Hadobenic acid - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Magnetic resonance contrast media

Included in the formulation

Multihance

solution in / in

Brakko Imajing SpA Italy

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:

Gadobenic acid is a paramagnetic contrast medium with a gadolinium chelate complex in its structure. Like all preparations of this group, gadobenic acid is highly hydrophilic and accumulates in areas of increased blood supply, for example, in tumors, hemangiomas, hematomas and others. The presence of paramagnetic properties allows gadobenic acid to significantly enhance the contrast and "visibility" of different formations on MRI shots compared to those made without contrast.

In the liver, the drug provides a persistent and prolonged increase in the intensity of the signal of normal parenchyma.

The results of phase II and III clinical trials involving patients with liver cancer showed that the average sensitivity and specificity of magnetic resonance imaging is 95% and 80% respectively.

When conducting magnetic resonance imaging of the brain and spinal cord, the drug enhances the contrast of healthy tissues in which there is no blood-brain barrier, tumors located outside the brain, and areas with damage to the blood-brain barrier.

When conducting magnetic resonance angiography, the drug improves image quality by increasing the intensity of the signal coming from the blood and reducing blood noise; reduces the number of artifacts associated with the movement of the patient due to the reduction of study time, and also eliminates artifacts associated with the flow of blood.

Pharmacokinetics:

The apparent half-distribution and half-life periods are 0.085-0.117 and 1.17-1.68, respectively. The apparent volume of distribution of 0.170-0.248 l / kg of body weight indicates that the drug is distributed in the plasma and in the extracellular space.

The ion of hapoenic acid is rapidly excreted from the body mainly by the kidneys and in a smaller amount - with bile through the gastrointestinal tract. Plasma clearance 0,098-0,133 l / h per kg of body weight and renal clearance 0,082-0,104 l / h per kg of body weight indicate the elimination of the drug mainly due to glomerular filtration. The indices of plasma concentration and the area under the concentration-time curve indicate the presence of a statistically significant linear dependence on the administered dose. The ion of hapoenic acid is excreted by the kidneys unchanged in the amount of 78-94% of the administered dose within 24 hours. 2 to 4% of the dose is released through the intestine.

Due to its hydrophilicity, the ion of hapoenic acid does not penetrate the blood-brain barrier and therefore does not accumulate in unchanged brain tissue and in the affected areas with a preserved blood-brain barrier. However, a violation of the penetrability of the blood-brain barrier or vascular damage (tumor, hematoma) creates the conditions for the penetration of the ion of gadobenic acid into the affected area.

Indications:

- Magnetic resonance imaging liver, in order to detect focal lesions in patients with suspected or confirmed primary liver cancer (hepatocellular carcinoma), as well as with metastatic liver damage;

- Magnetic resonance imaging head and spinal cord, to detect focal lesions, associated with the degradation of the blood-brain barrier, as well as for obtaining additional diagnostic information in comparison with magnetic resonance imaging without contrast;

- magnetic resonance angiography for detection wall-occlusive lesions of peripheral arteries and branches of the abdominal aorta.

ICD-10

XVIII.R90-R94.R93.3 The abnormalities detected in obtaining a diagnostic image during the examination of other parts of the digestive tract

XVIII.R90-R94.R93.2 Abnormalities detected in the diagnostic imaging of the liver and bile ducts

XVIII.R90-R94.R90.8 Other abnormalities detected in the diagnosis of the central nervous system

XVIII.R90-R94.R90 The abnormalities detected in obtaining diagnostic images during the examination of the central nervous system

XXI.Z00-Z13.Z03.5 Observation for suspected other cardiovascular disease

XXI.Z00-Z13.Z03.1 Observation for suspected malignant tumor

Contraindications:- hypersensitivity to the drug components, gadolinium chelate complexes, benzyl alcohol;

- pregnancy and the period of breastfeeding (unless there is an extreme need for research).

For studies of the central nervous system: children under 2 years of age (safety and efficacy not studied).

For examination of the liver and blood vessels: children under 18 years.

Carefully:

Renal failure.With the introduction of a single intravenous dose of gadobenic acid (0.2 mmol / kg body weight) in patients with chronic renal insufficiency with a creatinine clearance of> 30 to <60 ml / min, the mean elimination half-life is 3-9 hours, with creatinine clearance> 10 to <30 mL / min, the average half-life is 6.5 to 12.5 hours. For comparison, in healthy people the average half-life is 1.0-2.0 hours. However, the total elimination time of gadobenic acid is not associated with renal insufficiency. Also, there were no differences in the severity and composition of adverse reactions in patients with and without renal insufficiency. In healthy patients, after administration of gadobenic acid, there was no impairment of renal function.

Liver failure. In patients with impaired liver function with the introduction of a single intravenous dose of gadobenic acid, the pharmacokinetics change insignificantly compared with healthy people.

Caution should be given to patients with a high risk of cardiac arrhythmias (due to taking medications or having a pathology). It should be avoided administering the drug to patients with hepatic-renal syndrome,and also in the period before and after liver transplantation, except when it is impossible to obtain information by other methods, and it is of decisive importance.

Pregnancy and lactation:

Safety category by FDA - C. Data of clinical studies of the use of gadobenic acid in pregnant women are absent. Therefore, the drug should not be administered to pregnant women unless it is justified by a clear clinical need. It is recommended to abstain from breastfeeding within 24 hours after the introduction.

Dosing and Administration:

When examining the liver, a single dose for adults and children from 2 years - 0.1 ml / kg body weight 0.5-molar solution.

For CNS and magnetic resonance Angiography recommended dose 0.2 ml / kg body weight.

The drug is administered bolus by hand or by means of an automatic injector at a rate of 10 ml / min.

The maximum single dose of 0.4 mmol / kg body weight.

Application in elderly patients

The rate of removal of gadobenic acid from the body decreases slightly with age. Since these changes are at the border of the norm, you do not need to change the dose for the older age group.

Use in children

Application for magnetic resonance imaging head and spinal cord is not indicated in children under 2 years old. Application for magnetic resonance imaging liver and magnetic resonance angiography is not recommended in children under the age of 18 years.

Children aged 2 years with tumors of the central nervous system

Pharmacokinetics studies were performed in a group of 80 people (40 adults and 40 children) aged 2 to 47 years (intravenous administration). The pharmacokinetic parameters in adults corresponded to the values described earlier. The volume of distribution and clearance were lower in adolescents and children due to less body weight. The administration of gadobenic acid to children in doses calculated per kg of body weight demonstrates an adult profile of the concentration-time curve (AUC) and the maximum concentration (C_max). These data confirm the absence of the need to reduce the dose in children aged 2 years.

Side effects:Infections and infestations: nasopharyngitis.

From the nervous system: headache, dizziness, syncope, parosmia, hyperesthesia, tremor, increased intracranial pressure, hemiplegia.

On the part of the organs of vision: conjunctivitis.

From the organs of hearing and balance: tinnitus.

From the cardiovascular system: tachycardia, atrial fibrillation, atrioventricular block of the 1st degree, ventricular extrasystoles, sinus bradycardia, hypotension, hypertension, arrhythmia, myocardial ischemia, prolongation of the PR interval.

From the respiratory system: rhinitis, dyspnea, laryngospasm, congestion of the blood in the lungs, pulmonary edema.

From the digestive system: nausea, dry mouth, perversion of taste, diarrhea, vomiting, indigestion, drooling, abdominal pain, constipation, stool incontinence, necrotizing pancreatitis.

From the skin: itching, rash, face swelling, urticaria, increased sweating.

From the side of connective tissue and musculoskeletal system: pain in the back and muscles.

From the urinary system: incontinence, mandatory urges to urinate.

Systemic complications and complications at the site of administration: reaction in the area of injection, heat, asthenia, anemia, fever, chills, pain (including in the chest, at the injection site), hemorrhage in the injection area, extravasation, inflammation in the injection area.

Allergic reactions: anaphylactic reactions, including the development of anaphylactic shock.

ECG changes: blockade of the bundle branch, complete atrioventricular block, atrioventricular block of the first degree, inverted tooth T, long interval PR, long interval QT, short interval QT.

Deviation of laboratory indicators: hypochromic anemia, leukocytosis, leukopenia, basophilia, hypoproteinemia, hypocalcemia, hypercalcemia, albuminuria, glucosuria, hematuria, hyperlipidemia, hyperbilirubinemia, elevated serum iron concentrations, increased serum transaminase, alkaline phosphatase, lactate dehydrogenase, and creatinine concentrations.

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:

The drug should not be mixed in the same syringe with other medicines. In patients taking anthracyclines (daunorubicin, doxorubicin), tamoxifen, methotrexate, cisplatin, etoposide, paclitaxel, special precautions should be observed.

Special instructions:

When administering the drug, all precautions should be followed to avoid extravasation in order to avoid the development of local reactions.

After the administration of the drug, the doctor must monitor the patient's condition within 15 minutes, which should remain in the hospital for 1 hour.

It is not recommended to perform magnetic resonance imaging with contrast agents containing other chelating complexes of gadolinium within 7 hours after using the drug.

Instructions

Hadobenic acid (Acidum gadobenicum)