Iohexol-yuf
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IOHEXOL-UF
Composition:
Active substance: iohexol;
1 ml of solution contains iohexol 755 mg (equivalent to 350 mg of iodine);
Excipients: sodium calcium edetate, tromethamine, hydrochloric acid concentrated*, sodium hydroxide*, water for injections.
* pH adjusters.
Pharmaceutical form. Injection solution.
Main physicochemical properties: clear, colourless or slightly yellow solution.
Pharmacotherapeutic group. Iodine-containing X-ray contrast agents. Water-soluble, low-osmolar, non-ionic contrast agents. Iohexol. ATC code V08AB02.
Pharmacological Properties
Pharmacodynamics
Iohexol is a non-ionic, monomeric, tri-iodinated, water-soluble X-ray contrast agent.
In studies conducted in healthy volunteers, intravenous administration of iohexol did not result in significant alterations in most hemodynamic, clinical-biochemical, or coagulation parameters. Changes in some laboratory parameters were minor and are not considered clinically significant.
Pharmacokinetics
Distribution
Protein binding of the drug Iohexol-YUF with plasma proteins is so low (less than 2%) that it is not clinically significant and therefore may be disregarded.
Biotransformation
Metabolites of the drug have not been identified.
Excretion
Approximately 100% of iohexol administered intravenously is excreted unchanged by the kidneys within 24 hours in patients with normal renal function. The elimination half-life of the drug in patients with normal renal function is 2 hours.
Preclinical Safety Data
Iohexol has very low toxicity following intravenous administration in mice and rats. Animal studies have shown that iohexol has very low plasma protein binding and is effectively excreted by the kidneys. Toxicity to the cardiovascular and nervous systems is low.
Clinical Characteristics
Indications
Yohexol-YUF is intended solely for diagnostic procedures.
A radiopaque agent for use in children and adults for angiography, urography, phlebography, and contrast enhancement in computed tomography (CT).
Subarachnoid administration for lumbar, thoracic, and cervical myelography and CT of basal cisterns.
Arthrography, endoscopic retrograde pancreatography (ERP), endoscopic retrograde cholangiopancreatography (ERCP), herniography, hysterosalpingography, sialography, and gastrointestinal tract imaging.
Contraindications
Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
Severe thyrotoxicosis.
Special Precautions
Yohexol-YUF, like all parenteral preparations, should be inspected visually for particulate matter, discoloration, and integrity of packaging before administration. The solution should be drawn into a syringe immediately before use. Vials are intended for single use only.
Any unused medicinal product or waste material resulting from its use must be disposed of in accordance with local requirements.
Additional instructions for auto-injector/pump:
500 ml vials of contrast agent should only be used with auto-injectors/pumps designed for this volume. The vial should be punctured only once. The catheter connecting the auto-injector/pump to the patient must be replaced after each use.
Unused contrast agent remaining in the vial and in connecting tubing should be discarded at the end of the working day. Smaller vials may be used if necessary. The manufacturer's instructions for the auto-injector/pump must be followed during use.
Interaction with Other Medicinal Products and Other Forms of Interaction
The use of iodine-containing contrast agents in diabetic patients receiving metformin may lead to reversible renal impairment and lactic acidosis (see section "Special Warnings and Precautions for Use").
Patients who have received interleukin-2 or interferons within less than two weeks prior to the examination may be prone to delayed adverse reactions (erythema, influenza-like symptoms, or skin reactions).
Concomitant use of certain neuroleptics or tricyclic antidepressants may lower the seizure threshold and thus increase the risk of seizures associated with contrast agents.
Concurrent use of contrast agents with beta-blockers may reduce the threshold for hypersensitivity reactions and may require higher doses of beta-agonists in the treatment of such reactions.
Beta-blockers, vasoactive substances, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor antagonists may impair cardiovascular compensatory mechanisms regulating blood pressure changes.
All iodine-containing contrast agents may interfere with diagnostic tests assessing thyroid function; thus, the thyroid gland's ability to bind iodine may be reduced for several weeks.
High concentrations of contrast agents in blood serum and urine may affect laboratory test results for bilirubin, proteins, and inorganic compounds (e.g., iron, copper, calcium, phosphates); therefore, laboratory tests should not be performed on the day of examination.
Special precautions for use
General characteristics of non-ionic monomeric contrast agents
Hypersensitivity
A history of allergy, asthma, or adverse reactions to iodine-containing contrast agents requires increased attention. Therefore, a detailed medical history should be obtained before administering contrast agents. Patients with known hypersensitivity reactions in their history should receive contrast agents only when absolutely indicated.
Patients at risk of contrast agent intolerance may be premedicated with corticosteroids or H1- and H2-histamine receptor antagonists; however, these do not prevent anaphylactic shock and may mask its initial symptoms.
Patients with bronchial asthma have an increased risk of bronchospasm.
The risk of severe adverse reactions to the contrast agent Iohexol-YUF is very low. However, iodine-containing contrast agents may cause life-threatening, fatal anaphylactic/anaphylactoid reactions or other manifestations of hypersensitivity. Regardless of the amount or route of administration, symptoms such as angioedema, conjunctivitis, cough, pruritus, rhinitis, sneezing, and urticaria may indicate a serious anaphylactoid reaction requiring treatment. For this reason, necessary medications, equipment, and qualified medical personnel for immediate assistance should be available in advance in case of a serious adverse reaction. If shock develops, administration of the contrast agent must be stopped immediately and, if necessary, specific intravenous therapy initiated. It is recommended to use a permanent cannula or catheter to ensure rapid intravenous access during radiographic contrast procedures.
Patients receiving beta-blockers, especially those with asthma, may have a lower threshold for bronchospasm and may be less responsive to treatment with beta-agonists and epinephrine, possibly requiring higher doses. In such patients, atypical manifestations of anaphylaxis may occur, which could be mistakenly interpreted as vagal reactions.
Hypersensitivity reactions usually present as mild respiratory or skin symptoms such as slightly labored breathing, skin redness (erythema), urticaria, pruritus, or facial swelling. Severe reactions such as angioedema, subglottic edema, bronchospasm, and shock are rare. These reactions usually occur within one hour after administration of the contrast agent. In rare cases, hypersensitivity may be delayed (after several hours or days), although such delayed hypersensitivity reactions rarely threaten life and mainly affect the skin.
Patient monitoring
The patient should be under close observation for 30 minutes after the last administration of the contrast agent, as most adverse reactions occur during this period.
Coagulopathy
Serious, rarely fatal, thromboembolic complications leading to myocardial infarction and stroke have been reported during angiocardiographic procedures using both ionic and non-ionic contrast agents. During vascular catheterization procedures, strict adherence to angiographic techniques and frequent catheter flushing (e.g., with 0.9% sodium chloride solution containing heparin) are essential to minimize the risk of procedure-related thrombosis and embolism.
During catheterization, it should be considered that, in addition to the contrast agent, other factors may contribute to thromboembolic complications, such as duration of the procedure, number of injections, catheter type and syringe material, underlying diseases, and concomitant medication use.
The examination procedure should be as short as possible.
Patients with homocystinuria (risk of thromboembolism) should be monitored carefully.
In contrast to ionic contrast agents, non-ionic contrast agents exhibit a weaker in vitro inhibitory effect on coagulation.
Hydration
Adequate hydration of the patient should be ensured before and after administration of the contrast agent. If necessary, hydration should be administered intravenously until complete elimination of the contrast agent from the body.
This is particularly important for patients with dys- or paraproteinemia, multiple myeloma, diabetes mellitus, impaired renal function, hyperuricemia, as well as infants, young children, elderly patients, and patients in poor general condition.
In patients at risk, fluid and electrolyte balance should be monitored, and symptoms of decreased serum calcium levels should be observed.
Due to the risk of diuretic-induced dehydration, fluid and electrolyte rehydration should be performed initially to prevent the risk of acute kidney injury.
Patients at risk of developing thyrotoxicosis should be carefully evaluated before any administration of iodine-containing contrast agents.
Newborns whose mothers received iodine-containing contrast agents during pregnancy should have their thyroid function tested within the first week of life.
Cardiovascular system reactions
The agent should be used with caution in patients with severe cardiovascular diseases and pulmonary hypertension due to the risk of arrhythmia or hemodynamic disturbances, especially during intracoronary, left or right ventricular administration of contrast agents (see section "Adverse reactions").
Patients particularly susceptible to cardiac complications include those with heart failure, severe ischemic heart disease, unstable angina, valvular diseases, history of myocardial infarction, coronary bypass surgery, and pulmonary hypertension.
Reactions with ischemic ECG changes and arrhythmias occur more frequently in elderly patients and those with a history of heart disease.
In patients with heart failure, intravascular administration of contrast agents may cause pulmonary edema.
CNS disorders
Patients with acute cerebral pathology, brain tumors, and epilepsy are prone to seizures and require special attention. An increased risk of seizures and neurological reactions is observed in alcohol- and drug-dependent patients.
Cases of encephalopathy have been reported following administration of contrast agents such as iohexol (see section "Ad游戏副本 reactions"). Contrast-induced encephalopathy may manifest with symptoms and signs of neurological dysfunction such as headache, visual disturbances, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, loss of consciousness, coma, and cerebral edema. Symptoms usually appear within minutes or hours after iohexol administration and typically resolve within several days.
Factors that increase blood-brain barrier permeability facilitate the transfer of contrast agents into brain tissue and may lead to possible CNS reactions, such as encephalopathy.
The agent should be used cautiously in patients with acute ischemic stroke or acute intracranial hemorrhage, as well as in patients with conditions involving blood-brain barrier disruption, cerebral edema, acute demyelination, or progressive cerebral atherosclerosis. If contrast-induced encephalopathy is suspected, iohexol administration should be discontinued and appropriate treatment initiated.
Neurological symptoms caused by metastases, degenerative, or inflammatory processes may be exacerbated by the use of contrast agents.
Patients with symptomatic cerebrovascular diseases, stroke, or frequent transient ischemic attacks have an increased risk of induced neurological complications after intra-arterial administration. Intra-arterial administration of contrast agents may cause vasospasm with subsequent cerebral ischemic complications.
In isolated cases, temporary hearing loss or deafness has been observed after myelography, possibly related to a drop in cerebrospinal fluid pressure following lumbar puncture.
Renal reactions
Administration of iodine-containing contrast agents may cause increased serum creatinine levels and acute kidney injury. Special caution is required when examining patients at risk, particularly those with diabetes mellitus and impaired renal function.
Other predisposing factors for adverse renal reactions include prior renal insufficiency following contrast agent administration, history of kidney disease, age over 60 years, dehydration, progressive atherosclerosis, decompensated heart failure, high doses of contrast agents and multiple injections, direct administration of contrast agents into the renal artery, exposure to additional nephrotoxins, severe and chronic hypertension, hyperuricemia, paraproteinemia (myeloma and Waldenström's macroglobulinemia, plasmacytoma), or dyslipoproteinemia.
Measures to prevent adverse reactions:
- identification of patients at risk;
- ensuring adequate hydration via intravenous infusion when necessary, initiated before contrast agent administration and continued until its renal excretion;
- avoiding additional renal burden by avoiding nephrotoxic drugs, oral cholecystographic agents, arterial compression, renal arterial angioplasty, or major surgical interventions before complete elimination of the contrast agent;
- minimizing the dose to the lowest possible;
- postponing repeat contrast examinations until renal function has recovered to levels observed before the last administration.
Contrast agents may be administered for radiological procedures in patients undergoing hemodialysis. There is no need to adjust the interval between contrast agent injection and hemodialysis session.
Diabetic patients receiving metformin therapy
Administration of iodine-containing contrast agents to diabetic patients receiving metformin, especially those with impaired renal function, may lead to lactic acidosis.
To prevent lactic acidosis in diabetic patients receiving metformin therapy, serum creatinine levels should be measured before intravascular administration of an iodine-containing contrast agent, and the following precautions should be taken:
- Patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² (corresponding to chronic kidney disease (CKD) stages 1 or 2) do not require changes in metformin regimen.
- Patients with eGFR 30–59 mL/min/1.73 m² (CKD stage 3):
- patients with eGFR ≥ 45 mL/min/1.73 m² do not require changes in metformin regimen when contrast agent is administered intravenously;
- for patients receiving contrast agent via intra-arterial injection and patients with eGFR 30–44 mL/min/1.73 m² receiving contrast agent intravenously, metformin should be discontinued 48 hours before contrast agent administration and resumed 48 hours after administration if no deterioration in renal function is observed.
- Metformin is contraindicated in patients with eGFR < 30 mL/min/1.73 m² (CKD stages 4 and 5) or with concomitant conditions provoking liver dysfunction or hypoxia; such patients should avoid administration of iodine-containing contrast agents.
- In emergency patients with impaired or unknown renal function, the physician must assess the risk-benefit ratio of performing a contrast examination; metformin should be discontinued during contrast agent administration; after the procedure, the patient should be monitored for signs of lactic acidosis; if serum creatinine/eGFR values remain unchanged compared to pre-procedure levels, metformin should be resumed 48 hours after contrast agent administration.
- Metformin is contraindicated in patients with eGFR < 30 mL/min/1.73 m² (CKD stages 4 and 5) or with concomitant conditions provoking liver dysfunction or hypoxia; such patients should avoid administration of iodine-containing contrast agents.
- Patients with eGFR 30–59 mL/min/1.73 m² (CKD stage 3):
Patients with impaired renal and hepatic function
Special attention should be paid to patients with severe impairment of both renal and hepatic function, as significant delay in contrast agent clearance may occur. Patients on hemodialysis may receive contrast agents for radiological procedures.
Myasthenia
Administration of iodine-containing radiographic contrast agents may exacerbate symptoms of myasthenia.
Pheochromocytoma
For invasive procedures in patients with pheochromocytoma, prophylactic use of alpha-blockers is required to prevent hypertensive crisis.
Thyroid function disorders
Iodine-containing contrast agents affect thyroid function due to their free iodide content and additional iodide released during deiodination. This may cause hypothyroidism or even thyrotoxic crisis in susceptible patients.
Patients at risk include those with existing but undiagnosed hyperthyroidism; therefore, patients with latent hyperthyroidism (e.g., nodular goiter) and patients with functional autonomy (often, for example, elderly patients, particularly in iodine-deficient regions) should have their thyroid function evaluated before examination if the above conditions are suspected.
Before administration of an iodine-containing contrast agent, it must be ensured that the patient does not require thyroid scanning, thyroid function testing, or radioactive iodine therapy, as administration of iodine-containing contrast agents, regardless of route, affects test results for thyroid hormone levels and iodine uptake by the thyroid or metastases of thyroid cancer until urinary iodine excretion normalizes (see section "Interaction with other medicinal products and other forms of interaction").
Thyroid function disorders, indicated by hypothyroidism or transient suppression of thyroid function, have been reported after administration of iodine-containing contrast agents to adult patients and children, including infants. Some patients required treatment for hypothyroidism; see also section "Children".
Anxiety states
In cases of pronounced anxiety, a sedative may be prescribed.
Sickle cell anemia
Contrast agents may trigger disease manifestations in individuals homozygous for sickle cell anemia following intravenous or intra-arterial administration.
Other risk factors
Serious vasculitis or Stevens-Johnson syndrome have been observed in patients with autoimmune diseases.
Severe vascular and neurological diseases, particularly in elderly patients, are risk factors for reactions to contrast agent administration.
Extravasation
Extravasation of contrast agent from blood vessels (extravasation) rarely caused local pain, swelling, and erythema, which usually resolved without consequences. However, cases of inflammation and even tissue necrosis have been documented. General measures include elevation and cooling of the injection site if possible. Surgical decompression may be necessary if compartment syndrome develops.
Special precautions for use in children
Particular attention should be paid to children under 3 years of age, as cases of impaired thyroid function at an early age may adversely affect motor skills, hearing, and cognitive development and may require temporary T4 replacement therapy. The incidence of hypothyroidism in patients under 3 years receiving iodine-containing contrast agents has been reported to range from 1.3% to 15%, depending on patient age and dose of iodine-containing contrast agent, and occurs more frequently in newborns and premature infants. Newborns may also be negatively affected by iodine-containing agents via the mother during pregnancy. Thyroid function should be evaluated in all patients under 3 years of age after administration of iodine-containing contrast agents. If hypothyroidism is detected, appropriate treatment should be considered and thyroid function monitored until normalization.
Adequate hydration should be ensured before and after administration of the contrast agent, especially in infants and young children. Use of nephrotoxic agents should be discontinued. Glomerular filtration rate (GFR) decreases with age in infants, which may lead to delayed excretion of contrast agents.
Hemodynamic and electrolyte imbalances occur particularly easily in children under one year of age, especially newborns.
Intrathecal administration
After myelography, the patient should remain at rest for at least one hour, lying with the head and chest elevated at 20º. After this period, the patient may be discharged for outpatient care, but should avoid bending. If bed rest is required, the head and chest should remain elevated for the first 6 hours. If a low seizure threshold is suspected, the patient should be observed during this period. Outpatient patients should not be left unattended during the first 24 hours after the procedure.
Cerebral arteriography
Cardiovascular reactions such as bradycardia and increased or decreased blood pressure may occur more frequently in patients with progressive atherosclerosis, severe arterial hypertension, decompensated cardiac function, elderly patients, history of stroke or embolism, and headache.
Arteriography
During the procedure, injury to the artery, vein, aorta, and adjacent organs, pleurocentesis, retroperitoneal hemorrhage, spinal cord injury, and symptoms of paraplegia may occur.
This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially sodium-free.
Use during pregnancy or breastfeeding
Pregnancy
Results of experimental preclinical studies on reproductive performance, embryonic or fetal development, pregnancy course, and peri- and postnatal development do not indicate a direct or indirect harmful effect.
The safety of using Iohexol-YUF during pregnancy has not been established. Radiation exposure should be avoided during pregnancy if possible, and X-ray examinations, with or without contrast agents, should be prescribed with careful consideration due to potential risk.
Iohexol-YUF should be used during pregnancy only if absolutely necessary, according to the physician's recommendation and after careful benefit-risk assessment.
In addition to avoiding radiation exposure, the benefit-risk assessment should also consider the fetus's thyroid gland sensitivity to iodine.
In newborns exposed to iodine-containing contrast agents during intrauterine development, thyroid function should be monitored (see section "Special precautions for use").
Breastfeeding
Contrast agents pass into breast milk in small amounts and are minimally absorbed in the infant's intestine. After administration of iodine-containing contrast agents, breastfeeding can continue in the usual manner.
In a study, the amount of iohexol excreted in breast milk during the first 24 hours after administration was 0.5% of the dose adjusted for body weight. The amount of iohexol entering the infant's body during the first 24 hours after administration is only 0.2% of the pediatric dose.
Ability to affect reaction speed when driving or operating machinery
Driving or operating machinery is not recommended for one hour after the last administration or for 24 hours after intrathecal administration (see section "Special precautions for use"). If symptoms occur after myelography, the decision should be made individually.
Administration and Dosage
Dosage
The dose of the drug depends on the method of examination, age, body weight, cardiac output, the patient's general condition, and the technique of drug administration. Usually, the same concentration and volume of iodine are used as with other iodine-containing X-ray contrast agents. Before and after the administration of the contrast agent, as with other X-ray contrast agents, adequate hydration of the patient should be ensured.
The drug is intended for intravenous, intraarterial, intrathecal administration, and intracavitary administration.
Administration method
The following dosage regimens should be used as guidelines:
| Indications/Examination |
Concentration |
Doses |
Notes |
| Intravenous administration |
|||
| Urography Adults Children < 7 kg Children > 7 kg |
300 mg iodine/ml or 350 mg iodine/ml 300 mg iodine/ml 300 mg iodine/ml |
40–80 ml 40–80 ml 3 ml/kg 2 ml/kg |
In individual cases, doses exceeding 80 ml may be administered max. dose 40 ml |
| Phlebography (lower limbs) |
300 mg iodine/ml |
20–100 ml per limb |
|
| Digital subtraction angiography |
300 mg iodine/ml or 350 mg iodine/ml |
20–60 ml/injection 20–60 ml/injection |
|
| Contrast enhancement in CT Adults Children |
300 mg iodine/ml or 350 mg iodine/ml 300 mg iodine/ml |
100–200 ml 100–150 ml 1–3 ml/kg body weight, up to 40 ml |
Total iodine amount in injection usually up to 30–60 g In individual cases, administration up to 100 ml is possible |
| Intraarterial administration |
|||
| Arteriography Aortic arch Selective cerebral angiography Aortography Femoral artery angiography Other types |
300 mg iodine/ml 300 mg iodine/ml 350 mg iodine/ml 300 mg iodine/ml or 350 mg iodine/ml |
30–40 ml/injection 5–10 ml/injection 40–60 ml/injection 30–50 ml/injection Depends on examination method |
Dose per injection depends on site of administration |
| Cardioangiography Adults Left ventricle and aortic root Selective coronary angiography Children |
350 mg iodine/ml 350 mg iodine/ml 300 mg iodine/ml or 350 mg iodine/ml |
30–60 ml/injection 4–8 ml/injection depending on age, body weight and pathology |
max. dose 8 ml/kg |
| Digital subtraction angiography |
300 mg iodine/ml |
1–15 ml/injection |
Larger volumes (up to 30 ml) may be used depending on site of administration |
| Intrathecal administration |
|||
| Myelography* Cervical myelography (lumbar injection) Cervical myelography (lateral cervical injection) |
300 mg iodine/ml 300 mg iodine/ml |
7–10 ml 6–8 ml |
|
| Intracavitary administration |
|||
| Arthrography |
300 mg iodine/ml or 350 mg iodine/ml |
5–15 ml 5–10 ml |
|
| Hysterosalpingography |
300 mg iodine/ml |
15–25 ml |
|
| Sialography |
300 mg iodine/ml |
0.5–2 ml |
|
| Gastrointestinal tract examination Oral administration Adults Children Esophagus Preterm infants Rectal administration Children |
350 mg iodine/ml 300 mg iodine/ml or 350 mg iodine/ml 350 mg iodine/ml Doses diluted with water to concentration 100–150 mg iodine/ml |
individually 2–4 ml/kg body weight 2–4 ml/kg body weight 2–4 ml/kg body weight 5–10 ml/kg body weight |
Maximum dose – 50 ml Maximum dose – 50 ml Example: dilute Iohexol-YUF with water in ratio 1:1 or 1:2 |
| CT enhancement Oral administration Adults Children Rectal administration Children |
Dilute with water to concentration approximately 6 mg iodine/ml Dilute with water to concentration approximately 6 mg iodine/ml Dilute with water to concentration approximately 6 mg iodine/ml |
800–2000 ml solution, over a certain time period 15–20 ml solution/kg body weight (individually) |
Example: dilute with water in ratio 1:50 |
*To minimize the risk of adverse reactions, the total dose of iodine should not exceed 3 g.
Children
The drug can be used in children.
Cases of transient hypothyroidism have been reported in preterm infants, newborns, and other children following administration of iodine-containing contrast agents. Preterm infants have increased sensitivity to iodine. Cases of transient hypothyroidism have been reported in a breastfed infant whose mother had received iohexol repeatedly (see section "Special precautions").
Infants and young children should be adequately hydrated before and after administration of the contrast agent. Concomitant nephrotoxic drugs should be discontinued. Age-related reduction in glomerular filtration rate in infants may also lead to delayed elimination of the contrast agent.
Overdose
Preclinical data indicate a wide therapeutic window for the drug Iohexol-YU and no upper limit of standard recommended doses for intravascular administration. Symptomatic overdose is unlikely in patients with normal renal function if the administered dose does not exceed 2000 mg iodine/kg within a limited period. Prolonged administration of high doses may affect kidney function (elimination half-life – 2 hours). Accidental overdose may occur during complex angiographic procedures in children, especially with repeated administration of high doses.
In case of overdose, correction of fluid and electrolyte imbalances should be performed. Renal function should be monitored for the next 3 days. If necessary, hemodialysis should be used to remove excess drug. There is no specific antidote.
Adverse Reactions
General types of adverse reactions (common to all iodine-containing X-ray contrast agents)
The following are possible major adverse reactions associated with radiological procedures using non-ionic monomeric contrast agents. Information on adverse reactions depending on the route of administration is provided in the relevant sections below.
Hypersensitivity reactions may occur regardless of the dose or route of administration. Mild symptoms may be early signs of a serious anaphylactic reaction or shock. Administration of the contrast agent should be stopped immediately, and specific treatment including intravenous administration of medications should be initiated if necessary.
Transient increase in serum creatinine levels is frequently observed after administration of iodine-containing X-ray contrast agents, increasing the risk of contrast-induced nephropathy.
Iodism or "iodine mumps" is a very rare reaction to iodine-containing X-ray contrast agents, which may manifest as swelling and pain in the salivary glands for up to 10 days after the procedure.
Classification of adverse reaction frequencies is based on internal clinical documentation and published results from large-scale studies involving over 200,000 patients.
Adverse reactions are classified by frequency as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), and frequency not known (cannot be estimated from available data).
Immune system disorders
Rare: hypersensitivity reactions (may be life-threatening or fatal), including dyspnea, rash, erythema, urticaria, pruritus, skin reactions, vasculitis, conjunctivitis, cough, rhinitis, sneezing, angioedema, laryngeal edema, laryngospasm, bronchospasm, or non-cardiogenic pulmonary edema. These may occur immediately after administration and may indicate the development of shock. Hypersensitivity skin reactions may occur several days after administration.
Very rare: anaphylactic/anaphylactoid reactions (may be life-threatening or fatal).
Frequency not known: anaphylactic/anaphylactoid shock (may be life-threatening or fatal).
Nervous system disorders
Uncommon: headache.
Very rare: dysgeusia (transient metallic taste), vasovagal syncope.
Cardiac disorders
Rare: bradycardia.
Vascular disorders
Very rare: arterial hypertension, arterial hypotension.
Gastrointestinal disorders
Uncommon: nausea.
Rare: vomiting, abdominal pain.
Very rare: diarrhea.
Frequency not known: enlargement of salivary glands.
General disorders and administration site conditions
Common: sensation of warmth.
Uncommon: hyperhidrosis, sensation of cold, vasovagal reactions.
Rare: pyrexia.
Very rare: tremor (chills).
Adverse reactions associated with intravascular, intra-arterial, and intravenous administration
Please read the section "General types of adverse reactions" first. The frequency of adverse reactions listed below refers only to intravascular administration of non-ionic monomeric contrast agents.
The occurrence of adverse reactions following intra-arterial administration depends on the injection site and dose. In selective angiography and other procedures where the contrast agent reaches high concentrations in the target organ, organ dysfunction may occur.
Blood and lymphatic system disorders
Frequency not known: thrombocytopenia.
Endocrine disorders
Frequency not known: thyrotoxicosis, transient hypothyroidism.
Psychiatric disorders
Frequency not known: confusion, excitement, restlessness, anxiety.
Nervous system disorders
Rare: dizziness, paresis, paralysis, photophobia, somnolence.
Very rare: seizures, altered consciousness, cerebrovascular disorder, sensory disturbances (including hypesthesia), paresthesia, tremor.
Frequency not known: transient motor dysfunction (including speech disturbances, aphasia, dysarthria), transient contrast-induced encephalopathy (including transient memory loss, coma, retrograde amnesia, hemiparesis, disorientation, and cerebral edema).
Eye disorders
Rare: visual disturbances (including diplopia, blurred vision).
Frequency not known: transient cortical blindness.
Ear and labyrinth disorders
Frequency not known: transient hearing loss.
Cardiac disorders
Rare: arrhythmia (including bradycardia, tachycardia).
Very rare: myocardial infarction, chest pain.
Frequency not known: severe cardiac complications (including cardiac arrest, cardiopulmonary arrest), heart failure, coronary artery spasm, cyanosis.
Vascular disorders
Very rare: flushing.
Frequency not known: shock, arterial spasm, thrombophlebitis, thrombosis.
Respiratory, thoracic and mediastinal disorders
Common: transient changes in respiratory rate, respiratory distress.
Rare: cough, respiratory arrest.
Very rare: dyspnea.
Frequency not known: severe respiratory symptoms and signs, pulmonary edema, acute respiratory distress syndrome, bronchospasm, laryngospasm, apnea, asthma aspiration attack.
Skin and subcutaneous tissue disorders
Rare: rash, pruritus, urticaria.
Frequency not known: bullous dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), exacerbation of psoriasis, erythema, drug-related dermatitis, skin desquamation.
Musculoskeletal and connective tissue disorders
Frequency not known: arthralgia, muscle weakness, musculoskeletal spasm, back pain.
Renal and urinary disorders
Uncommon: acute kidney injury.
Frequency not known: increased blood creatinine levels.
General disorders and administration site conditions
Uncommon: pain and discomfort.
Rare: asthenic state (including malaise, fatigue).
Frequency not known: injection site reactions, including extravasation.
Injury, poisoning and procedural complications
Frequency not known: iodism.
Intrathecal administration
Please read the section "General types of adverse reactions" first. The frequency of adverse reactions listed below refers only to intrathecal administration of non-ionic monomeric contrast agents.
Adverse reactions may be delayed and occur several hours or days after intrathecal administration. Their frequency is approximately comparable to complications following lumbar punctures without contrast agent. Headache, nausea, vomiting, or dizziness are primarily related to decreased pressure in the subarachnoid space due to leakage of cerebrospinal fluid at the puncture site. To minimize pressure reduction, excessive removal of cerebrospinal fluid should be avoided.
Psychiatric disorders
Frequency not known: confusion, excitement, anxiety.
Nervous system disorders
Very common: headache (may be severe and prolonged).
Uncommon: aseptic meningitis (including chemical meningitis).
Rare: seizures, dizziness.
Frequency not known: abnormal electroencephalogram, meningeal signs, epileptic status, motor dysfunction (including speech disturbances, aphasia, dysarthria), paresthesia, hypesthesia, sensory disturbances, transient contrast-induced encephalopathy (including transient memory loss, coma, stupor, retrograde amnesia, hemiparesis).
Eye disorders
Rare: visual disturbances (including diplopia, blurred vision).
Frequency not known: transient cortical blindness, photophobia.
Ear and labyrinth disorders
Frequency not known: transient hearing loss.
Gastrointestinal disorders
Common: nausea, vomiting.
Musculoskeletal and connective tissue disorders
Rare: neck pain, back pain.
Frequency not known: muscle spasms.
General disorders and administration site conditions
Rare: limb pain.
Frequency not known: changes at the injection site.
Adverse reactions associated with intracavitary administration
Please read the section "General types of adverse reactions" first. The frequency of adverse reactions listed below refers only to intracavitary administration of non-ionic monomeric contrast agents.
Endoscopic retrograde cholangiopancreatography (ERCP)
Gastrointestinal disorders
Common: pancreatitis, increased blood amylase levels.
Oral administration
Gastrointestinal disorders
Very common: diarrhea.
Common: nausea, vomiting.
Uncommon: abdominal pain.
Hysterosalpingography (HSG)
Gastrointestinal disorders
Very common: lower abdominal pain.
Arthrography
Musculoskeletal and connective tissue disorders
Frequency not known: arthritis.
General disorders and administration site conditions
Very common: pain.
Myelography
General disorders and administration site conditions
Frequency not known: post-procedural pain.
Specific adverse reactions
Thromboembolic complications have been reported following contrast angiography of coronary, cerebral, renal, and peripheral arteries. The contrast agent may contribute to the development of such complications (see section "Special precautions for use").
Cardiac complications, including acute myocardial infarction, have been reported during or after contrast coronary angiography. Elderly patients and those with severe ischemic heart disease, unstable angina, or left ventricular dysfunction are at higher risk of complications (see section "Special precautions for use").
In isolated cases, the contrast agent may cross the blood-brain barrier, leading to accumulation in the cerebral cortex and resulting in neurological reactions, including seizures, transient motor and sensory disturbances, transient altered consciousness, transient memory loss, and encephalopathy (see section "Special precautions for use").
Anaphylactic reactions and anaphylactic shock may lead to profound arterial hypotension and associated symptoms, including hypoxic encephalopathy, renal and hepatic failure (see section "Special precautions for use").
In some cases, transudation of the contrast agent may cause local pain and swelling, which usually resolve without complications. Cases of inflammation, tissue necrosis, and compartment syndrome have been reported (see section "Special precautions for use").
Reporting of adverse reactions
Reporting suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Storage conditions
Store at temperatures not exceeding 25 °C, in the original packaging, and protected from secondary X-ray radiation.
Incompatibilities
Data on compatibility of this medicinal product with other medicinal products are lacking. Therefore, a separate syringe should be used for administration of Yohexol-YF, and it should not be mixed with other medicinal products.
Packaging
50 ml in glass vials; 1 vial per cardboard box.
100 ml in glass bottles; 1 bottle per cardboard box.
Prescription status. Prescription only.
Manufacturer. LLC "Yuria-Pharm".
Manufacturer's address and location of its operations
108 Kobzarska Street, Cherkasy, Cherkasy region, Ukraine. Tel.: (044) 281-01-01.