Gadobutrol (Gadobutrolum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Magnetic resonance contrast media

Included in the formulation
  • Gadovist®
    solution in / in 
    Bayer Pharma AG     Germany
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    V.08.C.A   Paramagnetic contrast media

    Pharmacodynamics:The drug is a neutral (nonionic) gadolinium (III) complex with a macrocyclic ligand - butrolol. The behavior of protons, placed in a strong a constant magnetic field, is converted by a magnetic resonance imager into an image. In a strong magnetic field, the protons go into an excited state, then with the disappearance of the field they again stabilize (the so-called relaxation of protons). Images are based on measuring the density and dynamics of relaxation (spin-lattice (T1) or longitudinal and spin-spin (T1) or transverse times) of protons. When magnetic resonance imaging visualization of normal and pathological tissues of the brain partially depends on the differences in the intensity of the radio-frequency signal caused by differences in the proton density, T1 and T2. Paramagnetic agents have more than one unpaired electron, which increases the proton relaxation rate in their molecular environment (the relaxing effect of the unpaired electron is 700 times higher than that of the proton). When placed in a magnetic field gadobutrol shortens the relaxation time T1 and T2 tissues, which accumulate, enhancing the visualization in the central nervous system of normal tissues that do not have a blood-brain barrier (for example, the pituitary gland and membranes). Gadobutrol even at low concentrations causes a significant increase in signal intensity. The introduction of gadobutrol makes it possible to obtain more accurate diagnostic information in comparison with the data of conventional magnetic resonance imaging in areas with impaired permeability of the blood-brain barrier, for example, in cases of primary or secondary tumors, inflammatory and demyelinating diseases.
    Pharmacokinetics:After intravenous administration, it is rapidly distributed in the extracellular space. Pharmacokinetics is dose-dependent: at a dose of less than 0.4 mmol / kg after the initial phase of the distribution, the elimination phase begins, and the plasma concentration decreases, the half-life is 1.81 hours, which corresponds to the rate of excretion by the kidneys; with a dose of 0.1 mM gadobutrol / kg after 2 minutes after administration, its concentration is 0.59 mmol / l, after 60 minutes - 0.3 mmol / l. Within 2 hours with urine, more than 50% of the dose administered is excreted,within 12 hours - more than 90%; renal clearance - 1,1-1,7 ml / min × kg; is excreted mainly by the kidneys (by glomerular filtration, unchanged), less than 0.1% of the injected substance is excreted with feces. The half-life in chronic renal failure increases in proportion to the degree of decrease in glomerular filtration. With mild or moderate degree of chronic renal failure completely excreted in the urine within 72 hours, with severe chronic kidney failure, 80% of the dose is excreted in the urine for 120 hours. Removed during hemodialysis. After three procedures of hemodialysis, about 98% of the administered dose is excreted from the body.
    Indications:This drug is intended solely for diagnostic purposes.

    Gadobutrol is shown to adults, adolescents and children aged 7 years to increase the contrast in magnetic resonance imaging total body, including:

    - Cranial and spinal magnetic resonance imaging;

    - Magnetic resonance imaging Head and neck area;

    - Magnetic resonance imaging chest and mammary glands;

    - Magnetic resonance imaging the abdominal cavity (including the pancreas, liver, spleen);

    - Magnetic resonance imaging areas of the small pelvis (including the prostate, bladder and uterus);

    - Magnetic resonance imaging retroperitoneal space (including the kidneys);

    - Magnetic resonance imaging musculoskeletal system and limbs;

    - magnetic resonance angiography;

    - Magnetic resonance imaging heart (including for evaluation of myocardial perfusion under conditions of pharmacological stress and diagnosis of tissue viability "delayed contrasting").

    Among the special indications for the spinal cord magnetic resonance imaging include: differential diagnosis between intra- and extramedullary tumors, detection of the boundaries of solid tumors in the spinal canal, determination of the prevalence of the intramedullary tumor. Perform perfusion studies, for example, in the diagnosis of stroke, recognition of focal cerebral ischemia or to assess blood supply to the tumor.

    ICD-10

    XXI.Z00-Z13.Z03   Medical surveillance and evaluation in case of suspected disease or pathological condition

    Contraindications:Increased sensitivity to gadobutrol; children under 2 years old (safety not investigated); availability of contraindications for magnetic resonance imaging (artificial pacemaker, coronary or vascular stenting for 6 weeks prior to manipulation, ferromagnetic implants, subarachnoid or epidural administration); pregnancy (safety not established); disturbance of kidney function of light and medium degree.
    Carefully:Severe renal dysfunction; severe cardiovascular diseases; low threshold of convulsive readiness.
    Pregnancy and lactation:The risk category for the fetus is FDA-B. There are no clinical data on the use of gadobutrol in pregnancy. Therefore, the drug should not be administered to pregnant women unless it is clearly necessary. Lactation: after the introduction of the drug, refrain from breastfeeding for 24 hours.
    Dosing and Administration:The dose depends on the indications. A single intravenous injection of 1 mmol / ml in a dose of 0.1 ml per 1 kg of body weight is usually sufficient. The maximum dose of gadobutrol is 0.3 mmol per 1 kg of body weight (equivalent to 0.3 ml per 1 kg of body weight).

    Application in elderly patients

    Use in the elderly has not been systematically studied. There is no data on the need to reduce the dosage of the drug in patients in this group, except for:

    - cases of severe renal failure;

    - doubtful allergological history;

    - patients with a low threshold of convulsive readiness.

    Use in children

    For children older than 7 years and adolescents, the recommended dose of gadobutrol is 0.1 mmol per 1 kg of body weight (equivalent to 0.1 ml per 1 kg of body weight) for all indications. The drug is not recommended for use in children under 2 years of age due to the lack of data on efficacy and safety.

    Side effects:The most frequent adverse reactions (≥ 0.5%) that were observed in patients receiving the drug are: headache, nausea and dizziness. The most serious adverse reactions in patients receiving the drug are cardiac arrest, severe anaphylactic / anaphylactoid reactions. Delayed allergic reactions (a few hours or days) were rare. In most cases, the side effects were characterized by a mild or moderate degree of severity.
    Overdose:There were no cases of overdose. The goals of therapy with a possible overdose are maintenance of vital functions, rapid administration of symptomatic therapy. The drug can be removed from the body by hemodialysis.
    Interaction:Pharmacologically incompatible with any other drugs.
    Special instructions:There have been reports of the development of nephrogenic systemic fibrosis due to the introduction of gadolinium-containing contrast agents, including gadobutrol, patients with the following diseases / conditions:

    - acute or chronic renal failure (glomerular filtration rate <30 ml / min / 1.73 m2);

    - Acute renal failure of any severity caused by hepatorenal syndrome, or in the period before and after liver transplantation.

    After three courses of dialysis, about 98% of gadobutrol is excreted from the body. For patients on hemodialysis, it should consider the expediency of the immediate onset of hemodialysis after administration of gadobutrol in order to accelerate the elimination of contrast agent.

    As with the use of other contrast agents for intravenous administration,The use of gadobutrol may be accompanied by hypersensitivity, idiosyncrasy. Severe clinical conditions, including shock, can develop.

    The risk is higher in cases when the reaction to a contrast agent developed earlier, with bronchial asthma and allergies in the anamnesis. Most of these reactions develop within 0.5-1 hour after administration. Careful monitoring with conditions for intensive care and resuscitation is necessary.

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