Unihexol^® (Solution) Instructions for Use

Marketing Authorization Holder

Unique Pharmaceutical Laboratories (India)

ATC Code

V08AB02 (Iohexol)

Active Substance

Iohexol (Rec.INN registered by WHO)

Dosage Forms

	Unihexol®	Solution for injection 240 mg iodine/ml: amp. 20 ml 5 pcs., fl. 50 ml or 100 ml 1 pc.
		Solution for injection 300 mg iodine/ml: amp. 20 ml 5 pcs., fl. 50 ml or 100 ml 1 pc.
		Solution for injection 350 mg iodine/ml: amp. 20 ml 5 pcs., fl. 50 ml or 100 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for injection transparent, from colorless to light yellow.

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

20 ml – glass ampoules (5) – thermal containers (1) – cardboard packs.
50 ml – glass vials (1) – cardboard packs.
100 ml – glass vials (1) – cardboard packs.

Solution for injection transparent, from colorless to light yellow.

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

20 ml – glass ampoules (5) – thermal containers (1) – cardboard packs.
50 ml – glass vials (1) – cardboard packs.
100 ml – glass vials (1) – cardboard packs.

Solution for injection transparent, from colorless to light yellow.

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

20 ml – glass ampoules (5) – thermal containers (1) – cardboard packs.
50 ml – glass vials (1) – cardboard packs.
100 ml – glass vials (1) – cardboard packs.

Clinical-Pharmacological Group

Radiocontrast non-ionic diagnostic agent for intravascular, intracavitary administration and oral intake

Pharmacotherapeutic Group

Radiocontrast agent

Pharmacological Action

In computed tomography, contrast visualization in the thoracic region is achieved within 1 hour, in the cervical region – about 2 hours, in the basal cisterns – 3-4 hours. Contrasting of joint cavities, uterine cavity, fallopian tubes, peritoneal protrusions, pancreatic and bile ducts, and the urinary bladder is achieved immediately after administration of the drug.

Pharmacokinetics

Approximately 100% of intravenously administered iohexol is excreted unchanged via normally functioning kidneys within 24 hours. C_max of iohexol in urine is determined approximately 1 hour after injection. Metabolites of the drug have not been detected. Binding to plasma proteins is minimal (less than 2%). Renal clearance – 99 ml/min, total clearance – 109 ml/min. C_max in blood plasma – 119 µg/ml, time to reach C_max – 2-6 hours. V_d – 157 ml/kg, T_1/2 – 3-4 hours.

Indications

The drug is used for the following diagnostic radiological examinations

• Cardioangiography;
• Arteriography;
• Urography;
• Phlebography;
• Contrast enhancement in computed tomography;
• Arthrography;
• Endoscopic retrograde pancreatography;
• Endoscopic retrograde cholangiopancreatography;
• Salpingography;
• Sialography;
• Gastrointestinal tract examinations.

ICD codes

Dosage Regimen

The drug is intended for intra-arterial, intravenous, intracavitary administration and oral intake. Before use, the drug should be visually inspected for the absence of insoluble particles, color changes and packaging integrity violations.

The drug should be drawn into a syringe immediately before use. Vials are intended for single use only; unused drug residues after opening the vial must be destroyed.

During drug administration, the patient should be in a horizontal position. Medical supervision of patients should be carried out for 30 minutes after the end of the procedure, as most adverse reactions occur during this period.

Intravenous administration

Excretory urography:adults – 40-80 ml of Unihexol^® 300 mg iodine/ml or Unihexol^® 350 mg iodine/ml; children > 7 kg – 3 ml/kg body weight of Unihexol^® 240 mg iodine/ml, or 2 ml/kg body weight of Unihexol^® 300 mg iodine/ml; injection volume – no more than 40 ml.

Lower limb phlebography:adults – 20-100 ml/per limb of Unihexol^® 240 mg iodine/ml or Unihexol^® 300 mg iodine/ml;

Digital subtraction angiography:adults – 20-60 ml/per injection of Unihexol^® 300 mg iodine/ml or Unihexol^® 350 mg iodine/ml;

Enhancement in computed tomography:adults – 100-250 ml of Unihexol^® 240 mg iodine/ml or 100-200 ml of Unihexol^® 300 mg iodine/ml or 100-150 ml of Unihexol^® 350 mg iodine/ml; total iodine amount is usually 30-60 g; children – 2-3 ml/kg body weight of Unihexol^® 240 mg iodine/ml or 1-3 ml/kg body weight of Unihexol^® 300 mg iodine/ml (injection volume should not exceed 40 ml).

Intra-arterial administration

1 . Angiography

Thoracic aortaadults – 30-40 ml per injection of Unihexol^® 300 mg iodine/ml.

Selective cerebral angiography:adults – 5-10 ml per injection of Unihexol^® 300 mg iodine/ml.

Aortography:adults – 40-60 ml per injection of Unihexol^® 350 mg iodine/ml.

Femoral artery angiography:adults – 30-50 ml per injection of Unihexol^® 300 mg iodine/ml or Unihexol^® 350 mg iodine/ml.

2. Cardioangiography

Adults– injection into the left ventricle and aortic root: 30-60 ml per injection of Unihexol^® 350 mg iodine/ml.

Selective coronary angiography:adults – 4-8 ml per injection of Unihexol^® 350 mg iodine/ml; children– depending on age, body weight and disease (maximum – 8 ml/ kg body weight) of Unihexol^® 300 mg iodine/ml or Unihexol^® 350 mg iodine/ml.

Digital subtraction angiography:adults – 1-15 ml per injection of Unihexol^® 240 mg iodine/ml or Unihexol^® 300 mg iodine/ml.

Intracavitary administration

Arthrographyadults – 5-20 ml of Unihexol^® 240 mg iodine/ml; or 5-15 ml of Unihexol^® 300 mg iodine/ml; or 5-10 ml of Unihexol^® 350 mg iodine/ml.

Retrograde pancreato- and cholangiography:adults – 20-50 ml of Unihexol^® 240 mg iodine/ml.

Herniography:adults – 50 ml of Unihexol^® 240 mg iodine/ml. Injection volume depends on the hernia volume.

Hysterosalpingography:adults – 15-50 ml of Unihexol^® 240 mg iodine/ml; or 15-25 ml of Unihexol^® 300 mg iodine/ml.

Sialography:adults – 0.5-2 ml of Unihexol^® 240 mg iodine/ml; or 0.5-2 ml of Unihexol^® 300 mg iodine/ml.

Enhancement in computed tomography

Oral contrastadults – Unihexol^® 300 mg iodine/ml or 350 mg iodine/ml is diluted with water in a ratio of 1:50 to a concentration of about 6 mg iodine/ml. Total solution volume – 800-2000 ml; children – 15-20 ml of solution per 1 kg body weight

Gastrointestinal tract examinations

Oral contrast:adults – the volume of the administered dose is selected individually (Unihexol^® 350 mg iodine/ml); children (esophagus) – 2-4 ml/kg body weight of Unihexol^® 300 mg iodine/ml or 2-4 ml/kg body weight of Unihexol^® 350 mg iodine/ml, total injection volume should not exceed 50 ml.

Adverse Reactions

General adverse reactions

Undesirable and adverse reactions to non-ionic radiocontrast agents are usually of moderate severity, reversible in nature and occur less frequently than with the use of ionic contrast agents.

Sensations of warmth throughout the body or a transient metallic taste in the oral cavity, discomfort or pain in the abdominal area, nausea, vomiting may be observed.

The occurrence of hypersensitivity reactions in the form of moderately severe respiratory disorders (dyspnea, bronchospasm) or skin reactions (rash, erythema, urticaria, itching) has been noted; in some cases, angioedema may develop. Allergic manifestations can occur either immediately after drug administration or after several days. Sometimes severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis may occur. Severe manifestations of hypersensitivity reactions, such as laryngeal edema, pulmonary edema and anaphylactic shock are rare.

Anaphylactoid reactions can occur regardless of the dose and route of administration; serious adverse effects may begin with minor manifestations of a hypersensitivity reaction. In this case, it is necessary to immediately stop the administration of the contrast agent and initiate appropriate therapy.

Vasovagal reactions in the form of arterial hypotension and bradycardia may occur. Occasionally, fever with the development of a convulsive syndrome may be noted.

Iodism or iodine mumps is a rare reaction to the administration of iodine-containing contrast agents, expressed as enlargement and tenderness of the salivary glands after the examination, lasting up to 10 days.

Adverse reactions associated with intra-arterial administration

The nature of adverse reactions observed during intra-arterial administration of radiocontrast agents depends on the injection site and the administered dose. During selective angiography and other examinations when the contrast agent enters the examined organ in high concentration, functional disorders of this organ may be observed. Pain along the vessels or a sensation of warmth during peripheral angiography occurs quite frequently.

A transient increase in serum creatinine levels is quite often observed, but it usually has no clinical significance; renal failure rarely develops.

When administered into the coronary, cerebral or renal arteries, arterial spasm may develop, leading to transient ischemia in the examined organ. Neurological reactions such as convulsions, transient sensory or motor function disturbances are rarely observed. In isolated cases, the radiocontrast agent may penetrate the blood-brain barrier, resulting in accumulation of the drug in the cerebral cortex, which allows visualization of brain tissue on computed tomography. This phenomenon may persist for 1-2 days and is accompanied by transient disorientation or cortical blindness.

Severe reactions from the cardiovascular system may occur, such as rhythm disturbances, decreased myocardial contractility or myocardial ischemia.

Adverse reactions associated with intravenous administration

Post-phlebographic thrombophlebitis or thrombosis develops very rarely. Isolated cases of arthralgia have been described.

Adverse reactions during intracavitary administration

General hypersensitivity reactions develop extremely rarely.

Endoscopic retrograde pancreatocholangiography some increase in serum amylase activity is often observed; rare cases of pancreatic necrosis development have been described.

Oral intake gastrointestinal disorders may be observed.

Hysterosalpingography moderate and transient pain in the lower abdomen is often noted.

Arthrography pain is often noted after the examination. Arthritis following drug administration rarely develops. There is a risk of developing infectious arthritis.

Herniography moderate pain reaction may occur after the examination.

Extravascular administration of contrast agents (extravasation) in rare cases can lead to the development of local pain and swelling, which usually resolve without any consequences. Cases of inflammation and tissue necrosis have been described. As therapeutic measures, cold and elevation of the limb are recommended. If compression symptoms develop, surgical decompression is recommended.

Contraindications

• Severe thyrotoxicosis;
• Local or systemic infections;
• Pregnancy;
• Hypersensitivity to the drug or its components.

Caution should be exercised in the presence of a history of allergy, bronchospasm or other undesirable reactions when using iodine-containing contrast agents. In these cases, the advisability of administering glucocorticosteroids or histamine H₁-receptor blockers should be considered.

Caution should be exercised when examining patients with decompensated cardiovascular diseases and pulmonary hypertension due to the risk of developing heart rhythm disturbances or worsening hemodynamic impairment.

The drug should be used with caution when examining patients with bronchial asthma, hay fever, multiple myeloma, food allergy, hepatic insufficiency, dehydration, multiple sclerosis, sickle cell anemia, obliterating thromboangiitis (Buerger’s disease), acute thrombophlebitis, severe atherosclerosis, in elderly persons, during lactation.

Patients with acute cerebral pathology, brain tumors or epilepsy are prone to developing convulsions and require special attention. In patients with alcoholism and drug addiction, the risk of developing convulsions and neurological reactions is increased.

To prevent the development of acute renal failure associated with the administration of the contrast agent, special caution is required when examining patients with impaired renal function, diabetes mellitus, patients with paraproteinemias (multiple myeloma, Waldenström’s macroglobulinemia).

Administration of iodine-containing contrast agents may exacerbate myasthenia gravis symptoms.

When performing invasive examinations and interventions in patients with pheochromocytoma, prophylactic administration of alpha-blockers is necessary to prevent the development of a hypertensive crisis.

Special caution is required when examining patients with moderate thyrotoxicosis, especially patients with multinodular goiter.

Use in Pregnancy and Lactation

Unihexol^® should not be used in pregnant women, except in cases where the benefit of its use outweighs the risk and such an examination is prescribed by a doctor out of necessity.

The drug is excreted in small amounts into breast milk and is absorbed in the intestine, so breastfeeding should be avoided for 24 hours after administration of Unihexol^®.

Use in Hepatic Impairment

The drug should be used with caution when examining patients with hepatic insufficiency.

Use in Renal Impairment

To prevent the development of acute renal failure associated with the administration of the contrast agent, special caution is required when examining patients with impaired renal function.

Pediatric Use

Dose adjustment is required.

Geriatric Use

The drug should be used with caution when examining elderly persons.

Special Precautions

Patient preparation and drug administration procedure

Before administering the contrast agent, it is necessary to obtain accurate information about the patient, including laboratory data (e.g., serum creatinine level, electrocardiogram, indication of allergy history, presence of pregnancy).

Before the examination, it is necessary to correct the patient’s water-electrolyte balance disorders and ensure sufficient intake of fluids and electrolytes into the patient’s body. This is especially important for patients with multiple myeloma, diabetes mellitus, polyuria or gout, as well as young children and elderly patients. The patient should stop eating 2 hours before the procedure.

Preliminary testing of individual sensitivity using small doses of the drug is not recommended due to the risk of severe hypersensitivity reactions.

Patients experiencing anticipatory anxiety before the procedure require premedication with sedatives.

The risk of developing severe adverse reactions to the drug is small, however, iodine-containing contrast agents can cause anaphylactoid reactions or other manifestations of hypersensitivity. In this regard, the sequence of therapeutic measures in case of their occurrence should be planned in advance and necessary medications and equipment should be available. Before and after the administration of the contrast agent, care must be taken to hydrate the patient’s body. This is especially important in patients with multiple myeloma, diabetes mellitus, impaired renal function, as well as elderly patients.

Separate syringes and needles should be used for the administration of Unihexol^® and it should not be mixed with other medicinal products.

Compared to ionic agents, non-ionic radiocontrast agents have less effect in vitro on the blood coagulation system. When performing angiographic examinations, the technique of their performance should be carefully observed and catheters should be frequently flushed (with heparinized saline) to minimize the risk of thrombosis and embolism associated with the intervention.

All iodine-containing radiocontrast agents affect the results of thyroid function tests, as the iodine-binding capacity of the gland may decrease for several weeks after the examination.

High concentrations of the drug in blood plasma or urine may affect the results of bilirubin, protein or inorganic substance (iron, copper, calcium and phosphate) levels, so these tests should not be performed on the day of the examination.

Biguanides should be discontinued 48 hours before the examination and resumed after complete stabilization of renal function.

Measures for the prevention of adverse reactions

• Identification of patients belonging to the high-risk group;
• Ensuring adequate hydration. Hydration can be achieved through continuous intravenous infusion, initiated prior to the administration of the contrast agent and continued until the renal excretion of the radiocontrast medium is complete;
• Repeat radiocontrast studies should not be performed until renal function has returned to its baseline level.

Particular caution should be exercised in patients with severe combined hepatic and renal impairment, as the clearance of contrast media is significantly reduced in these patients. Radiocontrast studies in patients on hemodialysis are possible provided that dialysis is performed immediately after the study.

Effect on the ability to drive vehicles and operate machinery

Driving vehicles and operating machinery should be avoided for 24 hours after the administration of the drug.

Overdose

The development of overdose symptoms is unlikely unless more than 2000 mg of iodine/kg is administered to the patient within a short period of time. The duration of the procedure when high doses of the drug are administered may affect renal function. Accidental overdose of the drug is possible during complex angiographic procedures in children, especially with multiple administrations of high doses.

Symptoms: cyanosis, bradycardia, acidosis, pulmonary hemorrhage, cardiac arrest, insomnia or drowsiness, weakness, increased fatigue, stupor, epileptic syndrome, coma, mental activity disorders: hallucinations, depersonalization, fear, disorientation, echolalia, depression, amnesia, psychosis, amblyopia, diplopia, photophobia, hyperesthesia, visual, auditory, or speech impairments, changes on the electroencephalogram, meningism, hyperreflexia or areflexia, hemiplegia, paralysis, tetraplegia, tremor, cerebral hemorrhage.

Treatment: in cases of overdose, measures should be taken to correct the resulting disturbances in water and electrolyte balance. Renal function should be monitored for the next 3 days. If necessary, hemodialysis can be used to remove excess drug. There is no specific antidote. Diazepam 10 mg is administered intravenously slowly; 20-30 minutes after the cessation of the convulsive seizure – phenobarbital 200 mg intramuscularly. Monitoring and maintenance of vital functions, implementation of symptomatic therapy.

Drug Interactions

The use of radiocontrast agents in diabetic patients taking biguanides (metformin) may lead to transient impairment of renal function and the development of lactic acidosis.

Patients who have taken interleukin-2 less than 2 weeks before the study are prone to an increased frequency of delayed adverse reactions (flu-like conditions or skin reactions).

In patients taking beta-blockers, the manifestations of anaphylaxis may be atypical and mistakenly taken for vagal reactions.

The drug is pharmaceutically incompatible with drugs of other groups.

Phenothiazine derivatives and other antipsychotic drugs (neuroleptics), MAO inhibitors, tetracyclic antidepressants, CNS stimulants, analeptics, antipsychotic drugs – the epileptic threshold is lowered and the risk of epileptic seizures increases.

Beta-blockers and other antihypertensive drugs increase the likelihood of arterial hypotension.

It enhances the nephrotoxic properties of other drugs.

Storage Conditions

Store at a temperature not exceeding 30°C (86°F). Do not freeze. Protect from light and secondary X-rays.
Keep out of reach of children.

Shelf Life

The shelf life is 3 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.