Gadopentetate acid

Gadopentetic acid is a non-ionic, low osmolality contrast agent that has a high magnetocaloric effect and is commonly used as a contrast agent.[ 1 ]

Indications Gadopentetic acid

Shown in the cases described below.

MRI procedures in the area of the spinal cord and brain.

To determine the presence of tumors with subsequent differential diagnostics (if there is a suspicion of schwannoma (auditory nerve), arachnoid endothelioma, metastases, as well as a tumor with infiltrative growth (for example, glioma)):

• when determining isointense or small tumors;
• suspicion of possible recurrence of a tumor after a radiotherapy procedure or after surgery;
• to differentiate the picture in the following rare formations - ependymoma, hemangioblastoma, as well as small pituitary adenomas;
• to improve the determination of the local spread of formations that have a non-cerebral etiology.

As an adjunct to spinal MRI:

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

MRI procedure for all areas of the body.

To diagnose formations in the following situations:

• improving the differentiation of malignant and benign tumors in the mammary glands of women;
• to differentiate between scar and tumor tissue after a course of treatment for formations inside the mammary glands in women;
• differentiation of tumor and scar tissue in the area of passive and active parts of the musculoskeletal system;
• differentiation of different areas of bone tumors (area of decay, tumor tissue, as well as the inflammatory focus);
• differentiation of different types of liver formations;
• distinguishing between formations located inside or outside the kidneys;
• to determine the size and differentiate tumors within different parts of the uterine appendages;
• to obtain a picture of any vessel inside the body (other than the coronary arteries) using an angiography procedure - this is necessary, among other things, to identify occlusions, stenosis, and collaterals;
• to perform targeted selection of necessary tissue samples (biopsy procedure) in the development of bone tumors;
• to distinguish between the development of a recurrent hernia in the area of scar tissue and the intervertebral disc;
• to display a picture of lesions in the myocardial area (acute form).

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Release form

It is produced as an injection solution in 10 or 20 ml bottles. The package contains 1 bottle.

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Pharmacodynamics

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

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

Gadopentetate dimeglumine is a highly paramagnetic compound that helps to significantly reduce the relaxation period even when using a weak concentration. The level of paramagnetic effect and relaxivity (detected by the spin-lattice relaxation period of water protons inside the plasma) is 4.95 l / (mmol / second). At the same time, the acidity level is 7, and the temperature is 39 ° C and is weakly affected by the effect of the magnetic field.

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

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

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Pharmacokinetics

Gadopentetate dimeglumine 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 drug dosage.

After the solution is administered, it is quickly distributed throughout the body – outside the cells.

One week after the radioactively labeled dimeglumine salt of Gadopentetic Acid entered the animals' bodies, its presence was determined by values that were much lower than 1% of the administered dose of the drug. Relatively high levels of gadolinium (its unsplit complex) were observed inside the kidneys. This compound does not pass through intact BBB and GTB. A small portion of the drug passes through the placenta and enters the fetus's blood, but it is quickly excreted.

If a solution of less than 0.25 mmol/kg (or 0.5 ml/kg) is used, after a few minutes, which is the distribution phase, the plasma value of the contrast agent decreases (the half-life is approximately 1.5 hours, which is approximately equal to the 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.

No biotransformation or release of the paramagnetic ion is observed.

Gadopentetate dimeglumine is excreted unchanged via the kidneys (via glomerular filtration). The portion of the drug excreted extrarenally 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 found in the urine. Less than 1% of the dose is excreted in the 5-day period after the procedure.

The clearance of the active substance inside the kidneys is approximately 120 ml/minute/1.73 m2 ^. This value is comparable to the clearance of ⁵¹ Cr-EDTA or inulin.

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Dosing and administration

The medicine is used in diagnostic procedures and should only be administered intravenously.

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

Dosages in the range of 0.14-1.5 T act independently of the influence of the magnetic field.

The required dosage is administered by injection only. Sometimes a bolus injection is acceptable. MRI examination using contrast enhancement can begin immediately after the drug has been administered to the patient.

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

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

If after the introduction of such a dosage, the MRI showed ambiguous results, but there is a serious suspicion of the presence of pathological formations in the patient, it will be advisable to perform a repeated procedure of drug administration (to clarify the diagnosis). It must be carried out within half an hour after the 1st procedure, and then perform MRI. The dosage remains the same (but for adults, the dose of the solution can be calculated using the parameter 0.4 ml/kg).

When excluding the recurrence of tumor formation or the development of metastases, the increased dosage of the drug used for adults (calculated at 0.6 ml/kg) allows for a more accurate diagnosis.

It is permitted to prescribe the medicine in doses of no more than 0.4 ml/kg (for children over 2 years old) and 0.6 ml/kg (for adults).

In the MRI procedure for the whole body of adults, as well as children (from the age of 4 months), in order to resolve the issues that arose during diagnosis, as well as to enhance the contrast of the image, a dosage calculated according to the scheme of 0.2 ml/kg is usually sufficient. However, it should be taken into account that there is only limited information on the experience of conducting MRI procedures for the whole body at the age of up to 2 years.

In special situations, such as tumors with poor vascularization or with a low degree of penetration into the extracellular area, it may be necessary to use 0.4 ml/kg of the drug to obtain the required contrast. This is especially true for low T1-weighted sequences during the scanning procedure.

When visualizing the vascular system (the area of the body examined during the procedure and the method used are also important here), adults may sometimes need to use the solution in the maximum dosage.

Children from 1 month to 2 years of age are allowed to be administered no more than 0.2 mg/kg of medicinal solution.

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

Thus, the following dosages are used for diagnostics:

• the average dose for children (from 1 month to 2 years) and adults when performing MRI of the whole body, as well as the brain and spinal cord - 0.2 ml/kg (this is equal to 0.1 mmol/kg);
• the average dose when performing complex diagnostics (as well as the maximum permissible dose for children) is 0.4 ml/kg (which is equal to 0.2 mmol/kg);
• The maximum dosage used for visualization of the vascular system is 0.6 ml/kg (which is equal to 0.3 mmol/kg).

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Use Gadopentetic acid during pregnancy

There is no clinical data on the use of the drug in pregnant women. Animal testing has shown no indirect or direct negative effects on the reproductive system, but the drug is still prohibited for use during pregnancy. The solution is only allowed in cases where the pregnant woman's condition requires the administration of Gadopentetic Acid dimeglumine salt.

Contraindications

Among the contraindications of the drug:

• intolerance to the active component or other elements of the drug;
• the presence of kidney dysfunction (in severe form – with a glomerular filtration rate of <30 ml/minute/1.73 m2 ⁾;
• people in the perioperative period during liver transplantation;
• newborns (age under 1 month).

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Side effects Gadopentetic acid

The use of drugs can cause the following side effects:

• hematopoietic system: the bilirubin and iron levels in the serum may change temporarily;
• immune system: allergic or anaphylactoid manifestations, angioedema, anaphylactoid shock, as well as itching, sneezing and coughing, conjunctivitis, runny nose, laryngospasm and bronchospasm, and also urticaria develop occasionally. It is possible to develop a state of shock, hypotension, as well as swelling in the pharynx or larynx;
• NS organs: headaches or dizziness rarely occur; occasionally there is a disorder of consciousness, speech or smell, disorientation, as well as a burning sensation, drowsiness and excitement. In addition, tremors, convulsions and paresthesias may develop, and along with this, coma and asthenia;
• visual organs: occasional pain in the eyes, visual disturbances and lacrimation;
• auditory organs: hearing disorders and ear pain develop occasionally;
• cardiovascular system organs: occasionally, clinically noticeable transient disturbance of the heart rate (bradycardia and tachycardia (or its reflex form)), development of arrhythmia, increase in blood pressure, disturbance of cardiac function (up to cardiac arrest);
• vascular system: isolated manifestations develop that are accompanied by vasodilation (peripheral type) and lead to a decrease in blood pressure and fainting. Confusion of consciousness, a feeling of excitement, cyanosis and a reflex form of tachycardia (can cause loss of consciousness) also appear, and thrombophlebitis develops;
• respiratory disorders: occasional transient changes in respiratory rate (increase or decrease), difficulty breathing, dyspnea, cough, wheezing and respiratory arrest are observed. There may also be a feeling of constriction in the throat or irritation, pulmonary edema, sneezing, pain in the larynx or pharynx (or discomfort in the latter);
• Gastrointestinal organs: taste disturbance, vomiting, and nausea rarely develop; occasional discomfort or pain in the stomach, dry mouth, diarrhea, toothache, increased salivation, pain in the soft tissues, and paresthesia inside the oral cavity;
• digestive organs: occasional transient changes (towards an increase) in the level of liver enzymes occur, and the blood bilirubin level also increases;
• subcutaneous fat, as well as skin: occasionally there appears redness with heat and vasodilation, angioedema, itching and urticaria with exanthema;
• bone structure and muscles: occasional pain in the limbs;
• urinary system and kidneys: isolated - sudden urge to urinate, urinary incontinence, and also an increase in creatinine levels along with acute renal failure in people who have been previously diagnosed with this pathology;
• General disorders and problems at the injection site: sensations of cold/heat and general pain rarely occur. In addition, local pain, swelling, extravasation, inflammatory processes, thrombophlebitis and phlebitis, tissue necrosis, swelling with paresthesia also develop. Along with this, erythema, hemorrhagic syndrome, and irritation may develop; pain in the sternum, joints and back, chills, and a feeling of discomfort may appear singly. Sweating increases, vasovagal manifestations, swelling of the face, a feeling of thirst and severe fatigue, peripheral swellings occur, a feverish state develops and the temperature changes (decreases or increases).

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Overdose

Accidental overdose after intravascular administration can provoke the development of such signs of disorder (they are caused by increased osmolarity of the drug):

• systemic manifestations (hypovolemia, increased pressure inside the pulmonary arteries, osmotic diuresis, and exicosis);
• local manifestations (pain inside the vessels).

Patients with renal insufficiency should have their renal function monitored closely.

The excretion of the substance is carried out using the hemodialysis procedure. However, there is no data that confirms the need for this procedure to prevent the development of NSF.

Since gadopentetic acid has a very low degree of absorption within the gastrointestinal tract (<1%), the likelihood of poisoning in case of accidental ingestion of the solution is extremely low.

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Interactions with other drugs

No interaction testing of the solution with other drugs has been performed.

Experience with the use of contrast agents has shown that people who use β-blockers for treatment are more prone to developing noticeable allergic reactions.

Interaction with other substances for diagnostic testing.

When determining the serum iron level using the complexometry method (for example, using bathophenanthroline) during the first days after the use of gadopentetic acid, the amount indicators may be incorrect (reduced). This can be explained by the fact that the solution contains a contrast component - DTPk.

Storage conditions

The solution should be kept in a place closed to children, in standard conditions for medicines. The temperature level should not exceed 25°C.

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Shelf life

Gadopentetic acid can be used for 5 years from the date of manufacture of the medicinal solution.

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