Description
Release form
Injection.
Pharmacological action of
Pharmacological action of
Contrast diagnostic paramagnetic ionic agent. It is a complex of the chelate compound versetamide and the paramagnetic gadolinium ion.
When placed in a magnetic field, gadeversetamide decreases the T1 and T2 relaxation times in the tissues in which it accumulates. At the recommended dose, gadeversetamide mainly affects the T1 relaxation time, which leads to an increase in the signal intensity in the tissues in which it accumulates. This provides increased image contrast during MRI and facilitates the visualization of abnormal structures in the studied organs and tissues.
Gadoversetamide does not penetrate the intact BBB and therefore does not accumulate in normal brain tissue or lesions with an intact BBB (for example, cysts, natural postoperative scars). In violation of the BBB or pathological vascularization, the active substance accumulates in the lesions, such as tumors, abscesses and areas of subacute infarction.
Pharmacokinetics
With iv administration, the pharmacokinetics of gadversetamide is described by a two-compartment model with an average T1 / 2 of 103.6 ± 19.5 min. Does not bind to plasma proteins in vitro. Vss in healthy volunteers is 162 ± 25 ml / kg. Biotransformation not defined.
Excreted mainly in urine 95.5 ± 17.4% within 24 hours after administration. In small quantities is determined in feces. The values of renal and plasma clearance in healthy volunteers are close and are 69 ± 15.4 and 72 ± 16.3 ml / h / kg, respectively.
With impaired renal function, the elimination of gadoversetamide slows down. The kinetics of gadoversetamide in plasma in patients with impaired liver function and normal renal function is the same as in healthy volunteers.
Indications
To increase contrast during MRI in patients with a BBB disorder or pathological vascularization of the brain, spinal cord, and related tissues.
To increase the contrast during MRI to visualize foci of pathological vascularization in the liver in patients with suspected liver structural abnormalities detected by CT.
Use during pregnancy and lactation
Adequate and strictly controlled studies of the safety of gadoversetamide during pregnancy have not been conducted. Application is possible only in cases where the expected benefit to the mother justifies the potential risk. With the introduction of the drug, breastfeeding should be interrupted and resumed 72 hours after the administration of gadversetamide.
In experimental studies, it is shown that gadoversetamide crosses the placental barrier, is determined in the tissues of the fetus, in breast milk.
Special instructions
Gadolinium-based contrast agents increase the risk of developing systemic nephrogenic fibrosis in patients with impaired drug excretion. The use of gadoversetamide in this category of patients should be avoided, except when magnetic resonance imaging using other contrast media is not available.
The risk of developing systemic nephrogenic fibrosis when using contrast agents based on gadolinium is increased in patients with chronic severe kidney disease with a glomerular filtration rate (GFR) of less than 30 ml / min / 1.73 m2, as well as in patients with acute kidney disease. In such cases, gadversetamide should not be used. In patients with chronic moderate diseases of the kidney with GFR of 30-59 ml / min / 1.73 m2), this risk is lower and even less in patients with mild kidney disease with (GFR of 60-89 ml / min / 1.73 m2). Systemic nephrotic fibrosis can lead to fatal or destructive fibrosis, which affects the skin, muscles, and internal organs.
The drug should not be used in patients with acute kidney damage and other conditions that may lead to impaired renal function. The risk of acute kidney damage is possible with surgical interventions, severe infections, toxic kidney damage, including caused by drugs with nephrotoxicity. In patients at risk of chronic kidney disease (including those over the age of 60 years, with diabetes mellitus, chronic arterial hypertension), GFR should be determined before administration of gadoversetamide.
Factors for increasing the risk of developing systemic nephrogenic fibrosis are repeated administration of a contrast agent, administration in doses higher than recommended, the degree of impaired renal function, and exposure time.
The safety of gadoversetamide in patients with sickle cell anemia has not been studied.
The potential risk of hemolysis after administration of gadoversetamide to patients with other types of hemolytic anemia has not been investigated.
Patients with a history of allergies, kidney failure, or hypersensitivity reactions to drug administration require observation within a few hours after the administration of gadeversetamide.
Since gadoversetamide is excreted by glomerular filtration, caution is required when administering the drug to patients with impaired renal function (GFR 30 and <90 ml / min / 1.73 m2). The dosage regimen for patients with impaired renal function has not been established. Gadoversetamide is excreted during dialysis. The possibility of developing hypersensitivity reactions, including serious, life-threatening, fatal anaphylactoid or cardiovascular reactions, especially in patients with clinical symptoms of hypersensitivity, should always be considered. an indication of a history of bronchial asthma and other respiratory diseases. The safety of gadoversetamide administration in repeated studies has not been studied. Magnetic resonance imaging is carried out under the supervision of a doctor who has sufficient experience and knowledge about this procedure, under conditions that can provide emergency treatment for the development of complications and severe reactions to the administration of a contrast medium. Safety and efficacy of gadeversetamide when used in pediatrics have not been established. The risk of adverse reactions in children may be increased due to immaturity of the kidneys and / or latent renal failure. Composition of Active ingredient: gadroversetamide 1 ml 330.9 mg hydrocetamide, hydroxyamide, calcium chloride, hydrochloride, calcium chloride dihydrate, sodium hydroxide and / or hydrochloric acid, water for injection. Dosage and Administration This drug should be administered as a peripheral injection at a dose of 0.2 ml / kg (100 ?mol / kg) of body weight. To ensure complete administration of the contrast medium, the injection should be completed with the aim of washing with the introduction of 5 ml of a solution of sodium chloride at a concentration of 9 mg / ml (0.9%). The MRI procedure should be completed within 1:00 after administration of a contrast medium. In case of cranial MRI, in case of strong clinical suspicion of the existence of a lesion or if accurate information on the quantity the size or volume of lesions can affect the monitoring of the patient s condition or treatment, for subjects with normal renal function, despite MRI improved with a single dose of contrast medium, a second bolus injection of 100 ?mol / kg can be administered within 30 minutes after the first injection, this can increase the diagnostic value of the procedure. The safety of repeated doses has not been established for children, adolescents, patients with renal failure, or elderly patients. Limited data on other gadolinium contrast agents provide that, in order to identify additional cranial metastases in a patient with known single operable metastases, MRI with an injection of Optimarku dose of 300 ?mol / kg body weight may increase diagnostic accuracy. Side effects of the From the nervous system: often – headache, dizziness, paresthesia less than 1% – agitation, anxiety, impaired consciousness, depersonalization, diplopia, dystonia, hallucinations, hyperesthesia, nervousness, drowsiness, tremor, vertigo. From the cardiovascular system: often – vasodilation less than 1% – arrhythmia, chest pain, arterial hypertension, arterial hypotension, palpitation, syncope, tachycardia, vascular spasm, pallor of From the digestive system: often – nausea, abdominal pain less than 1% – anorexia, increased appetite, constipation, dry mouth, dysphagia, belching, flatulence, increased salivation, thirst, vomiting From the body as a whole: often – asthenia less than 1% – allergic reactions, swelling of the face, fever, flu-like syndrome, malaise, irritation of the mucous membranes, stiff neck, neck pain, pelvic pain, increased sweating. From the hemopoietic system: less than 1% – thrombocytopenia. From the side of metabolism: less than 1% – increase in serum creatinine, edema, hypercalcemia, hyperglycemia, hypoglycemia, hyponatremia. From the musculoskeletal system: often – back pain less than 1% – arthralgia, leg cramps, myalgia, myasthenia gravis, muscle spasm. From the respiratory system: less than 1% – asthma, cough, shortness of breath, nosebleeds, hemoptysis, laryngospasm, pharyngitis, sinusitis, hoarseness. Dermatological reactions: less than 1% – erythema multiforme, pruritus, maculopapular rash, vesicular rash, dry skin, urticaria. From the sensory organs: less than 1% – amblyopia, conjunctivitis, hyperacusis, impaired smell, tinnitus. From the urinary system: less than 1% – dysuria, oliguria, frequent urination. Local reactions: less than 1% – reactions at the injection site, incl. edema, thrombophlebitis, inflammation. Overdose Gadoversetamide was used for patients at doses up to 700 μmol / kg (which is 7 times the standard dose). There are no reports of overdose. In patients with normal renal function, symptoms of acute poisoning are unlikely. Optimark can remove hemodialysis. However, there is no confirmation that hemodialysis is used to prevent nephrogenic systemic fibrosis (NSF). Treatment should be symptomatic. active substance Gadoversetamid lekarstvennaja form Solution for infusion