2010/06/23

Gadovist

Composition, structure and packing

The solution for i / in the introduction of 1 mmol / ml of a transparent, free from foreign inclusions. 1 ml gadobutrol 604.72 mg, equivalent to 1 mmol osmolarity at 37 ° C - 1117 mOsm / l solution osmolality at 37 ° C - 1603 mOsm / kg H2O viscosity at 37 ° C - 4.96 mPa × with. Excipients: sodium kalkobutrol, trometamol, hydrochloric acid 0.1M, water d / and.

Clinico-pharmacological group: Contrasting diagnostic drug for magnetic resonance imaging.

Pharmacological action

Paramagnetic contrast agents for magnetic resonance imaging (MRI). Contrast is due to the active component gadobutrolom, which is a neutral complex of gadolinium (III) with macrocyclic ligand - dihydroxy-gidroksimetilpropiltetraazatsiklododekan-triuksusnoy acid (butrolom). Induction of local oscillations of the magnetic field under the influence of strong magnetic moment of gadolinium T2-weighted pulse sequences leads to a change in signal from tissues (contrasting effect).

Gadobutrol even in low concentrations causes a significant shortening of the relaxation time. The ability to modify the relaxation time T1 and T2, which is determined by the effect on the spin-lattice and spin-spin relaxation times of protons in the plasma at pH = 7 and a temperature of 40 ° C, is quantitatively about 5.6 l / mmol × s and 6.5 l / mmol × with respectively. Ability to influence the relaxation time of only a small extent depends on the strength of the magnetic field.

Introduction

Gadovist provides a more accurate diagnostic information compared with data obtained by conventional MRI, in regions with high permeability of the BBB, or lack of it, lead to the violation of perfusion or increase in the extracellular space, such as in cases of primary tumors, inflammatory and demyelinating diseases. Gadovist does not activate the complement system and therefore the likelihood of anaphylactoid reactions is extremely low. Not detected binding gadobutrola any proteins or inhibition of enzyme activity. The results of clinical trials showed no negative effect on Gadovist overall health, as well as liver function, kidney and cardiovascular system.

Pharmacokinetics

Pharmacokinetics gadobutrola similar to the pharmacokinetics of other vysokogidrofilnyh biologically inert substances released by the kidneys (eg, mannitol or inulin).

Distribution

Introduced in / gadobutrol rapidly distributed in the extracellular space and in the unmodified form displayed by the kidneys by glomerular filtration. Not bound to plasma proteins.

Withdrawal

Extrarenal excretion of the drug is so small that can not be ignored. Indicators of pharmacokinetics in humans are proportional to injected dose gadobutrola. If the dose does not exceed gadobutrola 0.4 mmol / kg of body weight after the initial phase distribution is reached elimination phase and its level in plasma decreases with the period of half-life of 1.81 h (1.33-2.13 h), which corresponds to the rate of excretion by the kidneys.

At a dose gadobutrola 0.1 mmol / kg of body weight in 2 min after injection of its level in plasma was 0.59 mmol / l, and 60 min after injection - 0.3 mmol / liter. Within 2 h of urine output of more than 50% of the administered dose, and within 12 hours - more than 90%. If a given dose gadobutrola equals 0.1 mmol / kg body weight, about 100 ± 2.6% of the dose excreted in 72 h. Renal clearance gadobutrola in healthy individuals ranges from 1.1 to 1.7 ml / min × kg, thus it is comparable with the clearance inulin, indicating that the preferential breeding gadobutrola through glomerular filtration. Less than 0.1% of the administered substance excreted in feces. Metabolites in plasma and urine were not detected.

Pharmacokinetics in special clinical situations

T1 / 2 Gadovist in patients with impaired renal function increases in proportion to the degree of reduction of glomerular filtration. In patients with mild or moderate impaired renal function Gadovist completely excreted in urine within 72 h. In patients with severely impaired renal function 80% of the administered dose excreted in urine within 120 hours

Statement
contrast enhancement in MRI of the head and spine (the cranial and spinal imaging).

For spinal cord MRI
differential diagnosis between intra-and extramedullary tumor;
detection limits of solid tumors in the spinal canal and determining the prevalence of intramedullary tumors.

Gadovist has special advantages in the presence of the indications for the use of magnetic resonance contrast agents in high doses, for example, in cases where the identification or elimination of additional lesions may affect the treatment, or medical tactics, as well as the detection of small lesions and to visualize the lesions, difficult kontrastiruemyh usual means. Gadovist shown also for perfusion studies (in the diagnosis of stroke, recognition of focal cerebral ischemia and assessment of tumor blood supply).

Dosage regimen

The required dose injected into / in as bolus. MRI with high contrast can be started immediately (soon after the injection, depending on the applied pulse sequence and layout of the investigation). Optimal contrast enhancement usually occurs in approximately 15 minutes after Gadovist (this time depends on the characteristics and nature of tissue damage). Typically, high contrast persists until 45 min after injection Gadovist. With all the MRI contrast agents can be observed side effects such as nausea and vomiting.

Therefore, to minimize the risk of vomiting and aspiration of the possible, the patient must refrain from eating for 2 h before the study. When i / in the introduction of contrast medium sick (if possible) should be in the supine position.

After the introduction of Gadovist patient must remain under medical supervision for at least 30 minutes, because, as experience has shown the use of contrast agents, most of the undesirable side effects observed in this period. For studies with high-contrast best suited for scanning a T1-weighted pulse sequences.

For perfusion studies of brain recommend the use of T2-weighted pulse sequences. Stringing Gadovist to normal syringe should only immediately prior to the study. Not used in the course of a study of the drug must be destroyed. Choosing the dosing regimen for adults should be guided by the following rules. MRI of the head and spine (cranial and spinal imaging), as a rule, it is sufficient to / in the introduction Gadovist a dose of 0.1 ml / kg body weight (equivalent to 0.1 mmol / kg body weight).

If, despite the normal MRI with contrast enhancement, are suspected in the presence of pathology, or if you need more accurate information on the number, size and extent of lesions to develop tactics and medical treatment, diagnostic efficiency studies can be improved by introducing additional solution Gadovist at a dose of 0.1- 0.2 ml per 1 kg of body weight for 30 minutes after the last injection. To exclude metastasis or recurrence of the tumor, is injected in a dose Gadovist 0.3 ml per 1 kg of body weight, which often improves the diagnostic efficiency of research. This refers to lesions with a weak network of blood vessels, with a small extracellular space, or a combination of these factors, as well as to the use of scanning relatively less intense T1-weighted pulse sequences.

For perfusion studies of the brain is recommended to use T2-weighted pulse sequences in combination with MRI of the brain and spinal cord lesions to identify bulk or local ischemia in the absence of assumptions about the bulk lesions.

For this study it is recommended to use the injector; solution Gadovist injected a dose of 0.3 ml per 1 kg of body weight at a speed of 3-5 ml / sec. If necessary, the dose can be increased to 0.5 ml / 1 Kg body weight. In renal failure dose solution Gadovist should be no more than 0.1 ml / kg body weight. Clinical experience with Gadovist in patients younger than 18 years missing.

Side effect

On the part of the body as a whole: during bolus administration or immediately after a transient sensation may occur unusual taste or smell, and sometimes - nausea and vomiting; Cases vasodilation and arterial hypotension. It was also reported cases of transient headache and dizziness. There are reports of occurrence of convulsions, chills and fainting after the introduction of these drugs, but a causal relationship with their introduction has not yet proven.

Allergic reactions: hypersensitivity reactions to the introduction of Gadovist often develops in patients predisposed to allergy. In rare cases, anaphylactoid reactions are accompanied by disturbances of breathing and other symptoms, attained a degree of anaphylactic shock. Sometimes, after the introduction Gadovist observed skin reactions (rash, urticaria).

Local reactions: injection site due venopunktsii or the introduction of contrast agents may be short-term mild to moderate sensation of cold, heat or pain.

Other: accidental introduction of Gadovist okolososudistye tissue may cause pain lasting up to several minutes. Other tissue reactions were observed. Application Gadovist in some cases may cause delayed (within hours or days) of the reaction.

Contraindications
Hypersensitivity to the drug's components.

Pregnancy and lactation

Data on the use gadobutrola in pregnancy. Gadovist not recommended during pregnancy except in cases of extreme necessity. In experimental studies found no embryotoxicity or teratogenicity.

So far not investigated the possibility of penetration gadobutrola in milk lactating women. In experimental studies found that gadobutrol in minimal quantities (less than 0.01% of the administered dose) penetrates into breast milk. Therefore, after the introduction Gadovist breastfeeding should be interrupted for at least 24 hours

Application for violations of renal function

With care appoint Gadovist patients with severely impaired renal function, because in this situation elimination of the contrast medium is retarded. In severe cases, should be removed Gadovist from the body by hemodialysis. After 3 courses of dialysis from the body is derived approximately 98% contrast medium. In renal failure dose Gadovist solution should be no higher than 0.1 ml / kg body weight.

Cautions

Using gadoliniysoderzhaschih MRI contrast agents reported occurrence in some cases, anaphylactoid reactions.

Such reactions can develop and use Gadovist. The decision to use Gadovist patients with a predisposition to allergies should be especially carefully balanced, it should recognize the risks and benefits.

As with other contrast agents may cause delayed reactions (within a few hours or days after injection). In conducting the study must have products and tools (eg, endotracheal tube, oxygen for mechanical ventilation) for resuscitation. So far, renal dysfunction with the introduction of the drug were noted.
With care appoint Gadovist patients with severely impaired renal function, because in this situation elimination of the contrast medium is retarded. In severe cases, should be removed Gadovist from the body by hemodialysis. After 3 courses of dialysis from the body is derived approximately 98% contrast medium.
With care appoint Gadovist patients with severe cardiovascular disease, although the relevant information is still limited.

Gadovist, like other MRI contrast agents containing gadolinium chelate, requires special precautions when appointing patients with a low threshold for seizure activity. Pronounced state of excitation, anxiety and pain may increase risk of adverse reactions or increase adverse reactions caused by the introduction of contrast medium.

Effects on ability to drive vehicles and management mechanisms

Not detected.

Overdose

So far, no cases of overdose. The risk of acute toxicity in connection with the use of Gadovist unlikely.

Treatment: Accidental overdose Gadovist may be removed from the body by extracorporeal dialysis.

Drug Interactions

Drug Interactions with other drugs have been discovered.

Terms and Conditions of storage

The drug should be stored out of reach of children at or above 30 ° C. Shelf life - 3 years. After opening the vial under aseptic conditions Gadovist remained stable for 8 hours at room temperature.