Composition, form of production and packaging
A solution for intravenous administration from colorless to light yellow color, transparent, free from mechanical inclusions.
disodium gadoxetate 181.43 mg,
which corresponds to the concentration of gadoxetic acid 0.25 mmol
Auxiliary substances: caloxetic acid trisodium salt - 1 mg, trometamol - 1.211 mg, hydrochloric acid 3.6% (w / w) - 8.4 mg, sodium hydroxide (up to pH7.2-7.6) - 264 Ојg, water d / u - 901.195 mg .
5 ml - bottles of colorless glass (1) - packs of cardboard.
5 ml - bottles of colorless glass (5) - packs cardboard.
5 ml - bottles of colorless glass (10) - packs of cardboard.
7.5 ml - bottles of colorless glass (1) - packs of cardboard.
7.5 ml - vials of colorless glass (5) - packs cardboard.
7.5 ml - bottles of colorless glass (10) - packs of cardboard.
10 ml - vials of colorless glass (1) - packs cardboard.
10 ml - bottles of colorless glass (5) - packs of cardboard.
10 ml - bottles of colorless glass (10) - packs of cardboard.
5 ml - syringes of colorless glass (1) - packs cardboard.
5 ml - syringes of colorless glass (5) - packs cardboard.
5 ml - syringes of colorless glass (10) - packs cardboard.
7.5 ml - syringes of colorless glass (1) - packs cardboard.
7.5 ml - syringes of colorless glass (5) - packs cardboard.
7.5 ml - syringes of colorless glass (10) - packs cardboard.
10 ml - syringes of colorless glass (1) - packs cardboard.
10 ml - syringes of colorless glass (5) - packs cardboard.
10 ml - syringes of colorless glass (10) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
Contrast diagnostic drug for magnetic resonance imaging. It is a paramagnetic contrast agent based on gadolinium and is used for T1 - weighted magnetic resonance imaging (MRV) of the liver. On dynamic and delayed images, Primovist В® improves the detection of focal lesions of the liver (including their number, size, segmental distribution and visualization) and allows to obtain additional data on the characterization and classification of focal lesions of the liver, thereby increasing the reliability of the diagnosis.
The effect of increasing the contrast is due to a stable gadolinium complex - Gd-EOB-DTPA. The paramagnetic efficiency or relaxation ability, determined from the effect on the spin-lattice relaxation time of protons in plasma, is about 8.7 l / mmol / s at pH 7, temperature 39 В° C and magnetic field strength 0.47 T. It is only slightly dependent on the strength of the magnetic field. When scanning using T1-weighted pulse sequences, the shortening of the spin-lattice relaxation time of excited atomic nuclei caused by gadolinium ions leads to an increase in the signal intensity and, thus, to an increase in the contrast of the image of some tissues.
EOB-DTPA forms a stable complex with a paramagnetic gadolinium ion with extremely high thermodynamic stability (logK Gdl = -23.46). Gd-EOB-DTPA is a hydrophilic compound with high water solubility. The presence of the ethoxybenzyl group gives the complex lipophilic properties.
The physico-chemical characteristics of the ready-to-use solution of Primovist В® are listed below:
Osmolality at 37 В° C (mOsm / kg water) 688
Viscosity at 37 В° C (mPa.s) 1.19
Density 37 В° РЎ (g / ml) 1.0881
After IV introduction, the active substance diffuses rapidly into the intercellular space. 7 days after intravenous injection of Gd-EOB-DTPA in the body, rats and dogs are determined to be well below 1% of the dose received, with the highest concentration of the substance found in the kidneys and liver.
The active substance does not pass through intact BBB and only diffuses slightly through the placental barrier.
T 1/2 Gd-EOB-DTPA from human serum is 1 В± 0.1 h and is not substantially dependent on the doses received. T 1/2 in the terminal phase is 1.65 В± 0.23 h or less. The observed pharmacokinetics is linear up to a dose of 0.4 ml / kg (100 Ојmol / kg) of body weight.
Gd-EOB-DTPA is completely eliminated from the body in an equal proportion through the kidneys and the hepatobiliary system.
Pharmacokinetics in special clinical cases
In severe violations of kidney and liver functions, the nature of excretion changes accordingly.
In patients with severe impairment of liver function, T 1/2 of serum increases slightly, whereas in patients with severe renal insufficiency (requiring hemodialysis), T1/2 increases markedly.
Primovist В® is intended exclusively for diagnostic purposes.
- for carrying out T1-weighted magnetic resonance imaging (MRV) of the liver. On dynamic and delayed images, Primovist В® improves the detection of focal lesions of the liver (including their number, size, segmental distribution and visualization) and allows to obtain additional data on the characterization and classification of focal lesions of the liver, thereby increasing the reliability of the diagnosis.
General rules of the procedure
It is necessary to observe the generally accepted precautions when conducting magnetic resonance imaging. It is not recommended to perform magnetic resonance imaging if the patient has a pacemaker and / or ferromagnetic implants.
Within 2 hours before the examination, the patient should refrain from eating to reduce the risk of aspiration, since all contrast agents can cause side effects such as nausea and vomiting.
If possible, the patient should be in a horizontal position during the injection of the contrast agent. After the injection, the patient should be monitored for at least 30 minutes, since experience with the use of contrast agents indicates that most of the adverse events develop during this period.
Primovist В® is a ready-to-use aqueous solution that is administered undiluted by intravenous bolus injection at a rate of approximately 2 ml / s using a large diameter needle or a permanent catheter (the recommended size is 18-20 G). After injection of the contrast agent in / in the cannula, it should be washed with 0.9% sodium chloride solution.
The recommended dose of Primovit is 0.1 ml for adults (corresponding to 25 Ојmol) / kg of body weight).
After bolus injection of Primov, dynamic visualization in arterial, portogenous and equilibrium phases allows to obtain an unequal temporal picture of contrasting of different types of liver lesions. This information makes it possible to classify the detected formations (benign / malignant) and describe their specific characteristics.Such a method further improves the visualization of the hypervascular lesions of the liver.
The delayed (hepatocytic) phase begins approximately 10 minutes after the injection (in confirmatory studies, most of the data were obtained 20 minutes after the injection), with a visualization period of at least 120 minutes. In patients who require hemodialysis, as well as in patients with elevated levels of bilirubin (> 3 mg / dl), the visualization period is reduced to 60 minutes.
The contrasting of the liver parenchyma during the hepatocyte phase helps to determine the number of affected areas of the liver, their segmental distribution, visualization and boundaries, thereby improving the detection of lesions. The difference in liver damage by the nature of the contrast / washout dynamics of the contrast medium allows us to obtain additional information.
Hepatic excretion of Primovist provides contrasting of the bile excretory system.
None of the individual adverse reactions were observed at a frequency exceeding the infrequent level.
Based on the data for more than 1700 patients, the following undesirable phenomena were noted, which were classified by the researchers as related to the use of the drug.
Most adverse events were of mild to moderate intensity.
In the table below, adverse reactions are distributed throughout the body systems.
Not infrequently (? 1/1000, <1/100) Rarely (<1/1000)
From the side of the central nervous system and peripheral nervous system
Headache Dizziness Paresthesia Perversion of taste, parosmosis Vertigo (vestibular dizziness) Akathisia Tremor
From the side of the cardiovascular system
Boosting of blood pressure Hot flashes Blockage of the bundle of the bundle of Guiss Heartbeat
From the respiratory system
Shortness of breath Breathing difficulty
From the digestive system
Nausea Vomiting Dry mouth Nausea in the mouth Increased salivation
From the skin side
Rash Itching (general itching, itching in the eyes) Maculo-papular rash Increased sweating
From the musculoskeletal system
Common violations and local reactions
Pain in the chest Reactions at the injection site (extravasation at the injection site, burning sensation at the injection site, sensation of cold at the injection site, irritation at the injection site, pain at the injection site) Feeling of the fever Chills Feeling of discomfort Feeling tired Fatigue Unpleasant sensations
In very rare cases, anaphylactoid reactions may occur, incl. shock.
After Primovist administration, less than 1% of patients had a slight increase in serum levels of iron and bilirubin, which nevertheless returned to their original values вЂ‹вЂ‹within 1-4 days without any symptoms.
Additional adverse reactions reported spontaneously in the postmarketing period
In rare cases, tachycardia and anxiety have been reported.
Because these data came spontaneously, the frequency of these adverse reactions can not be determined. However, since they were not observed in clinical trials involving more than 1,700 patients, it can be considered that they occur rarely (<1/1000).
- Hypersensitivity to the active substance or to any of the auxiliary components of the drug.
Caution should be given to the drug:
- patients with allergic / pseudo-allergic reactions to any allergen in the past, as well as patients with bronchial asthma, t. they may be at increased risk of developing severe reactions. Most of these reactions occur within 30 minutes after drug administration. Nevertheless, as with the use of other contrast agents of this class, in rare cases, the development of delayed reactions (from several hours to days) is possible;
- for cardiovascular disease: data on the introduction of Primovist patients with severe cardiovascular diseases are limited, so in these cases, you need to be careful.
PREGNANCY AND LACTATION
Studies in animals have not revealed a risk of teratogenic effects or effects on fertility, fetal, and pre- and postnatal development. Primovist В® should be administered to pregnant women only after assessing the expected benefit of therapy for the matter and the potential risk to the fetus.
Animal studies have shown that Primovist В® is excreted in breast milk in a minimal volume (less than 0.5% of the dose received). Primovist В® should be administered to lactating women only after assessing the expected benefit of therapy for the substance and the potential risk to the fetus.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Primovist В® is intended exclusively for diagnostic purposes.
- contrast enhancement during T1-weighted magnetic resonance imaging of the liver to improve the detection of focal liver lesions (including their number, size, segmental distribution and visualization) and to obtain additional data on the characterization and classification of focal pathology of the liver.
APPLICATION FOR CHILDREN
Clinical experience of use in patients younger than 18 years is absent.
As for other drugs in this class, the administration of PrimaVista may be associated with the development of hypersensitivity reactions / allergic reactions or other manifestations of idiosyncrasy characterized by cardiovascular, respiratory or skin manifestations. Severe reactions are possible, incl. anaphylactic shock
As with other diagnostic procedures with contrast media, post-procedural follow-up is recommended.
For the treatment of hypersensitivity reactions, appropriate medicines and readiness for emergency resuscitation are needed.
The risk of developing hypersensitivity reactions increases with previous reactions to contrast agents, bronchial asthma or other allergic diseases. Patients in whom such reactions develop against the background of taking beta-blockers may be resistant to treatment with drugs that have a beta-agonist effect.
There have been reports of a relationship between nephrogenic systemic fibrosis (NSF) using some gadolinium-containing contrast agents in patients with acute or chronic severe renal dysfunction (glomerular filtration rate <30 ml / min / 1.783 m 2 ) and acute renal failure of any severity due to hepatic- renal syndrome or in a period close to a liver transplant.
Although the system exposure of gadolinium is low when the diagnostic dose of Primov is administered, and also that there are two ways of elimination (renal and hepatobiliary), there is a possibility of the emergence of an NSF after the introduction of PrimaVista. Therefore, prior to the introduction of Primovist, such patients should carefully weigh the benefit / risk relationship.
Before Primovist administration, all patients should be examined for possible impairment of renal function by collecting anamnesis and / or conducting laboratory tests.
Primovist В® can be removed from the body by hemodialysis. In patients who have already had hemodialysis at the time of Primovist, hemodialysis should be started quickly after the administration of PrimaVista in order to accelerate the elimination of the contrast agent.
It is necessary to strictly avoid the / m introduction of the drug, as it can be the cause of local intolerance reactions, including focal necrosis.
Rules of use / handling of medicinal forms
This drug is a ready-to-use solution intended for single use only.
Vials containing a contrast agent are not intended for multiple doses. Rubber cork should never be pierced more than once. The drug should be injected into the syringe immediately before administration to the patient.
The pre-filled syringe should be removed from the package and prepared for injection immediately before the examination.
Contrast substance, not used for one examination, is subject to destruction.
Use in Pediatrics
Clinical experience of use in patients younger than 18 years is absent.
Impact on the ability to drive vehicles and manage mechanisms
It is not known.
Preclinical safety data
The results of preclinical studies of the administration of repeated doses for toxicity, genotoxicity and toxic effects on reproduction indicate that there is no danger to humans.
Based on the results of animal studies of acute toxicity, there is no risk of acute intoxication when using PrimaVista.
The maximum dose of 0.4 ml / kg (100 Ојmol) of body weight that was tested for MPB was well tolerated. Among a limited number of patients, a dose of 2 ml / kg (500 Ојmol) of body weight was tested during clinical trials. These patients had an increased incidence of side effects, but no additional side effects were found.
Due to the small volume (max. 10 ml) and the extremely low absorption of Primov in the gastrointestinal tract, and also from acute toxicity data, intoxication due to accidental intake of contrast medium inside is extremely unlikely.
Treatment: with the occasional administration of the drug in excessive doses to patients with severe renal or hepatic insufficiency, Primovist В® can be removed from the body by hemodialysis.
Anionic preparations that are secreted mainly with bile (for example, rifampicin), can compete with Primovist during its isolation by the liver, changing the character of contrast enhancement. Animal studies have shown that compounds belonging to the class of rifamycins block the seizure of Gd-EOB-DTPA by liver cells, thereby reducing the effect of contrasting the liver. In this case, the expected benefit from the introduction of Primavera may not manifest itself to the full.
The interaction with other drugs is unknown.
An increased level of bilirubin or ferritin can reduce the effect of contrasting the liver with PrimaVista.
When determining the iron content in the serum by complexometric methods (for example, by complexation with ferrocin) for up to 24 hours after the examination with Primovist, false values вЂ‹вЂ‹may result because of the presence of a free complexing substance in the solution of the contrast agent.
In the absence of compatibility studies, this drug should not be mixed with other drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 5 years.
Primovist В® is chemically and physically stable. From the point of view of microbiology, this drug should be used immediately after the discovery.