Gadopentetic acid

Magnetist is a paramagnetic contrast medium.

[1], [2]

Indications of the magnevist

It is shown in the cases described below.

MRI procedures in the spinal region, as well as the brain.

To determine the presence of tumors with subsequent differential diagnosis (if there is suspicion of shvannomu (auditory nerve), arachnoidendothelioma, metastases, as well as a tumor that has infiltrative growth (for example, glioma)):

• when determining iso-intensive or small tumors;
• suspicion of a possible relapse of the appearance of a tumor after a radiotherapy procedure or after a surgical procedure;
• to differentiate the picture with the following rare formations: ependymoma, hemangioblastoma, and also small pituitary adenomas;
• to improve the definition of local distribution of formations that have no cerebral etiology.

As an additional tool in the process of spinal MRI:

• differentiation of extra-, as well as intramedullary formations;
• detection of large tumors within pathologically altered areas;
• evaluation of the development and spread of intramedullary formations.

The procedure of MRI in all parts of the body.

To diagnose an education in the following situations:

• improvement of differentiation of malignant and benign formations in the area of mammary glands in women;
• for distinguishing scar and tumor tissues after treatment of formations in women within the mammary glands;
• discrimination of tumor and scar tissue in the passive region, as well as active parts of the ODA;
• differentiation of different areas of bone tumors (decay region, tumor tissues, and inflammatory focus);
• differentiation of different types of liver formations;
• Identification of formations located inside or outside the kidneys;
• to find out the size, and also perform differentiation of tumors within different departments of the uterine appendages;
• to get a picture of any vessel inside the body (in addition to the coronary arteries) by angiography procedure - this is necessary, among other things, to detect occlusions, stenosis, and also collaterals;
• to conduct a targeted selection of necessary tissue samples (biopsy procedure) with the development of bone tumors;
• to distinguish the development of recurrent hernia in the scar tissue and intervertebral disc;
• to deduce a picture of lesions in the field of a myocardium (the acute form).

[3], [4]

Release form

Produced in the form of an injection solution in vials of 10 or 20 ml. Inside the package contains 1 bottle.

[5], [6], [7]

Pharmacodynamics

Magnetist is a contrasting paramagnetic substance that is used in MRI procedures. The di-N-methylglucamine salt of the substance Gadopentetic Acid (complex including gadolinium and DTPA) helps to increase the contrast.

In the process of using the T1-weighted sequence in the scanning procedure (proton MRI is used), the period of spin-lattice relaxation (T1) of excited nuclei inside atoms decreases, which is provoked by gadolinium ions. It helps to increase the intensity of the transmitted signal, as a result of which the contrast of the picture of individual tissues increases.

Diphenoglum gadopentetate is a highly paramagnetic compound that contributes to a significant reduction in the period of relaxation, even when using a weak concentration. The level of paramagnetic action, as well as the relaxation (determined by the period of spin-lattice relaxation of water protons inside the plasma) is 4.95 liters / (mmol / second). At the same time, the acidity level is 7, and the temperature is 39 ° C and the effect of the magnetic field on it is weak.

DTPk forms a powerful complex containing a paramagnetic gadolinium ion, which results in a very strong stability in in vivo and in vitro (the thermodynamic equilibrium constant log K = 22-23). Dimeglumine salt of hapopentetate dissolves rapidly in water and is considered a strong hydrophilic compound. Its distribution coefficient between the buffer, as well as n-butanol (pH = 7.6) is 0.0001. The component has no propensity to synthesize with protein or to a slowing interaction with enzymes (eg, Na ⁺ K ⁺ ATPase inside the myocardium). The drug does not activate the complementary system, so the probability of anaphylactoid reaction is extremely low.

With longer incubation, as well as high rates of dimegluminum gadopentetate, a weak in vitro effect on erythrocyte morphology occurs. The reversible process after administration of drugs can provoke the development of weak hemolysis inside the vessels. As a result, there is a slight increase in iron with bilirubin in the blood serum, which occurs during the first few hours after the injection.

[8], [9], [10], [11], [12], [13]

Pharmacokinetics

Dimeglumine gadopentate has properties similar to other bio-inert compounds that have a high hydrophilicity index (among them, inulin or mannitol). Pharmacokinetic parameters observed in humans are independent of the dosage of drugs.

After the introduction of the solution, its rapid distribution occurs in the body - outside the cells.

One week after the ingestion of the animals labeled with radioactive dimeglumine salt of Gadopentetic Acid substance, its presence was determined by indicators that were well below 1% of the administered dosage of drugs. A relatively high level of gadolinium (its uncleaved complex) was observed inside the kidneys. This connection does not pass through intact GEB and GTB. A small part of the medicine passes through the placenta and penetrates the fetus into the blood, but it is quickly excreted.

In the case of using a solution of less than 0.25 mmol / kg (or 0.5 ml / kg) after a few minutes that occupies the distribution phase, the plasma contrast value decreases (half-life is approximately 1.5 hours, which is approximately equal to rate of excretion through the kidneys).

In the case of administration of the substance in the amount of 0.1 mmol / kg (or 0.2 ml / kg of the drug) 3 minutes after the procedure, the plasma value of the drug was 0.6 mmol / l, and after 1 hour it reached 0.24 mmol / l .

There is no biotransformation or disengagement of the paramagnetic ion.

Gedopentatum dimeglumina excreted through the kidneys, unchanged (by filtering the glomeruli). Part of the drug, the excretion of which occurs extra-renal, is very small. About 83% (mean) of the dose is excreted 6 hours after the injection. In the first 24 hours, 91% of the drug dosage is detected in the urine. Less than 1% is the dose that is excreted in the period of 5 days after the procedure.

The clearance of the active substance inside the kidneys is approximately 120 ml / minute / 1.73 m  ². This indicator correlates with the clearance of ⁵¹ Cr-EDTA or inulin.

[14], [15], [16], [17], [18], [19]

Dosing and administration

The medicine is used in diagnostic procedures, it is only necessary to enter it in / in the method.

It is necessary to follow the generally accepted precautions in the process of performing an MRI: the doctor should first make sure that the patient does not have ferromagnetic implants, a pacemaker, etc.

Dosages in the range 0.14-1.5 T are effective irrespective of the effect of the magnetic field.

The required dosage is given only by injection. Sometimes it is permissible to perform a bolus injection. An MRI scan using contrast enhancement can begin immediately after the medication was administered to the patient.

During the procedure for administering the drug, the patient should, if possible, remain in a supine position. Also, after using the solution, it is necessary to closely monitor the patient's condition, since most adverse reactions occur within a half an hour from the time of administration.

Using a medicine for children (also aged 4 months to 2 years), adolescents, and also adults, the following doses should be used. To increase the contrast and resolve diagnostic issues, it is usually sufficient dosage, which is determined when calculating 0.2 ml / kg.

If after the introduction of such a dosage MRI showed mixed results, but there is a serious suspicion of the presence of pathological entities in the patient, it will be expedient to perform a repeated procedure of drug administration (to clarify the diagnosis). It should be done within half an hour after the 1st procedure, and then perform an MRI. Dosage at the same time remains the same (but for adults, you can calculate the dose of the solution at a parameter of 0.4 ml / kg).

With the exclusion of recurrence of tumor formation or development of metastasis, the increased dosage of drugs used for adults (calculation - 0.6 ml / kg) allows for more accurate diagnosis.

It is allowed to prescribe medication in doses not exceeding 0.4 ml / kg (children over 2 years old) and 0.6 ml / kg (adults).

In the MRI procedure for adults and children (from the age of 4 months), in order to solve the questions raised during the diagnosis, as well as to increase the contrast of the image, a dosage calculated in the 0.2 ml / kg scheme is usually sufficient. But it should be borne in mind that there are only limited information about the experience of conducting MRI procedures of the whole body before the age of 2 years.

In special situations, for example, in the case of tumors that have weak vascularization or a small degree of passage into the extracellular region in order to obtain the required contrast, there may be a need for applying 0.4 ml / kg of the drug. In particular, this applies to low T1-weighted sequences in the scanning procedure.

When visualizing the system of blood vessels (also important here is the area of the body to be examined and the method used to perform it), adults sometimes may need to apply the solution at the maximum dosage.

Children from 1 month to 2 years are allowed to prescribe no more than 0.2 mg / kg of drug solution.

The required amount of solution must be entered manually to prevent the possibility of an unintentional overdose. The procedure using an autoinjector is not performed.

Thus, the following dosages are used for diagnosis:

• the average dose for children (from 1 month to 2 years) and adults for MRI in the whole body area, as well as the brain and spinal cord - 0.2 ml / kg (this is 0.1 mmol / kg);
• the average dose for complex diagnosis (and the maximum allowable in children) is 0.4 ml / kg (which is 0.2 mmol / kg);
• the maximum dosage used to visualize the system of blood vessels is 0.6 ml / kg (which is 0.3 mmol / kg).

[26], [27]

Use of the magnevist during pregnancy

There is no clinical information regarding the use of the drug in pregnant women. According to the results of the animal test, there is no indirect or direct negative effect on the reproductive system, but the drug is still prohibited from prescribing during pregnancy. The use of the solution is allowed only in cases when the condition of the pregnant woman requires the introduction of the dimeglumin salt of Gadopentetic Acid.

Contraindications

Among the contraindications of the medicine:

• intolerance of the active component or other elements of the drug;
• the presence of disorders in the work of the kidneys (in severe form - with a glomerular filtration rate <30 ml / minute / 1.73 m  ² );
• people who are in the perioperative period during liver transplant;
• newborns (age less than 1 month).

[20], [21], [22]

Side effects of the magnevist

The use of drugs can cause such side effects:

• hematopoietic system: the indicator of bilirubin and iron inside the serum may change for a time;
• immune system: allergic or anaphylactoid manifestations, angioedema, anaphylactoid shock, as well as itching, sneezing and coughing, conjunctivitis, runny nose, laryngospasm and bronchial spasm develop sporadically, as well as urticaria. Perhaps the development of shock, hypotension, and edema in the pharynx or larynx;
• organs of the National Assembly: rarely there are headaches or dizziness; there is a disorder of consciousness, speech or smell, disorientation, as well as a feeling of burning, drowsiness and excitement. In addition, tremor, seizures and paresthesias may develop, and with it coma and asthenia;
• visual organs: single appear pain in the eyes, visual disturbances and lacrimation;
• auditory organs: hearing disorders and pain in the ears develop sporadically;
• CAS organs: a clinically perceptible transitory disorder of heart rate (bradycardia and tachycardia (or its reflex form)), the development of arrhythmia, an increase in the parameters of blood pressure, a disorder of the cardiac function (up to cardiac arrest) is possible;
• cardiovascular system: the manifestations that accompany vasodilation (peripheral type) develop sporadically and lead to a decrease in the level of pressure and fainting. There is also confusion, a feeling of excitement, cyanosis and a reflex form of tachycardia (can cause loss of consciousness), and thrombophlebitis also develops;
• respiratory disorders: single transient changes in the respiratory frequency occur (increase or decrease), difficulty in the respiratory process, dyspnoea, cough, rales and respiratory arrest. There may also appear compression sensations in the throat or irritation, pulmonary edema, sneezing, pain in the larynx or throat (or uncomfortable sensations in the latter);
• Gastrointestinal organs: rarely a taste disorder, vomiting, and nausea; there are uncomfortable feelings or pains in the stomach, dry mouth mucous membranes, diarrhea, toothache, increased salivation, pain in the soft tissue area, as well as paresthesia inside the mouth;
• digestive organs: transient changes occur (occasionally increase) in the level of liver enzymes, and the blood value of bilirubin also increases;
• subcutaneous fat and also skin: redness with heat and vasodilation appears alone, angioedema, itching and urticaria with exanthema;
• bone structure and muscles: pain pains in the limbs;
• urinary system and kidneys: single-arising sudden urge to urinate, urinary incontinence, and in addition an increase in creatinine levels along with an acute form of kidney failure in people who had previously been diagnosed with this pathology;
• general disorders and problems at the site of administration: rarely there are feelings of cold / heat, as well as general pain. In addition, local pains, swelling, extravasation, inflammatory processes, thrombophlebitis and phlebitis, tissue necrosis, and swelling with paresthesias also develop. Together with this, the development of erythema, hemorrhagic syndrome, and irritation is possible; single pains appear in the sternum, joints and back, chills, a feeling of discomfort. Sweating is increased, vasovagal manifestations occur, puffiness on the face, a feeling of thirst and severe fatigue, peripheral puffiness, a febrile condition develops and the temperature changes (decreases or increases).

[23], [24], [25]

Overdose

Accidental overdose after intravascular injection can provoke the development of such signs of impairment (they are caused by increased osmolarity of drugs):

• systemic manifestations (hypovolemia, increased pressure indices inside the pulmonary arteries, osmotic form of diuresis, as well as exsicosis);
• local manifestations (pain inside the vessels).

Patients with kidney failure need to perform ongoing monitoring of renal function.

Excretion of the substance is carried out using the procedure of hemodialysis. But at the same time there is no evidence that confirms the need to perform this procedure to prevent the development of the NSF.

Since Magnevist has a very weak degree of absorption within the gastrointestinal tract (<1%), in the case of an unintentional use of the solution inside, the probability of poisoning will be extremely low.

[28], [29], [30]

Interactions with other drugs

No tests were performed for the interaction of the solution with other drugs.

Experience using contrasting drugs has shown that people who use β-blockers for treatment are more prone to developing notable allergic manifestations.

Interaction with other substances for diagnostic testing.

When clarifying the serum iron level using the method of complexonometry (for example, using batofenantrolin) during the first days after the application of Magnevist, the quantity indicators may be incorrect (reduced). This can be explained by the fact that the solution contains a contrast component - DTPK.

[31], [32], [33]

Storage conditions

Keep the solution in a place that is closed from children, in standard conditions for medicines. The temperature level is not more than 25 ° C.

[34], [35], [36]

Shelf life

Magnetist can be used for 5 years from the date of manufacture of the drug solution.

[37]