Source: European Medicines Agency (EU) Revision Year: 2017 Publisher: Guerbet, 15, rue des Vanesses, 93420, Villepinte, France
Hypersensitivity to gadoversetamide or to other gadolinium containing products, or to any of the excipients listed in section 6.1.
Optimark is contraindicated:
As with any paramagnetic contrast agent, enhancement of MRI with gadoversetamide 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.
Allergoid and other idiosyncratic reactions also may occur with gadoversetamide, which could become manifest in form of cardiovascular, respiratory and skin reactions (see section 4.8). 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:
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.
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.
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.
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.
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/1.73m²) and/or acute kidney injury. Optimark is contraindicated in these patients (see section 4.3). 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 (see section 4.3).
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.
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.
Optimark should not be used in children below the age of two years. Safety and efficacy have not been studied in this age group.
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.
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.
20 ml of the solution contain 28.75 mg sodium.
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.
No formal interaction studies have been performed.
Optimark 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.
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 (see section 5.3). Optimark should not be used during pregnancy unless the clinical condition of the woman requires use of gadoversetamide.
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.
Non-clinical data did not reveal special hazards for humans based on conventional studies of reproductive toxicity. Clinical studies on fertility have not been performed.
Optimark has no or negligible influence on the ability to drive and use machines. Ambulant patients while driving vehicles or operating machinery should take into account that acute dizziness may uncommonly (≥1/1,000 to <1/100) occur (see section 4.8).
Most of the adverse reactions were of mild to moderate intensity and transient in nature. The most common adverse reactions were dysgeusia, feeling hot, headache and dizziness.
The majority of adverse reactions observed after the use of gadoversetamide were found to be adverse reactions of the nervous system, followed by general adverse reactions, gastrointestinal disorders/skin and subcutaneous tissue disorders.
Serious adverse reactions have been reported and include anaphylactic reactions, cardiovascular reactions, and allergic respiratory disorders. Treatment should be symptomatic and immediate access to necessary medicinal products and emergency equipment should be available should a serious event occur.
The following adverse reactions have been reported from clinical trials and from post-marketing use of gadoversetamide. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Uncommon: Anaphylactic reaction
Rare: Decreased appetite
Rare: Anxiety, Sleep disorder, Confusion and disorientation
Common: Headache, Dysgeusia
Uncommon: Dizziness, Hypoaesthesia, Paraesthesia, Parosmia
Rare: Convulsion, Tremor, Somnolence, Burning sensation
Very Rare: Syncope
Rare: Erythema of eyelid, Eye pain, Vision blurred, Conjunctivitis, Ocular hyperaemia
Rare: Tinnitus, Vertigo
Rare: Palpitations, AV block first degree, Extrasystoles, Tachycardia, Arrhythmia
Uncommon: Flushing
Rare: Hypotension, Hypertension
Uncommon: Nasal congestion, Throat irritation
Rare: Dyspnoea, Dysphonia, Rhinorrhoea, Throat tightness, Bronchospasm, Cough, Laryngeal/pharyngeal oedema, Pharyngitis, Rhinitis, Sneezing
Uncommon: Nausea, Diarrhoea
Rare: Salivary hypersecretion, Abdominal pain, Constipation, Dry mouth
Very Rare: Vomiting
Uncommon: Pruritus, Rash
Rare: Urticaria, Cold sweat, Erythema, Hyperhidrosis
Very Rare: Periorbital oedema
Not known: Nephrogenic systemic fibrosis (NSF)
Rare: Blood creatinine increased, Haematuria
Common: Feeling hot
Uncommon: Chest discomfort, Chest pain, Feeling cold (including peripheral coldness), Administration site reactions
Rare: Chills, Pain, Face oedema, Asthenic conditions including asthenia, fatigue, and malaise, Fever, Oedema peripheral, Feeling abnormal
Uncommon: Blood calcium abnormal
Rare: ALT increased, Urine analysis abnormal, Urine electrolytes abnormal, albumin in urine, CPK Increased, Haemoglobin decreased
Very Rare: Electrocardiogram QT prolonged
Local reactions have occurred at the injection site and may lead to local irritation type reactions.
Cases of nephrogenic systemic fibrosis (NSF) have been reported with Optimark (see section 4.4). Cases of gadolinium associated skin plaques, with demonstrated sclerotic bodies on histology, have been reported with some gadolinium-containing contrast agents in patients who do not otherwise have symptoms or signs of nephrogenic systemic fibrosis.
Optimark has been studied in children of 2 years and older with a similar safety profile as shown in the adult population.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, Optimark should not be mixed with other medicinal products.
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