Urographin (Solution) Instructions for Use

ATC Code

V08AA01 (Amidotrizoic acid)

Active Substance

Sodium amidotrizoate (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Radiocontrast ionic diagnostic agent for intravascular and intracavitary administration

Pharmacotherapeutic Group

Radiocontrast agent

Pharmacological Action

Radiocontrast agent. It increases image contrast due to the absorption of X-rays by the iodine that is part of amidotrizoate (diatrizoate).

The physicochemical properties of Urographin injection solutions are presented in the table.

Pharmacokinetics

Distribution

After intravascular administration, it rapidly distributes into the extracellular space. It does not penetrate the intact blood-brain barrier. With intravenous administration, plasma protein binding is less than 10%. Amidotrizoate does not penetrate erythrocytes.

Five minutes after intravenous bolus administration of Urographin at a dose of 1 ml/kg body weight, a plasma concentration of the drug corresponding to 2-3 g of iodine per 1 liter is achieved. A relatively rapid decrease in concentration is observed within 3 hours after administration, followed by a gradual decrease with a T_1/2 of 1-2 hours.

It is excreted in breast milk in minimal amounts.

Elimination

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

Within the range of clinically used doses, the distribution and elimination processes of Urographin are independent of its dose. This means that doubling or halving the dose of Urographin leads to a twofold increase or decrease in the blood concentration of the contrast agent and the amount eliminated per unit time in grams. However, due to increased 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 may be excreted in small amounts through the liver, albeit slowly. The drug is removed by hemodialysis. Regardless of the site of administration, complete elimination of the contrast agent is guaranteed to occur within a short period of time (even from tissues).

Indications

• Intravenous and retrograde urography;
• All types of angiographic studies;
• Arthrography;
• Endoscopic retrograde cholangiopancreatography (ERCP);
• Intraoperative cholangiography;
• Sialography;
• Fistulography;
• Hysterosalpingography.

ICD codes

Dosage Regimen

Solution

Patient preparation for the procedure

For abdominal angiography and urography, thorough cleansing of the patient’s stomach is recommended to facilitate diagnosis. Therefore, in the last two days before the examination, food that causes flatulence should be avoided (primarily legumes, salads, fruits, black and fresh bread, as well as any raw vegetables). The last meal on the eve of the examination should be no later than 6 p.m. In addition, it is advisable to take a laxative in the evening. Long intervals between meals and the prescription of laxatives are contraindicated for infants and young children.

Since anxiety, fear, and pain can cause side effects or enhance the reaction to the contrast agent, it is recommended to have a calming conversation with the patient or prescribe appropriate therapy before the study.

Patients with generalized myeloma, diabetes mellitus with nephropathy, polyuria, oliguria, hyperuricemia, as well as infants and young children, and elderly individuals should receive adequate hydration. Water and electrolyte balance disturbances must be corrected before the study.

General rules for the procedure

Ready-to-use Urographin should be a colorless or pale yellow transparent solution. The drug should not be used if the color of the solution changes, visible particles appear, or the integrity of the ampoules is compromised. The contrast agent should be drawn into the syringe immediately before the start of the study. Unused residues of the contrast agent from the study are no longer used.

The dose depends on the age, body weight, cardiac output, and general condition of the patient. In renal or heart failure, the dose of the contrast agent should be as low as possible. In these patients, it is desirable to monitor renal function for at least 3 days after the study.

When performing angiography, frequent flushing of the catheters used with saline solution is required to minimize the possible risk of thromboembolism. During intravascular administration of the radiocontrast agent, it is desirable for the patient to lie down. After injection, careful observation of the patient for at least 30 minutes is necessary, since most severe complications occur precisely in the first half hour after the injection.

If several administrations of the drug in high doses are required to clarify the diagnosis, the interval between injections should be 10-15 minutes to compensate for the increased serum osmolarity due to the influx of interstitial fluid. If more than 300-350 ml of contrast agent solution is administered as a single dose to adults, infusion of electrolyte solutions is required.

Pre-warming the solution before use

Warming the solution to body temperature before use makes the contrast agent easier to inject and better tolerated (due to reduced viscosity). When using a thermostat, only the number of ampoules of contrast agent intended for use should be warmed to 37°C (98.6°F). It has been shown that when protected from sunlight, longer (but not more than 3 months) storage of the drug at this temperature does not affect its chemical composition.

Test doses

Evaluating sensitivity using a small test dose of contrast agent is not recommended, as this does not predict the occurrence of a reaction. Moreover, the sensitivity test itself sometimes leads to serious and even fatal hypersensitivity reactions.

Intravenous urography

Injection

The injection rate of the drug 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, the dose of the 76% solution is 20 ml, and 60% is 50 ml. Increasing the dose of the 76% solution to 50 ml significantly improves diagnostic accuracy. A further increase in dose is possible if necessary due to special indications.

In children, due to the reduced physiological concentrating capacity of the immature nephron, relatively high doses of Urographin 76% are required.

Timing of imaging

The renal parenchyma is best visualized if the image is taken immediately after the end of the contrast agent administration.

For visualization of the renal pelvis and urinary tract in adults, the first image is taken at 3-5 minutes, and the second at 10-12 minutes after the administration of the contrast agent, with the lower limit of the specified time range for young patients and the upper limit for elderly individuals.

In infants and young children, the first image is recommended to be taken as early as 2 minutes after the administration of the contrast agent. If the images are low in contrast, late images may be necessary.

Infusion

When performing Urographin infusion in adults and adolescents, the administration time for the 60% or 76% solution (100 ml) should usually be no less than 5 minutes and no more than 10 minutes. For patients with heart failure, the recommended infusion time is 20-30 minutes.

Timing of imaging

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

Angiography

In cases where a particularly high iodine concentration is important, for example, in aortography, angiocardiography, or coronary angiography, the 76% solution is preferred. The dose depends on age, body weight, cardiac output, general condition of the patient, clinical problem, examination technique, and the volume of the vascular area under study.

Retrograde urography

The use of a 30% solution is sufficient, which can be obtained by diluting the 60% Urographin solution with water for injections in a ratio of approximately 1:1. To avoid cold irritation causing ureteral spasms, it is recommended to warm the contrast agent to body temperature.

If increased contrast is required for special studies, undiluted Urographin 60% can also be used. Despite its high concentration, symptoms of irritation are observed in extremely rare cases.

Other body cavities

When performing arthrography, hysterosalpingography, and especially ERCP, the process of contrast agent administration must be controlled using fluoroscopy.

Adverse Reactions

Adverse effects are presented with the following frequency assessment: frequent (>1%); infrequent (<1%, but >0.1%), rare (<0.1%).

Intravascular use

Adverse effects associated with the intravascular use of iodine-containing contrast agents are usually mild, moderate, and transient. However, severe and life-threatening reactions have been described. The frequency of adverse reactions when using ionic contrast agents is 12%, and for non-ionic drugs it is 3%.

Frequent nausea, vomiting, pain sensations, and feeling of heat.

From the respiratory system frequent – transient changes in respiratory rate, dyspnea, respiratory failure, and cough; rare – respiratory arrest, pulmonary edema.

From the cardiovascular system infrequent – clinically significant transient changes in heart rate, blood pressure, arrhythmias; rare – dangerous thromboembolic complications leading to myocardial infarction.

From the digestive system frequent – nausea, vomiting; infrequent – abdominal pain.

From the CNS (during cerebral angiography and other studies where the contrast agent reaches the brain with arterial blood): infrequent – dizziness, headaches, agitation or impaired consciousness, amnesia, speech, vision, hearing impairment, convulsions, tremor, paresis/paralysis, photophobia, transient blindness, coma, drowsiness; rare – severe thromboembolic complications leading to stroke.

From the urinary system rare – impaired renal function up to renal failure.

Dermatological reactions frequent – facial flushing (associated with vasodilation), rash, itching, erythema; rare – Stevens-Johnson syndrome, Lyell’s syndrome.

Local reactions pain is observed mainly during peripheral angiography. With extravascular administration of Urographin – pain, swelling (usually disappear without further complications); extremely rare – inflammation, tissue necrosis; infrequent – thrombophlebitis and venous thrombosis.

Allergic reactions moderately pronounced angioneurotic edema, conjunctivitis, cough, skin itching, rhinitis, and urticaria (can occur regardless of dose, method of administration and may be the first symptoms of an anaphylactic reaction). The development of more severe reactions is possible, accompanied by peripheral vasodilation and subsequent arterial hypotension, reflex tachycardia, respiratory disturbances, agitation, impaired consciousness, cyanosis, loss of consciousness. Rarely – bronchospasm, laryngospasm.

Other feeling of heat and headache, infrequent – malaise, chills, increased sweating, fainting; rare – change in body temperature, salivary gland swelling.

Administration into body cavities

After administration into body cavities, adverse reactions develop rarely, more often several hours after administration due to slow absorption from the injection site and distribution in the body, controlled by the diffusion process.

During ERCP, an increase in amylase levels is usually observed. Visualization of acini during ERCP is associated with an increased risk of subsequent pancreatitis. In rare cases, necrotizing pancreatitis has been described.

Allergic reactions systemic reactions are rare and mild, mainly manifested as skin reactions. However, the possibility of developing severe hypersensitivity reactions cannot be completely ruled out.

Contraindications

• Severe hyperthyroidism;
• Decompensated heart failure.

Endoscopic retrograde cholangiopancreatography should not be performed in acute pancreatitis.

Hysterosalpingography should not be performed during pregnancy and in acute inflammatory processes in the pelvic cavity.

The drug should not be used for myelography, ventriculography, and cisternography due to possible neurotoxic phenomena.

Use in Pregnancy and Lactation

In vivo and in vitro studies have not revealed mutagenic, teratogenic, embryotoxic, or genotoxic effects of amidotrizoate.

There is insufficient evidence of the safety of Urographin use during pregnancy. Since in any case, exposure to radiation should be avoided during pregnancy, the benefit and risk of performing an X-ray examination without or with the use of a radiocontrast agent must be carefully weighed.

Contrast agents of the Urographin type, which are excreted by the kidneys, are excreted in breast milk in very small amounts. When using the drug during lactation (breastfeeding), the risk of toxic effects in infants is low (according to available data).

Use in Hepatic Impairment

It should be used with caution in severe liver function disorders.

Use in Renal Impairment

The drug should be used with caution in severe renal impairment.

Special Precautions

It should be used with caution in case of hypersensitivity to iodine-containing contrast agents, severe impairment of liver and kidney function, heart failure, pulmonary emphysema, severe general condition of the patient, cerebral vascular atherosclerosis, decompensated diabetes mellitus, cerebral vascular spasms, subclinical hyperthyroidism, nodular goiter, and generalized myeloma.

In vivo and in vitro studies have not revealed a carcinogenic effect of the drug.

The listed precautions should be observed for all types of administration, however, the risk of adverse events is higher with intravenous administration.

After the administration of radiocontrast agents (such as Urographin), hypersensitivity reactions may develop, manifested by difficulty breathing, erythema, urticaria, itching, or facial swelling. Severe reactions are possible: angioneurotic edema (including of the vocal cords), bronchospasm, and anaphylactic shock. These reactions usually occur within one hour after the administration of the contrast agent. However, in rare cases, delayed reactions (after several hours to days) may occur. Patients with a history of severe allergic reactions or reactions to iodine-containing contrast agents have an increased risk of developing severe reactions.

The frequency of adverse reactions is higher in patients with a burdened allergic history (e.g., allergic reactions to seafood, hay fever, urticaria), with hypersensitivity to iodine, and with bronchial asthma. In this regard, an allergic history should be carefully collected before the administration of the contrast agent. If there are indications of a tendency to allergies, the need for prophylactic use of antihistamines and/or corticosteroids should be considered.

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

Hypersensitivity reactions may be more pronounced in patients taking beta-blockers. It should also be taken into account that against the background of beta-blocker use, resistance to standard therapy for hypersensitivity reactions may occur.

If a hypersensitivity reaction develops, the administration of the contrast agent should be stopped immediately and, if necessary, appropriate therapy should be initiated. Therefore, medications and everything necessary for artificial ventilation should be prepared in advance in the examination room.

The small amount of inorganic iodine contained in the solution of the iodine-containing contrast agent may affect thyroid function. Therefore, the need for a radiocontrast examination should be especially carefully assessed in patients with latent hyperthyroidism or goiter.

There is an increased risk of developing pronounced reactions in individuals with severe heart disease (especially heart failure and coronary artery disease).

Elderly individuals often have pathological vascular changes and neurological disorders, which increases the risk of developing adverse reactions to iodine-containing contrast agents.

The need for a radiocontrast examination should be especially carefully weighed in patients in poor general condition.

Intravascular administration

In rare cases, renal failure may occur. To prevent acute renal failure when administering a contrast agent, the following precautions should be observed: identify patients at increased risk (e.g., with a history of kidney disease, pre-existing renal failure, previous renal failure after contrast agent administration, with diabetes mellitus accompanied by nephropathy, with multiple myeloma, over 60 years of age, with progressive vascular diseases, with paraproteinemia, with severe chronic arterial hypertension, with gout, or when high or repeated doses are to be administered). Patients at increased risk of developing renal failure should receive adequate hydration before drug administration (preferably by intravascular infusion before and after the study; such infusion should continue until the contrast agent is completely eliminated from the kidneys).

Until the contrast medium is completely eliminated, additional stress on the kidneys should be avoided, such as the use of nephrotoxic drugs, administration of oral cholecystographic agents, application of an arterial clamp, renal artery angioplasty, or major surgical intervention. A new radiographic contrast examination should be postponed until kidney function is fully restored.

In patients on dialysis, radiographic diagnostic examination with a contrast medium can be performed, as iodine-containing contrast media are eliminated from the body through dialysis.

Intravascular administration of a radiographic contrast medium (eliminated by the kidneys) may lead to transient impairment of renal function. As a result, patients taking biguanides may develop lactic acidosis (as a precaution, biguanide intake should be discontinued 48 hours before and 48 hours after the radiographic contrast examination).

In patients with heart valve disease and pulmonary hypertension, administration of the contrast medium may lead to significant hemodynamic changes. In elderly patients and those with a history of heart disease, ischemic ECG changes and arrhythmias occur more frequently. In heart failure, intravascular administration of the contrast medium may cause pulmonary edema.

Intravascular administration of the contrast medium should be performed with particular caution in patients with acute cerebral infarction, acute intracranial hemorrhage, and other conditions accompanied by disruption of the blood-brain barrier integrity, cerebral edema, or acute demyelination. The incidence of seizures after administration of an iodine-containing contrast medium is higher in patients with intracranial tumors or metastases and with a history of epilepsy. Administration of the contrast medium may promote the appearance of neurological symptoms in cerebrovascular diseases, presence of intracranial tumors or metastases, degenerative or inflammatory diseases of the central nervous system. Intra-arterial administration of the contrast medium may lead to vascular spasm and subsequent cerebral ischemia. The risk of neurological complications is higher in patients with cerebrovascular diseases, a recent history of stroke, or frequent transient ischemic attacks.

In severe renal insufficiency, concomitant severe hepatic impairment may significantly slow the excretion of the contrast medium and necessitate hemodialysis.

Multiple myeloma or paraproteinemia may contribute to renal impairment upon administration of the contrast medium. In this case, particular attention should be paid to adequate hydration.

In patients with pheochromocytoma, due to the risk of a vascular crisis, preliminary administration of alpha-adrenergic blockers is recommended.

In patients with autoimmune disorders, cases of severe vasculitis or a syndrome similar to Stevens-Johnson syndrome may occur.

Administration of an iodine-containing contrast medium may exacerbate symptoms of myasthenia gravis.

Acute or chronic alcoholism may increase the permeability of the blood-brain barrier. This facilitates the penetration of the contrast medium into the brain tissue and may lead to CNS reactions. Particular caution should be exercised in patients with chronic alcoholism and individuals taking drugs, due to a possible lowering of the seizure threshold.

Ionic iodine-containing contrast media inhibit the blood coagulation system in vitro more strongly than non-ionic contrast media. Nevertheless, medical personnel should frequently flush the catheter with physiological saline (if possible, with the addition of heparin) during vascular catheterization and angiography and minimize the duration of the procedure to reduce the risk of thrombosis and embolism to a minimum.

According to available information, using plastic syringes instead of glass ones reduces, but does not completely eliminate, blood clotting in vitro. Caution should be exercised in patients with homocystinuria as they have an increased risk of thrombosis and embolism.

Administration into body cavities

Possible pregnancy should be ruled out before performing hysterosalpingography. The risk of adverse reactions during cholangiography, ERCP, or hysterosalpingography increases in the presence of inflammation of the bile ducts or fallopian tubes.

Effect on ability to drive and operate machinery

Delayed reactions to the intravascular administration of iodine-containing contrast media are rare. However, driving a car or operating machinery is not recommended for the first 24 hours after the examination.

Overdose

In case of accidental overdose or significant impairment of renal function, Urographin can be removed from the body by extracorporeal dialysis.

Drug Interactions

Iodine-containing radiographic contrast media eliminated by the kidneys reduce the ability of thyroid tissue to accumulate radioisotopes in diagnostic thyroid studies. This reduction may last up to 2 weeks (in some cases – longer).

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

The frequency of delayed adverse effects (fever, urticaria, flu-like symptoms, joint pain, itching) with the use of contrast media is higher in patients who have received antipsychotics.

Storage Conditions

The drug should be stored in a place protected from light and X-rays, out of the reach of children, at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.