Optimark
gadoversetamide
Gadoversetamide
This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What Optimark is and what it is used for
What you need to know before you are given Optimark
How Optimark is given
Possible side effects
How to store Optimark
Contents of the pack and other information
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Optimark contains the active substance gadoversetamide. Gadoversetamide is used as a ‘contrast agent’ in magnetic resonance imaging.
Optimark is for diagnostic use, only. It is used in adult patients and children of two years and older, who are undergoing magnetic resonance imaging (MRI), a type of scan where images of the internal organs are taken. Optimark is used to obtain a clearer scan in patients who have or are thought to have abnormalities in the brain, spine or liver.
if you are allergic
to the active substance gadoversetamide or
to any of the other ingredients of Optimark (see section 6), or
to other gadolinium contrast agents.
You must not be given Optimark if
you suffer from severe and/or acute 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 must not be used in newborn 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.
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
you are feeling thirsty and/or if you have only had small quantities or nothing to drink before the examination
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 on a controlled sodium diet
If any of these apply to you, your doctor will decide whether the intended examination is possible or not.
Optimark is not recommended in children who are below the age of two years.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Optimark should not be used during pregnancy unless strictly necessary.
Breast-feeding should be discontinued for at least 24 hours after you receive Optimark.
Medicinal product no longer authorised
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 taking this medicine.
If you are an ambulant patient and plan to drive or use tools or machines, take into account that dizziness may incidentally occur after you undergo a procedure involving the injection of Optimark. Up to 1 in 100 people may be affected.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose of up to 17 ml, i.e. it is essentially ‘sodium-free’.
10 ml vials and 15 ml vials contain less than 1 mmol sodium; i.e. they are essentially ‘sodium free‘. Higher doses contain 1 mmol sodium or more, which should be taken into consideration for patients
on a controlled sodium diet.
20 ml of the solution contain 28.75 mg sodium. 30 ml of the solution contain 43.13 mg sodium.
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.
The usual dose of 0.2 ml/kg body weight is the same in adults and children of 2 years and older. It would account for 14 ml for a 70 kg individual, and this volume would be 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. In adults, a second dose
may be given within 30 minutes of the first injection. When looking at certain abnormalities in the
brain, Optimark may need to be used at three times the usual dose in one injection in adults. 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.
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 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 medicines, this medicine can cause side effects, although not everybody gets them.
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:
Medicinal product no longer authorised
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).
Most of the side effects observed after the use of Optimark were of mild to moderate intensity and transient in nature. The most common side effects were a strange taste in the mouth, feeling hot, headache and dizziness.
Possible side effects are described in greater detail below.
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:
Frequency | Possible side effects |
Common (may affect up to 1 in 10 people) | headache, strange taste in the mouth, feeling hot |
Uncommon (may affect up to 1 in 100 people) | allergic/hypersensitivity reaction, dizziness, tingling sensation, numbness, reduced sense of smell, skin red and warm, nasal congestion, sore throat, nausea, diarrhoea, itching, rash, chest discomfort, chest pain, feeling cold including cold feeling in extremities, administration site reactions, changes in blood calcium levels |
Frequency | Possible side effects |
Rare (may affect up to 1 in 1000 people) | decreased appetite, feeling anxious, sleep disorder, drowsy feeling, burning sensation, a sensation of movement or spinning, ringing in the ears, eyelid redness, eye pain, vision blurred, bloodshot eyes, awareness of the heartbeat, irregular heartbeats, extra heartbeats, low blood pressure, shortness of breath, hoarseness, runny nose, throat constriction, mouth watering, abdominal pain, constipation, dry mouth, hives, cold sweat, redness, higher blood level of a substance (creatinine) usually eliminated by the kidneys, blood in urine, face swollen, weakness and similar symptoms like fatigue and general feeling of being unwell, fever, swelling in limbs, chill, pain, cold feeling in extremities, liver enzyme increased, urine analysis abnormal, mineral values in urine increased, protein in urine, heart and muscle enzyme increased, decreased haemoglobin, feeling confused and disoriented, shaking, convulsion, pink eye, fast heart beat, high blood pressure, tightening of the airways, swollen throat or voice box, raw throat, cough, itchy nose, sneezing, sweating |
Very rare (may affect up to 1 in 10,000 people) | swelling around the eyes, abnormal ECG heart tracing, fainting, vomiting |
Not known (frequency cannot be estimated from the available data) | hardening of the skin which may affect also soft tissue and internal organs (nephrogenic systemic fibrosis), feeling unwell |
There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may affect also soft tissue and internal organs).
Medicinal product no longer authorised
When Optimark was used in children aged 2 or older they had similar side effects as in adults.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety
of this medicine.
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 carton and on the syringe label after EXP.
Keep the syringe in the outer carton in order to protect from light. Do not refrigerate or freeze.
The medicine should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Do not use the solution if it is discoloured or particulate matter is present.
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.
The active substance is gadoversetamide.
1 ml contains 330.9 mg gadoversetamide, equivalent to 500 micromol. Each 10 ml syringe contains 3309 mg gadoversetamide.
Each 15 ml syringe contains 4963.5 mg gadoversetamide. Each 20 ml syringe contains 6618 mg gadoversetamide. Each 30 ml syringe contains 9927 mg gadoversetamide.
The other ingredients are: versetamide, calcium hydroxide, calcium chloride dihydrate, sodium hydroxide and/or hydrochloric acid, water for injections.
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 10 x 10 ml
1 x 15 ml 10 x 15 ml
1 x 20 ml 10 x 20 ml
1 x 30 ml 10 x 30 ml
Not all package sizes may be marketed.
Marketing Authorisation Holder: Guerbet
Medicinal product no longer authorised
15, rue des Vanesses
93420 Villepinte France
For any information about this medicine, please contact the Marketing Authorisation Holder.
Manufacturer
Mallinckrodt Medical Imaging Ireland Damastown
Mulhuddart, Dublin 15 Ireland
site .
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 adult patients and in children of two years and older with known or highly suspected pathology.
Hypersensitivity to gadoversetamide or to other gadolinium containing products or to any of the excipients.
Optimark is contraindicated in patients with severe renal impairment (GFR
< 30ml/min/1.73 m2) and/or acute kidney injury, in
patients who have had liver transplantation or in
patients in the perioperative liver transplantation period and in
neonates up to 4 weeks of age.
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.
Hypersensitivity
Allergoid and other idiosyncratic reactions also may occur 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.
Medicinal product no longer authorised
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.
Patients with impaired renal function
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 gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30ml/min/1.73 m²) and/or acute kidney injury. Optimark is contraindicated in these patients (see section Contraindications). 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 who have had or are undergoing liver transplantation and in neonates. The risk for development of NSF in patients with moderate renal impairment (GFR 30–59 ml/min/1.73 m²) is unknown; therefore, Optimark should only be used after careful risk-benefit evaluation in patients with moderate renal impairment. 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.
In patients with baseline renal impairment, acute kidney injury requiring dialysis has occurred with the use of Optimark. The risk of acute kidney injury may increase with an increased dose of the contrast agent. Administer the lowest dose possible for adequate imaging.
Children and adolescents
Optimark must not be administered with an autoinjector. The required dose should be administered by hand to children of 2 to 11 years to avoid overdosage by mistake.
Neonates and infants
Optimark should not be used in children below the age of two years. Safety and efficacy have not been studied in this age group.
Elderly
Medicinal product no longer authorised
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. it is essentially ‘sodium-free’.
10 ml vials and 15 ml vials contain less than 1 mmol sodium; i.e. they are essentially ‘sodium free‘. Higher doses contain 1 mmol sodium or more, which should be taken into consideration for patients on a controlled sodium diet.
20 ml of the solution contain 28.75 mg sodium. 30 ml of the solution contain 43.13 mg sodium.
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
There are no data from the use of gadoversetamide in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Optimark should not be used during pregnancy unless the clinical condition of the woman requires use of gadoversetamide.
Breast-feeding
It is unknown whether gadoversetamide is excreted in human milk. There is insufficient information on the excretion of gadoversetamide in animal milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued for at least 24 hours after the administration of Optimark.
Fertility
Nonclinical data did not reveal special hazards for humans based on conventional studies of reproductive toxicity. Clinical studies on fertility have not been performed.
Optimark should only be administered by physicians experienced in clinical MRI practice.
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.
Posology
The agent should be administered as a bolus peripheral intravenous injection at a dose of 0.2 ml/kg (100 micromol/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 %) solution for injection. The imaging procedure should be completed within 1 hour of administration of the contrast medium.
Repeat dose
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 0.2 ml/kg (100 micromol/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 (2 years and older), in
patients with renal impairment, or the elderly. The repeat dose is not recommended in these populations.
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 300 micromol/kg body weight of Optimark may lead to higher diagnostic confidence.
Medicinal product no longer authorised
Paediatric population
No dose adjustment is considered necessary in children more than 2 years of age.
Optimark is contraindicated in neonates up to 4 weeks of age. Use of Optimark is not recommended in children less than 2 years of age because the safety, efficacy, and impact of immature kidney function have not been studied in this age group.
Elderly (aged 65 years and above)
No dosage adjustment is considered necessary. Caution should be exercised in elderly patients.
Renal and hepatic impairment
Optimark is contraindicated in patients with severe renal impairment (GFR < 30 ml/min/1.73 m2) and/or acute renal injury and in patients who have had liver transplantation or in patients in the perioperative liver transplantation period. Optimark should only be used after careful risk/benefit evaluation in patients with moderate renal impairment (GFR 30-59 ml/min/1.73 m2) 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.
Method of administration
The agent should be administered as a bolus peripheral intravenous injection. 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 %) solution for injection. Insertion of a flexible in-dwelling venous catheter is recommended.
Optimark must not be administered with an autoinjector to children of 2 to 11 years.
Precautions to be taken before handling or administering the medicinal product
The container and the solution should be inspected prior to use.
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.
Optimark is intended for single use only; any unused portions should be discarded.
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.
Assembly and Inspection
Inspect the syringe for signs of leakage. Do not use if leakage is observed.
Medicinal product no longer authorised
After screwing the push rod into the syringe piston, it is important to turn the push rod an additional ½ 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.
If electronic patient records are used, the name of the product, the batch number and the dose should be entered into the patient record.