Tomovist

General characteristics. Structure:

1 ml of solution contains:

active ingredient: a gadopentetata of dimegluminum in terms of 100% dry matter of 469 mg;

excipients: pentetovy acid, Megluminum, water for injections.

Pharmacological properties:

Pharmacodynamics. The Tomovist – contrast paramagnetic means for MRT. The contrasting effect is caused by di-N-methylglucamine salt of a gadopentetat – a gadolinium complex with pentetovy acid (dietilentriaminpentauksusny acid – DTPA). When using the corresponding sequence of scanning for receiving proton magnetic and resonant visualization the gadolinium ion shortens time of spin-lattice relaxation of the excited atomic nuclei that increases signal strength and increases picture contrast of certain fabrics. Dimegluminum of gadopentetovy acid represents connection with the expressed paramagnetic properties, the shortening relaxation time even in low concentration is considerable. Paramagnetic efficiency or relaxation ability is determined by influence on time of spin-lattice relaxation of protons of plasma. DTPA forms a strong complex with a paramagnetic ion of gadolinium with extremely high stability. Gadopentetata dimegluminum is characterized by high hydrophily. This substance practically does not contact proteins and does not inhibit activity of enzymes (for example, myocardial Na/K-Atfazu), does not activate system of a complement and, therefore, has very low potential ability to cause anaphylactoid reactions. Drug is well transferred by patients and only in isolated cases can cause local or general collateral manifestations (usually benign). In big concentration of a gadopentetat dimegluminum exerts insignificant impact on morphology of erythrocytes, can cause an insignificant intravascular hemolysis. Administration of drug gives the chance to contrast sites with the broken blood-brain barrier (for example, a glioblastoma), and also other extra brain intracranial or intra spinal educations that increases the diagnostic value of a research in comparison with native scanning.

Pharmacokinetics. After intravenous administration drug quickly, within several minutes, is distributed in extracellular space. It does not kumulirutsya in healthy fabrics and does not get through intact hematoencephalic and gistogematichesky barriers, but collects in the changed areas (a cyst, a hem, disturbance of a vascular grid), promotes detection of tumors, abscesses, subacute heart attacks. A small amount of a gadopentetat of dimegluminum gets through a placental barrier, eliminirutsya quickly. An elimination half-life – 90 minutes. The main part of a gadopentetat of dimegluminum is removed by glomerular filtering in not changed look, the insignificant quantity is distinguished through digestive tract (less than 1% of the entered dose) and with breast milk (to 0,04% of the entered dose). 83% are removed within 6 hours after introduction, 91% of drug – within 24 hours. The renal clearance of a gadopentetat of dimegluminum makes about 120 ml/min., rated for 1,73 sq.m.

Pharmaceutical characteristics

Main physical and chemical properties: transparent colourless or slightly yellowish, either slightly yellowish-brownish, or slightly yellowish-greenish liquid.

Indications to use:

Magnetic and Resonant Tomography (MRT) of a head and spinal cord

It is carried out first of all for detection of tumors and the following differential diagnosis at suspicion on a meningioma, a neurinoma, including an acoustical nerve, invasive tumors (for example, a glioma) and metastasises; for detection of small tumors and/or tumors which are badly visualized; at suspicion on a recurrent tumor after operation or radiation therapy; for the differentiated image of such rare new growths as hemangioblastomas, ependymomas and small adenomas of a hypophysis; for improvement of definition of spread of tumors of not brain origin.

In addition at spinal MRT: differential diagnosis of intramedullary and extramedullary tumors, identification in patholologically the changed sites of solid tumors, assessment of spread of intramedullary tumors.

MRT of all body

Including a facial skull, the site of a neck, chest and belly cavities, mammary glands, bodies of a basin, a musculoskeletal system, and also visualization of vessels of all body.

By means of drug of Tomovist it is possible to obtain the diagnostic information allowing in a particular:

– to reveal or exclude existence of tumors, inflammations and vascular damages;

– to define prevalence and limits of these processes;

– to differentiate internal structure of these damages;

– to estimate blood supply normal and patholologically the changed fabrics;

– to distinguish tumoral fabrics from cicatricial after therapy;

– to reveal a recurrence of a protruded disk after operation;

– to carry out semi-quantitative assessment of function of kidneys in combination with zone anatomic diagnosis.

Route of administration and doses:

To use drug only for intravenous administration.

Patients cannot carry out MRT with kardio-and neurostimulators, ferromagnetic implants, with insulin pumps.

Drug should be gathered in the syringe just before use. The remains of a contrast agent, unused at a research, are not allowed to further use.

General requirements: in 2 hours prior to inspection for reduction of risk of aspiration the patient has to abstain from meal. In the presence in the anamnesis of allergic reactions carrying out premedication with use of antihistaminic and/or glucocorticoid means is possible.

To enter a necessary dose of drug struyno intravenously in the form of a bolyusny injection manually or by means of an injector. During an injection of contrast means the patient has to be in horizontal position. MRT-inspection should be begun right after an injection.

The pulse sequences with the T1-weighed images are the most suitable for contrast researches. In the range from 0,14 T to 1,5 T of the recommendation about Tomovist's use do not depend on tension of magnetic field.

Cranial and spinal tomography. The recommended dose for adults and children (including newborn, chest and teenage age) makes 0,2 ml of Tomovist on 1 kg of body weight of the patient. In cases when there is a serious clinical suspicion on existence of the pathological center, carrying out a repeated research in the same dose is possible; at adults it can be increased to 0,4 ml/kg of body weight. For more exact diagnosis at metastatic damages or a recurrence of tumors by the adult the dose of 0,6 ml/kg of body weight can be entered. Depending on a method and area of a research the maximum dose can be necessary for visualization of blood vessels (for example, an angiography).

The maximum single dose for adults – 0,6 ml/kg of body weight.

The maximum single dose for children – 0,4 ml/kg of body weight.

At MRT of all body at adults and children the recommended dose makes 0,2 ml/kg of body weight. In special cases, for example, at pathological educations with insignificant degree of vascularization and/or insignificant extent of penetration into extracellular space, for achievement of optimum contrasting there can be necessary Tomovist's introduction in a dose of 0,4 ml/kg of body weight, especially at use of rather weak T1-weighed sequences of scanning. For an exception of defeat or a recurrence of tumors at adults it is possible to increase a dose to 0,6 ml/kg of body weight. For visualization of vessels depending on area of a research and the used technique of MRT increase in a dose of Tomovist by the adult up to 0,6 ml/kg of body weight is possible.

The maximum single dose for adults – 0,6 ml/kg of body weight.

The maximum single dose for children – 0,4 ml/kg of body weight.

Experience of use of drug for MRT of all body of children up to 2 years is limited so far. Children up to 2 years should enter a necessary dose manually, without using an autoinzhektor, for prevention of damages.

Features of use:

Hypersensitivity. Administration of drug of Tomovist, as well as other intravenous contrast means, can be followed by anaphylactoid reactions / reactions of hypersensitivity or other reactions of an idiosyncrasy in the form of cardiovascular, respiratory and skin symptoms, up to reactions of heavy degree, including shock.

The risk of development of reactions of hypersensitivity is higher in the presence of the states and diseases provided below:

– reaction to the previous introductions of contrast means;

– bronchial asthma in the anamnesis;

– allergic diseases in the anamnesis.

At patients with allergic readiness (especially with allergic diseases in the anamnesis) the decision on Tomovist's use has to be made after especially careful assessment of a ratio risk/advantage.

The majority of these reactions arises within 30 minutes after administration of drug. Thus, after the research observation of the patient is recommended.

At patients with allergic readiness it is possible to consider a question of carrying out premedication antihistaminic drugs and/or glucocorticoids.

Always there have to be on call corresponding medicines for treatment of reactions of hypersensitivity, and also means of acute management.

The otstrochenny reactions (arising in several hours or days after introduction) can be observed.

The patients accepting β-blockers and which had hypersensitivity reactions can be insensitive to therapy by β-agonists..........

At the patients having cardiovascular diseases the probability of development of serious or even lethal effects of reactions of hypersensitivity of heavy degree is higher.

Depression of function of kidneys. Before use of drug of Tomovist of all patients it is necessary to inspect on existence of dysfunction of kidneys by collecting the anamnesis and/or carrying out laboratory analyses.

At purpose of drug patients with considerably impaired renal function should weigh especially carefully a ratio risk/advantage as these patients have considerably a znizhena drug removal speed. These patients in isolated cases can have an acute renal failure demanding dialysis or further depression of function of kidneys.

The risk of emergence of such phenomena is higher at increase in a dose of drug. As гадопентетат it is removed by kidneys, at patients with an impaired renal function there has to pass the sufficient period for removal before any following administration of drug. The elimination half-life at patients with a renal failure easy and moderate severity makes 3-4 hours. The elimination half-life at patients with a heavy renal failure is equal to about 11 hours, about 75% of the appointed dose are defined in urine for 2 days.

The Tomovist can be brought from an organism by a hemodialysis. After three episodes of a hemodialysis for 3 hours of each about 97% of the appointed dose it is brought out of an organism (about 70% with each episode of a hemodialysis).

For the patients who are already on a hemodialysis it is necessary to consider the possibility of bystry holding a session of a hemodialysis at once after administration of drug of Tomovist for the purpose of acceleration of removal of contrast means from an organism.

There are messages on cases of development of the nephrogenic system fibrosis (NSF) connected using gadoliniysoderzhashchy contrast agents including Tomovist at patients with:

– acute or chronic renal failure of heavy degree (glomerular filtration rate (GFR) <30 ml/min. / 1,73 sq.m) or

– an acute renal failure of any severity owing to a gepatorenalny syndrome or in the perioperatsionny period at transplantation of a liver.

This category of patients should use drug only after careful assessment of a ratio of risk and advantage, including consideration of possible alternative methods of visual diagnosis, and at use of the doses which are not exceeding 0,2 ml/kg of body weight.

Gerontological patients (65 years are more senior). Need for change of doses at this category of patients is not revealed. The difference in indicators of safety and efficiency between patients is not established 65 years and younger patients are more senior. Clinical observations did not reveal a difference in the answer between gerontological patients and younger patients.

Patients with a liver failure. As гадопентетат it is removed only in not changed look by kidneys, there is no neobkhomost in change of doses for patients with a moderate liver failure. Data on drug use to patients with a heavy liver failure still are absent.

Spasms. At the patients inclined to developing of spasms, or patients with intracranial defeats convulsive activity can be increased what it was reported in isolated cases with administration of drug about. Behind a condition of the patients inclined to developing of spasms, it is necessary to observe carefully, it is necessary to prepare the equipment and medicines necessary for the termination of spasms in case of their emergence in advance.

Ability to influence speed of response at control of motor transport or work with other mechanisms

 

It is unknown.

Side effects:

The majority of the side reactions connected using Tomovist were easy or seredny severity. It was more often specified such reactions as nausea, vomiting, a headache, dizziness and reactions in the place of an injection (for example feeling of pain, cold, heat).

The nephrogenic system fibrosis (NSF) and anaphylactoid reactions / an acute anaphylaxis were the most serious side reactions at use of drug.

The delayed hypersensitivity reactions / anaphylactoid reactions (of 1 o'clock and up to several days) were registered seldom.

From blood and lymphatic system: increase in level serumal железа*.

From immune system: hypersensitivity reactions / anaphylactoid reactions (for example an acute anaphylaxis *, anaphylactoid реакции*§, reactions гиперчувствительности*§, шок*§, arterial гипотензия*§, conjunctivitis, loss сознания*§, feeling of compression in a throat *, sneezing, urticaria, an itch, rashes, an erythema, диспноэ *, a stop дыхания*§, бронхоспазм*§, rattles, ларингоспазм*§, swelled гортани*§, the face edema *, reflex тахикардия§ swelled глотки*§, цианоз*§, ринит§, ангиоэдема*§).

From mentality: disorientation, excitement, concern.

From a nervous system: dizziness, headache, dysgeusia, spasms *, paresthesia, feeling of heat, tremor, coma *, drowsiness, somnolention *, disturbances of the speech, disturbance of a scent.

From organs of sight: visual disturbances, dacryagogue, eye pain.

From acoustic organs: hearing disorder, ear-ache.

From heart: tachycardia *, arrhythmia *, cardiac standstill *, decrease in frequency of cordial reductions / брадикардия*.

From vessels: thrombophlebitis, inflows, vazodilatation, syncopal states *, vazovagalny reactions, increase in arterial pressure.

Respiratory, mediastinal frustration, thorax pathology: feeling of irritation in throat throat/pain and a throat/sensation of discomfort in a throat, cough, short wind, a respiratory distress, increase or reduction of a respiration rate, a fluid lungs *, respiratory insufficiency.

From digestive tract: vomiting, nausea, abdominal pain, gastric discomfort, diarrhea, a dentagra, feeling of dryness in a mouth, feeling of paresthesia and pain in soft tissues of an oral cavity, hypersalivation.

From gepatobiliarny system: increase in level of bilirubin in blood, increase in level of liver enzymes.

From skin and a hypodermic fatty tissue: nephrogenic system fibrosis (NSF).

From a musculoskeletal system and connecting fabric: extremity pain, dorsodynia, arthralgias.

From kidneys and urinary system: an acute renal failure *, **, increase in level of creatinine in serum **, an urine incontience, sudden desires to an urination.

The general frustration and disturbances in an injection site: pain, a cryesthesia, reaction in an injection site (for example, a cryesthesia in the field of introduction, paresthesia, a swelling, a caumesthesia, pain, hypostasis, irritation, hemorrhages, an erythema, discomfort, некроз§, тромбофлебит§, флебит§, воспаление§, экстравазия§, thorax pain, a hyperthermia, peripheral hypostases, feeling недомогания§, feeling of fatigue, thirst, an adynamy, a fever, perspiration, fervescence, decrease in body temperature.

At patients with a renal failure to whom dialysis is shown at use of drug the delayed and tranzitorny reactions, similar inflammatory, such as, for example, fever, fever and increase in level of S-reactive protein were observed. At these patients of MRT the research using drug was conducted in a day before a hemodialysis.

Note:

 * Messages on life-threatening and/or lethal cases are possible.

** At patients against the background of previously diagnosed renal failure.

 § The reactions revealed during post-marketing observation of a gadopentetat.

Interaction with other medicines:

Any interactions with other medicines are unknown.

Interaction with diagnostic tests. When determining content of iron in blood serum by kompleksonometrichesky methods (for example, by means of a batofenantrolin) for the first days after administration of drug of Tomovist the quantitative index can be in a false manner reduced that is explained by existence in drug of free DTPK (dietilentriampentauksusny acid).

Contraindications:

Hypersensitivity to drug components.

Overdose:

So far it was not observed and not reported about any symptom of intoxication owing to inadvertent overdose during a clinical use.

At inadvertent overdose at patients with a renal failure it is necessary to control function of kidneys. Drug can be removed from an organism by a hemodialysis.

Use during pregnancy or feeding by a breast

 

Pregnancy. For a gadopentetat there are no sufficient clinical data about use to pregnant women. Results of researches on animals do not indicate existence of reproductive toxicity after repeated administrations of drug. The potential risk for the person is unknown. At purpose of drug pregnant women should weigh especially carefully a ratio risk/advantage.

Feeding by a breast. The minimum quantity of a gadopentetat (at most 0,04% of the dose entered intravenously) gets into milk in the course of a lactation. There are data that adsorption through digestive tract insignificant (about 4%). In clinically significant doses of influence on the child it is not expected.

Children

 

Experience of use of drug for MRT of all body of children up to 2 years is limited so far. Children up to 2 years should enter a necessary dose manually, without using an autoinzhektor, for prevention of damages.

Special security measures

 

Drug is sensitive to light. It is necessary to store capacity with drug in a cardboard box for protection against light. Just before use in operating time with a bottle there is no need for protection against light.

Drug cannot be used in cases of considerable discoloration of solution, emergence of parts or disturbances of integrity of packaging.

Tomovist it is necessary to gather in the syringe just before use. The rubber bung never should be punctured more than once. The remains of a contrast agent, unused at a research, are not suitable for further use, they should be utilized.

Storage conditions:

Period of validity. 2 years 6 months. Not to use drug after the termination of the period of validity specified on packaging. To store in original packaging at a temperature not over 25 ºС. To store in the place, unavailable to children. Not to freeze.

Issue conditions:

According to the recipe

Packaging:

On 5 ml or on 10 ml, or on 15 ml, or on 20 ml, or on 30 ml, or on 100 ml in a bottle. On 1 bottle in a pack.