Sanochemia
Reliable
Established active substance
Gadoteric acid, an active substance used for 30 years
- Over 91 million doses administered worldwide
- Available in more than 70 countries
- European leader in MRI (by volume)
Macrocyclic
- Where Gd³⁺ is ‘contained’ in the pre-organized cavity of the ligand.
& Ionic
- For a stronger metal-ligand electrostatic interaction.
…A unique chemical combination
Thermodynamically and kinetically stable molecule
… the higher the constants, the more stable the complex
High kinetic stability, due to the macrocyclic structure
To keep gadoteric acid (Gd) in chelated form for much longer.
Gd-DOTA = Gadoteric Acid –
Gd-BT-DO3A –
Gd-HP-DO3A –
Open-chain chelates –
– Gd-DOTA = Gadoteric Acid
– Open-chain chelates
The kinetic stability of macrocyclic chelates has proven to be dramatically superior to that of open-chain Gd chelates. The significantly higher kinetic inertness of macrocyclic GBCA (Gadolinium-Based Contrast Agents), compared to linear GBCA, undoubtedly contributes to the lower retention of macrocyclic GBCA in tissues.
High thermodynamic stability, due to ionicity
Thermodynamic stability (log Ktherm) of non-ionic and ionic Gd chelates
Non-ionic
Non-ionic
For GBCA, ionicity also contributes to a stronger bond between the Gd and the chelate. Macrocyclic and ionic GBCA demonstrate the highest thermodynamic and kinetic stability constants.
Reliable
With recognized physicochemical properties
Cyclolux®
Composition
- Active Substance – Gadoteric acid
1 ml of injection solution contains 279.32 mg of gadoteric acid (as meglumine salt), equivalent to 0.5 mmol/ml. - List of Excipients – Meglumine, DOTA, water for injections
- Transparent solution, colorless to yellow, free of visible particles
Physicochemical Properties
- pH – 6.5 – 8.0
- Viscosity at 37 °C. – 1.8 mPa.s
- Osmolarity at 37 °C – 1350 mOsm/kg H2O
European Commission decision confirms restrictions on the use of linear GBCA
On March 17, 2016, the European Medicines Agency (EMA) began a review of the risk of Gd deposition in brain tissue following the use of Gadolinium-based Contrast Agents (GBCAs) in patients undergoing MRI exams. On July 20, 2017, the EMA concluded its review of GBCAs, issuing recommendations to restrict the use of certain linear Gd agents; these recommendations were approved by the European Commission on November 23, 2017.
Summary of decision (on non-specific GBCA)
On March 17, 2016, the European Medicines Agency (EMA) began a review of the risk of Gd deposition in brain tissue following the use of Gadolinium-based Contrast Agents (GBCAs) in patients undergoing MRI exams. On July 20, 2017, the EMA concluded its review of GBCAs, issuing recommendations to restrict the use of certain linear Gd agents; these recommendations were approved by the European Commission on November 23, 2017.
Gd-CAS Macrocyclics
Gd-DOTA (gadoteric acid) Maintain
Gd-BT-DO3A (Gadobutrol) Maintain
Gd-HP-DO3A (Gadoteridol) Maintain
Macrocyclic agents are more stable and have a lower propensity to release gadolinium compared to linear agents. These products can continue to be used for their current indications, but at lower doses that sufficiently enhance images, and only when non-enhanced body scans are not suitable.
Gd-CAS Linears
Gd-DTPA-BMEA (Gadoversetamida) Suspended
Gd-DTPA (ácido gadopentético) Suspended
Gd-DTPA-BMA (Gadodiamida) Suspended
Gd-BOPTA (gadobenic acid) Restricted use for liver scans
The EMA recommended restrictions and suspensions for certain intravenous linear agents to avoid any potential risks associated with gadolinium deposition in the brain. Gadobenic acid can continue to be used for liver scans as it is taken up by the organ.
Trust. Safety. Quality.
Since the early 2000s, Antmed’s high-pressure syringes and pressure connection systems have been used by healthcare institutions. With perfect compatibility, reliable performance, and uncompromising operational safety, cardiologists, radiologists, technicians, and nurses have come to trust and choose Antmed’s quality products over the past 24 years. When our customers require our products for accurate diagnostics and effective treatments, we ensure that our high-pressure syringes and connection systems are of the highest quality to meet their needs and ensure patient safety.
For more information or before use, consult the Summary of Product Characteristics (SPC).
Below is a summary:
According to the SPC approved in Portugal (currently valid version approved on 24-02-2023)
Name of the medicine in Portugal
Cyclolux® 0.5 mmol/ml injection solution
Qualitative and quantitative composition
1 ml of injection solution contains 279.32 mg of gadoteric acid (as meglumine salt), equivalent to 0.5 mmol/ml.
List of excipients
Meglumine, DOTA, Water for injections.
Nature and content of the container:
1 and 10 disposable and transparent Type II glass vials of 10 ml and 20 ml (15 or 20 ml filled). Not all presentations may be marketed.
Therapeutic Indications
This medicine is intended for diagnostic purposes only.
Cyclolux® is a contrast agent indicated for contrast enhancement in Magnetic Resonance Imaging (MRI) to improve visualization/delineation in:
Adult and pediatric population (0-18 years)
- MRI of the central nervous system including brain, spinal, and adjacent tissue lesions
- Whole-body MRI including lesions in the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system.
Adult population
- Magnetic Resonance Angiography (MRA) including lesions or stenoses of non-coronary arteries.
Cyclolux® should only be used when diagnostic information is essential and not available with non-enhanced MRI.
Dosage and Administration
Dosage
The lowest dose that provides sufficient improvement for diagnostic purposes should be used. The dose should be calculated based on the patient’s body weight and should not exceed the recommended dose per kilogram of body weight detailed in the SPC.
Mode of Administration
The product is indicated for intravenous administration only.”
Drug interactions and other forms of interaction
Concurrent medications should be considered
Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists: these medications decrease the compensatory effectiveness of cardiovascular mechanisms in blood pressure issues. The radiologist should be informed before the injection of gadolinium complexes, and resuscitation equipment should be available.
Contraindications
Hypersensitivity to gadoteric acid, meglumine, or any medication containing gadolinium.
Adverse effects
The adverse effects associated with the use of gadoteric acid are typically of moderate to mild intensity and transient in nature. Local reactions at the injection site, nausea, and headaches are the most frequently observed reactions.
During clinical trials, nausea, headaches, local reactions at the injection site, cold sensation, hypotension, drowsiness, dizziness, warmth sensation, burning sensation, dermatitis, asthenia, dysgeusia, and hypertension were the most frequently observed adverse effects, with unusual occurrences (≥1/1000 to <1/100).
Post-marketing, the most common adverse reactions reported following the administration of gadoteric acid were nausea, vomiting, itching, and hypersensitivity reactions.
In hypersensitivity reactions, the most frequently observed were skin reactions, which may be localized, extended, or generalized. These reactions occur more frequently immediately (during the injection or within half an hour after the start of the injection) or, sometimes, can be delayed (one hour to several days after the injection), in the form of skin reactions.
Isolated cases of nephrogenic systemic fibrosis (NSF) with gadoteric acid have been reported, most of which were in patients coadministered with other gadolinium-based contrast agents (see section 4.4 of the SPC).
Adverse reactions are listed below by SOC (System Organ Class) and by frequency with the following guidelines: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), unknown (cannot be estimated from the available data). Data presented from clinical trials involve 2,822 patients when available, or from an observational study set involving 185,500 patients.”
System Organ Class: Frequency: adverse reaction
Immune system disorders:
Uncommon: hypersensitivity;
Very rare: anaphylactic reaction, anaphylactoid reaction
Psychiatric disorders:
Rare: anxiety;
Very rare: agitation
Nervous system disorders:
Uncommon: headache, dysgeusia, dizziness, drowsiness, paresthesia (including burning sensation);
Rare: pre-syncope;
Very rare: coma, seizure, syncope, tremor, parosmia
With confidence in the level of safety
Gadoteric acid belongs to the low-risk group of NSF-risk gadolinium-based contrast agents (GBCAs).
No unequivocal cases of Nephrogenic Systemic Fibrosis (NSF) have been reported since the market introduction of Cyclolux® (a product already marketed in Austria). Guidelines from the European Society of Urogenital Radiology (ESUR) on gadolinium-based contrast agents (GBCAs) and NSF define.
Contrast agents classified as having the lowest risk of NSF:
- Gadoterate meglumine (ionic cyclic chelate (DOTA))
- Gadobutrol (non-ionic cyclic chelate (BT-DO3A))
- Gadoteridol (non-ionic cyclic chelate (HP-DO3A))
Recommendations:
- These agents should be used with CAUTION in patients with eGFR < 30 ml/min. There should be at least a 7-day interval between two injections.
- Pregnant women: can be used to provide essential diagnostic information.
- Breastfeeding women: it should be discussed whether breast milk should be discarded for 24 hours after using the contrast agent.
Laboratory tests for renal function (eGFR) are not mandatory.
Recommendations for all patients:
- Never deny a patient a clinically appropriate MRI examination.
- In all patients, the smallest amount of contrast medium necessary to achieve a diagnostic result should be used.
- Always record the name and dose of the contrast agent used in the patient’s records.
T1-weighted hyperintensities in the Dentate Nucleus and Globus Pallidus have been reported on non-contrast MRI after repeated injections of linear GBCAs:
- In patients with normal renal function.
- Caused by the retention of gadolinium in the brain tissue.
The EMA stated that ‘there is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however, the EMA has recommended restrictions on some intravenous linear agents to prevent any risks that may be potentially associated with gadolinium deposition in the brain.
With confidence in the level of safety
Ocular disorders:
- Rare: eyelid edema
- Very rare: conjunctivitis, ocular hyperemia, blurred vision, increased tearing
Cardiac disorders:
- Rare: palpitations
- Very rare: tachycardia, cardiac arrest, arrhythmia, bradycardia
Vascular disorders:
- Uncommon: hypotension, hypertension
- Very rare: pallor, vasodilation
Respiratory, thoracic, and mediastinal disorders:
- Rare: sneezing
- Very rare: cough, dyspnea, nasal congestion, respiratory arrest, bronchospasm, laryngospasm, pharyngeal edema, dry throat, pulmonary edema
Gastrointestinal disorders:
- Uncommon: nausea, abdominal pain
- Rare: vomiting, diarrhea, excessive salivation
Dermal and subcutaneous tissue disorders:
- Uncommon: dermatitis
- Rare: urticaria, itching, hyperhidrosis
- Very rare: erythema, angioedema, eczema
- Unknown: nephrogenic systemic fibrosis
Musculoskeletal and connective tissue disorders:
- Very rare: muscle cramps, muscle weakness, back pain
General disorders and administration site conditions:
- Uncommon: sensation of warmth, sensation of cold, asthenia, local injection reactions (extravasation, pain, discomfort, edema, inflammation, cold)
- Rare: chest pain, chills
- Very rare: malaise, chest discomfort, fever, facial edema, necrosis at the injection site (in case of extravasation), superficial phlebitis
Investigations:
- Very rare: Decrease in oxygen saturation
Pharmacodynamic Properties
Pharmacotherapeutic Group: 19.2 – Contrast agents for magnetic resonance imaging, paramagnetic contrast agents
ATC Code: V08 CA 02 (Gadoteric acid)
Shelf Life: 3 years
Marketing Authorization Number:
- Registration No. 5850318 – 1 unit of 10 ml
- Registration No. 5850326 – 10 units of 10 ml
- Registration No. 5850334 – 1 unit of 15 ml
- Registration No. 5850342 – 10 units of 15 ml
- Registration No. 5850367 – 10 units of 20 ml
- Registration No. 5850359 – 1 unit of 20 ml
Text Revision Date: February 2023
Prescription Status: Prescription-only medication.
The following adverse reactions have been reported with other intravenous contrast agents for MRI:
System organ classification: Adverse Reaction
Blood and lymphatic system disorders:
- Hemolysis
Psychiatric disorders:
- Confusion
Ocular disorders:
- Transient blindness, eye pain
Ear and labyrinth disorders:
- Tinnitus, ear pain
Respiratory, thoracic, and mediastinal disorders:
- Asthma
Gastrointestinal disorders:
- Dry mouth
Dermal and subcutaneous tissue disorders:
- Bullous dermatitis
Renal and urinary disorders:
- Urinary incontinence, renal tubular necrosis, acute renal failure
Investigations:
- Prolonged PR interval on electrocardiogram, excess iron in the blood, excess bilirubin in the blood, excess ferritin in serum, abnormal liver function tests
Adverse Reactions in Children:
- The safety of pediatric patients has been considered in clinical trials and post-marketing studies. Compared to adults, the safety profile of gadoteric acid does not show any specificities in children. Most reactions are gastrointestinal symptoms or signs of hypersensitivity.
Reporting of Suspected Adverse Reactions:
- Reporting suspected adverse reactions after the authorization of the medicine is important as it allows for ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals are requested to report any suspected adverse reactions through the national reporting system.
A Broad Range of Indications for Cyclolux®
Cyclolux® is a contrast agent indicated for enhancing contrast in Magnetic Resonance Imaging (MRI) for improved visualization/definition in:
Adult and Pediatric Populations (0-18 years):
-
- MRI of the central nervous system, including brain, spinal cord, and adjacent tissues.
- Whole-body MRI, including lesions in the liver, kidneys, pancreas, pelvis, lungs, heart, breasts, and musculoskeletal system.
- Adult Population:
- Magnetic Resonance Angiography (MRA), including lesions or stenoses of non-coronary arteries.
Cyclolux® should be used only when diagnostic information is essential and not available with non-enhanced MRI.
Cyclolux® is intended for diagnostic purposes only and is available in various pharmaceutical forms (vials of 10, 15, and 20 ml).
A single dose/administration is 0.1 to 0.3 mmol/kg (i.e., 0.2 to 0.6 ml/kg)
Recommended dose of Cyclolux® for patients of all ages: Consult the Cyclolux® Summary of Product Characteristics (SPC) for information on dosage for specific indications or dosage adjustments for special populations. Cyclolux® is intended for intravenous administration only.
Even in infants and high-risk patients.
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