Megarei

Megarei is a paramagnetic contrast medium.

Indications of the megarea

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

Primarily it is carried out to determine intra- and extramedullary tumors, together with further differential diagnosis and detection of metastases. In addition, it is used to detect small tumors or tumors that are difficult to visualize. Another option is diagnosis if there is a suspicion of a relapse after a radiotherapy or a surgical procedure.

It is used additionally for procedures of spinal MRI: for differential diagnosis of intra- and extra-medullary neoplasms, and also for determining solid formations in pathologically altered areas and for assessing the range of prevalence of intramedullary neoplasms.

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

The medicinal substance helps to obtain diagnostic information that contributes to such functions:

• detection or exclusion of inflammations, neoplasms and damage in the vascular region;
• Assessment of the range of prevalence, and beyond this boundaries of these processes;
• differentiation of the internal damage data scheme;
• Assessment of blood supply volumes of healthy, as well as altered under the influence of disease tissues;
• the distinction between tissues having a tumor or cicatricial origin, after the treatment;
• the definition of relapse of protrusion after a surgical procedure;
• implementation of a semi-quantitative assessment of renal activity together with anatomical diagnosis of a zonal character.

Release form

Release of the medicine occurs in the form of an injection liquid, in flakonchikah volume of 10, 15 or 20 ml. Inside the box there is one such bottle.

Pharmacodynamics

Gadopentetova acid is a contrasting element of a paramagnetic nature, used for MRI procedures. Enhance the contrast of this component is due to di-N-methylglucamine salt (combination of gadolinium and pentetic acid (DTTP)).

When used during an MRI with an appropriate scanning sequence (for example, a weighted T1 method of the spin-echo type) caused by Gd ions, a decrease in the spin-lattice relaxation period (occurring inside the atomic nuclei in the excited state) leads to an increase in the intensity of the output signal. As a result, there is an increase in the contrast level in the image of individual tissues.

The di-meglumine salt of gadopentetic acid is a compound with a high level of paramagnetic activity. It contributes to a marked decrease in the relaxation time, even under conditions of use in low concentration. The parameter of paramagnetic efficiency is the effect on the relaxation process, which is revealed by the level of influence with respect to the duration of the spin-lattice proton relaxation inside the plasma. This figure is approximately 4.95 l / mmol / s. In this case, the dependence on the strength of the intensity of the magnetic field is very small.

DTPA forms a strong bond with the paramagnetic ion Gd, which has extremely high stability under in vivo conditions, as well as in vitro (logK = 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 n-butanol elements, 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 (eg, Na ⁺, as well as K ⁺ ATPase of the myocardium). The drug activates the complementary system, while leaving extremely low probability of induction of anaphylactic symptoms.

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

After the injection of the liquid, the reverse process is capable of provoking mild hemolysis inside the vessels. This fact explains the slight increase in iron values along with bilirubin inside the blood serum, sometimes observed in the first few hours after drug administration.

Pharmacokinetics

The activity of the 2-meglumine salt inside the body is similar to that of other inert bio-bonds, which have a high level of hydrophilicity (eg, inulin or mannitol).

Distribution processes.

After the injection, the element quickly passes inside the extracellular region. At a dosage size of 0.25 mmol / kg (or Δ0.5 ml / kg), after the early distribution stage for several minutes, the value of the contrast element within the plasma decreases to parameters similar to the rate of its renal excretion with a half-life of approximately 1,5 hour.

At a portion size of 0.1 mmol / kg (or Δ0.2 ml / kg), after 3 minutes after fluid administration, the plasma index was 0.6 mmol / l, and after 1 hour, 0.24 mmol / l.

After 1 week after the injection of the radiolabeled substance within the body of dogs and rats, significantly less than 1% of the used dosage was recorded. Higher rates of drugs were noted inside the kidneys - in the form of undecomposed compounds Gd.

The active substance does not pass through the intact GEB and the GBB. A small amount of drugs passing through the placenta and entering the blood of the fetus is excreted rather quickly.

Excretion.

Excretion of the unmodified element occurs through the kidneys, this process is helped by glomerular filtration. The part of the medicine that is extracted extrarenally is extremely small.

Approximately 83% of the portion is excreted through the kidneys after 6 hours after the injection procedure. About 91% of the dosage on the first day is found in the urine. On the 5th day after the procedure, less than 1% of the drug is excreted with feces.

The level of clearance of the substance inside the kidneys is 120 ml / minute / 1.73 m ², which can be compared with the inulin clearance index or 51 Cr-EDTA element.  

Parameters of the drug in people with disabilities.

The drug is completely excreted from the body through the kidneys even in the event of a disorder of their work (CC values above 20 ml / minute). The half-life increases in view of the strength of the severity of the disorder. At the same time, there is no increase in the volume of extrahepatic elimination.

After a long half-life of serum (approximately 30 hours), in case of severe disorders of renal activity (CC level below 20 ml / minute), the drug can be excreted by extracorporeal dialysis.

[1], [2]

Dosing and administration

The drug is administered exclusively by the intravenous route.

General instructions.

It is necessary to follow the generally accepted precautions during the MRI: the doctor must ensure that the patient does not have ferromagnetic implants, a pacemaker, and so on.

Recommendations for the use of drugs in the range of 0.14-1.5 T are independent of the level of the magnetic field voltage.

The required portion of the solution is administered intravenously by the jet method, using bolus injection. Upon its completion, the MRI procedure can be started.

Due to the fact that vomiting with nausea often become side effects of using any contrast agents for MRI, after the procedure, the patient needs at least 2 hours to refuse eating to reduce the likelihood of aspiration.

States of severe anxiety or agitation, and in addition 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.

Procedures for spinal or cranial MRI.

Children from 2 years old, and in addition adults should use such dosages of Megarei:

• In standard cases, in order to increase the contrast, and in addition to solving the clinical diagnostic problems, administering the dosage calculated according to the 0.2 ml / kg scheme will be sufficient;
• in situations where the above portion of the drug was administered and the lesion on the MRI was not detected (but there is a serious clinical suspicion of its presence), it is required to re-enter the same dosage to make the diagnosis more accurate. Adult medication can be administered according to the scheme of 0.4 ml / kg for half an hour after the 1st procedure. Subsequent scans are performed immediately after the injection.

When an adult is injected with an increased dose of the drug (0.6 ml / kg), it becomes possible to conduct more accurate diagnosis, which will exclude metastases or recurrence of neoplasm development.

The maximum size of the adult portion is 0.6 ml / kg, and the child's size is 0.4 ml / kg.

MRI examination of the whole body.

Adults, as well as children, the drug is administered in the following dosages.

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

In specific situations, for example, in pathological tumors with a low degree of vascularization or a low level of passage into the extracellular environment, a portion of 0.4 ml / kg may be needed to obtain the required contrast. In particular, this concerns the use of relatively weak weighted T1 sequences in scanning.

To exclude the development of lesions or recurrences of tumors, it is possible to administer a dose of 0.6 ml / kg (adult) - this will increase the accuracy of the diagnostic.

To visualize the vessels taking into account the area that is being examined, as well as the method of investigation, adults can inject the drug in a dosage of up to 0.6 ml / kg.

The size of the maximum permissible adult portion is 0.6 ml / kg, and the child's allowance is 0.4 ml / kg.

[5]

Use of the megarea during pregnancy

Pregnancy.

Information on the conduct of clinical tests using Megarea during pregnancy does not exist. The data of the tests carried out on animals do not show the presence of teratogenic or other embyrotoxic properties when the drug is administered to a pregnant individual.

But prescribing the drug to pregnant women should only after a particularly careful assessment of the relationship of benefit and the likelihood of negative consequences.

Lactation period.

The medication is excreted with the mother's milk in the minimum volume (not more than 0.04% of the administered portion). Previous experience shows that in this concentration the substance does not threaten the state of the infant.

Side effects of the megarea

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

• mental disorders: one notes a sense of disorientation;
• problems with the work of the National Assembly: occasionally there are headaches, dizziness or dysgeusia. Paresthesia, stupor, tremor, a burning sensation or drowsiness develops, and seizures (including epileptic seizures), anorexia and nystagmus;
• impairment of visual function: diplopia appears alone, pain in the eye, conjunctivitis, eye irritation, and, in addition, a discharge of tear fluid and a visual field defect;
• problems with cardiac activity: single arrhythmia, tachycardia, syncope, migraine, pallor, decrease / increase in blood pressure values, angina pectoris, non-specific change in ECG readings, death due to myocardial infarction or for other vague cause and vasodilation. In addition, thrombophlebitis with phlebitis, DVT and interfacial space syndrome, which requires surgery;
• Disorders of vascular function: heat flushes, thrombophlebitis, and also vasodilatation develop sporadically;
• disorders of respiratory activity: there is a single feeling of irritation or compression in the throat, dyspnoea, pain or discomfort in the larynx and throat, sneezing with cough, rhinorrhea, laryngospasm and breathing with whistling;
• problems with the function of the digestive tract: occasionally there is vomiting or nausea. Slight constipation, gastric discomfort, dry mouth mucosa, diarrhea, dental or abdominal pain, and paresthesia and pain sensations affecting the soft tissue in the mouth;
• lesions of the hypodermic layer and epidermis: there is an itching, swelling, urticaria, rashes, hyperhidrosis, TEN and polyforma erythema. In addition, pustules are formed;
• Dysfunction of the OA: single pain in the limbs;
• disorders of auditory activity: single pain or ringing in the ears;
• systemic manifestations and disorders at the site of injection: occasionally a feeling of heat or cold, pain, various symptoms at the site of administration *, as well as regional lymphangitis are recorded. Single pains in the sternum, peripheral or facial swelling, pyrexia, a feeling of thirst, severe fatigue, tremors and general malaise are observed. In addition to this, asthenia, pain in the pelvis, spasmodic muscle contractions and anaphylactoid signs.

* paresthesia, a feeling of warmth or cold, pain, swelling, hemorrhage, irritation and redness, and in addition discomfort at the site of administration.

Marked additionally (during postmarketing tests) negative symptoms:

• Lymph and blood flow disorders: an increase in serum iron values is observed;
• immune disorders: anaphylactic symptoms or anaphylaxis were recorded individually, as well as signs of intolerance;
• disturbances of the psyche: there was a single feeling of confusion of consciousness or excitement;
• problems with the activity of the National Assembly: there was a single sensation of drowsiness, parosmia, coma, speech and dizziness;
• visual disorders: sporadically appeared - lacrimation, eye pain and vision problems;
• auditory disorders: isolated ear pain and hearing loss;
• heart disorders: the tachycardia of a reflex character developed sporadically, the rhythm of the heart beat slowed, and in addition the heart stopped;
• problems with vascular activity: there was a single fainting, a shock state, a decrease or increase in the level of blood pressure, as well as a vasovagal reaction;
• impairment of respiratory function: the respiratory process stopped at a time, the respiratory rate increased or decreased, bronchial spasm, external respiration, laryngospasm, cyanosis, pulmonary, pharyngeal or laryngeal edema and runny nose developed;
• disorders affecting the functioning of the digestive tract: salivation was observed singly;
• problems with the work of the hepatobiliary system: the indices of liver enzymes or bilirubin inside the blood were increased individually;
• lesions in the epidermis with the subcutaneous layer: single appearances of edema Quincke;
• disorders of ODA function: arthralgia or pain sensations in the back developed sporadically;
• disturbances in the urinary ducts and kidneys: the serum creatinine * values were increased individually, urinary incontinence or renal insufficiency was noted in the acute stage *, and besides, there were sudden urge to urinate;
• systemic disorders and signs in the field of drug administration: a single development of hyperhidrosis or fever, an increase or decrease in temperature, and in addition, different types of symptoms at the site of administration **.

* in people with a history of renal function disorders.

** such as phlebitis with thrombophlebitis, extravasate, necrosis and inflammation in the area of administration.

In persons with kidney failure undergoing dialysis, temporary or delayed signs, similar to inflammation (fever or an increase in C-reactive protein), were often observed during the use of Megarei. In such people, MRI procedures using drugs were performed a day before hemodialysis.

There are isolated reports on the development of the NSF.

[3], [4]

Overdose

At the moment there is no information about the development of symptoms of poisoning due to an overdose of the substance in clinical use.

In connection with the hyperosmolality of the drug with occasional intoxication, such negative reactions can develop: an osmotic diuretic, an increase in pressure in the pulmonary artery, and in addition dehydration and hypervolemia.

People with kidney failure during treatment need to monitor kidney function.

In case of accidental poisoning or a significantly reduced renal function, the medication can be withdrawn from the body by hemodialysis.

[6]

Interactions with other drugs

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

[7], [8]

Storage conditions

Megarei must be kept in a dark place, closed from the access of children. It is prohibited to freeze the medicinal product. The temperature is not higher than 25 ° C.

[9]

Shelf life

Megarei can be used for 3 years from the date of manufacture of the drug.

Application for children

Megarey used for procedures in children aged 2 years.

There is only limited information on the use of this tool in infants up to 2 years of age.

Analogues

The analogues of the drug are Vazovist, Magnevist and Tomovist with Gadovist, and besides this, Lantavist, Multihans, Magnilek with Magneghita and Optimark with Omniskan.

[10]