Use of the drug Trazograph
2 days before the examination, the patient should avoid eating foods that can cause flatulence (legumes, salads, coarse black or freshly baked bread, milk and vegetables). The patient should not eat after 6 pm the day before or on the day of the examination. In the evening, a cleansing enema is performed; if necessary, a laxative is prescribed 2 days before the examination. On the day of the examination, the patient must fast. In bedridden patients, gases should be removed from the stomach and intestines. For intravenous urography in adult patients, the dose is 1-1.5 ml per 1 kg of body weight, for angiocoronary angiography - an average of 30-60 ml for the drug Trazograph 76% and 20-60 ml for the drug Trazograph 60%. The recommended average duration of administration is 2–3 minutes. The first x-ray examination is carried out 3–5 minutes, and the second – 10–12 minutes after infusion. For infants and young children, the dose is 2–3 ml per 1 kg of body weight. The average dose is 8 ml; the maximum dose, as a rule, should not exceed 20 ml. The first study is carried out 2-3 minutes after infusion. In patients with impaired renal function, the study is carried out after 30–40 minutes or later.
Trazograph 76% 20 ml No. 5 injection solution
Compound
active ingredients for 76%:
meglumine salt of diatrizoic acid, sodium salt of diatrizoic acid
1 ml of megluminic salt of diatrizoic acid 660 mg, sodium salt of diatrizoic acid 100 mg (which corresponds to a total iodine content of 370 mg)
excipients for 76%:
sodium calcium edetate, dihydrate; water for injections.
Dosage form
Injection.
Basic physical and chemical properties:
transparent, colorless or light yellow, slightly viscous liquid.
Pharmacotherapeutic group
Water-soluble high-osmolar nephrotropic radiocontrast agents.
ATX code V08A A01.
Pharmacodynamics
X-ray contrast agent Trazograph® 76% is a salt of amidotrizoic acid, which contains bound iodine, which absorbs x-rays.
Pharmacokinetics
Distribution
After administration, the amount of the drug that binds to blood plasma proteins does not exceed 10%.
5 minutes after intravenous administration of the drug Trazograph® 60% at a dose of 1 ml/kg body weight, a concentration in the blood plasma is achieved, which corresponds to 2-3 g of iodine per 1 liter. Within 3 hours after administration, a relatively rapid decrease in concentration is observed during the first 30 minutes, then a gradual decrease with a half-life of 1-2 hours.
Diatrizoic acid does not penetrate red blood cells; after intravascular administration, it is very quickly distributed in the intercellular substance, but does not penetrate the intact blood-brain barrier. The drug passes into breast milk only in minimal quantities.
Metabolism and Elimination
When administered in diagnostic doses, diatrizoic acid 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; no metabolites were detected.
The kinetic properties of distribution and excretion from the body of the drug Trazograph® did not depend on the dose within the clinically significant range. This means that when a double dose or half a dose is administered, the level of the drug in the blood and the amount of contrast agent excreted from the body, in grams/unit of time, will double or decrease respectively. However, due to the increase in osmotic diuresis with a double dose, the concentration of contrast agent in the urine does not increase to the same extent.
Patient characteristics
In patients with reduced renal function, amidotrizoate can also be eliminated extrarenally through the liver, although at a significantly reduced rate. Contrast agents are eliminated by the kidneys and can be easily removed from the body by extracorporeal hemodialysis. Regardless of the injection site, complete elimination occurs within a short period of time, even from tissues.
Indications
Intravenous and retrograde urography.
In addition, angiography, as well as arthrography, intraoperative cholangiography, endoscopic retrograde cholangiopancreatography (ERCP), sialography, fistulography, hysterosalpingography and other studies.
Contraindications
Hypersensitivity to the components of the drug, iodine-containing contrast agents. Existing hyperthyroidism, decompensated heart failure, severe renal and liver failure, active tuberculosis and pulmonary emphysema; myocardial damage (arrhythmia, ventricular fibrillation) severe arterial hypertension; shock and collapse; acute forms of phlebitis; epilepsy; significant increase in prothrombin index.
Trazograph® 60%, Trazograph® 76% cannot be used for myelography, ventriculography and cisternography due to the possible provocation of neurotoxic phenomena (pain, convulsions and coma, often fatal) during these studies.
Trazograph® 60% is not suitable for selective coronary angiography.
During pregnancy. In case of acute inflammatory processes in the pelvic cavity, hysterosalpingography cannot be performed.
Endoscopic retrograde cholangiopancreatography (ERCP) is contraindicated in acute pancreatitis.
Interaction with other drugs and other types of interactions
In patients suffering from diabetic nephropathy and taking biguanides, lactic acidosis may develop when a contrast agent is administered. To prevent this complication, you must stop taking biguanides 48 hours before the procedure. Before resuming the use of biguanides, ensure that there is no impairment of renal function.
Hypersensitivity reactions may be more severe in patients taking beta-blockers.
Patients taking antipsychotics are more likely to experience delayed reactions (eg, fever, rash, itching, joint pain) and flu-like symptoms.
The incidence of delayed reactions (eg, fever, rash, flu-like symptoms, joint pain and itching) is higher in patients taking interleukin.
Interaction with diagnostic tests
After intravascular administration of iodinated contrast agents, the ability of thyroid tissue to absorb radioisotopes for the diagnosis of thyroid diseases is reduced for a period of up to 2 weeks, and in some cases even for a longer period.
Features of application
Two days before the examination, the patient should avoid eating foods that contribute to bloating, especially legumes, salads, coarse black or freshly baked bread, milk and all vegetables. On the eve of the examination, the patient should not eat after 6 pm. In the evening, the intestines should be thoroughly emptied; if necessary, a laxative should be taken the last two days before the examination. On the day of the examination, the patient should fast. In bedridden patients, gases should be removed from the stomach and intestines.
Since anxiety, fear and pain can cause side effects or increase the reaction to the contrast agent, it is recommended to reassure the patient before the study or prescribe appropriate therapy.
Before administering Trazograph® 60%, Trazograph® 76%, it is necessary to normalize the patient’s water and electrolyte balance. This is especially important for patients with multiple myeloma, patients with decompensated diabetes mellitus, with polyuria, oliguria or gout, and elderly people who cannot limit their fluid intake before the study.
If the thyroid gland is being examined, you need to take iodine for several days, and sometimes for 2 weeks.
The following warnings and precautions apply to any route of administration, but the risk of the following situations is greater with intravascular administration.
- Hypersensitivity
From time to time, after the use of radiopaque agents such as Trazograph® 60% and Trazograph® 76%, hypersensitivity reactions are observed (see Section “Adverse Reactions”). They are usually characterized by non-serious respiratory or skin symptoms, such as mild respiratory distress, redness of the skin (erythema), urticaria, itching or swelling of the face. Serious adverse reactions may occur, such as angioedema, subchordal edema, bronchospasm and anaphylactic shock. Typically, such reactions are observed within 1 hour after administration of the contrast agent. However, in rare cases, delayed reactions (several hours or days after administration) are possible.
Patients with hypersensitivity or a previous reaction to radiocontrast agents containing iodine are at increased risk of a serious complication.
Before administering any contrast agent, the patient's history of allergic reactions (eg, seafood allergy, hay fever, urticaria), iodine sensitivity or radiographic contrast agents, and asthma should be ascertained, as serious reactions to contrast agents have been reported to be more common in patients with these conditions and premedication with antihistamines and/or corticosteroids can be used.
Patients with bronchial asthma are at particular risk of bronchospasm or hypersensitivity reactions.
Hypersensitivity reactions may be exacerbated in patients taking beta blockers, especially in the presence of bronchial asthma. In addition, it must be taken into account that patients taking beta-blockers may be refractory to standard beta-agonist therapy for hypersensitivity reactions.
If hypersensitivity reactions are observed (see section "Adverse Reactions"), the administration of the contrast agent should be stopped immediately and, if necessary, specific therapy should be administered intravenously. Therefore, it is recommended to use flexible indwelling cannulas (catheters) for intravenous administration of contrast media. In order to immediately begin emergency measures, emergency supplies (appropriate medications, endotracheal intubation tube and respirator) must always be ready.
- Thyroid dysfunction
Small amounts of free inorganic iodide from iodinated contrast media may interfere with thyroid function. Therefore, it is necessary to take a particularly careful approach to conducting research in patients with latent hyperthyroidism or goiter, despite the possible risk.
- Cardiovascular diseases
There is an increased risk of serious reactions in people with severe heart disease, and especially in patients with heart failure and coronary artery disease.
- Elderly patients
Vascular pathologies and neurological disorders, often observed in older people, constitute an increased risk of adverse reactions to iodinated contrast agents.
- General serious health condition
Particular care must be taken when conducting the study in patients with very poor general health, despite the possible risk.
Intravascular administration
- Kidney failure
In rare cases, temporary renal failure may occur. Precautions to prevent acute renal failure after administration of contrast media include:
- identification of high-risk patients, e.g. patients with a history of kidney disease, renal failure, renal failure after contrast agent administration, diabetes mellitus with nephropathy, volume depletion, multiple myeloma, people over 60 years of age, advanced stage patients vascular diseases, paraproteinemia, severe and chronic hypertension, gout, patients receiving large or repeated doses of the drug;
- ensure appropriate hydration in patients at risk before administration of contrast material, preferably by maintaining infusion before and after the procedure and to ensure that the contrast material is eliminated by the kidneys;
- avoiding additional load on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, artery clamping, renal arterial angioplasty, radical surgery to remove the contrast agent;
- postponing the date of a new study using a contrast agent until renal function indicators return to previous levels.
Hemodialysis patients may receive contrast agents for radiological procedures because iodine-containing substances are eliminated during dialysis.
- Metformin therapy
The use of intravenous radiocontrast agents, excreted by the kidneys, can lead to transient impairment of renal function. It may lead to lactic acidosis in patients taking biguanides.
In order to prevent complications, the use of biguanides should be discontinued 48 hours before the administration of a contrast agent and for at least 48 hours after it. It can be restored only after kidney function returns to normal.
- Cardiovascular diseases
In patients with valvular heart disease and pulmonary hypertension, the administration of a contrast agent can lead to pronounced hemodynamic changes. Reactions including ischemic ECG changes and severe arrhythmias are more common in the elderly and in patients with a history of heart disease.
Administration of contrast media may result in pulmonary edema in patients with heart failure.
- CNS disorders
Particular attention should be paid when administering contrast media to patients with acute ischemic stroke, acute intracranial hemorrhage, and other conditions involving blood-brain barrier damage, cerebral edema, or acute demyelination. Intracranial tumors or metastases and a history of epilepsy may increase the incidence of seizures after administration of iodinated contrast media.
When a contrast agent is administered, neurological symptoms may worsen through cerebrovascular disease, intracranial tumors or metastases, degenerative or inflammatory pathologies. Vasospasm and, as a consequence, cerebral ischemia can be caused by intra-arterial administration of a contrast agent. Patients with symptomatic cerebrovascular disease, recent stroke, or frequent transient ischemic attacks are at increased risk for neurological complications.
- Severe liver dysfunction
In cases of severe renal failure, the concomitant presence of severe liver dysfunction may significantly delay the clearance of the contrast agent, possibly requiring hemodialysis.
- Myeloma and paraproteinemia
Myeloma or paraproteinemia may create conditions for the development of renal failure after administration of a contrast agent. Adequate hydration is mandatory.
- Pheochromocytoma
Patients with pheochromocytoma may develop a severe hypertensive crisis (sometimes beyond control) after intravenous contrast agent administration. Premedication with alpha-receptor blockers is recommended.
- Patients with autoimmune disorders
Cases of severe vasculitis or Stevens-Johnson syndrome-like syndromes have been reported in patients with a history of autoimmune disorders.
- Bulbospinal palsy (myasthenia gravis)
Administration of iodinated contrast agents may worsen the symptoms of bulbospinal palsy.
- Alcoholism
Acute or chronic alcoholism can increase the permeability of the blood-brain barrier. This facilitates the passage of the contrast agent into the brain tissue, which can lead to CNS reactions. Particular attention should be paid to patients with alcohol and drug dependence due to the possibility of a reduced threshold for seizure activity.
- Coagulation
Ionic iodinated contrast agents have greater anticoagulant activity in vitro than non-ionic contrast agents. However, medical personnel performing vascular catheterization should take into account that in addition to the contrast agent, numerous factors can contribute to the development of thromboembolic phenomena, including the duration of the procedure, the number of injections, the material from which the catheter and syringe are made, the state of the underlying disease and the concomitant drug. Therefore, when performing a vascular catheterization procedure, care should be taken to monitor angiographic technique, frequently flush the catheter with saline (if possible, with the addition of heparin), and reduce the duration of the procedure to minimize the risk of procedure-related thrombosis and embolism.
The use of plastic syringes instead of glass has been reported to reduce, but not eliminate, the likelihood of in vitro blood clotting.
It is recommended to pay special attention to patients with homocystinuria, due to the increased risk of thrombosis and embolism.
Use with caution in patients with sickle cell anemia.
Introduction to body cavities
Before performing hysterosalpingography, it is necessary to exclude the possibility of pregnancy.
Inflammation of the bile ducts and fallopian tubes may increase the risk of reactions after cholangiography, ERCP and hysterosalpingography procedures.
The drug should not be used for myelography, ventriculography or cisternography, since neurotoxic phenomena may occur during these studies.
Instructions for use
Trazograph® 60% and Trazograph® 76%, ready for research, are a colorless or light 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. The rubber stopper of the bottle can be pierced only once to prevent large quantities of microparticles from getting into the solution from the stopper.
Any remaining contrast agent that was not used during the study should no longer be used.
The ability to influence reaction speed when driving a vehicle or operating machinery
After administration of the drug, in rare cases, a slowdown in psychomotor reactions is possible. You should avoid driving vehicles and other machinery for 24 hours after administration of the drug.
Use during pregnancy or breastfeeding
The safety of using Trazograph® 60%, Trazograph® 76% in pregnant patients has not been proven. Therefore, radiation exposure should be avoided during pregnancy, carefully weighing the benefits of any radiographic examination (with or without contrast) against the possible risks.
Breastfeeding.
Contrast agents like Trazograph® 60%, Trazograph® 76%, excreted from the body by the kidneys, pass into breast milk in very small quantities, the likelihood of causing harm to the baby is low, however, before prescribing the drug during breastfeeding, the possible danger to the baby must be taken into account.
Directions for use and doses
General rules
- Diet tips
To facilitate diagnosis, abdominal angiography and urography are recommended when the bowels are empty. Despite this, for two days before the examination you should avoid foods that cause flatulence, in particular legumes, salads, fruits, black and fresh bread, as well as any raw vegetables. The last meal should be no later than 18:00 in the evening before the examination day. It is also advisable to take a laxative in the evening. However, newborns and children should not have a long interval between meals, and they should not be given laxatives.
- Hydration
Adequate hydration must be ensured before and after intravascular and intrathecal administration of contrast media. This especially applies to patients with multiple myeloma, diabetes mellitus, accompanied by nephropathy, polyuria, oliguria, hyperuricemia, as well as newborns, infants and young children and elderly patients. If there are violations, correction of the water and electrolyte balance is necessary before the examination.
Newborns and young children (from 1 month to 2 years).
Children under 1 year of age and especially newborns are susceptible to electrolyte imbalance and hemodynamic changes. The dose of contrast agent to be administered, the technical execution of the radiological procedure and the condition of the patient should be carefully calculated.
- State of concern
Severe states of agitation, anxiety and pain may increase the risk of side effects and increase the body's reactions associated with the administration of a contrast agent. It is recommended that these patients be prescribed sedatives.
- Tolerance test
It is not recommended to conduct preliminary testing of individual sensitivity using small doses of the drug due to the lack of prognostic significance and the risk of developing severe hypersensitivity reactions.
- Warm up before use
Contrast agents warmed to body temperature before use are better tolerated and easier to administer due to reduced viscosity. Using a thermostat, heat the calculated number of ampoules required exclusively for examinations for 1 day to 37 °C. Provided that the product is protected from daylight, the chemical purity does not change. However, the period should not exceed three months.
Dosage for intravascular administration
It is advisable to carry out intravascular administration of a contrast agent while the patient is in a supine position. After its administration, it is necessary to monitor the patient for at least 30 minutes, since most adverse reactions occur during this period.
The dosage may vary depending on the age, body weight, cardiac output and general condition of the patient.
For patients with severe renal or heart failure and for patients with severe general condition, the lowest possible dose of contrast agent should be used. In such patients, it is recommended to monitor renal function for at least 3 days after drug administration.
Between individual injections, it is necessary to provide the body with sufficient time for the outflow of interstitial fluid in order to compensate for the increase in plasma osmolality. To achieve this in adequately hydrated patients, the required period is 10-15 minutes. If it is necessary in some cases to exceed the total dose of 300-350 ml of contrast agent per study, adults are advised to administer additional water and possibly electrolytes.
Recommended Doses
Intravenous urography
- Injection
Trazograph® 76% and 60% are equally suitable for intravenous urography.
The intravascular injection rate is usually 20 ml/min. For patients with heart failure who are prescribed a dose of 100 ml or more, administration over at least 20-30 minutes is recommended.
Dosages.
For adults
The dose of Trazograph® 76% is 20 ml, Trazograph® 60% is 50 ml. Increasing the dose of Trazograph® 76% to 50 ml significantly increases the likelihood of a more accurate diagnosis. Its further increase is possible if necessary due to special indications.
For children
Due to the reduced physiological concentration capacity of the still immature nephron of the kidneys, children require relatively high doses of Trazograph® 76%:
children under 1 year - 7-10 ml;
at the age of 1 to 2 years - 10-12 ml
aged 2 to 6 years – 12-15 ml
aged 6 to 12 years – 15-20 ml
over 12 years old - as for adults.
Snapshot time
The best contrast image of the renal parenchyma can be obtained if the image is taken immediately after the end of the administration of the contrast agent.
To visualize the renal pelvis and urinary tract, the first image should be taken 3-5 minutes, and the second - 10-12 minutes after administration of the contrast agent, and for young patients one should focus on the lower limit, and for elderly patients - the upper limit of the specified period of time .
For newborns and infants and young children, it is recommended to take the first image within 2 minutes after the administration of the contrast agent. If the images appear to have low contrast, it may be necessary to take later photographs.
Angiography
Trazograph® can also be used for angiographic studies. The use of a 76% solution is preferred in cases where a particularly high iodine concentration is important, for example for aortography, angiocardiography or coronary angiography. The dose should be set depending on the diagnostic task, research technique, nature and volume of the vascular area being examined.
Introduction to body cavities
Retrograde urography
You can use Trazograph® 60%. Despite its high concentration, symptoms of irritation are extremely rare. To avoid the effect of a lower temperature solution leading to ureteral spasms, it is recommended to warm the contrast agent to body temperature.
Other body cavities
When performing arthrography, hysterosalpingography and especially ERCP, contrast injections should be carried out under fluoroscopic control.
Children
Due to the reduced physiological concentration capacity of the still immature nephron, relatively high doses of the drug are required in children. Therefore, children should mainly use Trazograph® 76%.
Infants (<1 year of age), and especially newborns, are sensitive to fluid and electrolyte imbalances and hemodynamic disturbances. The dose of contrast agent to be administered should be carefully calculated, the radiological procedure should be carried out carefully and the patient's condition should be taken into account.
Overdose
In case of overdose, the manifestations of adverse reactions may increase.
In case of accidental overdose with intravascular administration, the loss of water and electrolytes must be compensated by infusion. Renal function requires monitoring for at least the next three days.
If necessary, hemodialysis can be used to remove the bulk of the contrast agent from the patient's circulatory system.
Adverse reactions
From the heart:
abnormal heart rate, cardiac arrhythmia; tachycardia, including reflex; bradycardia cyanosis; cardiac dysfunction; transient ECG changes; ventricular fibrillation; asystole; heart failure; severe thromboembolic events leading to myocardial infarction.
From the side of blood vessels:
circulatory disorders, accompanied by peripheral vasodilation and subsequent hypotension, collapse, hot flashes, possibly increased blood pressure, vasculitis.
From the blood and lymphatic system:
inhibition of blood coagulation and platelet aggregation, disseminated intravascular coagulation, thrombocytopenia, hemolysis, platelet microangiopathy.
From the endocrine system:
hyperthyroidism.
From the nervous system:
dizziness, headache, agitation, amnesia, subchordal edema, increased symptoms of myasthenia gravis, speech impairment, visual impairment, hearing impairment, photophobia, temporary loss of vision, tremor/shivering, convulsions, epileptic seizures, coma, disorientation, drowsiness, paresis/paralysis, confusion, loss of consciousness, severe thromboembolic events leading to stroke.
From the urinary system:
impaired renal function, reversible renal failure (including acute).
From the immune system:
anaphylactic/hypersensitivity reactions, including anaphylactic shock, angioedema, conjunctivitis, increased lacrimation, cough, rhinitis, sneezing.
From the skin and subcutaneous tissue:
skin rash, itching, redness/erythema with vasodilation, pale skin, urticaria, skin reactions, including Stevens-Johnson syndrome, Lyell's syndrome.
From the respiratory system:
transient disturbance of respiratory rate, shortness of breath, respiratory distress, cough, bronchospasm, laryngeal spasm/edema, respiratory arrest, pulmonary edema.
From the gastrointestinal tract:
nausea, vomiting, abdominal pain, metallic taste in the mouth.
Common disorders:
feeling of heat, weakness, malaise, fever, vasovagal reactions, sweating, increased body temperature, swelling of the salivary glands.
Local reactions:
changes at the injection site, including pain, swelling, inflammation, possible development of phlebitis and thrombosis; if the drug flows paravasally, increased pain, swelling, tissue necrosis.
With intravascular administration
Adverse effects associated with intravascular administration of iodinated contrast agents are usually mild to moderate in severity and transient in nature. However, severe, life-threatening and fatal reactions have been reported. The prevalence of adverse reactions in patients treated with ionic contrast agents was found to be more than 12% compared to more than 3% in the case of non-ionic contrast agents.
Most often, with intravascular use, reactions such as nausea, vomiting, pain and a general feeling of heat are observed.
When introduced into other body cavities
After administration of a contrast agent into body cavities, adverse reactions rarely occur. Most of them develop within a few hours after administration due to slow absorption from the injection site and distribution throughout the body, mainly through a controlled process of diffusion.
After ERCP (endoscopic retrograde cholangiopancreatography), a slight increase in amylase levels is common. Acinar contrast imaging has been shown to be associated with an increased risk of developing pancreatitis after ERCP. Isolated cases of necrotizing pancreatitis have been described.
Cases of vasovagal reactions associated with hysterosalpingosis are uncommon.
Anaphylactic reactions/hypersensitivity
Systemic hypersensitivity is rare, mostly mild, and usually occurs in the form of reactions. However, the possibility of developing a severe hypersensitivity reaction cannot be completely excluded. For a complete description of anaphylactic reactions, see the relevant information in the sections “On the side of the immune system”, “On the side of blood vessels”, “On the side of the respiratory system”.
Best before date
5 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Protect from light and secondary x-rays. Keep out of the reach of children. Do not freeze.
Package
Contrast agents should not be mixed with other medications to avoid possible incompatibility.
Vacation category
20 ml of the drug in an ampoule, 5 ampoules packed on a tray with Thermocol. One tray per cardboard box.
(branch).
Manufacturer's location and address of place of business
Plot No. 4, Phase - IV, G. Ay. Di. Si. Industrial Estate, Panoli Town - 394116, Bharuch District, India.
© Translation into Russian by the editorial team of apteka24.ua.
Source: “State register of medicinal facilities of Ukraine”, 2020.
Contraindications to the use of the drug Trazograph
Absolute - severe forms of hyperthyroidism, decompensated heart failure, intolerance to iodine-containing drugs, severe renal and liver failure, active tuberculosis and emphysema, myocardial diseases, severe hypertension (arterial hypertension), shock and collapse, acute phlebitis (for phlebography). Relative - cerebral atherosclerosis, decompensated diabetes mellitus, increased blood clotting, mild forms of nodular goiter, plasmacytoma, pregnancy, severe general condition of the patient.
