Megarey

Megarey is a paramagnetic contrast agent.

Indications Megarea

It is used when performing MRI procedures on areas of the spinal cord and, along with it, the brain.

It is primarily used to identify intra- and extramedullary tumors, along with further differential diagnostics and detection of metastases. In addition, it is used to identify small tumors or tumors that are difficult to visualize. Another option for use is diagnostics in the presence of a suspicion of tumor recurrence after radiation therapy or surgery.

It is additionally used in spinal MRI procedures: in differential diagnostics of intra- and extramedullary neoplasms, as well as to identify solid formations in pathologically altered areas and to assess the range of prevalence of intramedullary neoplasms.

MRI procedures of the whole body are also performed. This includes: the facial part of the skull, the cervical region, the sternum with the peritoneum, the mammary glands, the pelvic organs, the musculoskeletal system and the entire vascular system of the body.

The drug helps to obtain diagnostic information that contributes to the following functions:

• detection or exclusion of the presence of inflammation, neoplasms and damage in the vascular area;
• assessment of the range of prevalence, and in addition, the boundaries of these processes;
• differentiation of the internal pattern of damage data;
• assessment of the volume of blood supply to healthy tissues, as well as tissues altered by disease;
• distinguishing tissues of tumor or cicatricial origin after treatment;
• determination of recurrence of protrusion after surgical procedure;
• performing a semi-quantitative assessment of renal function together with anatomical diagnostics of a zonal nature.

Release form

The drug is released in the form of an injection liquid, in bottles of 10, 15 or 20 ml. The box contains 1 such bottle.

Pharmacodynamics

Gadopentetic acid is a paramagnetic contrast agent used for MRI procedures. This component is able to enhance contrast due to di-N-methylglucamine salt (a combination of gadolinium and pentetic acid (DTPA)).

When used during MRI with an appropriate scanning sequence (e.g., T1-weighted spin-echo), the Gd-induced decrease in the spin-lattice relaxation period (occurring inside excited atomic nuclei) leads to an increase in the intensity of the emitted signal. As a result, an increase in the contrast level is observed when imaging individual tissues.

Di-meglumine salt of gadopentetic acid is a compound with a high level of paramagnetic properties. It contributes to a noticeable reduction in the relaxation period even when used in low concentrations. The paramagnetic efficiency index is the effect on the relaxation process, which is determined by the level of influence on the spin-lattice proton relaxation period inside the plasma. This index is approximately 4.95 l/mmol/s. At the same time, the dependence on the strength of the magnetic field is very insignificant.

DTPA forms a strong bond with the paramagnetic ion Gd, which has extremely high stability in vivo, as well as in vitro (logK index = 22-23).

Di-meglumine salt is highly soluble in water, being a compound with a high hydrophilicity value. At the same time, its distribution coefficient between the elements n-butanol, as well as the buffer at a pH level of 7.6, is 0.0001. The component is not characterized by specific protein synthesis and a slowing effect on enzymes (for example, Na ⁺, as well as K ⁺ ATPase of the myocardium). The drug activates the complement system, while leaving the likelihood of inducing anaphylactic symptoms extremely low.

When using the drug in higher doses or with a prolonged incubation procedure, the active element of the drug has an insignificant effect in vitro on erythrocyte morphology.

After injection of the liquid, the reverse process can provoke a slight hemolysis inside the vessels. This fact explains the slight increase in iron values together with bilirubin inside the blood serum, sometimes observed in the first few hours after the drug administration.

Pharmacokinetics

The activity of 2-meglumine salt inside the body is similar to the action of other inert bio-binders with a high level of hydrophilicity (for example, inulin or mannitol).

Distribution processes.

Following injection, the element rapidly passes into the extracellular space. At dose levels up to 0.25 mmol/kg (or Δ0.5 ml/kg), after an early distribution phase lasting several minutes, the intraplasmic contrast element decreases to parameters similar to its renal excretion rate with a half-life of approximately 1.5 hours.

With a dose size of 0.1 mmol/kg (or Δ0.2 ml/kg), the plasma value was 0.6 mmol/L 3 minutes after fluid administration and 0.24 mmol/L 1 hour later.

One week after the injection of the radioactively labeled substance, significantly less than 1% of the used dose was registered inside the body of dogs and rats. Higher levels of the drug were noted in the kidneys - in the form of undecomposed Gd compounds.

The active substance does not pass through intact BBB and GTB. The small amount of the drug that passes through the placenta and enters the fetal blood is excreted fairly quickly.

Excretion.

Excretion of the unchanged element occurs via the kidneys, a process aided by glomerular filtration. The portion of the drug excreted extrarenally is extremely small.

Approximately 83% of the dose is excreted via the kidneys within 6 hours of the injection procedure. Approximately 91% of the dose on day 1 is found in the urine. On day 5 after the procedure, less than 1% of the drug is excreted in the feces.

The clearance rate of the substance inside the kidneys is 120 ml/minute/1.73 m2 ^, which can be compared with the clearance rate of inulin or the element 51Cr-EDTA.

Drug parameters in people with disorders.

The drug is completely excreted from the body through the kidneys even in the case of kidney dysfunction (CC values above 20 ml/minute). The half-life increases depending on the severity of the disorder. No increase in the volume of extrahepatic elimination is observed.

After a long half-life in serum (approximately 30 hours), in case of severe renal impairment (creatinine clearance level below 20 ml/minute), the drug can be removed from the body using extracorporeal dialysis.

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Dosing and administration

The medicine is administered exclusively intravenously.

General instructions.

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

Recommendations for the use of LS in the range of 0.14-1.5 T do not depend on the level of magnetic field voltage.

The required portion of the solution is administered intravenously by jet method, using a bolus injection. Once it is completed, the MRI procedure can begin.

Because vomiting and nausea are common side effects of any MRI contrast agent, the patient should fast for at least 2 hours after the procedure to reduce the risk of aspiration.

States of severe anxiety or excitement, as well as severe pain, may increase the likelihood of developing negative symptoms or potentiate the effects associated with the contrast agent. Such patients should be prescribed sedatives.

Spinal or cranial MRI procedures.

Children from 2 years old, and also adults should use the following dosages of Megareya:

• in standard cases, in order to enhance contrast, and in addition to resolve any clinical and diagnostic issues that may arise, the introduction of a dosage calculated according to the scheme of 0.2 ml/kg will be sufficient;
• in situations where the above dose of the drug has been administered and the lesion has not been detected on MRI (but there is a serious clinical suspicion of its presence), it is necessary to re-administer the same dosage to make the diagnosis more accurate. Adults can be administered the drug according to the scheme 0.4 ml/kg for half an hour after the 1st procedure. The subsequent scan is performed immediately after the injection.

When an adult is given an increased dose of the drug (0.6 ml/kg), it becomes possible to conduct a more accurate diagnosis, which will allow one to exclude metastases or relapse of the tumor.

The maximum serving size for adults is 0.6 ml/kg, and for children – 0.4 ml/kg.

MRI scan of the whole body.

For adults and children, the drug is administered in the dosages indicated below.

Often, to obtain good contrast and identify the desired lesions, it is sufficient to administer the drug in a dose of 0.2 ml/kg.

In specific situations, such as pathological tumors with low vascularity or low levels of extracellular penetration, a dose of 0.4 ml/kg may be required to obtain the required contrast. This is especially true when using relatively weak T1-weighted sequences in scanning.

To prevent the development of lesions or relapses of neoplasms, it is allowed to administer a dose of 0.6 ml/kg (for adults) - this will increase the accuracy of the diagnostics.

To visualize the vessels, taking into account the area being examined and the method of examination, adults may be administered the drug at a dosage of up to 0.6 ml/kg.

The maximum permissible portion size for adults is 0.6 ml/kg, and for children - 0.4 ml/kg.

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Use Megarea during pregnancy

Pregnancy.

There is no information regarding clinical trials using Megareya during pregnancy. Animal test data do not show any teratogenic or other embryotoxic properties when administering the drug to a pregnant individual.

However, the drug should be prescribed to pregnant women only after a particularly careful assessment of the balance between benefits and the likelihood of negative consequences.

Lactation period.

The drug is excreted in breast milk in minimal amounts (no more than 0.04% of the administered portion). Previous experience shows that in such a concentration the substance does not threaten the health of the infant.

Side effects Megarea

The use of the medication may lead to the appearance of side effects:

• mental disorders: a feeling of disorientation is noted occasionally;
• problems with the functioning of the nervous system: headaches, dizziness or dysgeusia occasionally occur. Paresthesia, stupor, tremor, burning sensation or drowsiness develop sporadically, as well as convulsions (including epileptic seizures), anorexia and nystagmus;
• visual impairment: diplopia, pain in the eye area, conjunctivitis, eye irritation, and also tear secretion disorder and visual field defect may occasionally appear;
• problems with cardiac activity: arrhythmia, tachycardia, syncope, migraine, pallor, decrease/increase in blood pressure, angina, non-specific changes in ECG readings, death due to myocardial infarction or other unspecified cause and vasodilation occur sporadically. In addition, thrombophlebitis with phlebitis, DVT and interfascial space syndrome, which requires surgery;
• vascular dysfunction: hot flashes, thrombophlebitis, and vasodilation develop occasionally;
• respiratory disorders: occasional sensations of irritation or constriction in the throat, dyspnea, pain or discomfort in the larynx and throat, sneezing with coughing, rhinorrhea, laryngospasm and wheezing;
• problems with the gastrointestinal tract: vomiting or nausea occasionally occurs. Constipation, gastric discomfort, dry mouth, diarrhea, toothache or abdominal pain, as well as paresthesia and pain affecting the soft tissues in the mouth are observed sporadically;
• lesions of the subcutaneous layer and epidermis: itching, swelling, urticaria, rashes, hyperhidrosis, TEN and erythema multiforme occur sporadically. In addition, pustules are formed;
• dysfunction of the musculoskeletal system: occasional painful sensations in the extremities;
• hearing disorders: occasional pain or ringing in the ears;
• Systemic manifestations and disorders at the injection site: a sensation of heat or cold, pain, various symptoms at the injection site*, as well as regional lymphangitis are occasionally recorded. Pain in the sternum, peripheral or facial swelling, pyrexia, a feeling of thirst, severe fatigue, tremors and general malaise are observed isolatedly. In addition, asthenia, pain in the pelvis, spastic muscle contractions and anaphylactoid symptoms are also observed.

*paresthesia, feeling of heat or cold, pain, swelling, bleeding, irritation and redness, as well as discomfort at the injection site.

Additional negative symptoms noted (during post-marketing testing):

• lymph and blood flow lesions: an increase in serum iron levels is observed sporadically;
• immune disorders: anaphylactic symptoms or anaphylaxis, as well as signs of intolerance, have been reported in isolated cases;
• mental disorders: occasional feelings of confusion or agitation;
• problems with the functioning of the nervous system: a feeling of drowsiness, parosmia, coma, speech disorder and dizziness were observed occasionally;
• visual disturbances: occasionally there were lacrimation, eye pain and vision problems;
• hearing impairment: ear pain and hearing loss were observed in isolated cases;
• cardiac disorders: occasionally, reflex tachycardia developed, the heart rate slowed down, and in addition, the heart stopped;
• problems with vascular activity: occasional fainting, shock, decrease or increase in blood pressure, as well as vasovagal reaction;
• respiratory dysfunction: occasional cessation of the respiratory process, an increase or decrease in respiratory rate, development of bronchospasm, impaired external respiration, laryngospasm, cyanosis, pulmonary, pharyngeal or laryngeal edema and runny nose;
• disorders affecting the gastrointestinal tract: salivation was observed sporadically;
• problems with the functioning of the hepatobiliary system: isolated increases in liver enzymes or bilirubin in the blood;
• lesions in the epidermis with subcutaneous layer: isolated occurrences of Quincke's edema;
• disorders of the musculoskeletal system: arthralgia or pain in the back developed occasionally;
• urinary tract and kidney dysfunction: isolated increases in serum creatinine levels*, urinary incontinence or acute renal failure*, and sudden urges to urinate;
• systemic disorders and signs in the area of drug administration: isolated development of hyperhidrosis or fever, increase or decrease in temperature, and in addition, various types of symptoms in the area of administration**.

*in people with a history of renal dysfunction.

**such as phlebitis with thrombophlebitis, extravasation, necrosis and inflammation in the injection area.

In individuals with kidney failure undergoing dialysis, temporary or delayed signs similar to inflammation (fever or increased C-reactive protein) have been frequently observed during the use of Megarea. In these individuals, MRI procedures using LS were performed the day before hemodialysis.

There are isolated reports of the development of NSF.

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Overdose

There is currently no information on the development of symptoms of poisoning as a result of overdose of the substance during clinical use.

Due to the hyperosmolality of the drug, the following adverse reactions may develop in case of accidental intoxication: osmotic diuresis, increased pressure in the pulmonary artery, and also dehydration and hypervolemia.

In people with renal impairment, renal function should be monitored during treatment.

In case of accidental poisoning or significantly reduced renal function, the drug can be removed from the body using hemodialysis.

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Interactions with other drugs

In case of determination of the iron level in the blood serum using complexometric procedures (for example, with the participation of bathophenanthroline), during the first days the quantitative value may be reduced due to the presence of the contrast agent free DTPA in the solution.

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Storage conditions

Megarey should be kept in a dark place, out of reach of children. Freezing the medicine is prohibited. The temperature level should not exceed 25°C.

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Shelf life

Megarey can be used for 3 years from the date of manufacture of the medicinal product.

Application for children

Megaray is used to perform procedures on children aged 2 years and older.

There is limited information regarding the use of this product in infants under 2 years of age.

Analogues

Analogues of the drug are Vazovist, Magnevist and Tomovist with Gadovist, and in addition to this Lantavist, Multihans, Magnilek with Magnegita and Optimark with Omniscan.

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