Unipac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT UNIPAKE® (UNIPAQUE®)

Composition:

Active ingredient: iohexol;

1 ml of 300 mg/ml solution contains: iohexol 647 mg, equivalent to iodine 300 mg/ml;

1 ml of 350 mg/ml solution contains: iohexol 755 mg, equivalent to iodine 350 mg/ml;

Excipients: trometamol, calcium disodium edetate, hydrochloric acid concentrated, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear solution ranging from colorless to pale yellow.

Osmolality and viscosity values of the medicinal product are provided below:

Concentration	Osmolality*, Osm/kg H2O at 37 °C	Viscosity (mPa*s) 20 °C	Viscosity (mPa*s) 37 °C
300 mg/ml iodine 350 mg/ml iodine	0.67 (0.605–0.739) 0.84 (0.760–0.928)	9.6–9.9 18.3–18.6	6.9–7.3 12.2–12.6

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

Pharmacological Properties.

Pharmacodynamics.

Iohexol is a non-ionic, tri-iodinated, water-soluble X-ray contrast agent. After intravenous injection of iohexol, no significant alterations in most hemodynamic, clinical-biochemical, or coagulation parameters have been observed. Time to achieve maximum radiographic contrast in conventional myelography is up to 30 minutes (visualization is no longer possible after 1 hour). In computed tomography, contrast visualization in the thoracic region is possible for up to 1 hour, in the cervical region for about 2 hours, and in the basal cisterns for 3–4 hours. Contrast enhancement of joint cavities, uterine cavity, fallopian tubes, peritoneal recesses, pancreatic and bile ducts, and urinary bladder is achieved immediately after administration.

Pharmacokinetics.

Approximately 100% of iohexol administered intravenously is excreted unchanged via normally functioning kidneys within 24 hours. Maximum concentration of iohexol in urine is reached within 1 hour after injection. The elimination half-life of the drug in patients with normal renal function is 2 hours. No metabolites of the drug have been identified. Protein binding of iohexol to plasma proteins is clinically insignificant (less than 2%) and therefore may be disregarded.

Clinical characteristics.

Indications.

Yunipak® is intended solely for diagnostic purposes.

A radiopaque contrast agent for use in children and adults for performing cardioangiography, arteriography, urography, phlebography, and contrast enhancement in computed tomography (CT); lumbar, thoracic, and cervical myelography, CT cisternography after subarachnoid administration; arthrography, endoscopic retrograde pancreatography (ERP), endoscopic retrograde cholangiopancreatography (ERCP), herniography, hysterosalpingography, sialography, and gastrointestinal tract examinations.

Contraindications.

• Hypersensitivity to iohexol, other iodine-containing preparations, or to any of the excipients of the medicinal product;
• severe thyrotoxicosis;
• presence of local or systemic infections (for myelography);
• immediate repeat intrathecal administration of the agent following failed myelography;
• epilepsy and cerebral infections (for subarachnoid administration);
• pregnancy or breastfeeding;
• concomitant use of the agent (with intrathecal administration) with glucocorticosteroids.

Interaction with other medicinal products and other types of interactions.

The use of contrast agents in diabetic patients receiving biguanides (metformin) may lead to reversible renal function impairment and lactic acidosis (see section "Special precautions").

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

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 up to several weeks.

High concentrations of contrast agents in blood serum and urine may affect laboratory results for bilirubin, proteins, and inorganic compounds (e.g., iron, copper, calcium, phosphates); therefore, laboratory tests should not be performed on the same day.

Treatment with beta-blockers may reduce the threshold for hypersensitivity reactions and may require higher doses of beta-agonists to treat such reactions. Beta-blockers, vasoactive substances, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor antagonists may impair the effectiveness of cardiovascular compensatory mechanisms in response to changes in arterial pressure.

Phenothiazine derivatives and other antipsychotic agents (neuroleptics), monoamine oxidase inhibitors, tricyclic antidepressants, central nervous system stimulants, and analeptics—lower the epileptic threshold and increase the risk of contrast-induced seizures. The use of these agents should be discontinued at least 48 hours before myelography; they should not be used to prevent nausea or vomiting during or after myelography, or within 24 hours following the procedure. In cases where the procedure is necessary for patients taking these medications, consideration should be given to prophylactic administration of anticonvulsants.

Special precautions for use.

The product must not be mixed in the same syringe with other diagnostic or medicinal agents.

The solution should be drawn into a syringe immediately before use. After opening the container, the solution must be used immediately.

Any unused portion of the product must not be reused.

Prior to administration, as with all parenteral products, the solution should be visually inspected for the presence of insoluble particles, color changes, and packaging integrity.

Do not use if the container contains visible solid particles.

Do not use if the holographic label Unique is missing or damaged.

It is advisable to warm the solution to body temperature before injection.

Prior to administration of a radiopaque agent, accurate patient information must be obtained, including important laboratory data (serum creatinine level, electrocardiogram, history of allergy). Before the procedure, fluid and electrolyte imbalances in the patient must be corrected, and adequate fluid and electrolyte intake ensured.

The patient should discontinue food intake 2 hours before the procedure.

General characteristics of use of non-ionic monomeric contrast agents.

Hypersensitivity. A history of allergy, asthma, or adverse reactions to iodine-containing contrast agents in the patient requires heightened attention. Therefore, a detailed medical history must be obtained before administering contrast agents. The medicinal product should be administered to patients with allergic diathesis or known hypersensitivity reactions only when there are absolute indications for the procedure.

In cases of contrast agent intolerance, premedication with corticosteroids or H1- and H2-histamine receptor antagonists may be considered; 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 agent is very low. However, iodine-containing contrast agents may cause life-threatening anaphylactic/anaphylactoid reactions or other manifestations of hypersensitivity. Regardless of the amount and 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, appropriate treatment measures should be planned in advance in case of serious adverse reactions, and necessary medications, equipment, and qualified medical personnel for immediate assistance must be available. If shock develops, contrast agent administration must be stopped immediately, and specific intravenous treatment initiated if necessary. It is recommended to use a permanent cannula or catheter to ensure rapid intravenous access during radiographic contrast procedures.

Patients receiving beta-adrenergic 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 these patients, atypical symptoms of anaphylaxis may occur, which could be misinterpreted as a vagal reaction.

Hypersensitivity reactions typically manifest as mild respiratory or skin symptoms, such as mild dyspnea, skin flushing (erythema), urticaria, pruritus, or facial swelling. Severe reactions such as angioedema, subglottic edema, bronchial spasm, 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), but such cases rarely threaten life and mainly affect the skin.

Coagulopathy. Catheter angiography using contrast agents is associated with a risk of induced thromboembolic complications. Serious, rarely fatal thromboembolic events causing myocardial infarction and stroke have been reported during angiocardiographic procedures using both ionic and non-ionic contrast agents. Careful attention to angiographic technique and frequent catheter flushing (e.g., with heparinized saline) should be maintained during vascular catheterization procedures to minimize the risk of procedure-related thrombosis and embolism.

During catheterization, factors other than the contrast agent that may influence the development of thromboembolic complications include duration of examination, number of injections, type of catheter and syringe material, underlying diseases, and concomitant medication use.

A separate syringe and needle should be used for administering the agent, and the agent must not be mixed with other medicinal products.

The examination procedure should be as short as possible.

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

In vitro, non-ionic contrast agents exert a weaker coagulation-inhibiting effect than ionic contrast agents.

Hydration. Adequate hydration of the patient must be ensured before and after administration of the contrast agent. If necessary, hydration should be administered intravenously until excretion of the contrast agent is complete. This is particularly important for patients with dys- and paraproteinemia, multiple myeloma, diabetes mellitus, impaired renal function, hyperuricemia, as well as for infants, young children, elderly patients, and patients in poor general condition.

In patients at increased risk, fluid and electrolyte balance should be monitored, and symptoms of decreased serum calcium levels carefully observed. Due to the risk of diuretic-induced dehydration, fluid and electrolyte rehydration should be performed first to prevent acute kidney injury.

Cardio-circulatory reactions. Caution is required when examining patients with severe cardiovascular diseases and pulmonary hypertension due to the risk of cardiac rhythm disturbances and hemodynamic alterations, especially with intracoronary, left, and right ventricular administration of contrast agents (see section "Adverse reactions"). Patients most 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.

Ischemic ECG changes and arrhythmias occur more frequently in elderly patients and patients with a history of heart disease.

Intravascular administration of contrast agents in patients with heart failure may cause pulmonary edema.

Central Nervous System Disorders.

Cases of encephalopathy have been reported with the use of contrast agents such as iohexol (see section "Adverse reactions"). Contrast-induced encephalopathy may present with symptoms and signs of neurological dysfunction, such as headache, visual disturbances, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, 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 with caution intravascularly in patients with acute cerebral infarction or acute intracranial hemorrhage, patients with diseases involving blood-brain barrier disruption, and patients with cerebral edema, acute demyelination, or progressive cerebral atherosclerosis. If contrast-induced encephalopathy is suspected, iohexol administration should be discontinued and appropriate medical monitoring initiated.

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

Patients with symptomatic cerebrovascular diseases, history of stroke, or frequent transient ischemic attacks have an increased risk of contrast-induced neurological complications after intra-arterial injection of contrast agents.

Intra-arterial administration of contrast agents may induce vascular spasm leading to subsequent cerebral ischemic events.

Patients with acute cerebral pathology, brain tumors, and epilepsy are prone to seizures and require special attention. There is an increased risk of seizures and neurological reactions in patients with alcoholism and drug addiction. Rare cases of temporary hearing loss or deafness have been observed after myelography, probably related to decreased cerebrospinal fluid pressure due to lumbar puncture.

Renal reactions. The use of iodine-containing contrast agents may cause an increase in serum creatinine levels and acute kidney injury. To prevent these conditions, special caution should be exercised in patients with pre-existing renal function impairment and diabetes mellitus, as they belong to the risk group.

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

Measures to prevent adverse reactions:

• identification of patients belonging to the risk group;
• ensuring adequate hydration; if necessary, this may be achieved via continuous intravenous infusion initiated before contrast agent administration and continued until its renal excretion;
• prevention of additional renal burden from nephrotoxic drugs, oral cholecystographic agents, renal artery compression, renal angioplasty, or surgical procedures—until contrast agent elimination; minimizing the dose to the lowest possible;
• repeat radiographic contrast examinations should be performed only after complete normalization of renal function following the last administration.

Contrast agents may be administered to patients undergoing hemodialysis.

There is no need to coordinate the timing of contrast agent injection with hemodialysis sessions.

Diabetic patients receiving metformin therapy. The use of iodine-containing contrast agents in 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 iodine-containing contrast agents, and the following preventive measures taken.

Patients with eGFR ≥60 mL/min/1.73 m² (chronic kidney disease (CKD) stages 1 and 2) may continue metformin in their usual regimen.

Patients with eGFR 30–59 mL/min/1.73 m² (CKD stage 3):

• Patients receiving intravenous contrast agent with eGFR ≥45 mL/min/1.73 m² may continue metformin in their usual regimen.
• Patients receiving intra-arterial contrast agent and patients receiving intravenous contrast agent with eGFR 30–44 mL/min/1.73 m² should discontinue metformin 48 hours before contrast agent administration and resume only 48 hours after administration, provided renal function has not deteriorated.

Metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m² (CKD stages 4 and 5) or with intercurrent illness causing liver dysfunction or hypoxia; iodine-containing contrast agents should be avoided.

For emergency patients with impaired renal function or unknown renal function, the physician must weigh the risks and benefits of contrast examination. Metformin should be discontinued at the time of contrast agent administration. After the procedure, the patient should be monitored for signs of lactic acidosis. Metformin may be resumed 48 hours after contrast agent administration if serum creatinine/eGFR levels have not changed compared to pre-procedure levels.

Patients with impaired liver and kidney function. Extreme caution is required in patients with severe combined liver and kidney dysfunction, as they exhibit significantly reduced contrast agent clearance. Patients on hemodialysis may receive contrast agents for radiological procedures. There is no need to coordinate the timing of contrast agent injection with hemodialysis sessions.

Myasthenia. Administration of iodine-containing radiopaque agents may exacerbate symptoms of myasthenia.

Phaeochromocytoma. Prophylactic use of alpha-blockers is required during invasive procedures in patients with phaeochromocytoma to prevent hypertensive crises.

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

Patients with undiagnosed hyperthyroidism represent a risk group; therefore, thyroid function should be evaluated before examination in patients suspected of latent hyperthyroidism (e.g., nodular goiter) or functional autonomy (often elderly patients, especially in iodine-deficient regions).

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

Reports indicate that after administration of iodine-containing contrast agents in adult and pediatric patients, including infants, thyroid function tests showed hypothyroidism or transient thyroid suppression. Some patients required treatment for hypothyroidism. See also section "Children."

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

Sickle cell anemia. Contrast agents may promote sickling in individuals homozygous for sickle cell anemia following intravenous and 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 individuals, are risk factors for reactions to contrast agent administration.

Extravasation. Leakage of contrast agent from blood vessels (extravasation) rarely caused local pain and swelling, which resolved without consequences. However, cases of tissue inflammation and necrosis have been documented. Therefore, elevation and cooling of the injection site are recommended. Surgical decompression may be necessary if compartment syndrome develops.

Patient monitoring

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

Intrathecal administration

After myelography, the patient should remain at rest for at least 1 hour, lying with the head and chest elevated by 20º. After this period, the patient may be discharged as an outpatient but should avoid bending. If bed rest is maintained, the head and chest should remain elevated for the first 6 hours. Monitoring is required during this period if a low seizure threshold is suspected. Outpatient patients 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 cases of early-onset thyroid dysfunction 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 subject age and dose of iodine-containing contrast agent, and occurs more frequently in newborns and premature infants. Newborns may also be negatively affected by intrauterine exposure to iodine-containing agents. 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 treatment 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 very easily in children under 1 year, especially in newborns.

Cerebral arteriography. Cardiovascular reactions such as bradycardia and increased or decreased blood pressure may occur more frequently in patients with progressive atherosclerosis, severe hypertension, cardiac decompensation, elderly patients, patients with history of stroke or embolism, and headache.

Arteriography. Depending on the procedure used, possible complications include injury to the artery, vein, aorta, and 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., it is practically sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy. The safety of using the medicinal product during pregnancy has not been established. Results of experimental preclinical studies on reproduction, embryonic or fetal development, pregnancy course, and peri- and postnatal development do not indicate direct or indirect harmful effects. Radiation exposure during pregnancy should be avoided if possible; radiographic examination, with or without contrast agent, should be carefully considered due to potential risks.

Junipak® may be used during pregnancy only if absolutely 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 when evaluating benefit-risk.

In newborns exposed to iodine-containing contrast agents in utero, thyroid function should be monitored (see section "Special precautions for use").

Breastfeeding. Contrast agents pass into breast milk to a small extent, and minimal amounts are absorbed in the infant's intestine. Therefore, the risk to the infant is low.

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 entering the infant's body within the first 24 hours after administration is only 0.2% of the pediatric dose.

Ability to affect reaction speed when driving vehicles or operating machinery.

No studies on the effect of the agent on the ability to drive vehicles or operate machinery have been conducted. Driving vehicles and operating complex machinery are not recommended within the first 24 hours after intrathecal administration of contrast agents (see section "Special precautions for use"). If symptoms occur after myelography, decisions should be made individually.

Method of Administration and Dosage

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

During administration, the patient should remain in a horizontal position.

The dose of the drug depends on the type of examination, age, body weight, cardiac output, the patient's general condition, and the technique of administration. Usually, the same concentration and volume of iodine are used as with other iodine-containing contrast agents. Adequate hydration of the body should be ensured before and after administration of the contrast agent.

Intravenous administration

Indications	Concentration	Dose per 1 injection	Comments
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 3 mL/kg 2 mL/kg (maximum dose–40 mL)	In individual cases, doses higher than 80 mL may be used
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 (maximum dose–40 mL)	Total amount of iodine, usually, 30–60 g. In individual cases, administration up to 100 mL possible

Intraarterial administration

Indications	Concentration	Dose per injection	Comments
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 300 mg iodine/ml	30–40 ml/injection 5–10 ml/injection 40–60 ml/injection 30–50 ml/injection Depends on the study method	Dose per injection depends on the 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 (maximum dose – 8 mg/kg body weight)
Digital subtraction angiography	300 mg iodine/ml	1–15 ml/injection	Higher doses (up to 30 ml) may be used depending on the site of injection (up to 30 ml)

Intrathecal administration

Indications	Concentration	Dose per 1 injection	Comments
Myelography* Cervical myelography (lumbar injection) Cervical myelography (cervical lateral injection)	300 mg iodine/ml 300 mg iodine/ml	7–10 ml 6–8 ml

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

Intracavitary administration

Indications	Concentration	Dose per 1 injection	Comments
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 Diluted with water to a concentration of 100–150 mg iodine/mL	Individually determined 2–4 mL/kg body weight 2–4 mL/kg body weight 5–10 mL/kg body weight	Maximum dose – 50 mL Example: dilute 300 or 350 preparation with water in a ratio of 1:1 or 1:2
CT enhancement Oral administration Adults Children Rectal administration Children	Dilute with water to a concentration of approximately 6 mg iodine/mL Dilute with water to a concentration of approximately 6 mg iodine/mL Dilute with water to a concentration of approximately 6 mg iodine/mL	800–2000 mL of solution over a certain time period 15–20 mL of solution/kg body weight Individually determined	Example: dilute 300 or 350 preparation with water in a ratio of 1:50

Children. Junipaq® can be used in pediatric practice.

Overdose.

Preclinical data indicate a wide therapeutic window of the drug and no upper limit of standard acceptable doses for intravascular administration. The risk of developing overdose symptoms is minimal unless the patient receives more than 2000 mg/kg of iodine within a short period. Prolonged procedures with 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 water-electrolyte balance disturbances is required. Kidney function should be monitored for the next 3 days. If necessary, hemodialysis should be applied to remove excess drug.

There is no specific antidote. Treatment should be aimed at maintaining vital body functions.

Adverse Reactions.

General Adverse Reactions.

Listed below are the possible main adverse effects associated with radiological procedures using non-ionic contrast agents.

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

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

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

Immune system disorders: hypersensitivity reactions (which 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, anaphylactic/anaphylactoid reactions (which may be life-threatening or fatal), anaphylactic/anaphylactoid shock (which may be life-threatening or result in fatality). These may develop immediately after administration or several days later.

Nervous system disorders: seizures, headache, dysgeusia (transient metallic taste), vasovagal syncope (syncope).

Cardiovascular system disorders: bradycardia, arterial hypertension, arterial hypotension.

Gastrointestinal system disorders: nausea, vomiting, abdominal pain, diarrhea, enlargement of salivary glands.

General disorders: sensation of warmth, hyperhidrosis, sensation of cold, vasovagal reactions, pyrexia, tremor (chills).

Injury, poisoning, and procedural complications: iodism.

Adverse Reactions Associated with Intravascular (Intra-arterial and Intravenous) Administration.

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

Blood and lymphatic system disorders: thrombocytopenia.

Immune system disorders: hypersensitivity reactions, including life-threatening or fatal anaphylaxis, severe pustular, exfoliative, or bullous reactions.

Endocrine system disorders: thyrotoxicosis, transient hypothyroidism.

Psychiatric disorders: anxiety, excitement, restlessness, confusion.

Nervous system disorders: dizziness, paresis, paralysis, photophobia, somnolence, seizures, impaired consciousness, cerebrovascular disorder, encephalopathy, stupor, sensory disturbances (including hypesthesia), paresthesia, tremor, headache, dysgeusia, transient motor dysfunction (including speech disorders, aphasia, dysarthria), transient contrast-induced encephalopathy (including transient hemiplegia or delirium, temporary memory loss, disorientation, coma, retrograde amnesia, hemiparesis, and cerebral edema).

Eye disorders: visual disturbances (including blurred vision, diplopia, photosensitivity reactions), transient cortical blindness.

Ear and labyrinth disorders: transient hearing loss.

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

Respiratory system disorders: transient changes in respiratory rate, respiratory distress, cough, apnea, dyspnea, severe respiratory symptoms and signs, non-cardiogenic pulmonary edema, acute respiratory distress syndrome, bronchospasm, laryngospasm, apnea, asthma attack due to aspiration.

Gastrointestinal system disorders: diarrhea, nausea, vomiting, enlargement of salivary glands, abdominal pain, exacerbation of pancreatitis.

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, erythema, acute generalized exanthematous pustulosis, bullous dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), sudden worsening of psoriasis, erythema, exudation of the agent, skin desquamation.

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

Renal and urinary system disorders: acute kidney injury, increased blood creatinine levels.

General disorders and administration site conditions: sensation of warmth, pain and discomfort, asthenic state (including malaise, fatigue), tremor (chills), hyperthermia, injection site reactions, including extravasation.

Injury, poisoning, and procedural complications: iodism.

Adverse Reactions Associated with Intrathecal Administration.

Adverse reactions related to intrathecal administration of contrast agents may be delayed and occur several hours or even days after the procedure. Their frequency is approximately similar to that of complications following lumbar puncture without contrast agent administration. To minimize pressure reduction, excessive removal of cerebrospinal fluid should be avoided.

Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

Psychiatric disorders: confusion, excitement, anxiety.

Nervous system disorders: headache (may be severe and prolonged), aseptic meningitis (including chemical meningitis), seizures, dizziness, dysgeusia, vasovagal syncope, EEG rhythm disturbances, meningeal signs, epileptic status, transient contrast-induced encephalopathy (including transient hemiplegia or delirium, temporary memory loss, coma, stupor, retrograde amnesia, hemiparesis, disorientation), transient motor dysfunction (including speech disorders, aphasia, dysarthria), paresthesia, hypesthesia, sensory disturbances.

Eye disorders: transient cortical blindness, photophobia.

Ear and labyrinth disorders: tinnitus, transient hearing loss.

Gastrointestinal system disorders: abdominal pain, enlargement of salivary glands, nausea, vomiting, diarrhea.

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

General disorders and administration site conditions: limb pain, sensation of warmth, pyrexia, tremor (chills), changes at the injection site.

Adverse Reactions Associated with Intracavitary Administration.

Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

Nervous system disorders: headache, dysgeusia, vasovagal syncope.

Gastrointestinal system disorders: nausea, abdominal pain, enlargement of salivary glands, vomiting, diarrhea; in hysterosalpingography – lower abdominal pain.

General disorders and administration site conditions: sensation of warmth, pyrexia, tremor (chills).

Endoscopic Retrograde Cholangiopancreatography (ERCP/ERCP).

Gastrointestinal system disorders: pancreatitis, increased blood amylase.

Oral Administration.

Gastrointestinal system disorders: diarrhea, nausea, vomiting, abdominal pain.

Hysterosalpingography (HSG).

Gastrointestinal system disorders: lower abdominal pain.

Arthrography.

Musculoskeletal and connective tissue disorders: arthritis.

General disorders and administration site conditions: pain.

Herniography.

General disorders and administration site conditions: post-procedural pain.

Extravascular Administration:

Local pain and swelling, inflammation, and tissue necrosis.

Specific Adverse Reactions.

Thromboembolic complications have been reported in association with contrast angiography of coronary, cerebral, renal, and peripheral arteries. The contrast agent may contribute to the development of complications (see section "Special Precautions").

Cardiac complications, including acute myocardial infarction during or after contrast coronary angiography, have been reported. Elderly patients and those with severe ischemic heart disease, unstable angina, and left ventricular dysfunction are at higher risk of complications (see section "Special Precautions").

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 impairment of consciousness, transient memory loss, and encephalopathy (see section "Special Precautions").

Anaphylactoid reactions and anaphylactoid shock may lead to profound hypotension and associated symptoms, including hypoxic encephalopathy, renal and hepatic failure (see section "Special Precautions").

In some cases, transudation of the contrast agent causes local pain and swelling, which usually resolves without complications. Cases of inflammation, tissue necrosis, and compartment syndrome have been reported (see section "Special Precautions").

Pediatric Patients. The possibility of transient hypothyroidism should be considered in premature infants, newborns, and other children following administration of iodine-containing contrast agents.

Premature infants have increased sensitivity to iodine. Cases of transient hypothyroidism have been reported in breastfed premature infants. Iohexol has been repeatedly administered to breastfeeding women (see section "Special Precautions").

Infants and young children should receive adequate hydration before and after administration of the contrast agent. Nephrotoxic drugs should be discontinued. Glomerular filtration rate decreases with age in infants, potentially leading to delayed excretion of contrast agents.

Shelf Life. 3 years.

Storage Conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. Protect from direct light.

Keep out of reach of children.

Incompatibility. The medication should not be mixed with other medicinal products.

Packaging.

Iodine 300 mg/mL – 20 mL in an ampoule; 5 ampoules per tray; 1 tray per cardboard box;

50 mL, 100 mL, or 200 mL in a vial; 1 vial per box.

Iodine 350 mg/mL – 20 mL in an ampoule; 5 ampoules per tray; 1 tray per cardboard box;

50 mL, 100 mL, or 200 mL in a vial; 1 vial per box.

Prescription Category. Prescription only.

Manufacturer.

"Unique Pharmaceuticals Laboratories" (a division of "J.B. Chemicals and Pharmaceuticals Ltd.").

Manufacturer's Address and Location of Business Activity.

Plot No. 4, Phase-IV, GIDC Industrial Estate, Panoli - 394 116, Bharuch District, India.