients with compromised renal function, clearance of gadoversetamide will be slowed and the interference with calcium determination by OCP prolonged. Gadoversetamide does not affect other methods of measuring serum calcium, such as the arsenazo III colorimetric method, atomic absorption spectroscopy, and inductively coupled plasma mass spectroscopy.

Special precautions for disposal and other handling
Optimark is intended for single use only; any unused portions should be discarded. Optimark pre-filled syringes should be used immediately. Do not use the solution if it is discoloured or particulate matter is present. If non-disposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents.

Pre-filled syringes:

Assembly and Inspection
Inspect the syringe for signs of leakage. Do not use if leakage is observed.

After screwing the push rod into the syringe piston, it is important to turn the push rod an additional turn so that the grey piston rotates freely.

Prior to using the syringe, twist off grey tip cap and discard. Syringe is now ready for needle or infusion tubing attachment.

Discard syringe and unused portion of the solution after use.
Any unused product or waste material should be disposed of in accordance with local requirements. The peel-off tracking label on the pre-filled syringes should be stuck onto the patients record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.