Urographin® (Urografin®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceSodium amidotrisoateSodium amidotrisoate
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    • Dosage form: & nbsp

    Injection.

    Composition:

    Active substances

    1 ml Urographina 76% (0.76 g / ml) contains: 597.3 mg of amidotrizic acid and 159.24 mg of meglumine in aqueous solution;

    1 ml Urografina 60% (0.6 g / ml) contains: 471.78 mg of amidotrizic acid and 125.46 mg of meglumine in an aqueous solution;

    Excipients: sodium calcium edetate, sodium hydroxide, water for injection
    Description:

    Transparent, colorless or slightly colored liquid.

    Pharmacotherapeutic group:X-ray contrast medium
    ATX: & nbsp

    V.08   Contrast substances

    Pharmacodynamics:

    Urographin® improves the contrast of the image due to the absorption of X-rays by iodine, which is part of amidotrizoate.

    The physico-chemical properties of the Urografina injection solutions are presented in the table.

    Uurografine

    60%

    76%

    Concentration of iodine (mg / ml)

    292

    370

    Osmolality

    1,50

    2,10

    (osmol / kg HgO) at

    37 ° C

    Viscosity (mPascal sec)

    At 20 ° C

    7,2

    18,5

    At 37 ° C

    4,0

    8,9

    Density (g / ml)

    At 20 ° C

    1,330

    1,418

    At 37 ° C

    1,323

    1,411

    PH value

    6,0-7,0

    6,0-7,0

    In studies in vivo and in vitro no data have been identified that indicate possible mutagenic, teratogenic,embryotoxic and genotoxic properties of amidotrizoate. The risk of oncogenic effects in humans has not been revealed.

    Pharmacokinetics:

    Distribution

    With intravenous administration of the drug, its association with plasma proteins does not exceed 10%. Five minutes after the intravenous bolus administration of Urograine 60% at a dose of 1 ml per kg of body weight, the concentration of the drug in plasma is achieved, corresponding to 2-3 g of iodine per liter. Within 3 hours after administration, a relatively rapid decrease in the concentration is observed, followed by a gradual decrease with a half-life of 1-2 hours.

    Amidotrizoat does not penetrate into the red blood cells. After intravascular injection, it is quickly distributed in the intercellular substance. Does not penetrate the intact blood-brain barrier and only in minimal amounts penetrates into the breast

    Metabolism and elimination

    When administered in diagnostic doses, amidotrizoate is subjected to glomerular filtration in the kidneys. About 15% of the injected drug is excreted unchanged in urine within 30 minutes after the administration, and more than 50% - within 3 hours.

    In the range of clinically applied dosages, the observed kinetics of Urograman distribution and elimination is independent of its dose.This means that doubling or a 2-fold decrease in the dose of Urographin leads to a twofold increase or decrease in the content of contrast medium in the blood and its elimination in grams per unit time. However, due to an increase in osmotic diuresis when the dose is doubled, the concentration of the contrast agent in the urine does not increase to the same extent.

    Patients with renal insufficiency

    If renal function is impaired, amidotrisoic acid can be eliminated extrarenally by the liver, albeit at a slower rate. Nephrotropic contrast agents can be easily removed from the body by means of extracorporeal hemodialysis.

    Regardless of the place of administration of Urographin, complete elimination of contrast medium is guaranteed in a short period of time even from tissues.

    Indications:

    Intravenous and retrograde urography.

    In addition, for all angiographic studies, as well as for arthrography, intraoperative cholangiography, endoscopic retrograde cholangiopancreatography (ERCP), sialography, fistulography, hysterosalpingography, and others.

    Contraindications:

    Severe hyperthyroidism, decompensated heart failure.

    Do not apply Urografine for myelography, ventriculography and cisternography, in connection with possible neurotoxic phenomena.

    Hysterosalpingography is not performed during pregnancy or in the presence of acute inflammatory processes in the pelvic region.

    Endoscopic retrograde cholangiopancreatography ERCP is not performed with acute pancreatitis.

    Carefully:

    With extreme caution apply the drug with increased sensitivity to iodine-containing contrast agents, severe disorders of liver or kidney function, cardiovascular failure, pulmonary emphysema, severe general condition, arteriosclerosis of the brain, decompensated diabetes mellitus, spasm of cerebral vessels, subclinical hyperthyroidism, nodular goiter and generalized myeloma.

    Pregnancy and lactation:

    A study of the toxic effect of meglumidine or sodium amidotrizoate on reproductive function does not indicate the ability of Urographine, when it is unintentionally administered during pregnancy, to cause teratogenic or embryotoxic effects.

    Sufficient evidence of the safety of Urografen in pregnant women is not available. Since whenever possible in any case during pregnancy, the effects of radiation should be avoided, it is necessary to carefully compare the benefits and risks of X-ray examination without or in the presence of radiopaque.

    Contrast agents such as Urographin, for which the renal elimination pathway is characteristic, penetrate into breast milk in very small amounts.

    According to available data, the risk to infants from the introduction of diatrizoic acid salts to mothers is low.

    Dosing and Administration:

    - Preparation of the patient for the procedure

    With angiography of the abdominal cavity and urography, it is recommended to thoroughly clean the patient's stomach to facilitate diagnosis. Therefore, in the last two days before the examination, avoid foods that cause flatulence (especially legumes, salads, fruits, black and fresh bread, as well as any vegetables in raw form). The last meal on the eve of the examination should be no later than 18 hours. In addition, it is advisable to take an evening laxative.Thoracic and small children, large intervals in the intake of food, as well as the appointment of a laxative are contraindicated.

    Because anxiety, fear and pain can cause side effects or intensify the reaction to a contrast agent, it is recommended that a sedative conversation or sedative medication be performed before the study.

    Patients with generalized myeloma, diabetes mellitus with nephropathy, polyuria, oliguria, hyperuricemia, as well as infants and young children, elderly patients should be adequately hydrated. Prior to the study should be eliminated violations of water-electrolyte exchange (if any).

    - General rules of procedure

    To type the system contrast medium in a syringe or injection ciciac1 immediately before the start of the study.

    Ready for use Urografine should be a colorless or pale yellow transparent solution. The drug can not be used when changing the color of the solution, the appearance of visible particles or destruction of the integrity of the ampoules.

    The remnants of contrast medium not used in the study are no longer used.

    The dose depends on the age, body weight, heart choice and general condition of the patient.

    In patients suffering from renal or cardiovascular failure, the dose of contrast agent should be as low as possible. In these patients it is desirable to monitor kidney function for at least 3 days after the study.

    When performing angiography, frequent rinsing of used catheters with saline is required to minimize the possible risk of thromboembolism. With intravascular introduction of an X-ray contrast medium, it is desirable that the patient is lying. After the injection, careful monitoring of the patient for at least 30 minutes is necessary, since most of the serious complications occur exactly in the first half hour after the injection.

    If several high single doses are required to clarify the diagnosis, the interval between injections should be 10-15 minutes to compensate for increased serum osmolarity due to the inflow of interstitial fluid. If adults are injected more than 300-350 ml of contrast medium, an internal infusion of solutions of electrolytes is administered.

    - Preheating before use

    The contrast agent is better tolerated and easier to administer with reduced viscosity, which is achieved by heating to body temperature. When using a thermostat, only the amount of ampoules of contrast medium that is to be used should be heated to 37 ° C. It is shown that, when protected from sunlight, the presence of the drug at this temperature for a longer time does not affect its chemical composition. However, this period should not exceed 3 months.

    - Test Samples

    It is not recommended to evaluate the sensitivity with a small test dose of the contrast agent, since it does not predict the occurrence of the reaction. Moreover, the definition of sensitivity in itself sometimes leads to serious and even fatal reactions due to hypersensitivity.

    Intravenous urography

    - Injection

    The rate of administration is usually 20 ml / min. For patients with heart failure who are prescribed a dose 100 ml or more, the recommended duration of administration is at least 20-30 minutes.

    Dosage

    For adults:

    Dose Urografina 76% - 20 ml, Urografina 60% - 50 ml.Increasing the dose of Urographin 76% to 50 ml significantly improves the accuracy of diagnosis. A further increase in the dose is possible if this is necessary due to special indications.

    For children:

    Because of the reduced physiological concentration ability of the still immature nephron in children, relatively high doses of Urografina 76% are required:

    children under 1 year old: 7-10 ml; 1- 2 years : 10-12 ml; 2- 6 years: 12-15 ml; 6-12 years old: 15-20 ml; over 12 years: as for adults

    Snapshot Time

    Renal parenchyma is best displayed if you take a picture immediately after the end of the contrast agent.

    For visualization of the renal pelvis and urinary tract, the first image is taken 3-5 minutes later, and the second one is taken 10-12 minutes after the contrast agent is injected, and for younger patients it is necessary to orientate to the lower one, and for the elderly, to the upper limit of the specified time range.

    For infants and young children, the first picture is recommended to be done within 2 minutes after the administration of the contrast agent. If images are poorly contrasted, late photographs may be necessary.

    - Infusion Adults and teenagers

    Typically, the infusion time of Urogramin 60% or 76% (100 ml) should not be less than 5 minutes and not more than 10 minutes. For patients with heart failure, infusion time is recommended 20 - 30 minutes.

    Snapshot Time

    The first picture should be taken immediately after the end of the infusion. Subsequent shots can be obtained within the next 20 minutes or later in case of excretion disturbance.

    Angiography

    Urografine can also be used for angiographic studies. The dose depends on the age, body weight, minute volume of the heart, the general condition of the patient, the clinical problem, the test procedure and the volume of the vascular site being studied.

    Retrograde urography

    Usually, approximately 30% solution is sufficient for this purpose, which can be obtained by diluting 60% of Urografine with water for injection (Aqua pro injectione) in a ratio of approximately 1: 1. To avoid irritation with cold causing ureteral spasms, it is recommended to heat the contrast medium to body temperature.

    If special studies require an increased degree of contrast, then you can also use undiluted Urographin 60%. Despite its high concentration, irritation symptoms are observed in extremely rare cases.

    Keeping in other body cavities

    In the conduct of arthrography, hysterosalpingography and especially ERCP, the process of administering a contrast agent should be monitored with fluoroscopy.

    Side effects:

    To express the approximate frequency of undesirable effects in the text, their definitions are used: "typical", "atypical", "rare":

    -typical: frequency> = 1: 100

    - atypical: frequency <1: 100, but> = 1: 1000

    -Some: frequency <1: 1000

    Intravascular application

    Side effects associated with intravascular application of iodine-containing contrast agent are usually mild, moderate and transient. However, severe and life-threatening reactions are described. The frequency of adverse reactions with the use of ion contrast media is 12%, and non-ionic preparations - 3%.

    The most common reactions are nausea, vomiting, pain and a feeling of heat.

    - Anaphylactoid reactions / hypersensitivity

    Usually, moderate angioedema, conjunctivitis, coughing, itching, rhinitis, runny nose and urticaria are observed. These reactions can occur independently of the dose, the method of administration, and may be the first symptoms of a shock reaction.The introduction of the contrast medium should be immediately stopped and, if necessary, the initiation of specific therapy through venous access (see "Special instructions").

    Treaction, turgent emergency therapy can have the form of discirculatory disorders, accompanied by peripheral vasodilation and subsequent hypotension, reflex tachycardia, respiratory failure, agitation, impaired consciousness and cyanosis with possible transition to the unconscious state.

    Bronchospasm, laryngospasm or laryngeal edema and hypotension are rare reactions.

    Seldom reactions to the administration of contrast medium are rare (see "Special instructions").

    - General reactions

    Usually there is a feeling of heat and a headache. Malaise, chills or sweating and vasovagal reactions (fainting) are atypical.

    In rare cases, there is a change in body temperature and edema of the salivary glands.

    - Respiratory system

    Typical are transient changes in respiratory rate, dyspnea, respiratory failure and cough. Stopping breathing and pulmonary edema are rare reactions.

    - The cardiovascular system

    Clinically significant transient changes in heart rate, blood pressure, rhythm disturbances or function, and cardiac arrest are not typical.

    Expressed reactions requiring urgent therapy can be expressed in the form of peripheral vasodilation and subsequent hypotension, reflex tachycardia, dyspnea, excitation, impaired consciousness and cyanosis with possible transition to the unconscious state.

    The dangerous thromboembolic complications leading to myocardial infarction are rarely reported.

    - Gastrointestinal tract

    Nausea and vomiting are typical reactions. Pain in the abdomen is not typical.

    - Cerebral circulation

    Angiography of the brain and other studies in which the contrast medium reaches the brain with arterial blood may be accompanied by neurological complications related to atypical headaches, dizziness, headache, disturbance of consciousness, amnesia, speech, vision, hearing, seizures, tremor, paresis / paralysis, photophobia, transient blindness, coma, drowsiness.

    Severe thromboembolic complications leading to a stroke are classified as rare.

    - Kidneys

    Tank rare cases are described violations kidney function and kidney failure.

    - Leather

    Typical reactions are: moderate angiogenic edema, reddening of the face with vasodilatation, rash, skin itch, erythema.

    In rare cases, the skin-mucous syndrome (for example, Stevens-Johnson syndrome or Lyell's syndrome) can develop.

    - Local irritation

    Local pains are observed mainly at peripheral angiography. The peri-vascular introduction of Urographin causes the appearance of local pains, swelling, which usually disappear without the development of further complications. Inflammation and even tissue necrosis are described as extremely rare complications. Thrombophlebitis and vein thrombosis are not typical.

    Introduction to the body cavity

    After injection into the body cavity, adverse reactions develop rarely. Most of them occur within a few hours after administration due to slow absorption from the area of ​​administration and distribution in the body controlled by the diffusion process.

    When ERCP is carried out, an increase in the level of amylase is usually observed. Visualization of the acini with ERCP is accompanied by an increased risk of subsequent pancreatitis.In rare cases, necrotic pancreatitis is described

    - Anaphylactoid reactions / hypersensitivity

    Systemic hypersensitivity reactions are rare, they are weakly expressed and mainly manifested as skin reactions. However, the possibility of developing severe hypersensitivity reactions can not be completely ruled out.

    Overdose:

    In case of an accidental overdose or a greatly reduced renal function, Urografine can be removed from the body by extracorporeal dialysis.

    Interaction:

    In patients receiving beta-blockers, hypersensitivity reactions are more pronounced.

    The frequency of delayed side effects (eg, fever, urticaria, influenza-like symptoms, joint pain, pruritus) when using contrast agents is higher in patients receiving interleukin.

    Special instructions:

    The following precautions should be observed for all types of administration, but the risk of side effects is higher with intravenous administration.

    - Hypersensitivity

    In some cases, after the introduction of radiopaque agents, such as Urografine, allergic hypersensitivity reactions may occur.

    These reactions usually manifest in the form of not severe respiratory and skin symptoms: shortness of breath, redness of the skin (erythema), hives, itching or swelling of the face. Severe reactions are possible: vascular edema, laryngeal edema below the folds of the vocal

    crevices, bronchospasm and allergic shock. Typically, these reactions occur within one hour after the administration of the contrast agent. However, in rare cases, deferred reactions may occur (within a few hours - days)

    Patients with hypersensitivity or those who previously had reactions to iodine-containing contrast agents have an increased risk of developing severe reactions.

    The frequency of adverse reactions is higher in patients with an allergic anamnesis (for example, allergy to sea products, hay fever, urticaria), with sensitivity to iodine or radiopaque means and suffering from bronchial asthma. In this regard, before the introduction of a contrast agent, the patient should be interviewed for a susceptibility to allergies. In such cases, the need to prevent the use of antihistamines and / or glucocorticosteroids should be considered.

    Patients with bronchial asthma have an increased risk of developing bronchospasm or hypersensitivity reactions.

    Hypersensitivity reactions can be enhanced in patients taking beta-blockers, especially in the presence of bronchial asthma. Moreover, it is necessary to take into account that patients taking beta-blockers can be resistant to standard therapy of hypersensitivity reactions with beta-agonists.

    With the development of a hypersensitivity reaction, the administration of the contrast agent should be stopped immediately and, if necessary, the initiation of a special treatment through venous access. To carry out emergency therapy, appropriate medicines, an endotracheal tube and an artificial respiration device should be ready.

    - Thyroid dysfunction

    A small amount of inorganic iodine present in the solution iodine-containing contrast agent, can affect the function of the thyroid gland.
    Therefore, the need to conduct radiopaque studies in patients with latent hyperthyroidism or goitre should be carefully evaluated.

    - Cardiovascular diseases

    There is an increased risk of developing severe reactions in people with severe heart disease, especially those who suffer from heart failure and coronary artery disease.

    - Elderly age

    Elderly people often have pathological changes in blood vessels and neurological disorders, which increases the risk of adverse reactions to iodine-containing contrast media.

    - General poor health

    The need for X-ray examination with contrast should be carefully weighed in patients with general poor health.

    Intravascular administration

    - Renal insufficiency

    In rare cases, kidney failure may occur. The following preventive measures should be taken to prevent acute renal failure when a contrast agent is administered:

    Identify patients with risk factors, such as, for example, a history of kidney disease, existing renal failure, renal failure after a history of contrast, diabetes mellitus with nephropathy, multiple myeloma, age over 60 years, progressive vascular disease,

    paraproteinemia, severe arterial hypertension, gout, administration of large or repeated doses of the drug.

    Before the introduction of a contrast agent, adequate hydration should be performed in patients at increased risk. Preferably, this should be done by intravascular infusion before and after the study. Infusion should be continued until the contrast agent is completely removed from the kidneys.

    Until the complete excretion of the contrast agent, an additional burden on the kidneys in the form of nephrotoxic drugs, the administration of cholecystographic oral preparations, the imposition of an arterial clamp, angioplasty of the arteries of the kidneys, or large surgical intervention should be excluded.

    Postpone a new radiopaque study until the kidney function is completely restored.

    In patients on dialysis, X-ray diagnosis can be performed with a contrast agent, since iodine-containing contrasting funds are removed from the body through dialysis.

    - Treatment with metformin

    The use of the intracavitary radiopaque means excreted by the kidneys can lead to transient renal dysfunction. As a result, patients taking biguanides may experience lactatacidosis (as a precaution, taking biguanides should be stopped 48 hours before the study with contrast and not taken for at least 48 hours afterwards).

    - Cardiovascular diseases

    In patients with heart valve diseases and pulmonary hypertension, the administration of a contrast agent can lead to marked hemodynamic changes. In elderly patients and patients with heart disease, an ischemic changes in the ECG and arrhythmia occur more often.

    In patients with heart failure, intravascular injection of a contrast agent may cause pulmonary edema.

    - CNS disorders

    With extreme caution, intravascular administration of the contrast agent should be performed in patients with acute cerebral infarction, with acute intracranial hemorrhage and other diseases accompanied by a violation of the integrity of the blood-brain barrier, edema of the brain or acute demyelination.The frequency of seizures after administration of an iodine-containing contrast agent is higher in patients with intracranial tumors or metastases and with epilepsy in the anamnesis. The introduction of a contrast agent may contribute to the appearance of neurological symptoms in diseases of the cerebral vessels, the presence of intracranial tumors or metastases, degenerative or inflammatory diseases of the central nervous system. Intraarterial administration of the contrast agent can lead to the phenomena of vasospasm and subsequent cerebral ischemia. The risk of neurologic complications is higher in patients with symptoms of cerebrovascular disease, recent stroke or frequent transient ischemic attacks.

    - Severe liver dysfunction

    In the case of severe kidney failure, concomitant severe impairment of liver function can significantly slow the excretion of contrast agent and lead to the need for hemodialysis.

    - Myeloma and paraproteinemia

    Myeloma or paraproteinaemia may contribute to impaired renal function when a contrast agent is administered. In this case, special attention should be given to adequate hydration.
    - Pheochromocytoma
    Patients with pheochromocytoma due to the danger of development; a preliminary introduction of a-adrenoblockers is recommended.
    - Patients with autoimmune diseases
    Patients with autoimmune disorders may experience severe vasculitis or a syndrome similar to Stephen-Johnson syndrome.
    - Myasthenia gravis (myasthenia gravis)
    The introduction of an iodine-containing contrast agent may increase the symptoms of myasthenia gravis (myasthenia gravis).
    - Alcoholism
    Acute or chronic alcoholism can increase the permeability of the blood-brain barrier. This facilitates the penetration of the contrast agent into the brain tissue and can lead to reactions from the CNS. Particular care should be exercised in alcoholics and people taking drugs, because of the possible lowering of the threshold of convulsive readiness.
    - Blood coagulation system
    Ionic iodine-containing contrast agents, in contrast to non-ionic contrast agents, more strongly inhibit the blood coagulation system in vitro. Nevertheless, medical personnel with catheterization and angiography should often wash the catheter with saline (if possible with the addition of heparin)and minimize the duration of the study to minimize the risk of thrombosis and embolism. According to available information, the use of plastic syringes instead of glass reduces, but does not exclude the complete clotting of blood in vitro.
    Care should be taken in patients with homocystinuria because they have the risk of thrombosis and embolism.
    Introduction to the body cavity
    When conducting hysterosalpingography, a possible pregnancy should be excluded. The risk of side reactions during holayagiografii, ERCP, or hysterosalpingography increased in the presence of inflammation of the bile duct or fallopian tubes.

    Effect on the ability to drive transp. cf. and fur:

    As with other iodine-containing contrast media, after intravascular administration UROGRAFINA In rare cases, there is the possibility of slowing down the reactions, which can disrupt the ability to drive vehicles and work with other mechanisms.

    Form release / dosage:

    1. To 20 ml in ampoules of neutral colorless or orange glass. 10 vials are placed in plastic or other dense containers (trays) is placed in a cardboard box.
    2. "In Balk" - 120 ampoules, placed on 10 pieces in plastic or other dense containers (pallets), which are placed in a cardboard box.

    Packaging:ampoules of orange glass (10) -pallet-boxes, cardboard
    ampoules (10) -pallet-boxes, cardboard
    Storage conditions:

    At a temperature of no higher than 30 ° C, protected from light and X-rays, a place inaccessible to children

    Shelf life:

    Shelf life

    5 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-001850
    Date of registration:16.07.2010
    The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany
    Manufacturer: & nbsp
    Information update date: & nbsp04.07.2013
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