Composition, form of production and packaging
The injection solution is clear, colorless or slightly colored.
1 ml * 1 amp.
meglumine amidotrisoate 520 mg 10.4 g
sodium amidotrizoate 80 mg 1.6 g
* - iodine content of 292 mg / 1 ml.
Excipients: sodium calcium edetate, sodium hydroxide, water d / u.
20 ml - ampoules (5) - plastic contoured packages (2) - cardboard packs.
The injection solution is clear, colorless or slightly colored.
1 ml * 1 amp.
meglumine amidotrisoate 660 mg 13.2 g
sodium amidotrizoate 100 mg 2 g
* - the content of iodine is 370 mg / 1 ml.
Excipients: sodium calcium edetate, sodium hydroxide, water d / u.
20 ml - ampoules (5) - plastic contoured packages (2) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Radiopaque preparation. Increases the contrast of the image due to the absorption of X-rays by iodine, which is part of amidotrizoate (diatrizoate).
The physico-chemical properties of the Urografina injection solutions are presented in the table.
Urografin 60% 76%
Concentration of iodine (mg / ml) 292 370
Osmolality (osmol / kg H 2 O) at 37 В° C 1.5 2.10
Viscosity (mPascal sec)
At 20 В° C 7.2 18.5
At 37 В° C 4.0 8.9
Density (g / ml)
At 20 В° C 1.330 1.418
At 37 В° C 1.323 1.411
PH value 6.0-7.0 6.0-7.0
PHARMACOKINETICS
Distribution
After intravascular injection, it is quickly distributed in the intercellular substance. Does not penetrate intact GEB. With IV administration, binding to plasma proteins is less than 10%. Amidotrizoat does not penetrate into the red blood cells.
5 minutes after iv bolus administration of Urografine at a dose of 1 ml / kg of body weight, the concentration of the drug in plasma is achieved, corresponding to 2-3 g of iodine per 1 liter. Within 3 hours after administration, a relatively rapid decrease in the concentration is observed, followed by a gradual decrease from T 1/2 to 1-2 hours.
Minimal quantities are excreted in breast milk.
Excretion
When administered in diagnostic doses, amidotrizoate is subjected to glomerular filtration in the kidneys. About 15% of the injected drug is excreted unchanged in the urine for 30 minutes after the administration, and more than 50% - within 3 hours.
In the range of clinically applied doses, the distribution and elimination of Urographin do not depend on its dose. This means that a 2-fold increase or 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.
Pharmacokinetics in special clinical cases
In patients with impaired renal function, amidotrizoate can be excreted in small amounts through the liver, albeit with a slowdown. The drug is removed during hemodialysis. Regardless of the place of administration, the complete excretion of contrast medium is guaranteed in a short period of time (even from tissues).
INDICATIONS
- in / in and retrograde urography;
- all types of angiographic studies;
- arthrography;
- endoscopic retrograde cholangiopancreatography (ERCP);
- intraoperative cholangiography;
- Sialografiya;
- Fistulography;
- Hysterosalpingography.
DOSING MODE
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.
Since anxiety, fear and pain can cause side effects or intensify the response to a contrast agent, it is recommended that a patient be sedated or prescribed appropriate therapy before carrying out the study.
Patients with generalized myeloma, diabetes mellitus with nephropathy, polyuria, oliguria, hyperuricemia, as well as infants and young children, and the elderly should be adequately hydrated. Before the study, violations of the water-electrolyte balance must be eliminated.
General rules of the procedure
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. To dial into the syringe, the contrast agent should be immediately before the start of the study. The remnants of contrast medium not used in the study are no longer used.
The dose depends on the age, body weight, cardiac output and the general condition of the patient. In renal or heart 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. When intravascular introduction of radiopaque means 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 injections of the drug in high 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 injected more than 300-350 ml of a contrast medium solution, infusion of solutions of electrolytes is required.
Preheating the solution before use
Heating the solution to the body temperature before use causes the contrast agent to be more easily introduced and better tolerated (due to reduced viscosity). When using a thermostat, only the amount of ampoules of contrast medium that is to be used should be heated to 37 В° C. It is shown that during sunlight protection, a longer (but not more than 3 months) storage of the drug at this temperature does not affect its chemical composition.
Test Samples
Do not recommend to assess the sensitivity with a small test-dose contrast medium, because this does not allow to predict the occurrence of the reaction. Moreover, the definition of sensitivity in itself sometimes leads to serious and even lethal hypersensitivity reactions.
Intravenous urography
Injection
The injection rate for injection is usually 20 ml / min. For patients with heart failure who are prescribed a dose of 100 ml or more, the recommended duration of administration is at least 20-30 minutes.
Doses
For adults, a dose of 76% solution is 20 ml, 60% - 50 ml. Increasing the dose of 76% solution 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.
Children due to a lower physiological concentration ability of the still immature nephron require relatively high doses of Urograine 76%.
Age Dose of Urographine
Up to 1 year 7-10 ml
From 1 year to 2 years 10-12 ml
From 2 to 6 years 12-15 ml
From 6 to 12 years, 15-20 ml
Older than 12 years old for adults
Snapshot Time
Renal parenchyma is best displayed if you take a picture immediately after the end of the contrast agent.
To visualize the renal pelvis and urinary tract in adults, 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 focus on the lower one, and for the elderly, on the upper limit of the indicated time range.
In 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
When infusing Urographin for adults and adolescents, usually the time of administration of a solution of 60% or 76% (100 ml) should not be less than 5 minutes and more than 10 minutes. For patients with heart failure, the recommended infusion time is 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
In cases where an especially high concentration of iodine is important, for example, in aortography, angiocardiography or coronary angiography, a 76% solution is preferred. 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
It is sufficient to use a 30% solution, which can be obtained by diluting 60% solution of Urografine with water for injection in a ratio of approximately 1: 1. To avoid irritation with cold causing ureteral spasms, it is recommended to warm the contrast agent 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.
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 EFFECT
Side effects are presented with the following estimate of incidence: often (> 1%); sometimes (<1%, but> 0.1%), rarely (<0.1%).
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 incidence of adverse reactions with ion contrast media is 12%, and non-ionic drugs - 3%.
Often: nausea, vomiting, pain and a feeling of heat.
On the part of the respiratory system: often - transient changes in respiratory rate, shortness of breath, respiratory failure and cough; rarely - respiratory arrest, pulmonary edema.
From the cardiovascular system: sometimes - clinically significant transient changes in heart rate, blood pressure, rhythm disturbances; rarely - dangerous thromboembolic complications leading to myocardial infarction.
On the part of the digestive system: often - nausea, vomiting; sometimes - pain in the abdomen.
From the side of the central nervous system (with angiography of the brain and other studies in which the contrast medium reaches the brain with arterial blood): sometimes - dizziness, headaches, agitation or impaired consciousness, amnesia, speech, vision, hearing, convulsions, tremor, paresis / paralysis, photophobia, transient blindness, coma, drowsiness; rarely severe thromboembolic complications leading to a stroke.
From the side of the urinary system: rarely - a violation of kidney function up to kidney failure.
Dermatological reactions: often - redness of the face (associated with vasodilation), rash, itching, erythema; rarely Stevens-Johnson syndrome, Lyell's syndrome.
Local reactions: pain is observed mainly in peripheral angiography. With extravascular administration of Urografina - pain, swelling (usually disappear without the development of further complications); extremely rare - inflammation, tissue necrosis; sometimes thrombophlebitis and vein thrombosis.
Allergic reactions: moderately pronounced angioedema, conjunctivitis, cough, itching, rhinitis and urticaria (can occur regardless of dose, method of administration and are the first symptoms of anaphylactic reaction). Perhaps the development of more severe reactions, accompanied by the expansion of peripheral vessels and subsequent arterial hypotension, reflex tachycardia, respiratory disorders, agitation, impaired consciousness, cyanosis, loss of consciousness. Rarely - bronchospasm, laryngospasm.
Other: a feeling of heat and a headache, sometimes - malaise, chills, increased sweating, fainting; rarely - a change in body temperature, swelling of the salivary glands.
Introduction to the body cavity
After injection into the body cavity, adverse reactions develop rarely, often several 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. Nontrotic pancreatitis is described in rare cases.
Allergic reactions: systemic reactions are rare and are poorly expressed, manifested mainly as skin reactions. However, the possibility of developing severe hypersensitivity reactions can not be completely ruled out.
CONTRAINDICATIONS
- pronounced hyperthyroidism;
Decompensated heart failure.
Endoscopic retrograde cholangiopancreatography can not be performed with acute pancreatitis.
Hysterosalpingography can not be performed during pregnancy and acute inflammatory processes in the pelvic cavity.
The drug can not be used for myelography, ventriculography and cisternography in connection with possible neurotoxic phenomena.
PREGNANCY AND LACTATION
In studies in vivo and in vitro, no mutagenic, teratogenic, embryotoxic and genotoxic effects of amidotrizoate have been identified.
Sufficient evidence of the safety of Urografina during pregnancy is not. Since in any case during pregnancy one should try to avoid the effects of radiation, it is necessary to carefully compare the benefits and risks of conducting an X-ray examination without or using radiopaque.
Contrast agents such as Urografina, which are excreted by the kidneys, are excreted in breast milk in very small quantities. When using the drug during lactation (breastfeeding), the risk of toxic effects in infants is small (according to available data).
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution apply the drug for severe violations of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should be used in cases of severe violations of the liver.
SPECIAL INSTRUCTIONS
With caution should be used with increased sensitivity to iodine-containing contrast agents, with severe violations of liver and kidney function, heart failure, emphysema, severe general condition of the patient, cerebral arteriosclerosis, decompensated diabetes mellitus, cerebral vasospasm, subclinical hyperthyroidism, nodular goiter and generalized myeloma.
In in vivo and in vitro studies, no oncogenic action of the drug was detected.
The above precautions should be observed for all types of administration , but the risk of side effects is higher when in / in the introduction.
After the introduction of radiopaque agents (such as Urografine), hypersensitivity reactions can occur, manifested by difficulty breathing, erythema, urticaria, itching, or facial edema. Severe reactions are possible: angioedema (including vocal cords), bronchospasm and anaphylactic 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 severe allergic reactions or with reactions to iodine containing contrast agents in history have an increased risk of developing severe reactions.
The frequency of adverse reactions is higher in patients with a history of allergic anamnesis (for example, allergic reactions to sea products, hay fever, urticaria), with increased sensitivity to iodine, bronchial asthma. In this regard, before the introduction of a contrast agent should carefully collect allergic anamnesis. When indicating an inclination to allergies, consideration should be given to the need to use antihistamines and / or SCS for prevention.
Patients with bronchial asthma have an increased risk of developing bronchospasm or hypersensitivity reactions.
Hypersensitivity reactions can be more pronounced in patients taking beta-blockers. It should also be taken into account that, against the background of the use of beta-blockers, resistance to standard therapy of hypersensitivity reactions is possible.
With the development of a hypersensitivity reaction, the administration of the contrast agent should be stopped immediately and, if necessary, initiated the appropriate therapy. Therefore, in the study room, you should prepare medicines and everything necessary for carrying out the ventilation.
A small amount of inorganic iodine, contained in a solution of 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 is especially careful.
There is an increased risk of developing severe reactions in people with severe heart disease (especially with heart failure and ischemic heart disease).
In the elderly, pathological vascular changes and neurological disorders often occur, which increases the risk of adverse reactions to iodine-containing contrast media.
The need for radiopaque testing should be carefully weighed in patients with a poor general condition.
Intravascular administration
In rare cases, may cause kidney failure. To prevent acute renal failure in the administration of contrast agents should observe the following precautions: identify patients at increased risk (eg, kidney disease history, with pre-existing renal insufficiency, with pre-existing renal insufficiency after administration of contrast medium, amid accompanied by nephropathy of diabetes diabetes, multiple myeloma, aged 60 years, with progressive vascular disease, with paraproteinemia, with severe chronic tion hypertension, gout, or impending introduction of a high or repeated doses).Patients at risk of developing renal failure should conduct adequate hydration before administration (preferably by intravascular infusion before and after the study, following infusion should be continued until complete elimination of contrast medium from the kidneys).
Until complete removal of the contrast agent should exclude additional load on the kidneys in the form of use of nephrotoxic drugs, oral administration holetsistograficheskih preparations overlay arterial clamp, renal artery angioplasty or a large surgery. New radiopaque study should be postponed until full recovery of renal function.
Patients on dialysis can be carried out X-ray examination by means of a contrast agent, because iodine-containing contrast agents excreted by dialysis.
When administered intravascularly radiopaque means (kidneys is output) may develop transient disturbances of kidney function. As a result, patients taking biguanides, lactic acidosis can occur (as a precaution receiving biguanides should be stopped 48 hours before and 48 hours after the X-ray contrast studies).
In patients with valvular heart disease and pulmonary hypertension administration of contrast agents may lead to pronounced haemodynamic changes. In elderly patients and in heart disease more likely to occur in the history of ischemic ECG changes and arrhythmias. In heart failure, intravascular contrast agent may cause pulmonary edema.
With special caution should be intravascular contrast agent in patients with acute cerebral infarction, acute intracranial hemorrhage and other diseases accompanied by breach of the integrity of the BBB, brain edema, acute or demyelination. The incidence of seizures after administration of iodine-containing contrast media was higher in patients with intracranial tumors or metastases with a history of epilepsy. Introduction of contrast agents may contribute to the appearance of neurological symptoms in diseases of the brain vessels, the presence of intracranial tumors or metastases, degenerative or inflammatory diseases of the CNS. Intraarterial administration of a contrast agent may lead to phenomena vasospasm and subsequent cerebral ischemia.The risk of neurological complications is higher in patients with cerebrovascular disease, a stroke or a recent history of frequent transient ischemic attacks.
In severe renal insufficiency concomitant severe impairment of liver function can appreciably slow down the excretion of contrast agent and lead to the need for dialysis.
Myeloma or paraproteinemia can disturb the kidney when administered contrast agent. In this case, you should pay particular attention to adequate hydration.
Patients with pheochromocytoma due to the risk of vascular crisis recommended pre-treatment with alpha-blockers.
Patients with autoimmune disorders may be cases of severe vasculitis or similar syndrome Stevens-Johnson syndrome.
The introduction of iodine-containing contrast media can amplify the symptoms of myasthenia gravis (myasthenia gravis).
Acute or chronic alcoholism may increase the permeability of the BBB. This facilitates the penetration of contrast agent in the brain tissue and can lead to reactions on the part of the central nervous system. Particular caution should be exercised in patients with chronic alcoholism and people who use drugs, due to a possible reduction in seizure threshold.
Ionic iodine-containing contrast media, compared with non-ionic contrast media strongly inhibit in vitro blood coagulation system. Nevertheless medical personnel during catheterization and vascular angiography should be frequently rinse 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.
Reportedly use of plastic instead of glass syringes reduces but does not eliminate the clotting of blood in vitro. Care should be taken in patients with homocystinuria because they have the risk of thrombosis and embolism.
Introduction into the body cavity
In conducting hysterosalpingography to exclude possible pregnancy. The risk of side reactions during cholangiography, ERCP, or hysterosalpingography increased in the presence of inflammation of the bile duct or fallopian tubes.
Impact on the ability to drive vehicles and manage mechanisms
Delayed reactions to intravascular administration of iodine-containing contrast media are rare. However, the driving or working with moving mechanisms are undesirable during the first 24 hours after the study.
OVERDOSE
Accidental overdosing or abuse with significant renal Urografin can be removed from the body by extracorporeal dialysis.
DRUG INTERACTION
Iodine-containing radiopaque means outputted via the kidneys, reduce the ability of the thyroid tissue to accumulate in diagnostic radioisotopes thyroid studies. This reduction can take up to 2 weeks (in some cases - more).
In patients receiving beta-blockers, hypersensitivity reactions are more pronounced.
The frequency of the delayed side effects (fever, rash, flu-like symptoms, joint pain, itching) in the application of contrast media is higher in patients treated with neuroleptics.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored protected from light and X-rays reach of children at a temperature not higher than 30 В° C. Shelf life - 5 years.
