Tomohexol®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TОMOHEXOL® (TOMOHEXOL)

Composition:

active substance: iohexol;

1 ml of solution contains iohexol calculated as 100 % substance, equivalent to iodine:

Excipients: edetate disodium calcium, tromethamine, diluted hydrochloric acid,
water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: clear, colorless or slightly yellow liquid (solution).

Pharmacotherapeutic group.
Iodine-containing X-ray contrast agents. Water-soluble, low-osmolar, non-ionic X-ray contrast agents. ATC code V08A B02.

Pharmacological properties.

Pharmacodynamics.

Iohexol is a non-ionic monomeric tri-iodinated water-soluble X-ray contrast agent.

In studies of healthy volunteers, following intravenous injection of iohexol, no significant deviations in most hemodynamic, clinical-biochemical, or coagulation parameters were observed. Changes in some laboratory parameters were minor and are not considered clinically significant.

Pharmacokinetics.

Approximately 100 % of iohexol administered intravenously is excreted unchanged via normally functioning kidneys within 24 hours. The elimination half-life of the drug in patients with normal renal function is 2 hours. Metabolites of the drug have not been identified. Protein binding of iohexol is not clinically significant (less than 2 %) and may therefore be disregarded.

Clinical characteristics.

Indications.

Tomohexol® is intended only for diagnostic procedures.

An X-ray contrast agent for use in children and adults for arthrography, angiography, arteriography, urography, phlebography, and contrast enhancement in computed tomography (CT), lumbar, thoracic, and cervical myelography, CT cisternography, hysterosalpingography, sialography, endoscopic retrograde pancreatography (ERCP), endoscopic retrograde cholangiopancreatography (ERCP), herniography, and gastrointestinal tract examinations.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients.
• Marked thyrotoxicosis.

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 impairment of renal function and to lactic acidosis (see section "Special precautions for use").

Patients who have received interleukin-2 less than 2 weeks prior to the examination may be prone to delayed adverse reactions (erythema, flu-like symptoms or skin reactions).

Concomitant use of certain neuroleptics or tricyclic antidepressants may lower the seizure threshold and thereby increase the risk of contrast-induced seizures.

Treatment with beta-blockers may reduce the threshold for hypersensitivity reactions and may also require higher doses of beta-agonists to treat hypersensitivity reactions.

Beta-blockers, vasoactive substances, ACE inhibitors, and angiotensin receptor antagonists may impair cardiovascular compensatory mechanisms for 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 a period of 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 same day.

Special precautions for use.

As with all parenteral preparations, Tomohexol® should be visually inspected before administration for the presence of particulate matter, discoloration, or packaging defects. Since Tomohexol® does not contain preservatives, the solution should be drawn into a syringe immediately before use. Vials are intended for single use only. Any unused portion of the solution should be discarded.

General precautions for non-ionic monomeric contrast agents.
Hypersensitivity. A history of allergy, asthma, or adverse reactions to iodine-containing contrast agents requires special attention. Therefore, a detailed medical history should be obtained before administering contrast agents. Patients with allergic diathesis or known hypersensitivity reactions should receive the agent only when absolutely necessary.

In patients with known contrast agent intolerance, premedication with corticosteroids or H1- and H2-histamine receptor antagonists may be considered, although such premedication does not prevent anaphylactic shock and may mask its initial symptoms.

Patients with bronchial asthma are at increased risk of bronchospasm.

The risk of severe adverse reactions to Tomohexol® is very low. However, iodine-containing contrast agents may cause life-threatening, potentially fatal anaphylactic/anaphylactoid reactions or other manifestations of hypersensitivity. Regardless of the dose or route of administration, symptoms such as angioedema, conjunctivitis, cough, pruritus, rhinitis, sneezing, and urticaria may indicate a serious anaphylactoid reaction requiring immediate treatment. Therefore, emergency procedures should be planned in advance, and necessary medications, equipment, and qualified medical personnel should be readily available to provide immediate assistance. If shock develops, contrast agent administration must be stopped immediately, and specific intravenous treatment initiated as needed. It is recommended to maintain a patent intravenous cannula or catheter throughout the radiographic procedure to ensure rapid intravenous access.

Patients receiving beta-blockers, especially asthmatics, may have a lower threshold for bronchospasm and may be less responsive to treatment with beta-agonists and epinephrine, potentially requiring higher doses. In such patients, symptoms of anaphylaxis may be atypical and may be mistaken for vagal reactions.

Hypersensitivity reactions typically manifest as mild respiratory or cutaneous symptoms, such as slightly labored breathing, skin flushing (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 (occurring several hours or days later), although such delayed reactions are rarely life-threatening and primarily affect the skin.

Coagulopathy. Serious, occasionally fatal, thromboembolic complications leading to myocardial infarction and stroke have been reported during angiographic 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 sodium chloride solution containing heparin) are essential to minimize the risk of thrombosis and embolism.

During catheterization, factors other than the contrast agent itself may contribute to thromboembolic complications, including duration of the procedure, number of injections, catheter type and syringe material, underlying medical conditions, and concomitant medications.

The procedure should be as short as possible.

Patients with homocystinuria (at risk of thromboembolism) should be monitored carefully.

In contrast to ionic contrast agents, non-ionic contrast agents have a weaker in vitro inhibitory effect on blood coagulation.

Hydration. Adequate hydration (fluid loading) of the patient before and after contrast agent administration is essential. If necessary, hydration should be provided intravenously until excretion of the contrast agent is complete.

This is particularly important for patients with dysproteinemia or paraproteinemia, multiple myeloma, diabetes mellitus, renal dysfunction, hyperuricemia, as well as infants, young children, elderly patients, and those in poor general condition.

In high-risk patients, fluid and electrolyte balance should be monitored, and symptoms of hypocalcemia should be observed.

Due to the risk of diuretic-induced dehydration, fluid and electrolyte rehydration should be performed prior to contrast administration to prevent acute kidney injury.

Cardiovascular reactions. Caution is advised when examining patients with severe cardiovascular disease or pulmonary hypertension due to the risk of arrhythmias or hemodynamic disturbances, particularly with 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 disease, history of myocardial infarction, coronary bypass surgery, or pulmonary hypertension.

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 induce pulmonary edema.

CNS disorders. Cases of encephalopathy have been reported following administration of contrast agents such as iohexol (see section "Adverse Reactions"). Contrast-induced encephalopathy may present with neurological symptoms and signs such as headache, visual disturbances, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, loss of consciousness, coma, and cerebral edema. These symptoms typically appear within minutes to hours after iohexol administration and usually resolve within several days.

Factors that increase blood-brain barrier permeability may facilitate the passage of contrast agents into brain tissue and may trigger central nervous system reactions, including encephalopathy. The agent should be used cautiously in patients receiving intravascular administration who have acute ischemic stroke or acute intracranial hemorrhage, as well as those 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 medical treatment initiated.

Neurological symptoms caused by metastases, degenerative, or inflammatory processes may be exacerbated by contrast agents.

Patients with symptomatic cerebrovascular disease, history of stroke, or frequent transient ischemic attacks are at increased risk of contrast-induced neurological complications following intra-arterial injection. Intra-arterial injection of contrast agents may induce vasospasm leading to cerebral ischemic complications.

Patients with acute cerebral pathology, brain tumors, or epilepsy are prone to seizures and require special attention. The risk of seizures and neurological reactions is increased in alcohol- and drug-dependent patients. Transient hearing loss or deafness has been observed in isolated cases after myelography, possibly related to decreased cerebrospinal fluid pressure following lumbar puncture.

Renal reactions. To prevent increased serum creatinine levels and contrast-induced acute kidney injury, special caution is required in patients at risk: those with diabetes mellitus or renal dysfunction.

Other risk factors for adverse renal reactions include prior contrast-induced renal failure, history of kidney disease, age over 60 years, dehydration, progressive atherosclerosis, decompensated heart failure, high doses of contrast agents, multiple injections, direct injection into the renal artery, exposure to other nephrotoxic agents, severe or chronic hypertension, hyperuricemia, paraproteinemia (myeloma, Waldenström's macroglobulinemia), or dysproteinemia.

Measures to prevent adverse reactions:

• Identification of patients at risk;
• Ensuring adequate hydration, if necessary, via intravenous infusion initiated before contrast administration and continued until the agent is excreted;
• Avoiding additional renal stress by refraining from nephrotoxic drugs, oral cholecystographic agents, arterial compression, renal artery angioplasty, or major surgery until the contrast agent is eliminated; minimizing the dose;
• Avoiding repeat contrast studies until renal function has returned to baseline levels observed before the last contrast administration.

Contrast agents may be administered to patients undergoing hemodialysis.

There is no need to adjust the timing between contrast agent injection and hemodialysis session.

Diabetic patients receiving metformin therapy. Administration of iodine-containing contrast agents to diabetic patients receiving metformin, particularly those with renal impairment, may lead to lactic acidosis. To prevent lactic acidosis in diabetic patients on metformin therapy, serum creatinine levels should be measured before intravascular administration of iodine-containing contrast agents, and the following precautions should be taken:

• Patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² (corresponding to stages 1 and 2 of chronic kidney disease [CKD]) 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 during intravenous contrast administration;
  • Patients receiving contrast via intra-arterial injection, and patients with eGFR 30–44 mL/min/1.73 m² receiving intravenous contrast, should discontinue metformin 48 hours before contrast administration. Metformin may be resumed no earlier than 48 hours after contrast administration, provided 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 causing hepatic dysfunction or hypoxia. Such patients should avoid iodine-containing contrast agents.
• In emergency situations where renal function is impaired or unknown, the physician must assess the risk-benefit ratio of contrast examination. Metformin should be discontinued at the time of contrast 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 may be resumed 48 hours after contrast administration.

Patients with impaired liver and kidney function. Special attention should be given 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 gravis. Administration of iodine-containing radiographic contrast agents may exacerbate symptoms of myasthenia gravis.

Pheochromocytoma. In patients with pheochromocytoma undergoing invasive procedures, prophylactic alpha-blockers should be administered to prevent hypertensive crises.

Thyroid function disorders. Iodine-containing contrast agents affect thyroid function due to their free iodide content and additional iodide released during deiodination. This may induce hyperthyroidism or even thyrotoxic crisis in susceptible individuals.

Patients with undiagnosed hyperthyroidism are at risk; therefore, thyroid function should be evaluated before examination in patients with latent hyperthyroidism (e.g., nodular goiter) or functional autonomy (commonly elderly patients, particularly in iodine-deficient regions).

Before administering an iodine-containing contrast agent, it must be confirmed that the patient does not plan to undergo thyroid scanning, thyroid function testing, or radioactive iodine therapy, as iodine-containing contrast agents, regardless of route of administration, interfere with thyroid hormone assays and iodine uptake by the thyroid gland or thyroid cancer metastases until urinary iodine excretion returns to normal (see section "Interaction with other medicinal products and other forms of interaction").

Studies of thyroid function after administration of iodine-containing contrast agents in adult and pediatric patients (including infants) indicate a risk of hypothyroidism or transient suppression of thyroid function. Some patients may require treatment for hypothyroidism.

Anxiety. In cases of severe anxiety, a sedative may be prescribed.

Sickle cell anemia. Contrast agents may precipitate sickling in individuals homozygous for sickle cell anemia following intravenous or intra-arterial administration.

Other risk factors. Serious vasculitis or Stevens-Johnson-like syndromes have been observed in patients with autoimmune diseases.

Severe vascular and neurological diseases, especially in elderly patients, are risk factors for reactions to contrast agents.

Extravasation. Extravasation of contrast agent (leakage from blood vessels) rarely causes local pain, swelling, and erythema, which usually resolve without sequelae. However, cases of inflammation and even tissue necrosis have been reported. General measures include elevation and cooling of the injection site when possible. Surgical decompression may be necessary if compartment syndrome develops.

Patient monitoring. After contrast agent administration, patients should be observed for at least 30 minutes, as most serious adverse reactions occur within this period. The patient should remain in the hospital (but not necessarily in the radiology department) for one hour after the last contrast administration and should return to the radiology department if any symptoms develop.

Intrathecal administration. After myelography, the patient should remain at rest for at least one hour in a supine position with the head and chest elevated by 20º. After this period, the patient may be discharged, but should avoid bending. During bed rest, the head and chest should remain elevated for the first 6 hours. Patients suspected of having a low seizure threshold should be observed during this period. Outpatients should not be left unattended during the first 24 hours after the procedure.

Use in children. Particular attention should be paid to children under 3 years of age, as hypothyroidism in early life may adversely affect motor function, 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 age and dose, and is more common in newborns and premature infants. Newborns may also be affected by iodine-containing agents via the mother during pregnancy. Thyroid function should be evaluated in patients under 3 years after administration of iodine-containing contrast agents. If hypothyroidism is detected, appropriate treatment should be considered, and thyroid function monitored until normalization.

Infants require adequate hydration before and after contrast agent administration. Nephrotoxicity management should be carefully considered.

Glomerular filtration rate decreases with age in infants, potentially leading to delayed excretion of contrast agents.

Hemodynamic and electrolyte imbalances occur particularly easily in children under one year of age, especially in newborns.

Cerebral angiography. Cardiovascular reactions such as bradycardia and increased or decreased blood pressure may occur more frequently in patients with progressive atherosclerosis, severe hypertension, decompensated heart failure, advanced age, history of stroke or embolism, or headache.

Arteriography. The procedure may cause injury to arteries, veins, aorta, or adjacent organs, pleurocentesis, retroperitoneal hemorrhage, spinal cord injury, and symptoms of paraplegia.

This medicinal product contains less than 1 mmol/ dose of sodium, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy. The safety of Tomohexol® during pregnancy has not been established. Preclinical experimental data on reproductive toxicity, embryofetal development, pregnancy maintenance, and perinatal and postnatal development do not indicate direct or indirect harmful effects. Radiation exposure during pregnancy should be avoided when possible. X-ray examinations, with or without contrast agents, should be prescribed cautiously due to potential risks.

Tomohexol® may be used during pregnancy only if clearly necessary, according to physician recommendations and after careful benefit-risk assessment.

In addition to avoiding radiation exposure, the potential sensitivity of the fetal thyroid gland to iodine should be considered during benefit-risk assessment.

Thyroid function should be monitored in newborns exposed to iodinated contrast agents in utero (see section "Special precautions for use").

Breastfeeding. Contrast agents pass into breast milk in small amounts, and minimal absorption occurs in the infant's intestine. Therefore, risk to the infant is unlikely.

Breastfeeding may continue after administration of iodine-containing contrast agents. In one study, the amount of iohexol excreted in breast milk within the first 24 hours after administration was 0.5% of the dose adjusted for body weight. The amount of iohexol absorbed by the infant during the first 24 hours after administration is only 0.2% of a pediatric dose.

Ability to drive or operate machinery.

Driving and operating complex machinery are not recommended during the first 24 hours after intrathecal administration of contrast agents. If symptoms occur after myelography, decisions should be made on an individual basis.

Administration and 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 administration. The same concentration and volume of iodine are usually used as with other iodine-containing X-ray contrast agents. Adequate hydration of the body must be ensured before and after administration of the contrast agent, as with other X-ray contrast agents.

The drug is intended for intra-arterial, intravenous, intrathecal, intracavitary administration, oral intake, and rectal administration in adults and children.

Table 2

Concentrations and doses of the drug used

*To minimize the risk of adverse reactions, the total iodine dose should not exceed 3 g.

Children.

The drug may be used in children.

One should be aware of the possibility of developing transient hypothyroidism in premature infants, newborns, and other children following administration of iodine-containing contrast agents.

Premature infants are more sensitive to iodine. Cases of transient hypothyroidism have been reported in breastfed premature infants whose mothers had received multiple doses of the drug Tomohexol® (see section "Special precautions").

Adequate hydration should be ensured in infants and young children before and after administration of the contrast agent. Concomitant use of 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 iohexol and no upper limit for standard acceptable doses for intravascular administration. The risk of developing overdose symptoms is minimal unless more than 2000 mg/kg of iodine is administered within a short period. Prolonged administration of high doses of the drug 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. Kidney function should be monitored for the next 3 days. Hemodialysis may be applied if necessary 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 main adverse effects associated with radiological procedures using non-ionic contrast agents.

Hypersensitivity reactions may occur regardless of the dose and route of administration. Mild symptoms may be the first signs of a serious anaphylactic reaction/shock. Administration of the contrast agent should be stopped immediately, and specific therapy with intravascular administration of medications should be initiated if necessary.

Transient increase in S-creatinine is a common occurrence after administration of iodine-containing X-ray contrast agents, increasing the risk of contrast-induced nephropathy.

Iodism or iodine-induced parotitis is a very rare reaction to iodine-containing X-ray contrast agents. It may manifest as swelling and pain in the salivary glands for up to 10 days after the procedure.

The frequency of adverse reactions is based on internal clinical documentation and published large-scale studies involving over 200,000 patients.

Adverse effects are classified by frequency of occurrence 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), unknown (frequency 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 develop immediately after administration or several days later and may indicate the development of shock. Skin reactions may occur several days after administration. Very rare: anaphylactic/anaphylactoid reaction (may be life-threatening or fatal). Unknown: anaphylactic/anaphylactoid shock (may be life-threatening or result in a fatal outcome).

Nervous system disorders. Uncommon: headache. Very rare: dysgeusia (transient metallic taste), vasovagal syncope.

Cardiovascular system disorders. Rare: bradycardia. Very rare: arterial hypertension, arterial hypotension.

Gastrointestinal disorders. Uncommon: nausea. Rare: vomiting, abdominal pain. Very rare: diarrhea. Unknown: enlargement of salivary glands.

General disorders. Common: sensation of heat. Uncommon: hyperhidrosis, sensation of cold, vasovagal reactions. Rare: pyrexia. Very rare: tremor (chills).

Injury, poisoning, and procedural complications. Unknown: iodism.

Adverse reactions associated with intravascular (intra-arterial and intravenous) administration.

Please read first the section "General types of adverse reactions". The frequency of adverse reactions listed below relates only to intravascular administration of non-ionic monomeric contrast agents.

The development of adverse reactions that may occur during intra-arterial administration depends on the injection site and dose. In selective angiography and other procedures where the contrast agent at high concentration reaches the organ under examination, dysfunction of that organ may occur.

Blood and lymphatic system disorders. Unknown: thrombocytopenia.

Endocrine system disorders. Unknown: thyrotoxicosis, transient hypothyroidism.

Psychiatric disorders. Unknown: confusion, excitement, restlessness, anxiety.

Nervous system disorders. Rare: dizziness, paresis, paralysis, photophobia, somnolence. Very rare: seizures, disturbance of consciousness, cerebrovascular disorder, stupor, sensory disturbances (including hypoesthesia), paresthesia, tremor. Unknown: transient motor dysfunction (including speech disorders, aphasia, dysarthria), transient contrast-induced encephalopathy (including temporary memory loss, disorientation, coma, retrograde amnesia, hemiparesis, and cerebral edema).

Eye disorders. Rare: visual disturbances (including diplopia and blurred vision). Unknown: transient cortical blindness.

Ear and labyrinth disorders. Unknown: transient hearing loss.

Cardiovascular system disorders. Rare: arrhythmia (including bradycardia, tachycardia). Very rare: myocardial infarction, flushing, chest pain. Unknown: severe cardiac complications (including cardiac arrest, cardiopulmonary arrest), heart failure, coronary artery spasm, cyanosis, shock, arterial spasm, thrombophlebitis, and thrombosis.

Respiratory system disorders. Common: transient changes in respiratory rate, respiratory distress. Rare: cough, respiratory arrest. Very rare: dyspnea. Unknown: severe respiratory symptoms and signs, pulmonary edema, acute respiratory distress syndrome, bronchospasm, laryngospasm, apnea, asthma attack due to aspiration.

Gastrointestinal disorders. Rare: diarrhea. Unknown: exacerbation of pancreatitis.

Skin and subcutaneous tissue disorders. Rare: rash, pruritus, urticaria. Unknown: bullous dermatitis; Stevens-Johnson syndrome; toxic epidermal necrolysis; acute generalized exanthematous pustulosis; drug reaction with eosinophilia and systemic symptoms (DRESS); exacerbation of psoriasis; erythema; drug-related dermatitis; skin exfoliation.

Musculoskeletal and connective tissue disorders. Unknown: arthralgia, muscle weakness, musculoskeletal spasm, back pain.

Renal and urinary disorders. Uncommon: acute kidney injury. Unknown: increased blood creatinine levels.

General disorders and administration site conditions. Uncommon: pain and discomfort. Rare: asthenic state (including malaise, fatigue). Unknown: reactions at the injection site, including extravasation.

Injury, poisoning, and procedural complications. Unknown: iodism.

Intrathecal administration.

Please read first the section "General types of adverse reactions". The frequency of adverse reactions listed below relates only to intrathecal administration of non-ionic monomeric contrast agents.

Adverse reactions may occur several hours or days after intrathecal administration. Their frequency approximately corresponds to the frequency of complications after lumbar punctures without contrast agent. To minimize pressure reduction, excessive removal of cerebrospinal fluid should be avoided.

Psychiatric disorders. Unknown: confusion, excitement, anxiety.

Nervous system disorders. Very common: headache (may be severe and prolonged). Uncommon: aseptic meningitis (including chemical meningitis). Rare: seizures, dizziness. Unknown: abnormal electroencephalogram, meningeal syndrome, epileptic status, transient contrast-induced encephalopathy (including transient memory loss, coma, stupor, retrograde amnesia, hemiparesis, disorientation), motor dysfunction (including speech disorders, aphasia, dysarthria), paresthesia, hypoesthesia, and sensory disturbances.

Eye disorders. Unknown: transient cortical blindness, photophobia.

Ear and labyrinth disorders. Unknown: transient hearing loss.

Gastrointestinal disorders. Common: abdominal pain, vomiting.

Musculoskeletal and connective tissue disorders. Rare: neck pain, back pain. Unknown: muscle spasms.

General disorders and administration site conditions. Rare: limb pain. Unknown: changes at the injection site.

Adverse reactions associated with intracavitary administration.

Please read first the section "General types of adverse reactions". The frequency of adverse reactions listed below relates only to intracavitary administration of non-ionic monomeric contrast agents.

Endoscopic retrograde cholangiopancreatography (ERCP).

Gastrointestinal disorders. General: pancreatitis, increased blood amylase.

Oral administration.

Gastrointestinal disorders. Very common: diarrhea. Common: nausea, vomiting. Rare: abdominal pain.

Hysterosalpingography (HSG).

Gastrointestinal disorders. Very common: lower abdominal pain.

Arthrography.

Musculoskeletal and connective tissue disorders. Unknown: arthritis.

General disorders and administration site conditions. Very common: pain.

Myelography.

General disorders and administration site conditions. Unknown: 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 complications (see section "Special precautions for use"). Cardiac complications, including acute myocardial infarction, have been reported during or after contrast coronary angiography. Elderly patients or those with severe ischemic heart disease, unstable angina, and left ventricular dysfunction have a higher risk of complications (see section "Special precautions for use").

In isolated cases, the contrast agent may cross the blood-brain barrier, resulting in accumulation of the agent in the cerebral cortex, which may cause neurological reactions, including seizures, transient motor or sensory disturbances, transient disturbance of consciousness, transient memory loss, and encephalopathy (see section "Special precautions for use").

Anaphylactoid reactions and anaphylactoid shock may lead to profound 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").

Shelf life.

3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging, protected from secondary X-ray radiation, at a temperature not exceeding 25°C. Keep out of reach of children.

Incompatibilities. Data on compatibility with other medicinal products are lacking; therefore, a separate syringe should be used for administration of Tomohexol® and the agent should not be mixed with other medicinal products.

Packaging.

Injection solution 240 mg iodine/ml: 20 ml in an ampoule. 5 ampoules per pack. 20 ml, 50 ml, or 100 ml in a vial. 1 vial per pack.

Injection solution 300 mg iodine/ml, 350 mg iodine/ml: 20 ml in an ampoule. 5 ampoules per pack. 20 ml, 50 ml, 100 ml, 200 ml, 500 ml in a vial. 1 vial per pack.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's location and address of place of business.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.