Instructions Dotavist solution for injection 279.32 mg/ml bottle 15 ml No. 1
Composition
active ingredient: gadoteric acid;
1 ml of solution contains 279.32 mg (0.5 mmol) of gadoteric acid, which corresponds to 376.92 mg of gadoterate meglumine;
Excipients: meglumine, water for injection.
Dosage form
Solution for injection.
Main physicochemical properties: transparent colorless or slightly yellowish solution, practically free of mechanical inclusions.
Pharmacotherapeutic group
Paramagnetic contrast agents. Gadoteric acid. ATX code V08C A02.
Pharmacological properties
Pharmacodynamics
Gadoteric acid has paramagnetic properties that enhance contrast in magnetic resonance imaging (MRI). Gadoteric acid has no specific pharmacodynamic activity and is biologically highly inert.
Pharmacokinetics
After intravenous injection, gadoteric acid is distributed in the extracellular fluids of the body. Gadoteric acid does not bind to plasma albumin.
In patients with normal renal function, the plasma half-life is approximately 90 minutes. Gadoteric acid is excreted unchanged by glomerular filtration. In renal failure, plasma clearance is slowed.
In animals, the level of excretion of gadoteric acid into milk is low, and penetration through the placental barrier is slow.
There are currently no data on kinetics in the elderly, children, pregnant or breastfeeding women, or patients with liver damage.
Indication
It is used exclusively for diagnostic purposes if the use of magnetic resonance imaging (MRI) without contrast enhancement is not possible.
Adults
Contrast enhancement in MRI.
MRI of the brain and spinal cord: detection of tumors of the brain, spine, surrounding tissues, prolapsed intervertebral discs, infectious diseases.
MRI of the whole body, including visualization of pathology of the kidneys, heart, uterus, ovaries, organs of the thoracic and abdominal cavity, and bone and joint pathology.
Angiography.
Children (0–18 years)
Contrast enhancement in MRI.
MRI of the brain and spinal cord: detection of tumors of the brain, spine, surrounding tissues, prolapsed intervertebral discs, infectious diseases.
MRI of the whole body, including visualization of pathology of the kidneys, heart, uterus, ovaries, organs of the thoracic and abdominal cavity, and bone and joint pathology.
Contraindication
Hypersensitivity to gadoteric acid, meglumine or any medicinal product containing gadolinium.
Interaction with other medicinal products and other types of interactions
No interactions with other drugs have been observed. Adequate drug-drug interaction studies have not been conducted.
Concomitant medications to consider. Beta-blockers, vasoactive agents, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists – these medications reduce the effectiveness of the cardiovascular compensation mechanism for blood pressure disorders. Before administering gadolinium compounds, the radiologist should be informed that the patient is taking these medications, and equipment for resuscitation measures should be prepared in advance.
Application features
Do not use the intrathecal route of administration. Strictly follow the rules for intravenous injection: extravasation may lead to local intolerance reactions requiring conventional local treatment.
The usual precautions for MRI should be observed: patients with pacemakers, ferromagnetic vascular clamps, infusion pumps, nerve stimulators, cochlear implants, or suspected intracorporeal metallic foreign bodies, especially in the eye, are contraindications to MRI.
As with other gadolinium-containing contrast agents, hypersensitivity reactions, including life-threatening reactions, may occur. Hypersensitivity reactions may be allergic (described as anaphylactic reactions if identified as serious) or non-allergic. Reactions may be immediate (less than 60 minutes) or delayed (up to 7 days). Anaphylactic reactions occur immediately and can be fatal. Anaphylactic reactions are not dose-related, may occur even after the first dose of the drug, and are often unpredictable. Regardless of the dose administered, there is always a risk of hypersensitivity. Patients who have already developed a reaction during a previous administration of a gadolinium-containing contrast agent are at increased risk of developing another reaction with subsequent administration of the same drug or possibly other drugs, so these patients are at high risk of developing allergic reactions. The administration of gadoteric acid may exacerbate symptoms of existing asthma. In patients with asthma whose course has worsened as a result of taking the drug, the decision to use gadoteric acid should be made after a careful assessment of the risk/benefit ratio. It is known that in patients taking beta-blockers, especially in case of concomitant bronchial asthma, hypersensitivity reactions may be exacerbated by the use of iodinated contrast media. These patients may be refractory to standard treatment of hypersensitivity reactions with beta-agonists. Before injection of any contrast medium, the patient should be asked about his/her allergic history (e.g., allergy to seafood, hay fever, urticaria), sensitivity to contrast media, and the presence of bronchial asthma, since a higher frequency of adverse reactions to contrast media has been reported in patients with these conditions. In addition, premedication with antihistamines and/or glucocorticoids may be considered. The examination should be performed under close medical supervision. In the event of a hypersensitivity reaction, the contrast medium should be discontinued immediately and specific therapy should be initiated if necessary. Venous access should be maintained throughout the examination. Appropriate medications (e.g. adrenaline and antihistamines), an endotracheal tube and a respirator should be available to provide immediate emergency care.
Kidney dysfunction
Before administering gadoteric acid, it is recommended that all patients be screened for renal dysfunction with interpretation of laboratory test results.
Nephrogenic systemic fibrosis (NSF) has been reported with the use of some gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30 ml/min/1.73 m2). Patients undergoing liver transplantation are at particular risk because the incidence of acute renal failure is high in this group. Since there is a possibility that NSF may also occur with gadoteric acid, the drug should be used in patients with severe renal impairment and in patients before and after liver transplantation only after careful risk/benefit assessment and if the diagnostic information is important but not available with non-contrast MRI.
Following administration of gadoteric acid, hemodialysis may be used to remove gadoteric acid from the body. There is no evidence to recommend initiating hemodialysis for the prevention or treatment of NSF in patients not already receiving hemodialysis.
Elderly patients
Since renal clearance of gadoteric acid may be reduced in elderly patients, it is especially important to monitor individuals aged 65 years and older for the development of renal dysfunction.
Children
Newborns and young children
Due to immature renal function in neonates under 4 weeks of age and children under 1 year of age, gadoteric acid should only be used in these patients after careful consideration of all risks.
CNS disorders
As with other gadolinium-containing contrast agents, special precautions are necessary in patients with a low seizure threshold. Precautions should be taken, such as close monitoring of the patient. All equipment and medications needed to treat seizures should be prepared in advance.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects of the drug on the ability to drive and use machines have been conducted. Patients receiving the drug on an outpatient basis should be aware that they may suddenly feel nauseous while driving or operating machinery.
Use during pregnancy or breastfeeding
Pregnancy
There are no data on the use of gadoteric acid in pregnant women. Studies in animal models do not indicate direct or indirect harmful effects with respect to reproductive function. Gadoteric acid should not be used during pregnancy unless the clinical condition of the woman requires its use.
Gadolinium-containing contrast agents are excreted in breast milk in small amounts. Given the small amount of the drug excreted in breast milk and the poor absorption from the intestine, no effects on the newborn are expected when using clinical doses. The question of continuing or discontinuing breastfeeding for 24 hours after gadoteric acid administration should be left to the discretion of the physician and the nursing mother.
Method of administration and doses
The lowest dose that provides sufficient contrast for diagnostic purposes should be used.
The dose should be calculated based on the patient's body weight. This dose should not exceed the recommended dose per kilogram of body weight, as detailed in this section.
Adults, including the elderly.
MRI of the brain and spinal cord. In most cases, the recommended dose is 0.1 mmol/kg, i.e. 0.2 ml/kg, which is sufficient to provide diagnostically adequate contrast.
If clinical suspicion of a lesion persists despite normal MRI findings, a subsequent injection of 0.2 mmol/kg, i.e. 0.4 mL/kg, over 30 minutes may facilitate tumor visualization and aid in treatment selection.
Whole body MRI and angiography.
An administration of 0.1 mmol/kg, i.e. 0.2 ml/kg, is recommended to ensure diagnostically adequate contrast.
Angiography: in exceptional cases (e.g. failure to obtain adequate quality images of a large vascular area), a second sequential injection of 0.1 mmol/kg, i.e. 0.2 ml/kg, may be justified. However, if 2 sequential doses of Dotavist are to be administered before angiography of individual areas (such as arteries of the legs or lungs), 0.05 mmol/kg, i.e. 0.1 ml/kg of the drug may be administered in each dose, depending on the available imaging equipment.
Special populations.
Kidney dysfunction
In patients with mild or moderate renal impairment (GFR ≥ 30 mL/min/1.73 m2), the adult dose should be used.
In patients with severe renal impairment (GFR <30 ml/min/1.73 m2), in patients before and after liver transplantation, Dotavist should only be used after careful risk/benefit assessment, and if the diagnostic information is important but not available with MRI without contrast. If Dotavist is necessary, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a scan. Due to the lack of information on repeated administration, Dotavist injections should not be repeated if the interval between injections is less than 7 days.
Elderly patients (aged 65 years and over)
There is no need for dose adjustment. Use with caution in elderly patients.
Liver dysfunction
In patients with impaired liver function, the adult dose is used. However, caution is recommended, especially in the perioperative period of liver transplantation.
Children (0-18 years old)
MRI of the brain and spinal cord/MRI of the whole body
The recommended maximum dose of gadoteric acid is 0.1 mmol/kg body weight. No more than one dose should be administered during a scan.
Due to immature renal function in neonates up to 4 weeks of age and children up to 1 year of age, Dotavist should only be used after careful consideration of all factors, at a dose not exceeding 0.1 mmol/kg body weight. In the absence of information on repeated administration, injections of Dotavist should not be repeated if the interval between injections is less than 7 days.
Angiography
Gadoteric acid is not recommended for angiography in children under 18 years of age due to insufficient data on its efficacy and safety when prescribed for this purpose.
Method of application
The drug is intended for intravenous administration only.
Intravenous administration of contrast media should, if possible, be performed with the patient in the supine position. After administration, the patient should be observed for at least half an hour, as experience shows that most adverse effects occur during this period.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless opened in controlled and validated aseptic conditions.
Pediatric population
Depending on the amount of Dotavist to be administered to the child, it is best to use Dotavist vials with a volume adapted to that amount in order to administer the most accurate volume of the drug.
In newborns and infants, the required dose should be administered manually.
Children
Due to immature renal function in neonates under 4 weeks of age and children under 1 year of age, gadoteric acid should only be used in these patients after careful consideration of all risks.
Overdose
Gadoteric acid can be removed by hemodialysis. However, there is no evidence that hemodialysis is useful for the prevention of nephrogenic systemic fibrosis (NSF).
Adverse reactions
Side effects associated with the use of gadoteric acid are usually mild to moderate in intensity and short-lived. The most commonly observed are injection site reactions, nausea, and headache.
During clinical trials, the most commonly observed adverse reactions were nausea, headache, injection site reactions, chills, hypotension, somnolence, dizziness, feeling hot, burning sensation, rash, asthenia, dysgeusia and hypertension, with a frequency estimated as uncommon (≥1/1000 - <1/100).
In post-marketing studies, the most common adverse reactions following administration of gadoteric acid were nausea, vomiting, pruritus, and hypersensitivity reactions.
Among the hypersensitivity reactions, skin reactions were most commonly observed, which may be localized, widespread or generalized.
These reactions most often occur immediately (during the injection or within one hour after the start of the injection), sometimes with a delay (from one hour to several days after the injection), manifesting in such cases as skin changes.
Immediate-type hypersensitivity reactions include one or more effects that occur simultaneously or sequentially, and are most often disorders of the skin, respiratory system, gastrointestinal tract, joints and/or cardiovascular system.
Each symptom can be a warning sign of the onset of shock and very rarely leads to death.
Isolated cases of NSF have been reported with gadoteric acid, most of which occurred in patients who were concurrently administered other gadolinium-containing contrast agents.
Table 1 below lists adverse reactions by system organ class and frequency using the following convention: very common (≥ 1/10), common (≥ 1/100 to 1 <1/10), uncommon (≥ 1/1,000 to 1 <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000), frequency not known (cannot be estimated from the available data). Data are presented from clinical trials.
Table 1.
| Organ system class | Frequency: adverse reaction |
| On the part of the immune system | Uncommon: hypersensitivity Very rare: anaphylactic reaction, anaphylactoid reaction |
| From the psyche | Rare: anxiety Very rare: agitation |
| From the nervous system | Uncommon: headache, dysgeusia, dizziness, somnolence, paraesthesia (including burning sensation) Rare: presyncope Very rare: coma, convulsions, syncope, tremor, parosmia |
| From the organs of vision | Rare: eyelid edema Very rare: conjunctivitis, eye hyperemia, blurred vision, increased lacrimation |
| Cardiovascular system | Rare: palpitations Very rare: tachycardia, cardiac arrest, arrhythmia, bradycardia |
| From the vascular side | Uncommon: hypotension, hypertension Very rare: pallor, vasodilation |
| Respiratory, thoracic and mediastinal disorders | Rare: sneezing Very rare: cough, shortness of breath, nasal congestion, respiratory arrest, bronchospasm, laryngospasm, pharyngeal edema, dry throat, pulmonary edema |
| Gastrointestinal tract | Uncommon: nausea, abdominal pain Rare: vomiting, diarrhea, hypersecretion of salivary glands |
| Skin and subcutaneous tissue disorders | Uncommon: rash Rare: urticaria, pruritus, hyperhidrosis. Very rare: erythema, angioedema, eczema. Not known: nephrogenic systemic fibrosis |
| Musculoskeletal and connective tissue disorders | Very rare: muscle cramps, muscle weakness, back pain |
| General disorders and local complications at the injection site | Uncommon: feeling hot, feeling cold, asthenia, injection site reactions (extravasation, pain, discomfort, swelling, inflammation, coldness). Rare: chest pain, chills Very rare: malaise, chest discomfort, pyrexia, facial edema, injection site necrosis (with extravasation), superficial phlebitis |
| Research | Very rare: decreased oxygen saturation |
The following adverse reactions have been reported with other intravenous MRI contrast agents:
| Organ system class | Adverse reaction |
| Blood and lymphatic system disorders | Hemolysis |
| From the psyche | Confusion of consciousness |
| From the organs of vision | Transient blindness, eye pain |
| From the hearing organs | Tinnitus, ear pain |
| Respiratory, thoracic and mediastinal disorders | Asthma |
| Gastrointestinal tract | Dry mouth |
| Skin and subcutaneous tissue disorders | Bullous dermatitis |
| Renal and urinary disorders | Urinary incontinence, acute tubular necrosis, acute renal failure |
| Research | ECG PR interval prolongation, blood iron increased, blood bilirubin increased, serum ferritin increased, liver function test abnormal |
The safety of the drug in children has been evaluated in clinical trials and post-marketing surveillance. Compared to adults, the safety profile of gadoteric acid did not demonstrate any specificities in children. Most reactions are gastrointestinal symptoms or signs of hypersensitivity.
Reporting potential adverse reactions
It is important to report potential adverse reactions after a medicinal product has been placed on the market. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any potential adverse reactions via the national reporting system or to the applicant for the medicinal product.
Expiration date
5 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Does not require special storage conditions.
Keep out of reach of children.
Packaging
15 ml of solution in vials. 1 vial in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
