PRYMOVYST

Active material: Gadoksetovaya acid
When ATH: V08CA10
CCF: Contrast diagnostic drug for magnetic resonance imaging
ICD-10 codes (testimony): Z03
When CSF: 30.01.02
Manufacturer: BAYER SCHERING PHARMA AG (Germany)

Pharmaceutical form, composition and packaging

The solution for the on / in the colorless to pale yellow, clear, free of mechanical impurities.

Excipients: kaloksetovoy acid trisodium salt, trometamol, hydrochloric acid, Sodium hydroxide, water d / and.

5 ml – colorless glass vials (1) – packs cardboard.
5 ml – syringes of colorless glass (1) – packs cardboard.
7.5 ml – colorless glass vials (1) – packs cardboard.
7.5 ml – syringes of colorless glass (1) – packs cardboard.
10 ml – colorless glass vials (1) – packs cardboard.
10 ml – syringes of colorless glass (1) – packs cardboard.

Pharmacological action

Contrast diagnostic drug for magnetic resonance imaging. Is a paramagnetic contrast agent gadolinium-based and is used for the T1 -weighted magnetic resonance imaging (LRA) liver. In the dynamic and delayed images Primovist^® improves the detection of focal liver lesions (incl. their number, size, segmental distribution and visualization) and provides additional data on the characterization and classification of focal liver lesions, thereby increasing the accuracy of diagnosis.

The effect of contrast enhancement due to the stable gadolinium complex – -EOB Gd-DTPA. The paramagnetic efficacy, or relaxation ability, determined from the effect on spin-lattice relaxation time of protons in plasma, is about 8.7 l / mmol / with pH 7, temperature 39 ° C, and the magnetic field 0.47 T. It is only slightly dependent on the magnetic field. When scanning using T1-weighted pulse sequences shortening of the spin-lattice relaxation time of excited atomic nuclei, caused by gadolinium ions, It leads to an increase in signal intensity and, thus, to increase the image contrast of certain tissues.

EOB-DTPA forms a stable complex with the paramagnetic gadolinium ion with an extremely high thermodynamic stability (logK_GDL= -23.46). Gd-EOB-DTPA is hydrophilic compound having high water solubility. Have etoksibenzilnoy group attached complex lipophilic properties.

Physico-chemical characteristics of the ready-to-use solution of the drug Primovist^® listed below:

Pharmacokinetics

Distribution

After the on / in the active substance diffuses rapidly into the intercellular space. Through 7 days after i / v injection of Gd-EOB-DTPA in rats and dogs below essentially determined 1% dose received, The highest concentration of the substance detected in the kidney and liver.

The active substance passes through the intact BBB and only slightly diffuses through the placental barrier.

Deduction

T_1/2 Gd-EOB-DTPA in Human Serum is 1 ± 0.1 hours and not significantly dependent on the dose received. T_1/2 in the terminal phase – 1.65± 0.23 hours or less. The observed pharmacokinetics is linear up to a dose 0.4 ml / kg (100 mmol / kg) body weight.

Gd-EOB-DTPA is completely eliminated from the body in equal proportions by the kidneys and hepatobiliary system.

Pharmacokinetics in special clinical situations

In severe renal dysfunction and hepatic excretion character changed accordingly.

In patients with severe hepatic impairment T_1/2 serum increased marginally, whereas patients with severe renal insufficiency (requiring hemodialysis) T_1/2 markedly increased.

Testimony

Prymovyst^® It intended solely for diagnostic purposes.

- Contrast enhancement during T1-weighted magnetic resonance imaging of the liver to improve detection of focal liver lesions (incl. their number, size, segmental distribution and visualization) and additional data on the characterization and classification of focal liver disease.

Dosage regimen

General rules of procedure

You must comply with the general safety precautions for magnetic resonance imaging. We do not recommend carrying out magnetic resonance imaging in the presence of a pacemaker in a patient and / or ferromagnetic implants.

During 2 hours before the examination the patient should refrain from eating to reduce the risk of aspiration, since all the contrast agents can cause such side effects as nausea and vomiting.

Possibly, during injection of contrast medium into the patient must be in a horizontal position. After the injection is to observe the condition of the patient during, at least, 30 m, since experience with contrast media shows, Most adverse events that develops in this period.

Doses

Prymovyst^® It is a ready-to-use aqueous solution, which is incorporated by undiluted I / bolus injection at about 2 ml / s through a large diameter needle or indwelling catheter (Recommended size 18-20 G). After injection, the contrast agent / in the cannula should be flushed 0.9% sodium chloride.

The recommended dose Primovista^® It is for Adult 0.1 ml (corresponding 25 mmol)/kg body weight).

Visualization

After bolus injection Primovista^® Dynamic visualization of arterial, portovenoznoy and equilibrium phases allows you to get a picture of unequal temporal contrast various types of liver lesions. This information makes it possible to classify the identified education (benign / malignant) and to describe their specific characteristics. This method further improves the visualization of hypervascular liver lesions.

Delayed (gepatocitarnaя) phase begins approximately 10 min after injection (supporting research in most of the data were obtained through 20 min after injection), at the same time visualization lasts at least 120 m. Patients, who require hemodialysis, as well as in patients with elevated bilirubin (>3 mg / dL) imaging period is reduced to 60 m.

Contrast the liver parenchyma during the hepatocyte phase helps determine the number of liver lesions, their segmental distribution, visualization and borders, improving, thus, detectability of lesions. The difference between the nature of liver lesions contrasting dynamics / washout of contrast medium allows you to get more information.

Hepatic excretion Primovista^® provide opacification of the biliary system.

Side effect

None of the individual adverse reactions were observed with a frequency, exceeding the level infrequently.

The majority of adverse reactions were mild to moderate intensity. Based on these (more than 1400 patients), The following adverse events were noted, are classified by researchers as, probably, and no doubt associated with the use of the drug.

The table below shows adverse reactions divided by body system.

In very rare cases may occur anaphylactoidnye reaction, incl. shock.

After the introduction of the Primovista^® less than 1% patients noted a slight increase in serum iron levels and bilirubin, that, Nonetheless, returning to the initial values for 1-4 days with no symptoms.

Contraindications

-hypersensitivity to the active substance or to any of the supporting components of the drug.

FROM caution should designate product:

-patients with allergic/psevdoallergičeskimi reactions to any allergen in the past, as well as patients with bronchial asthma, tk. they may be at increased risk for severe reactions. Most of these reactions occur within 30 minutes after administration. Nonetheless, As with other contrast agents of this class, in rare cases delayed reactions may develop (from several hours to days);

- With cardiovascular disease: data administration Primovista^® patients with severe cardiovascular disease are limited, so in these cases it is necessary to use caution.

Pregnancy and lactation

Animal studies showed no risk of teratogenic effects or effects on fertility, embryonic, as well as the pre- and postnatal development. Prymovyst^® It should be administered to pregnant women only after evaluation of the benefit / risk.

Animal studies have shown, that Primovist^® in a minimum volume (less 0.5% dose received) excreted in breast milk. Prymovyst^® lactating women should be introduced only after the evaluation of the benefit / risk.

Cautions

Introduction Primovista^® It may be associated with the development of anaphylactoid reactions / hypersensitivity reactions or other manifestations of idiosyncrasy, characterized by cardiovascular, respiratory or cutaneous manifestations. There are severe reactions, incl. anaphylactic shock.

As with the other diagnostic procedures, contrast media, posleprotsedurnoe recommended patient monitoring.

The risk of hypersensitivity reactions is increased in the presence of previous reactions to contrast media, bronchial asthma or other allergic diseases. Patients, at which such reactions occur in patients receiving beta-blockers, may be resistant to treatment with drugs, having beta-agonist activity.

Due to the potential development of severe hypersensitivity reactions after injection of a contrast agent, necessary readiness for emergency resuscitation.

Should be strictly avoided in / m injection. According to the experimental results of Primovist^® It has a good local tolerance after intravascular (in / in / a) introduction, and after the introduction of paravenoznogo. However / m introduction causes local intolerance reactions (Local chemotoxicity), including focal necrosis and poetomuneobhodimo strictly avoid this route of administration in humans.

Preclinical safety data

Preclinical studies booster doses for toxicity, genotoxicity and toxic effects on reproduction indicate the absence of any risk to humans.

Terms of Use / handling dosage forms

This medicine is a ready-to-use solution, intended only for single use.

Bottles, containing contrast agent, do not involve multiple doses of fence. The rubber stopper should never be pierced more than once. This drug should be typed into the syringe immediately before administration to the patient.

The pre-filled syringe must be removed from the package and ready for injection immediately before observation.

The contrast agent, not used in one examination, be destroyed.

Use in Pediatrics

Clinical experience in patients under 18 years missing.

Effects on ability to drive vehicles and management mechanisms

Unknown.

Overdose

Based on the results, animal studies of acute toxicity, the risk of acute intoxication when using Primovista^® missing.

The maximum dose 0.4 ml / kg (100 mmol) body weight, which was tested for use in MRI, well tolerated. Among the limited number of patients in clinical trials tested dose 2 ml / kg (500 mmol) body weight. In these patients, there was an increased incidence of adverse events, but no additional side effects were found.

Due to the small volume (maximally 10 ml) and extremely low absorption Primovista^® in the digestive tract, and based on the data on the acute toxicity, intoxication due to accidental receiving the contrast agent into the extremely unlikely.

Treatment: Accidental administration of excessive doses of substances to patients with severe renal or hepatic insufficiency Primovist^® It can be removed from the body by hemodialysis.

Drug Interactions

Anionic drugs, stand out, mainly, the bile (eg, rifampicin), can compete with Primovistom^® during its release by the liver, changing nature of the contrast enhancement. Animal studies have shown, Compounds, belonging to the class of rifamycins, capture block Gd-EOB-DTPA liver cells, thereby reducing the effect of contrasting liver. In this case the expected benefit from the introduction of Primovista^® It may not manifest fully.

Personal interactions with other drugs known.

Elevated levels of bilirubin or ferritin can reduce the hepatic contrast effect Primovistom^®.

In determining the content of iron in serum complexometric methods (eg, by complexation with ferrocine) prior to 24 hours after the examination with Primovistom^® false values ​​can be obtained due to the presence of free chelating agent in the solution of the contrast agent.

Pharmaceutical interaction

In the absence of compatibility studies, the drug must not be mixed with other medicaments.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 5 years.

Primovist chemically and physically stable. From the viewpoint of Microbiology, This preparation should be used immediately after the opening.