Instructions Tomohexol solution for injection 350 mg iodine/ml bottle 100 ml No. 1
Composition
active ingredient: iohexol;
1 ml of solution contains iohexol in terms of 100% substance equivalent to iodine:
| mg iodine/ml | 240 | 300 | 350 |
| mg iohexol/ml | 518 | 647 | 755 |
Excipients: sodium calcium edetate, tromethamine, diluted hydrochloric acid, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent colorless or light yellow liquid (solution).
Pharmacotherapeutic group
Iodine-containing radiopaque contrast agents. Water-soluble low-osmolar nephrotropic radiopaque contrast agents. ATX code V08A B02.
Pharmacological properties
Pharmacodynamics
Iohexol is a nonionic monomeric triiodinated water-soluble radiopaque contrast agent.
In a study of healthy volunteers after intravenous injection of iohexol, no significant deviations were found in most hemodynamic parameters, clinical and biochemical parameters, and coagulation parameters. Changes in some laboratory parameters were insignificant and are not considered clinically significant.
Pharmacokinetics
Approximately 100% of intravenously administered iohexol is excreted unchanged by the kidneys within 24 hours. The elimination half-life in patients with normal renal function is 2 hours. No metabolites have been identified. The binding of iohexol to plasma proteins is of no clinical significance (less than 2%) and therefore may be disregarded.
Indication
Tomohexol is intended for diagnostic purposes only.
Radiocontrast agent for performing arthrography, angiography, arteriography, urography, phlebography and contrast enhancement in computed tomography (CT), lumbar, thoracic, cervical myelography, CT cisternography, hysterosalpingography, sialography, endoscopic retrograde pancreatography (ERPG), endoscopic retrograde cholangiopancreatography (ERCP), herniography and gastrointestinal tract studies in children and adults.
Contraindication
Hypersensitivity to the active substance or to other components of the drug.
Severe thyrotoxicosis.
Interaction with other medicinal products and other types of interactions
The use of iodinated contrast agents in diabetic patients taking metformin may lead to reversible renal impairment and lactic acidosis (see section "Special warnings and precautions for use").
Patients who took interleukin-2 less than 2 weeks before the study are prone to late adverse reactions (flu-like symptoms or skin reactions).
All iodinated contrast agents may interact with diagnostic tests for thyroid function, so the ability of the thyroid gland to bind iodine may be reduced for up to several weeks.
High concentrations of contrast agents in serum and urine may affect laboratory results for bilirubin, proteins, and inorganic compounds (e.g., iron, copper, calcium, phosphates), so laboratory tests should not be performed on the same day.
Treatment with beta-blockers may lower the threshold for hypersensitivity reactions, and higher doses of beta-agonists may be required to treat hypersensitivity reactions. Beta-blockers, vasoactive agents, ACE inhibitors, angiotensin receptor antagonists may reduce the effectiveness of cardiovascular mechanisms to compensate for changes in blood pressure. Concomitant use of some neuroleptics or tricyclic antidepressants may lower the seizure threshold and thus increase the risk of contrast-induced seizures.
Application features
As with all parenteral products, Tomohexol should be inspected visually for particulate matter, discoloration, and damage to the packaging prior to administration. Since Tomohexol does not contain preservatives, the product should be drawn into a syringe immediately before use. The vials are for single use only. Any unused portion should be discarded.
General features of the use of nonionic monomeric contrast agents.
History of allergy, asthma, or adverse reactions to iodinated contrast agents warrants special attention. In these cases, premedication with corticosteroids or H1- and H2-histamine receptor antagonists should be considered.
In patients taking beta-blockers, manifestations of anaphylaxis may be atypical and mistaken for vagal reactions.
Compared with ionic drugs, nonionic contrast agents have less effect in vitro on the blood coagulation system. When performing vascular catheterization procedures, angiographic examination techniques should be followed very carefully and catheters should be flushed frequently (e.g. with sodium chloride solution with heparin added) to minimize the risk of thrombosis and embolism associated with the intervention.
Adequate hydration is essential before and after contrast medium administration. This is especially important for patients with multiple myeloma, diabetes, renal impairment, infants, young children, and the elderly.
Caution should be exercised when examining patients with severe cardiovascular disease and pulmonary hypertension due to the risk of developing arrhythmias or hemodynamic disturbances.
Patients with acute cerebral pathology, brain tumors and epilepsy are prone to the development of seizures and require special attention. Increased risk of seizures and neurological reactions in alcohol- and drug-dependent patients. Rare cases of temporary hearing loss or deafness have been observed after myelography, which is probably associated with a decrease in cerebrospinal fluid pressure due to lumbar puncture.
To prevent the development of contrast-induced nephropathy, renal dysfunction or acute renal failure associated with the administration of contrast media, special care is required when examining patients with pre-existing renal dysfunction and patients with diabetes mellitus who are at risk. The same applies to the examination of patients with paraproteinemias (myeloma, Waldenström's macroglobulinemia). Iodine-containing contrast media should be used with caution in patients with pheochromocytoma or patients at risk.
Measures to prevent adverse reactions:
identification of patients at risk; ensuring adequate hydration; if necessary, this can be achieved by continuous intravenous infusion, which is started before the contrast agent is administered and continued until it is excreted by the kidneys; preventing additional stress on the kidneys that occurs with the use of nephrotoxic drugs, oral cholecystography agents, renal artery clamping, renal artery angioplasty, surgical operations, until the contrast agent is excreted from the body; repeated X-ray contrast studies should be performed after complete normalization of renal function after the last administration of the drug.
Diabetic patients taking metformin: The use of iodinated contrast agents in diabetic patients taking metformin, especially in patients with impaired renal function, may lead to lactic acidosis.
To prevent lactic acidosis in diabetic patients treated with metformin, serum creatinine should be measured before intravascular administration of iodinated contrast media and precautions should be taken in the following cases.
Normal serum creatinine (<130 μmol/L)/normal renal function: Metformin should be discontinued at the time of contrast administration and not resumed for 48 hours or until renal function/serum creatinine has returned to normal.
Increased serum creatinine (>130 μmol/l)/renal impairment. Metformin should be discontinued and the contrast medium examination postponed for 48 hours. Metformin therapy should only be resumed if renal function/serum creatinine remains unchanged. In urgent cases where renal function is impaired or unknown, the physician should assess the risk/benefit ratio for the patient and take precautionary measures: discontinue metformin. It is particularly important to ensure adequate hydration of patients before and for 24 hours after the contrast medium administration. Renal function (in particular serum creatinine), serum lactic acid and blood pH should be monitored.
There is a potential risk of developing hepatic failure. Particular caution should be exercised in patients with severe combined renal and hepatic impairment, as this group of patients has a significantly reduced clearance of contrast agents. Patients on hemodialysis may receive contrast agents for radiological procedures.
There is no need to correlate the time between contrast medium injection and hemodialysis session, as there is no evidence that hemodialysis prevents the development of contrast-induced nephropathy in patients with impaired renal function.
The release of contrast medium from the vessels was rarely accompanied by local pain and swelling, which passed without consequences. However, cases of inflammation and tissue necrosis have been recorded. As a general measure, it is recommended to elevate and cool the injection site if possible. In the event of compartment syndrome, surgical decompression is possible.
Patient monitoring: After contrast medium administration, the patient should be observed for at least 30 minutes, as most serious adverse reactions occur within this time. However, more delayed adverse reactions are also possible.
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, the patient can be transferred to an outpatient regimen, but the patient should avoid tilting. When bed rest is observed, the elevated position of the head and chest should be maintained for the first 6 hours. If a low seizure threshold is suspected, the subject should be observed during this period. Outpatients should not be left alone for the first 24 hours after the examination.
Features of use in children.
It should be remembered about the possibility of developing transient hypothyroidism in premature infants, newborns and other children in connection with the administration of iodinated contrast agents. Premature infants have an increased sensitivity to iodine. It is necessary to monitor thyroid function. When using iodinated contrast agents, pregnant women should monitor thyroid function in newborns during the first week of life.
Infants in particular should be adequately hydrated before and after contrast media administration. Treatment of nephrotoxicity should be considered. Depending on age, glomerular filtration rate in infants decreases, which may lead to delayed excretion of contrast media.
In children under 1 year of age and especially in newborns, hemodynamic and electrolyte imbalance disorders occur particularly easily.
This medicinal product contains less than 1 mmol sodium/dose, i.e. essentially sodium-free.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effect of the drug on the ability to drive and use machines have been conducted. It is not recommended to drive or operate complex machinery during the first 24 hours after intrathecal administration of contrast media. If symptoms occur after myelography, the decision should be made individually.
Use during pregnancy or breastfeeding
Pregnancy. The safety of the drug during pregnancy has not been established. The results of experimental preclinical studies on reproduction, embryonal or fetal development, pregnancy, peri- and postnatal development do not indicate the existence of direct or indirect harmful effects. Radiation should be avoided during pregnancy if possible, and caution should be exercised when prescribing X-ray examinations, with or without contrast media, due to the possible risk.
Tomohexol should only be used during pregnancy if clearly needed, according to a doctor's recommendations and after a careful assessment of the benefit/risk ratio.
Breastfeeding. Contrast media pass into breast milk to a small extent and minimal amounts are absorbed in the intestines. Therefore, the risk to the fetus is unlikely.
Breastfeeding can be continued after administration of iodinated contrast media. In a study, the amount of iohexol excreted in breast milk during the first 24 hours after administration was 0.5% of the weight-adjusted dose. The amount of iohexol absorbed by the infant during the first 24 hours after administration is only 0.2% of the infant dose.
Method of administration and doses
The dose of the drug depends on the examination method, age, body weight, cardiac output, general condition of the patient and the technique of administration of the drug. Usually the same concentration and volume of iodine is used as for another iodinated radiopaque agent. Before and after the use of the contrast agent, as with other radiopaque agents, it is necessary to ensure adequate hydration of the body.
The drug is intended for intraarterial, intravenous, intrathecal, intracavitary administration, oral administration, and rectal administration in adults and children.
Concentrations and doses of the drug used
Indication
| Iodine concentration, mg/ml | Volume of the drug, ml | Special instructions | |
| Intravenous administration | | | |
| Urography | | | |
| Adults | 300 mg iodine/ml or 350 mg iodine/ml; | 40–80 ml 40–80 ml | In some cases, more than 80 ml may be administered. |
| Children (body weight less than 7 kg) | 240 mg iodine/ml or 300 mg iodine/ml | 4 ml/kg 3 ml/kg | |
| Children (body weight more than 7 kg) | 240 mg iodine/ml or 300 mg iodine/ml; | 3 ml/kg 2 ml/kg (max. dose 40 ml) | |
| Phlebography (lower extremities) | 240 mg iodine/ml or 300 mg iodine/ml | |
| Digital subtraction angiography | 300 mg iodine/ml or 350 mg iodine/ml | 20–60 ml/injection 20–60 ml/injection | |
| Contrast enhancement on CT scan | | | |
| Adults | 240 mg iodine/ml, or 300 mg iodine/ml or 350 mg iodine/ml | 100–250 ml 100–200 ml 100–150 ml | The total amount of iodine in the injection is usually 30-60 g. |
| Children | 240 mg iodine/ml 300 mg iodine/ml | 2–3 ml/kg body weight (up to 40 ml) 1–3 ml/kg body weight (up to 40 ml) | In some cases, it is possible to administer up to 100 ml. |
| Intraarterial administration | | | |
| Arteriography: | | | |
| Aortic arch | 300 mg iodine/ml | 30–40 ml/injection | The volume per injection depends on the injection site. |
| Selective cerebral angiography | 300 mg iodine/ml | 5–10 ml/injection | |
| Aortography | 350 mg iodine/ml | 40–60 ml/injection | |
| Femoral artery angiography | 300 mg iodine/ml or 350 mg iodine/ml | 30–50 ml/injection | |
| Other types | 300 mg iodine/ml | depends on the research method | |
| Cardioangiography: | | | |
| Adults | | | |
| Left ventricle and aortic root | 350 mg iodine/ml | 30–60 ml/injection | |
| Selective coronary angiography | 350 mg iodine/ml | 4–8 ml/injection | |
| Children | 300 mg iodine/ml or 350 mg iodine/ml | The dose depends on age, body weight and disease (max. dose 8 ml/kg) | |
| Digital subtraction angiography | 240 mg iodine/ml or 300 mg iodine/ml | 1–15 ml/injection | Depending on the injection site, larger volumes (up to 30 ml) may be used. |
| Intrathecal administration | | | |
| Myelography* | | | |
| Lumbar or thoracic myelography (lumbar insertion) | 240 mg iodine/ml | 8–12 ml | |
| Cervical myelography (lumbar insertion) | 240 mg iodine/ml or
300 mg iodine/ml
| 10–12 ml 7–10 ml | |
| Cervical myelography (lateral cervical insertion) | 240 mg iodine/ml or 300 mg iodine/ml | 6–10 ml 6-8 ml | |
| CT cisternography (lumbar insertion) | 240 mg iodine/ml | 4–12 ml | |
| Intracavitary administration | | | |
| Arthrography | 240 mg iodine/ml, or 300 mg iodine/ml or 350 mg iodine/ml | 5–20 ml 5–15 ml 5–10 ml | |
| ERPG/ERCPG | 240 mg iodine/ml | 20–50 ml | |
| Herniography | 240 mg iodine/ml | 50 ml | The volume of injection depends on the size of the hernia. |
| Hysterosalpingography | 240 mg iodine/ml or 300 mg iodine/ml | 15–50 ml 15–25 ml | |
| Sialography | 240 mg iodine/ml or 300 mg iodine/ml | 0.5–2 ml | |
| Gastrointestinal tract examination | | | |
| Oral use | | | |
| Adults | 350 mg iodine/ml | Determined individually | |
| Children's esophagus | 300 mg iodine/ml or | 2–4 ml/kg body weight | Maximum dose – 50 ml |
| 350 mg iodine/ml | 2–4 ml/kg body weight | Maximum dose – 50 ml | |
| Premature babies | 350 mg iodine/ml | 2–4 ml/kg body weight | |
Rectal use Children | Doses diluted with water to a concentration of 100–150 mg iodine/ml | 5–10 ml/kg body weight | For example: dilute Tomohexol-240, Tomohexol-300 or Tomohexol-350 with water 1:1 or 1:2 |
| CT enhancement | | | |
| Oral use | | | |
| Adults | Dilute with water to a concentration of about 6 mg iodine/ml | 800–2000 ml of the resulting solution over a specified period | For example: dilute Tomohexol-300 or Tomohexol-350 with water 1:50 |
| Children | Dilute with water to a concentration of about 6 mg iodine/ml | 15–20 ml of the resulting solution/kg of body weight | |
| Rectal administration | | | |
| Children | Dilute with water to a concentration of about 6 mg iodine/ml | Determined individually | |
* To minimize the risk of adverse reactions, the total dose of iodine should not exceed 3 g.
Children
The drug can be used in pediatric practice.
Overdose
In case of overdose, it is necessary to correct water and electrolyte imbalance. Kidney 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
Common types of adverse reactions (typical for all iodine-containing radiopaque agents).
Below are the possible main side effects associated with X-ray procedures using non-ionic contrast agents.
Hypersensitivity reactions may occur regardless of the dose administered and the route of administration. Mild symptoms may be the first signs of a serious anaphylactic reaction/shock. The contrast medium should be discontinued immediately and specific therapy with intravascular administration of drugs should be initiated if necessary.
Transient increases in S-creatinine are common after the use of iodinated radiocontrast agents, increasing the risk of contrast-induced nephropathy.
Iodism or iodine mumps is a very rare reaction to the administration of iodine-containing radiopaque agents. It can manifest as swelling and pain in the salivary glands for up to 10 days after the examination.
Immune system disorders: hypersensitivity reactions (including dyspnoea, rash, erythema, urticaria, pruritus, skin reactions, vasculitis, angioedema, laryngeal oedema, laryngospasm, bronchospasm or non-cardiogenic pulmonary oedema may develop either immediately after administration of the drug or several days later), anaphylactic/anaphylactoid reactions, anaphylactic/anaphylactoid shock.
Nervous system: headache, dysgeusia (transient metallic taste), vasovagal syncope.
From the cardiovascular system: bradycardia, arterial hypertension, arterial hypotension.
On the part of the digestive system: nausea, vomiting, diarrhea, pain/discomfort in the epigastric region, increase in the size of the salivary glands.
General disorders: feeling hot, pyrexia, shivering (chills).
Injuries, poisonings and procedural complications: iodism.
Adverse reactions associated with intravascular (intraarterial and intravenous) administration.
The development of adverse reactions that may occur during intra-arterial administration depends on the injection site and dose of the drug. During selective angiography and other studies, when a high concentration of contrast agent penetrates the organ being examined, dysfunction of this organ may occur.
Immune system disorders: hypersensitivity reactions, including life-threatening or fatal anaphylaxis, severe pustular, exfoliative or bullous reactions.
On the part of the endocrine system: thyrotoxicosis, transient hypothyroidism.
On the part of the psyche: confusion of consciousness.
Nervous system: dizziness, convulsions, impaired consciousness, encephalopathy, stupor, sensory disturbances (including hypoesthesia), paresthesia, tremor, headache, dysgeusia, transient motor dysfunction (including speech disorders, aphasia, dysarthria), transient contrast encephalopathy (including transient hemiplegia or delirium, temporary memory loss, disorientation, coma, retrograde amnesia).
On the part of the organs of vision: transient cortical blindness.
From the organs of hearing and balance: transient hearing loss.
Cardiovascular system: arrhythmia (including bradycardia, tachycardia), myocardial infarction, hyperemia, arterial hypertension, severe cardiac complications (including cardiac arrest, cardiorespiratory arrest), coronary artery spasm, chest pain, shock, arterial spasm, ischemia, thrombophlebitis and thrombosis.
Respiratory system: cough, dyspnea, non-cardiogenic pulmonary edema, acute respiratory symptoms, bronchospasm, laryngospasm, asthma attack.
On the part of the digestive system: diarrhea, nausea, vomiting, enlargement of the salivary glands, abdominal pain, exacerbation of pancreatitis, acute pancreatitis.
Skin and subcutaneous tissue disorders: erythema multiforme, acute generalized exanthematous pustulosis, bullous dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced skin reaction accompanied by eosinophilia and systemic manifestations, sudden exacerbation of psoriasis.
Musculoskeletal and connective tissue disorders: arthralgia.
Renal and urinary disorders: renal dysfunction, including acute renal failure.
General disorders and administration site conditions: feeling hot, pain and discomfort, asthenic state (including malaise, fatigue), shivering (chills), hyperthermia, injection site reactions including transudation, back pain.
Intrathecal administration.
Adverse reactions may occur several hours or days after intrathecal administration. Their frequency is approximately the same as that after lumbar punctures without contrast medium. Excessive cerebrospinal fluid removal should be avoided to minimize pressure reduction.
Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.
Nervous system: headache (may be severe and prolonged), aseptic meningitis (including chemical meningitis), convulsions, dizziness, dysgeusia, vasovagal syncope, encephalogram rhythm disturbances, meningism, transient contrast encephalopathy (including transient hemiplegia or delirium, temporary memory loss, coma, stupor, retrograde amnesia), transient motor dysfunction (including speech disorders, aphasia, dysarthria), paresthesia, hypoesthesia, sensory disorders.
From the organs of vision: transient cortical blindness, photophobia.
From the organs of hearing and balance: transient hearing loss.
On the part of the digestive system: abdominal pain, enlarged salivary glands, nausea, vomiting, diarrhea.
Musculoskeletal and connective tissue disorders: neck pain, back pain, spasms.
General disorders and administration site conditions: pain in extremity, feeling hot, pyrexia, shivering (chills), injection site conditions.
Adverse reactions associated with intracavitary administration.
Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.
Nervous system: headache, dysgeusia, vasovagal syncope.
From the digestive system: nausea, abdominal pain, enlarged salivary glands, vomiting, diarrhea; with hysterosalpingography - pain in the lower abdomen.
General disorders and administration site conditions: feeling hot, pyrexia, shivering (chills).
Endoscopic retrograde pancreatography/cholangiopancreatography (ERPG/ERCP).
On the part of the digestive system: pancreatitis, increased amylase in the blood.
Oral use.
On the part of the digestive system: diarrhea, nausea, vomiting, abdominal pain.
Hysterosalpingography (HSG).
On the part of the digestive system: pain in the lower abdomen.
Arthrography.
Musculoskeletal and connective tissue disorders: arthritis.
General disorders and administration site conditions: pain.
Herniography.
General disorders and administration site conditions: post-procedure pain.
Certain adverse reactions.
Thromboembolic complications have been reported in association with contrast-enhanced coronary, cerebral, renal and peripheral angiography. The contrast agent may contribute to the development of complications (see section 4.4). Cardiac complications, including acute myocardial infarction, have been reported during or after contrast-enhanced coronary angiography. Elderly patients or patients with severe coronary artery disease, unstable angina and left ventricular dysfunction were at higher risk of developing complications (see section 4.4).
In rare cases, the contrast agent may cross the blood-brain barrier, resulting in accumulation of the drug 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 warnings and 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 warnings and precautions for use").
In some cases, transudation of contrast medium causes local pain and swelling, which are usually asymptomatic. Cases of inflammation, tissue necrosis and compartment syndrome have been reported (see section "Special warnings and precautions for use").
Pediatric patients. It should be remembered about the possibility of developing transient hypothyroidism in premature infants, newborns and other children in connection with the administration of iodinated contrast agents.
Premature infants are hypersensitive to iodine. Transient hypothyroidism has been reported in premature infants who are breastfed. Iohexol has been administered to breastfeeding women on several occasions (see section "Special warnings and precautions for use").
Infants in particular should be adequately hydrated before and after contrast medium administration. Treatment of nephrotoxicity should be considered.
Depending on age, glomerular filtration rate decreases in infants, which may lead to delayed excretion of contrast agents.
Expiration date
3 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
Store in the original packaging in a place protected from secondary X-ray radiation at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
100 ml in a bottle. 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
