1 ml of solution contains: Active ingredient : 604.72 mg (1.0 mmol) gadobutrola. Excipients: sodium kalkobutrol 0.513 mg, 1.211 mg trometamol, 0.1 M hydrochloric acid to pH 7.2 ± 0.2, water for injections to 1 mL.
Physical and chemical properties
Gadobutrol very soluble in water and has extremely high hydrophilic (its distribution coefficient between n-butanol and buffer at pH of 7.6 is approximately 0.006).The macrocyclic ligand forms a stable complex with the paramagnetic gadolinium ion, which is characterized as an extremely high stability in vivo, or in vitro.
The following are physicochemical properties dianabol results solution (1 mmol / ml).
|The osmolarity at 37 ° C (mOsm / liter of solution)||1117|
|Osmolality at 37 ° C (mOsm / kg water)||1603|
|Viscosity at 37 ° C (mPa.s)||4.96|
contrast agent for magnetic resonance imaging (MRI).
ATC code V08CA09
Pharmacological properties Pharmacodynamics dianabol results – is a paramagnetic contrast agent for magnetic resonance imaging (MRI). Contrast enhancement due to its gadobutrola active ingredient, which is a neutral (non-ionic) complex of gadolinium (III) with a macrocyclic ligand – acid (butrolom).
When using T2 * -weighted sequences the induction of local pulse inhomogeneity of the magnetic field under the influence of strong magnetic moment of gadolinium at high concentrations (bolus) causes a change in the signal from the tissue (contrast enhancement).
Gadobutrol even in low concentrations induces a significant shortening of relaxation time. Quantitatively, the ability to change the relaxation time T1 and T2, which is determined by the influence on the spin-lattice and spin-spin relaxation time of protons in plasma at pH 7 and 40 ° C is about 5.6 l / mmol * s and 6.5 l / mmol * s, respectively. Ability to influence the relaxation time is only slightly dependent on the strength of the magnetic field.
Introduction dianabol results provides a more accurate diagnostic information compared with conventional MRI data in the areas with impaired permeability of the blood-brain barrier, for example in cases of primary or secondary tumors, inflammatory and demyelinating diseases.
dianabol results does not activate the complement system and, therefore, the probability of induction of the substance of anaphylactoid reactions is extremely low.
Not detected binding gadobutrola any proteins or inhibit their enzyme activity.
Results from clinical studies showed no negative effect on overall health dianabol results, as well as liver, kidney and cardiovascular system.
Behavior gadobutrola in the body similar to that of other highly hydrophilic biologically inert substances excreted by the kidneys (e.g., mannitol or inulin).
Introduced intravenously gadobutrol is rapidly distributed in the extracellular space and in unchanged form excreted by the kidneys by glomerular filtration. Extrarenal elimination is so insignificant that it can not be taken into account.
Indicators pharmacokinetics in humans are proportional to the dose administered gadobutrola. If the dose is not more than 0.4 gadobutrola mmol per 1 kg of body weight, the elimination phase occurs after the initial distribution phase and its concentration in plasma decreases with a half-life of 1.81 hours (1,33- 2,13 hours), which corresponds to the rate of excretion kidneys. At a dose gadobutrola 0.1 mmol / kg of body weight in 2 minutes post-injection plasma level was 0.59 mmol / l, and 60 minutes after injection, – 0.3 mmol / l. Within two hours the urine output over 50% of the administered dose and for 12 hours – 90%. If gadobutrola dose administered is 0.1 mg / kg of body mass, 100.3 ± 2.6% of the dose is excreted in 72 hours. Gadobutrola renal clearance in healthy individuals ranging from 1.1 to 1.7 mL / min * kg;so that it is comparable with inulin clearance, indicating the predominant breeding gadobutrola by glomerular filtration. Less than 0.1% of the injected substance excreted in the feces. No metabolites could not be detected in plasma and urine.
Half-life of gadobutrol in patients with impaired renal function increases in proportion to the degree of reduction in glomerular filtration. In patients with mild or moderate renal impairment Gadobutrol completely excreted in the urine within 72 hours. In patients with severe renal impairment, at least 80% of the administered dose was excreted in the urine within 120 hours.
MRI of the central nervous system, liver, kidneys with contrast or magnetic resonance angiography (MRA) with contrast, with the introduction of a single dose of gadobutrol were performed in 140 children (2 to 17 years) in the clinical trials phase I / II. These studies demonstrated that the pharmacokinetics of gadobutrol in children aged 2 years and older is similar to the pharmacokinetics in adults.Pharmacokinetic metrics such as total creatinine clearance, area under the curve (AUC) and volume (V) increases in proportion to body weight. Gender and age of the additional effect on the pharmacokinetics do not have. 98.7% (average value) of the administered dose excreted by the kidneys gadobutrola within 6 hours, which confirms gadobutrola rapid clearance in children.
This medicinal product is intended solely for diagnostic purposes. dianabol results shown to adults, adolescents and children aged 2 years to increase the contrast in magnetic resonance imaging of the whole body, including:
– Contrast enhancement during cranial and spinal MRI.
– Contrast enhancement during MRI of the head and neck.
– Contrast enhancement during MRI of the chest
– contrast enhancement during breast MRI
– contrast enhancement during MRI of the abdomen (in tonnes. h of the pancreas, liver and spleen)..
– contrast enhancement during MRI of the pelvic area (including prostate, bladder and uterus)…
– contrast enhancement during the MPT retroperitoneal space (including the kidneys)..
– contrast enhancement during MRI of the musculoskeletal system and extremities.
– contrast enhancement with magnetic resonance angiography (MRA).
– contrast enhancement during MRI of the heart (including for the assessment of myocardial perfusion under pharmacological stress and diagnose tissue viability.. “delayed opacification”)
Among the specific indications for spinal MRI include: differential diagnosis between intra- and extramedullary tumors, identifying the boundaries of solid tumors in the spinal canal and determining the prevalence of intramedullary tumors.
The solution dianabol results (1 mmol / ml) has special advantages when indicated to the use of MRI agents in high doses, for example in cases where the identification or elimination of additional lesions can affect treatment, or medical tactic, and the detection of small lesions or for imaging lesions kontrastiruemyh difficult by conventional means.
dianabol results solution (1 mg / ml) can also be used for perfusion studies: when diagnosing stroke recognition focal cerebral ischemia or tumor perfusion assessment.
Absolute contraindications for the use of dianabol results is not (see. “Special Instructions”).
dianabol results should be used with caution in the following conditions:
– Hypersensitivity to any of the ingredients of the drug
– severe renal impairment
– severe cardiovascular disease
– low seizure threshold.
Pregnancy and lactation
In animal experiments, there was no evidence of any embryotoxic or teratogenic action of diagnostic doses of dianabol results. In the study of repeated doses of gadobutrol, only the introduction of pregnant animals to toxic doses (exceeding the diagnostic dose of 8 – 17 times) caused a delay in the development of embryos and their mortality, but did not lead to teratogenicity.
However, data from clinical trials of gadobutrol in pregnancy. Therefore, dianabol results should not be administered to pregnant women unless it is dictated by the obvious need
So far not studied the possibility of falling into the milk gadobutrola lactating women.
As shown by experiments on animals, dianabol results in minimum quantities (less than 0.01% of the administered dose) passes into breast milk. After the introduction dianabol results breastfeeding should be interrupted for at least 24 hours.
Dosage and administration General information The necessary dose is administered intravenously as a bolus. Conducting of magnetic resonance imaging with high contrast can be started at once (shortly after the injection depending on the pulse sequences used and the study protocol).
Optimum contrast enhancement is observed during the arterial phase, during (MRA) with the contrast and for a period of time, measured in minutes, after injection dianabol results® for other studies (depending on the type of fault / tissue).
During the MRI general safety rules must be followed (see. “Special Instructions”).
T1-weighted pulse sequences are most suitable for the study with contrast.
before administration should be carefully inspect the vial, a syringe or cartridge. When a significant change in color, the detection of visible particles or breakage of packing the drug should not be used.
Dial dianabol results® drug in the syringe should only immediately prior to administration. The rubber stopper of the vial should not be pierced more than 1 times.
dianabol results® drug in the syringe must be removed from packaging and prepared for injection immediately prior to administration. Syringe tip cap should be removed immediately prior to administration.
The drug dianabol results® cartridges should be administered a specialist in accordance with the instructions supplied with the equipment to use cartridges. The introduction of the drug should be performed under sterile conditions.
Unused in one study of the drug should be destroyed.
Do not mix the drug dianabol results ® with other drugs because of the compatibility data are not available.
choosing the dosing regimen for adults, should be guided by the following rules.
The dose depends on the indication. A single intravenous dianabol results® preparation (1 mg / ml) at a dose of 0.1 ml per 1 kg body weight will usually suffice. The maximum dose of the drug is dianabol results® 0.3 mmol per 1 kg body weight (equivalent to 0.3 ml per 1 kg body weight).
- (MRI) of the entire body (excluding MPA).
Usually, it is sufficient dianabol results® intravenous preparation (1 mg / ml) at a dose of 0.1 ml per 1 kg body weight (equivalent to 0.1 mmol per 1 kg of body weight).
Additionally for spinal and cranial MRI
Usually, it is sufficient dianabol results® intravenous preparation (1 mg / ml) at a dose of 0.1 ml per 1 kg body weight (equivalent to 0.1 mmol per 1 kg of body weight).
If the suspicions remain about the presence of lesions or require more precise information on the number, size and prevalence of lesions, diagnostic efficiency studies can be improved further by introducing a solution dianabol results® preparation (1 mg / ml) at a dose of 0.1 ml or even 0, 2 ml per 1 kg body weight for 30 minutes after the last injection.
To eliminate metastases or tumor recurrence, dianabol results® administered drug solution in a dose of 0.3 ml per 1 kg of body weight, which often improves the diagnostic efficacy study. This refers to lesions with a weak network of blood vessels with 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, and it is recommended to use an injector dianabol results® drug solution (1 mg / ml), which is administered at a dose of 0.3 ml per 1 kg of body weight at a rate of 3-5 ml / sec.
- Magnetic resonance angiography.
One scan area:
7.5 ml for body weight less than 75 kg of
10 ml for 75 kg body weight or more (corresponding to 0.1-015 mmol per 1 kg body weight)
Two or more regions of scans:
15 ml for body weight less than 75 kg of
20 ml for 75 kg body weight or more (corresponding to 0.2-0.3 mmol per 1 kg body weight)
Use in children:
Children older than 2 years and adolescents dianabol results® recommended dose of the drug is 0.1 mmol / kg body weight (equivalent to 0.1 ml per 1 kg of body weight) for all indications (see “Indications” section.). dianabol results® The drug is not recommended for use in children under the age of 2 years due to lack of efficacy and safety data.
The overall safety profile of the drug dianabol results® based on clinical data in over 5,700 patients, as well as postmarketing observations.
The most common adverse reactions (≥ 0.5%), which have been observed in patients receiving the drug dianabol results® include: headache, nausea and dizziness.
The most serious adverse reactions in patients treated with the drug D adovist® are cardiac arrest, severe anaphylactic / anaphylactoid reactions.
Delayed allergic reaction (in a few hours or days) seldom observed.
In most cases, side effects were characterized by mild to moderate severity. Adverse reactions that have been observed at the administering dianabol results® are presented in Table 1. The data are based on the classification MeDRA organ systems (Medical Dictionary for Regulatory Activities). Lists the most appropriate medical terms (version MeDRA 14.1). Adverse reactions are classified but the frequency of symptoms. the frequency grouping is as follows: common (≥ 1/100 of up to <1/10). uncommon (≥ 1/1000 on to <1/100). rare (≥ 1/10 from 000 to <1/1000). Adverse reactions identified during post-marketing observations or reactions, for which the frequency ne can be calculated are listed in the table under “Frequency not known”.
Adverse reactions reported during clinical trials and during post-marketing studies in patients treated with the drug dianabol results®.
|System-organ classes||Often||Infrequently||Rarely||The frequency is not known|
|The immune system||Hypersensitivity / anaphylactic and anaphylactoid reactions (anaphylaxis 1.2 , cardiovascular failure 1,2 , respiratory arrest 1.2 , bronchospasm, cyanosis 1 , laryngeal edema 1.2 , decrease in body temperature 2 , high blood pressure 1 , pain chest, swelling of the face1 , angioedema 1 , conjunctivitis 1 , swelling of the eyelids 1 , “tides”, enhanced sweating 1 , cough 1 , sneezing 1 , sensation of heat 1 , pallor.|
|Nervous system||Headache||Dizziness, dysgeusia, paresthesia||Loss of consciousness (passing out), seizures, parosmiya|
|Violations of the cardiovascular system||Tachycardia, palpitations||Cardiac arrest 2|
|Respiratory system||Dyspnea 2|
|Gastro-intestinal system||Nausea||vomiting||Dry mouth|
|Skin and subcutaneous structures||Erythema, pruritus (including generalized form), rash (including maculo-papular rash with itching)||Nephrogenic systemic fibrosis|
|General pathology and changes at the injection site||Reactions at the injection site 3 , sensation of heat||Malaise, chills|
1 – hypersensitivity anaphylactic reactions, which were discovered only in the post-marketing studies (frequency not known) 2 cases associated with life-threatening and / or fatal 3 Reactions at the injection site (various types) include the following: bleeding at the injection site, burning at the injection site, feeling cold at the injection site, feeling of warmth at the injection site, erythema and rash at the injection site, pain at the injection site hematoma at the injection site.
single administration dianabol results ® (1 mmol / ml) at a dose of 1.5 ml of 1 kg body weight or higher was well tolerated.
So far, no symptoms of intoxication associated with an overdose of the drug dianabol results ® in its clinical application. Based on acute toxicity studies the risk of acute intoxication due to the use of the drug dianabol results ® is highly unlikely.
The inadvertent overdosage as a precaution it is recommended the monitoring functions of the cardiovascular system (including ECG) and control of renal function.
The drug dianabol results ® can be removed from the body by hemodialysis (see. “Special Instructions” section).
Interaction with other medicinal products and other forms of interaction
Do not mix with other drugs dianabol results as compatibility data otststvuyut.
Interactions with other drugs are not vyavleno.
In patients with known hypersensitivity to the drug required particularly careful assessment of risk / benefit ratio of application preparation dianabol results ® . As with other contrast agents for intravenous drug use dianabol results ® can be accompanied by symptoms of hypersensitivity reactions -anafilaktoidnymi and other manifestations of idiosyncrasies characterized by reactions with cardiovascular, respiratory or skin reactions, turning into severe conditions including shock.
The risk of hypersensitivity reactions is higher in case:
-predshestvuyuschey reactions to the contrast agent.
-allergicheskih diseases in history.
Most of these reactions develop over a period of 0.5-1 hours after administration.
In patients with a predisposition to the development of allergic reactions, the decision to use dianabol results the drug should only be taken after careful assessment of risk / benefit ratio.
Rarely observed the delayed allergic reaction (a few hours – days after the administration) (see “Side effects” section.).
After the diagnostic procedure with the drug dianabol results ® (as well as after the application of other contrast agents), we recommend monitoring of the patient.
The examination need to have drugs and equipment for resuscitation.
Patients taking beta-blockers, the development of hypersensitivity reactions may be resistant beta adrenomimeticheskim effect, used to treat such reactions.
– Severe renal impairment
is still impaired renal function were observed.
Before drug administration dianabol results ® all patients should be checked for renal dysfunction by history data collection and / or laboratory tests.
It is necessary to carefully evaluate the risk / benefit ratio of the drug in patients with severely impaired renal function, as in such cases the elimination of the contrast medium is retarded. After three courses of dialysis from the body is derived approximately 98% of gadobutrol. For patients on hemodialysis should consider the advisability of immediate initiation of hemodialysis after administration of the drug dianabol results ® , in order to accelerate the elimination of the contrast agent.
Reported cases of nephrogenic systemic fibrosis (NSF) in connection with the administration of gadolinium-containing contrast agents, including drug dianabol results ® , patients with the following diseases / conditions:
– acute or chronic renal insufficiency (glomerular filtration rate <30 ml / min / 1, 73 m 2 ) or
– acute renal insufficiency of any severity due to hepatorenal syndrome, or in the period before and after liver transplantation.
Despite the fact that the dianabol results formulation ® has a very high stability of the complex, due to their macrocyclic structure, there is the possibility of using the ASN dianabol results formulation ® . Therefore, these patients use the drug dianabol results ® should only after careful evaluation of the benefit / risk (see. “Side effects” section)
– Spasmodic state
Special care is required when assigning dianabol results ® drug as well as other contrast agents containing gadolinium chelate, patients with a low seizure threshold.
Effects on ability to drive vehicles and use complex mechanisms
The solution for intravenous administration of 1 mg / ml.
15 ml or 30 ml of colorless glass vials type I, with rubber stoppers, crimped aluminum caps provided with plastic caps. 1 bottle of 30 ml or 5 vials of 15 ml but with instruction on use is placed in a cardboard box.
In 5 ml or 7.5 ml in a glass syringe of colorless glass of type I. By 1 syringe in a blister made of PVC and laminated paper. On 5 blisters with instruction on use is placed in a cardboard box.
15 ml in 65 ml plastic cartridge capacity. On 5 cartridges together with instructions for use placed in a cardboard box.