Composition, form of production and packaging
The solution for intravenous administration is clear, colorless or slightly yellowish.
1 ml
gadodiamide 0.5 mmol
Excipients: sodium sodium cyanide 12.0 mg, 1M sodium hydroxide solution or 1M hydrochloric acid solution (to pH 5.5-7.0), water d / and up to 1 ml.
10 ml - vials of colorless glass (type I) (1) - packs cardboard.
15 ml - bottles of colorless glass (type I) (1) - packs cardboard.
20 ml - bottles of colorless glass (type I) (1) - packs cardboard.
10 ml - vials of colorless glass (type I) (10) - packs cardboard.
15 ml - bottles of colorless glass (type I) (10) - packs of cardboard.
20 ml - bottles of colorless glass (type I) (10) - packs cardboard.
10 ml - syringes (1) from transparent polypropylene - packs cardboard.
15 ml - syringes (1) from transparent polypropylene - packs cardboard.
20 ml - syringes (1) from transparent polypropylene - packs cardboard.
10 ml - syringes (10) from transparent polypropylene - packs cardboard.
15 ml - syringes (10) from transparent polypropylene - packs cardboard.
20 ml - syringes (10) from transparent polypropylene - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Gadodiamide is a neutral paramagnetic contrast medium for MRI. Strengthens contrast, facilitates visualization of abnormal structures and formations of the central nervous system (CNS), because free electrons of gadolinium atoms, having paramagnetic properties, generate a local magnetic field that accelerates the reorientation of extracellular fluid protons induced by the magnetic field of the apparatus; causes a signal amplification in the areas of the blood-brain barrier (BBB). Optimal contrast enhancement occurs in the first minutes after the injection (depending on the type of pathological process and the tissue being examined) and lasts 45 minutes.
PHARMACOKINETICS
Distribution and Metabolism
Gadodiamide does not penetrate intact GEB. The drug is quickly distributed in the extracellular fluid. V d (200 В± 61 ml / kg) corresponds to the volume of extracellular fluid. Gadodiamide is not metabolized, does not bind to plasma proteins.
Excretion
The half-distribution period is approximately 4 min, and the half-excretion period (T 1/2 ) is about 70 min. Gadodiamide is excreted mainly by the kidneys. The renal and total clearance of Gadodiamide is almost identical (1.7 and 1.8 ml / min / kg, respectively) and correspond to the clearance of drugs that are excreted mainly by glomerular filtration. In patients with impaired renal function (glomerular filtration rate (GFR) <30 ml / min / 1.73 m), T 1/2 is prolonged in proportion to the degree of decrease in the rate of filtration.
In patients with normal renal function, about 85% of the drug passes into the urine at 4 hours after iv injection of Gadodiamide, after 95% -95% after 24 hours.
INDICATIONS
- MRI of the brain and spinal cord in adults and children older than 4 weeks;
- Contrasting the whole body in adults and children over 6 months old;
- MP angiography in adults;
- MRI of the heart in adults for assessing coronary heart disease (CHD) by visualization under conditions of myocardial perfusion (at load / at rest and delayed study with contrast enhancement), to detect and determine the localization of IHD, identify ischemia and infarction in patients with known or presumed IHD.
DOSING MODE
In / in jet, once through the catheter with a syringe. With a body weight of the patient up to 100 kg - 0.1 mmol / kg (0.2 ml / kg); with a body weight of more than 100 kg - 10 mmol (20 ml). The drug is injected into the syringe immediately before use; To ensure complete administration of the dose, the cannula is washed with 5 ml of 0.9% sodium chloride solution. The beginning of the study - a few minutes after the introduction, the end within 1 hour (no more).
With MRI, the heart performs two injections to study myocardial perfusion under load and at rest. 2 hours before the procedure, the patient should not eat. When performing IV bolus injection for MRI of the heart, it is recommended to use a suitable injector with a speed of infusion of up to 8 ml / s. When the drug is administered, the patient should be in a horizontal position. Within 30 minutes after the end of the procedure, medical supervision of the patient is carried out. It is during this period that most of the adverse reactions occur.
Contrasting the central nervous system (CNS)
The recommended dose for adults and children is 0.1 mmol / kg body weight (equivalent to 0.2 ml / kg body weight) per body weight up to 100 kg; at a body weight of more than 100 kg, 20 ml are usually sufficient to provide a diagnostically adequate contrast.
If there is a suspicion of brain metastases, a dose of 0.3 mmol / kg body weight (equivalent to 0.6 ml / kg body weight) may be administered to adult patients weighing up to 100 kg. With a body weight of more than 100 kg, a dose of 60 ml is usually sufficient. A dose of 0.3 mmol / kg body weight can be administered in the form of a single bolus injection. In the case of indistinct images after injection at a dose of 0.1 mmol / kg of body weight, a second bolus injection at a dose of 0.2 mmol / kg of body weight (equivalent to 0.4 ml / kg of body weight) is administered after 20 minutes.
Full Body Contrasting
For adults and children older than 6 months, the recommended dose is 0.1 mmol / kg body weight (equivalent to 0.2 ml / kg body weight) with a body weight of up to 100 kg or in some cases 0.3 mmol / kg of body weight (equivalent to 0.6 ml / kg body weight ). If the patient has a body weight of more than 100 kg, 20 ml, or 60 ml, is usually sufficient for diagnostic contrasting (for some cases). The required dose should be administered once iv.
MRI in contrast enhancement should be started immediately after the administration of contrast medium, depending on the pulse mode used and the protocol of the study. The optimum gain is noted a few minutes after the injection (time is determined by the type of tissue damage). Usually, the gain is maintained up to 45 minutes after the administration of contrast medium. With contrast enhancement by the gadodiomide, it is optimal to use T1-weighted pulse sequences.
Angiography
For adult patients, the recommended dose is usually 0.1 mmol / kg body weight (equivalent to 0.2 ml / kg body weight). In the case of stenosis of the abdominal and iliac arteries, a higher dose up to 0.3 mmol / kg of body weight (equivalent to 0.6 ml / kg) is used, which allows obtaining additional diagnostic information. For optimal contrast, visualization should be performed on the first pass of the contrast medium, during and immediately after injection, depending on the equipment used.
CHD
For adult patients, the recommended dose for assessing myocardial perfusion is usually 0.15 mmol / kg body weight (equivalent to 0.3 ml / kg body weight), which is divided into 2 separate doses of 0.075 mmol / kg body weight (equivalent to 0.15 ml / kg body weight) and Enter with an interval of? 10 minutes. The first injection is administered under conditions of pharmacological stress, the second - at rest. The drug that causes pharmacological stress should be injected through a separate catheter. In the case of assessing late gain, a total dose of 0.15 mmol / kg body weight is recommended. In patients 65 years of age and older, dose adjustment is not required.
SIDE EFFECT
The frequency of side effects is classified according to the recommendations of the World Health Organization: very often (> 1/10); often (> 1/100, <1/10);infrequently (> 1/1000, <1/100); rarely (> 1/10 000, <1/1000); very rarely (1/10 000), the frequency is unknown (can not be estimated from the available data).
Disorders from the immune system: infrequently - allergic reactions of the skin and mucous membranes, hypersensitivity; frequency unknown - anaphylactoid reactions, incl. anaphylactic shock.
Disorders of the psyche: rarely - anxiety.
From the nervous system: often - headache; infrequently - dizziness, paresthesia, transient dysgeusia; rarely - cramps, tremors, drowsiness, transient dysosmia.
Disorders from the side of the organ of vision: rarely - visual impairment.
Violations from the heart: the frequency is unknown - tachycardia.
Violations from the vessels: infrequently - "hot flashes".
Disturbances from the respiratory system, chest and mediastinal organs: rarely - shortness of breath, cough; frequency unknown - sneezing, sore throat, bronchospasm, severe respiratory failure.
Disorders from the digestive tract: often - nausea, infrequently - vomiting, diarrhea.
Disturbances from the skin and subcutaneous tissues: infrequently - itching of the skin; rarely - a rash, hives; edema, including facial edema and angioedema.
Disorders from the musculoskeletal and connective tissue: rarely - arthralgia, myalgia.
Disorders from the kidneys and urinary tract: rarely acute renal failure; frequency unknown - development of nephrogenic systemic fibrosis (NFR) in patients with severe renal dysfunction (GFR <30 mL / min / 1.73 m 2 ).
Other: fever, chills, hyperemia of the facial skin, asymptomatic change in serum iron content (8 to 48 hours after administration).
Local reactions: soreness in the injection site.
CONTRAINDICATIONS
- severe renal dysfunction (GFR <30 ml / min / 1.73 m 2 );
- postoperative liver transplant;
- Pregnancy;
- the period of breastfeeding;
- newborn babies up to 4 weeks;
- Hypersensitivity to the active component or any auxiliary substance of the drug.
With caution: anemia (sickle cell and hemolytic), hemoglobinopathy, hepatic insufficiency, patients with hepatorenal syndrome, allergies, bronchial asthma, epilepsy or brain diseases, the presence in the history of development of unwanted reactions to the introduction of radiopaque substance (with the exception of allergic reactions).
PREGNANCY AND LACTATION
There is no experience of using gadodiamide in women during pregnancy. Do not use the drug for examination of pregnant women, except when the MRI with contrast enhancement is very necessary and the intended benefit to the mother from its use exceeds the potential risk to the fetus.
Until now, the possibility of getting gadodiamide in the milk of a nursing woman has not been studied. After the introduction of the mother's drug, breastfeeding should be discontinued and its resumption is possible not earlier than 24 hours after the administration.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe disorders of kidney function (GFR <30 ml / mn / 1.73 m 2 ).
In patients with moderate-grade kidney disease (GFR 30-59 mL / min / 1.73 m 2 ), the drug can be used only after a thorough assessment of the potential benefit and possible risk from the study, and is limited to the introduction of a standard dose (0.1 mmol / kg body weight ), and the interval between administration of the drug should be at least 7 days.
With caution should be used in patients with hepatorenal syndrome.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The use of the drug is contraindicated in the postoperative period of liver transplantation.
With caution should be used in patients with hepatic insufficiency, in patients with hepatorenal syndrome.
APPLICATION FOR CHILDREN
The use of the drug is contraindicated in newborn infants under 4 weeks of age.
In children under 1 year, the drug is only possible after a thorough assessment of the potential benefit and possible risk from the study, and is limited to the introduction of a standard dose (0.1 mmol / kg body weight), and the interval between administration of the drug should be at least 7 days.
SPECIAL INSTRUCTIONS
MRI is technically contraindicated in patients with an artificial pacemaker, stented vessels. The absence of contrast enhancement during MRI is not an unambiguous testimony to the absence of pathological processes. Some types of disseminated malignancies or inactive plaques with multiple sclerosis do not enhance the signal.
The presence or absence of contrast enhancement can be used to conduct a differential diagnosis of various types of pathological processes. In connection with the possibility of developing an anaphylactic shock during the introduction of the drug, it is necessary to create all conditions for immediate intensive therapy.
When using the drug should be particularly careful in the presence of patients in the history of allergy, bronchial asthma, tk. they may be at a higher risk of developing bronchospasm; as well as when examining patients who have a history of developing unwanted reactions to the introduction of radiopaque substance (with the exception of allergic reactions); patients with epilepsy or diseases of the brain; can be at risk of increased seizure. It should be borne in mind that most allergic reactions develop within half an hour after the administration of the drug.
Gadodiamide affects the results of measuring the concentration of calcium, serum iron in the blood using some colorimetric methods (it is not recommended to use these methods within 12-24 hours after the introduction of the gadodiamide). The drug contains sodium in the composition, which must be taken into account for patients who follow a diet with a low sodium content.
Before the study, it is necessary to investigate the function of the kidneys. there is a risk of developing NSF in patients with moderate renal insufficiency (GFR 30-59 ml / min / 1.73 m 2 ).
In patients taking beta-adrenoblockers, the manifestations of anaphylaxis with gadodiamide can be atypical and mistaken for vagal reactions.
In children under 1 year and patients with moderate-grade kidney disease (GFR 30-59 ml / min / 1.73 m 2 ), the drug can be used only after a thorough assessment of the potential benefit and possible risk from the study, and is limited to the introduction of a standard dose (0.1 mmol / kg body weight), and the interval between administration of the drug should be at least 7 days.
Caution should be observed when using gadodiamide in patients with hepatorenal syndrome.
One vial of the drug is used for only one patient, unused residues are discarded. When changing the color of the solution or the presence of large particles, it can not be used.
Impact on the ability to drive vehicles and manage mechanisms
Special studies on the impact on the ability to drive vehicles or work with machinery were not conducted. However, given the side effects profile, when using the drug in outpatients, they should avoid driving or potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.
OVERDOSE
Overdose is unlikely in patients with normal renal function.
Treatment: symptomatic. In the case of large doses in patients with renal insufficiency, the gadodiamide can be removed from the body by hemodialysis. There is no specific antidote.
DRUG INTERACTION
Pharmaceutically incompatible with other medicines.
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, protected from light and secondary X-rays at a temperature of 2 to 30 В° C. Shelf life - 3 years.
