Vizipak - instructions for use, dose, side effects, contraindications

Active substanceIodixanolIodixanol

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Visipac®

solution for injections

JI Halskea Limited United Kingdom

Iodixanol

solution for injections

JODAS EKSPOIM, LLC Russia

Dosage form: & nbspinjection

Composition:

Vizipak® 270 mg iodine / ml

1 ml of the solution contains:

active substance: iodixanol 550 mg;

Excipients: trometamol 1,20 mg, sodium chloride 1.87 mg, calcium chloride dihydrate 0.07 mg, sodium calcium edetate 0.10 mg, hydrochloric acid, 5 M solution to pH 6.8-7.6 1,6 mcl, water for injection 0.73 ml.

Visipac® 320 mg iodine / ml

1 ml of the solution contains:

active substance: iodixanol 652 mg;

Excipients: trometamol 1,20 mg, sodium chloride 1.11 mg, calcium chloride dihydrate 0.04 mg, sodium calcium edetate 0.10 mg, hydrochloric acid, 5 M solution to pH 6.8-7.6 1,6 mcl, water for injection 0.68 ml.

Description:

A clear, colorless or pale yellow solution.

Pharmacotherapeutic group:X-ray contrast medium

ATX: & nbsp

V.08.A Radiocontrast iodine-containing substances

Pharmacodynamics:

Physicochemical characteristics

Iodixanol is a nonionic, dimeric, hexaiodinated, water-soluble radiocontrast agent. The pH of the preparation is 6.8-7.6.

A pure iodixanol aqueous solution at all clinical concentrations used has a lower osmolality than whole blood and non-ionic monomeric contrast agents at the same concentrations.Vizipak® is isotonic with respect to normal body fluids due to the addition of electrolytes.

The osmolality and viscosity of Visipac® are listed below:

Concentration	Osmolality (mOsmol/kg H₂ABOUT)	Viscosity (mPa·from)
Concentration	37 ° C	20 ° С	37 FROM
270 mg iodine / ml	290	11,3	5,8
320 mg iodine / ml	290	25,4	11,4

Pharmacodynamics

Iodixanol is a nonionic iodine-containing radiopaque preparation. After injection, organically bound iodine concentrates in the vessels and some tissues (kidneys, thyroid gland, etc.) of the cerebrospinal fluid, making them radiopaque.

After administration, the organically bound iodine, located in blood vessels and tissues, absorbs radiation.

Application of the drug iodixanol in 3% of patients with diabetes mellitus with a serum level of creatinine of 1.3-3.5 mg / dl was accompanied by an increase in the level of creatinine by ≥0.5 mg / dl, but no patient experienced an increase of ≥1.0 mg / dl. With the use of Visipac®, the secretion of enzymes (alkaline phosphatase and N-acetyl-β-glucosaminidase) in the proximal tubules of the kidneys was weaker than after administration of nonionic monomeric contrast agents and the same as after administration of ionic dimeric contrast agents.

Such cardiovascular indices as end-diastolic pressure in the left ventricle, systolic pressure in the left ventricle, heart rate, interval QT and the current velocity in the femoral artery was less altered after iodixanol administration than after the administration of other contrast agents.

Pharmacokinetics:

Iodixanol is rapidly distributed in the extracellular fluid of the body. The distribution period averages about 21 minutes. The apparent volume of distribution coincides with the volume of extracellular fluid (0.26 l / kg body weight), which indicates the distribution of the drug only to the extracellular fluid. Metabolites of iodixanol were not detected. The proteins bind less 2% preparation.

The half-life on average is about 2 hours. Iodixanol mainly excreted by the kidneys through glomerular filtration. After intravenous administration of iodixanol to healthy volunteers, approximately 80% of the administered dose is withdrawn in urine within 4 hours in the unchanged form and 97% of the drug within 24 hours. Only 1.2% of the administered dose is excreted intestine within 72 hours. The maximum concentration of the drug in the urine is reached approximately 1 hour after the injection.

In the range of recommended doses, pharmacokinetics does not have a dose-response relationship.

Indications:

Vizipak® is for diagnostic use only.

Radiopaque means for carrying out:

- cardioangiography, coronary angiography, cerebral angiography, peripheral angiography, abdominal aortography (in /a DSA), urography, phlebography, contrast enhancement in CT and examination of the gastrointestinal tract;

- lumbar, thoracic and cervical myelography;

- arthrography and hysterosalpingography (GHA).

In children for cardioangiography, urography, contrast enhancement for CT and examination of the gastrointestinal tract.

Contraindications:

Hypersensitivity to the active ingredient or any auxiliary substance.

Data on serious adverse reactions to iodixanol in the anamnesis.

Manifesting thyrotoxicosis.

Carefully:

When Care should be taken when using nonionic radiocontrast agents:

- if there is a history of allergy, asthma or other adverse reactions to iodine-containing radiopaque agents. Premedication with corticosteroids or antihistamines is recommended;

- in the study of patients with severe cardiovascular diseases and pulmonary hypertension, because of the risk of developing hemodynamic disorders or arrhythmias;

- in the study of patients with acute cerebral pathology, tumors or epilepsy in an anamnesis, in connection with the predisposition of this category of patients to convulsions. The risk of seizures and neurological reactions is also increased in patients suffering from alcoholism or drug dependence;

- in the study of patients with severe combined disorders of the liver and kidneys, since they significantly reduced the clearance of radiocontrast agents;

- to prevent the development of acute renal failure after the introduction of radiopaque means should pay special attention to patients at increased risk of kidney failure and diabetes, as well as patients with paraproteinaemia (myelomatosis and macroglobulinemia Waldenstrem);

- in the study of patients with hyperthyroidism. In patients with multinodular goitre after the introduction of iodine-containing radiocontrast agents, there is a risk of developing hyperthyroidism.With the introduction of radiopaque means for premature infants, consideration should be given to the possibility of developing transient hyperthyroidism;

- when examining patients with hypovolemia, adequate hydration should be provided, at least 100 ml every hour for 4 hours before the test and 24 hours after the test;

- in the study of patients with multiple myeloma, diabetes mellitus, impaired renal function, newborns, children under one year and elderly patients, adequate hydration is necessary before and after the administration of the radiopaque.

- Patients with diabetes mellitus metformin, before intravascular administration of iodine-containing radiocontrast agents, the drug should be discontinued for at least 48 hours before and within 48 hours after the procedure.

In emergency cases, when the kidney function is unknown, the doctor should evaluate the risk / benefit ratio of the contrast agent: stop using metformin, carry out water stress, monitor kidney function, monitor the appearance of the initial signs of lactic acidosis.

Pregnancy and lactation:

The drug should not be used in pregnant women, unless the intended benefit to the mother from its use outweighs the potential risk to the fetus, and such a study is prescribed by the doctor as necessary.

Contrast agents are excreted to breast milk to a small extent. Therefore, the likelihood of harm to the child when breastfeeding is unlikely. However, if you need to administer the drug, stop breastfeeding before you inject the drug and do not resume at least 24 hours after the test.

Hysterosalpingography should not be performed in pregnant women and in the presence of acute pelvic peritonitis.

Dosing and Administration:

General information

The drug is intended for intravascular (intra-arterial, intravenous) and intrathecal administration, intracavitary administration and for oral administration in gastrointestinal examinations. Like all preparations for parenteral administration, Visipac® must be visually inspected before use for lack of insoluble particles, discoloration, and packaging integrity problems.

Vizipak® should be injected into the syringe immediately before use. Unused remnants of the drug for further use are not allowed.

Additional instructions for using the autoinjector

Bottles with a radiocontrast agent with a capacity of 500 ml should be used only together with the corresponding autoinjector. In this case, a single puncture of the vial plug is performed. The output tube of the autoinjector changes after each patient.

The unused preparation, left in the vial and the connecting tubes, is destroyed at the end of the working day. If necessary, bottles of a smaller volume may also be used. When working with an autoinjector, follow the instructions for using it.

Preparation of the patient

Before applying radiopaque, you need to obtain accurate information about the patient, including laboratory data (including serum creatinine, ECG, allergy, pregnancy).

Before the study, the patient should eliminate violations of water electrolyte balance and provide adequate rehydration, especially in patients with multiple myeloma, diabetes mellitus,polyuria or gout, as well as in newborns, infants, young children and elderly patients.

Procedure of drug administration

Before the introduction of Vizipak® it is necessary to heat up to body temperature, as well as other radiopaque preparations.

When performing angiographic studies, you should carefully follow their procedure and often flush the catheter (eg, 0.9% sodium chloride solution with heparin) to minimize the risk of thrombosis and embolism.

Recommended dosing regimen

Dosage depends on the type and method of study, age, body weight, hemodynamic status, the general condition of the patient. Usually the same concentration and volume are used as with other iodine-containing radiopaque agents. In some studies, sufficient diagnostic information was obtained using iodixanol with a slightly lower concentration of iodine.

The recommended dosage regimen is shown in the table below.

Doses for intra-arterial administration are indicated for a single injection, which can be repeated.

Indication / Examination	Concentration		Scope
Intraarterial (in/a) introduction
Arteriography
Selective cerebral	150/270/320⁽¹⁾ mg iodine / ml		5-10 ml / injection
Aortography	270/320 mg iodine / ml		40-60 ml / injection
Peripheral	150/270/320 mg iodine / ml		30-60 ml / injection
Selective visceral in /a DSA	270 mg iodine / ml		10-40 ml / injection
Cardioangiography
Adults
Left ventricle and aorta root	320 mg iodine / ml		30-60 ml / injection
Selective coronary angiography	320 mg iodine / ml		4-8 ml / injection
Children	270/320 mg iodine / ml		Depending on age, body weight and pathology (max, total volume not more than 10 ml / kg)
Intravenous (iv) administration
Urography
Adults	270/320 mg iodine / ml		40-80 ml⁽²⁾
Children (body weight <7 kg)	270/320 mg iodine / ml		2-4 ml / kg
Children (body weight> 7 kg)	270/320 mg iodine / ml		2-3 ml / kg All doses, depending on age, body weight and pathology (max 50 ml)
Phlebography	270 mg iodine / ml		50-150 ml / limb
Gain at CT
CT of head (adults)	270/320 mg iodine / ml		50-150 ml
CT of the body (adults)	270/320 mg iodine / ml		75-150 ml
CT of head and body (children)	270/320 mg iodine / ml		2-3 ml / kg up to 50 ml All doses, depending on age, body weight and pathology (in some cases, up to 150 ml per child can be administered)
Intrathecal administration
Lumbar and thoracic	270 mg iodine / ml or		10-12 ml (3)
myelography (lumbar injection)	320 mg iodine / ml		10 ml⁽³⁾
Cervical myelography	270 mg iodine / ml or		10-12 ml⁽³⁾
(cervical or lumbar injection)	320 mg iodine / ml		10 ml⁽³⁾
Introduction to the body cavity Dose is selected individually for optimal visualization
Arthrography	270 mg iodine / ml		1-15 ml
Hysterosalpingography (GHA)	270 mg iodine / ml		5-10 ml (the recommended dose can be exceeded several times, for example, with back flowing into the vagina (doses up to 40 ml were used)
Gastrointestinal	Dose is selected individually for optimal visualization
Oral:
Adults
Evaluation of the passage of the gastrointestinal tract	320 mg iodine / ml		Doses of 80-200 ml were used
Esophagus	320 mg iodine / ml		Doses of 10-200 ml were used
Stomach	320 mg iodine / ml		Doses of 20-200 ml were used
Children	270/320 mg iodine / ml		5 ml / kg body weight, doses of 10-240 ml
Rectal:
Children		270/320 mg iodine / ml	Doses of 30-400 ml were used

(1) Both concentrations can be used, but in most cases 270 mg / iodine ml is recommended.

(2) In some cases, the administration of more than 80 ml.

(3) To reduce possible adverse reactions, the total dose should not exceed 3.2 g of iodine.

Elderly patients

Dose adjustments in elderly patients are not required.

Follow-up of the patient after the procedure

After the introduction of radiopaque, the patient should be monitored for at least 30 minutes, since most serious adverse reactions develop during this time period.However, the experience shows that hypersensitivity reactions can develop in a few hours and even days after the injection.

Side effects:

Unwanted adverse reactions to non-ionic radiopaque preparations are usually moderately expressed, are reversible. Serious reactions or fatal cases were very rare. After the administration of the iodine-containing contrast agent, an insignificant transient increase in serum creatinine is observed, which usually has no clinical significance. The incidence of adverse events is classified as follows: very often (≥1/10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10000 to < 1/1000), very rarely (<1/10000), is unknown (can not be determined from available data). These values are based on the primary clinical documentation and published research data, in which more than 48,000 patients participated.

Intravascular administration

Immune system disorders:

Infrequent: hypersensitivity.

Unknown: anaphylactoid reaction, anaphylactoid shock; severe skin reactions in the form of bullae and pustules.In patients with autoimmune diseases, there have been cases of development of vasculitis and Stevens-Johnson syndrome.

Disorders of the psyche:

Unknown: confusion.

Impaired nervous system:

Infrequently: a headache.

Rarely: dizziness.

Very rarely: disturbances in the sensory sphere, including perversion of taste sensations, paresthesia, amnesia.

It is not known: motor dysfunction, impaired consciousness, convulsions, transient encephalopathy caused by extravasation of a contrast drug, which can manifest as disorders of sensory, motor or general neurological functions.

Disorders from the side of the organ of vision:

Very rarely: transient cortical blindness.

Disorders from the cardiovascular system:

Rarely: arrhythmia (including bradycardia, tachycardia), myocardial infarction.

Very rarely: cardiac arrest.

Unknown: ventricular hypokinesia, spasms of the coronary arteries, cardiac arrest and respiration.

Vascular disorders:

Rarely: lowering blood pressure.

Very rarely: increased blood pressure, ischemia.

Unknown: spasm of the arteries, thrombosis, thrombophlebitis.

Disturbances from the respiratory system, chest and mediastinal organs:

Rarely: cough.

Very rarely: dyspnea.

Unknown: noncardiogenic pulmonary edema.

Disorders from the gastrointestinal tract:

Infrequent: nausea, vomiting.

Very rarely: pain / discomfort in the abdomen.

Disturbances from the musculoskeletal and connective tissue:

Unknown: arthralgia.

Disorders from the kidneys and urinary tract:

Very rarely: renal dysfunction, including acute renal failure.

General disorders and disorders at the site of administration:

Infrequent: a feeling of heat, pain in the chest.

Rarely: pain, discomfort, chills, fever, reactions at the injection site, incl. extravasation.

Very rarely: chilliness, asthenic conditions (malaise, fatigue).

Trauma, intoxication and complications of manipulation:

Unknown: iodism.

Intrathecal administration:

After intrathecal administration, unwanted effects may occur several hours or more days after the diagnostic procedure. The frequency of unwanted effects is the same as after lumbar puncture.

With the introduction of other nonionic iodine-containing radiocontrast agents, cases of meningeal irritation, photophobia, meningism, and chemical meningitis have been described.Also, the possibility of developing infectious meningitis should be considered. In the application of other nonionic iodine-containing radiopaque substances, in very rare cases, such transient disorders of cerebral function as convulsions, confusion, impaired motor or sensory function have also been reported. In this case, changes in the EEG were observed only in some patients.

Immune system disorders:

Unknown: hypersensitivity.

Impaired nervous system:

Infrequent: headache (can be severe and prolonged).

It is not known: dizziness, transient encephalopathy caused by extravasation of the contrast medium, which can be manifested by disorders of sensory, motor or general neurological functions.

Disturbances from the gastrointestinal tract:

Infrequently: vomiting.

Unknown: nausea.

General disorders and disorders at the site of administration:

Unknown: chills, pain at the injection site.

Hysterosalpingography (GHA):

Immune system disorders:

Unknown: hypersensitivity.

Impaired nervous system:

Often: headache.

Disorders from the gastrointestinal tract:

Very often: abdominal pain.

Often: nausea.

Unknown: vomiting.

Violations of the genitals and breast:

Very often: vaginal bleeding.

General disorders and disorders at the site of administration:

Often: a feeling of heat.

Unknown: chills, pain at the injection site.

Arthrography:

Immune system disorders:

Unknown: hypersensitivity.

General disorders and disorders at the site of administration:

Often: pain at the injection site.

Unknown: chills.

Gastrointestinal:

Immune system disorders:

Unknown: hypersensitivity.

Disturbances from the gastrointestinal tract:

Often: diarrhea, abdominal pain, nausea.

Infrequently: vomiting.

General disorders and disorders at the site of administration:

Unknown: chills.

Overdose:

Overdose is unlikely in patients with normal renal function. In case of using high doses of the drug, the duration of the procedure (the half-life of the drug is approximately 2 hours) is of great importance with respect to the effect on the kidneys.

There is no specific antidote, treatment is symptomatic, hemodialysis is possible.

Interaction:

When used concomitantly with antipsychotic drugs, analgesics and antidepressants, Vizipak® can reduce the convulsive threshold, increasing the risk of adverse reactions.

Use of Visipac® in patients with diabetic nephropathy who take biguanides (metformin), can lead to a transient disruption of kidney function and the development of lactic acidosis. As a precaution, it is necessary to stop taking biguanides 48 hours before the test and resume after complete stabilization of kidney function.

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

In patients taking beta-adrenoblockers, when iodixanol is used, manifestations of anaphylaxis can be atypical and mistaken for vagal reactions.

Special instructions:

Distort results of thyroid radioisotope studies (the iodo-binding capacity of the thyroid tissue remains reduced within 2 weeks after administration).

The introduction of iodine-containing radiocontrast agents may aggravate the symptoms of myasthenia gravis.

When performing invasive studies and interventions in patients with pheochromocytoma, prophylactic use of alpha-adrenoblockers is necessary to prevent hypertensive crises.

Patients on hemodialysis can be given radiopaque means.

Evidence that hemodialysis in patients with impaired renal function prevents the development of contrast-induced nephropathy (CIN) is absent. Consequently, there is no need for a correlation between the time of introduction of radiopaque means and the conduct of hemodialysis.

In patients with impaired renal and hepatic function, the clearance of the drug can be significantly reduced.

High concentrations of the drug in the patient's plasma can affect the results of laboratory studies to determine the concentration of bilirubin, proteins, iron, calcium, copper and phosphate. Therefore, such tests should not be performed on the day of the study.

Particular care should be taken in patients with hyperthyroidism. Patients with multinodular goiter have an increased risk of developing hyperthyroidism after the introduction of iodine-containing radiocontrast agents.In preterm infants after the administration of the drug, there is the possibility of developing transient hyperthyroidism.

Nonionic contrast media have a less pronounced effect on the blood coagulation system in vitrothan ionic contrast media.

When installing an intravascular catheter, you should carefully follow the procedure angiography, and rinse the catheter (eg, 0.9% sodium chloride solution with heparin) to reduce the risk of thrombosis and embolism.

The risk of developing serious reactions with the use of the drug Vizipak® is considered to be small. However, iodine-containing radiopaque agents can cause anaphylactoid reactions or other manifestations of hypersensitivity. Possible development of hypersensitivity reactions in the form of moderate respiratory or skin symptoms (eg, dyspnea, rash, erythema, urticaria, pruritus, severe skin reactions, angioedema, low blood pressure, bronchospasm, pulmonary edema, fever, laryngeal edema).

Reactions can occur immediately after the injection or a few days later. Hypersensitivity reactions can occur regardless of the dose and mode of administration, mild symptoms may be harbingers of a serious anaphylactoid reaction / shock.

In the case of a hypersensitivity reaction, the administration of an X-ray contrast agent should be immediately discontinued and, if necessary, a specific treatment is started.

Patients taking beta-blockers may develop atypical symptoms of hypersensitivity, which can be mistaken for vasovagal reactions.

It is necessary to think in advance the procedure for dealing with serious reactions and to have the necessary preparations and equipment for emergency assistance at the ready. It is recommended to always install a cannula or catheter to ensure rapid intravenous access throughout the radiographic procedure.

Prevention of adverse reactions:

- identification of patients at risk;

- ensuring adequate hydration of the patient, if necessary by continuous intravenous infusion, started before the introduction of the drug and continuing until it is excreted by the kidneys;

- preventing the additional burden on the kidneys arising from the use of nephrotoxic drugs, drugs for oral cholecystography, clamping of the renal arteries, angioplasty of the renal arteries, surgical operations, before removing the drug from the body;

- repeated studies using radiopaque means should be performed not earlier than when the kidney function is restored to the original level.

Information on cases of extravasation of the drug Vizipak® is absent.

Presumably, due to its isotonicity, Visipack® causes less local pain and swelling than hyperosmolar radiopaque agents. When extravasation should be raised and cooled affected area. With the development of the compression syndrome, surgical decompression may be required.

Intrathecal administration:

After myelography, the patient should be in a horizontal position for 1 hour with a raised head and chest raised to 20 °. After that, the patient can walk gently, but should not bend over. If the patient remains in bed, then within 6 hours his head and chest should remain elevated. If you suspect a low convulsive threshold, the patient should remain under medical supervision during this period of time. Outpatient patients can not be left unattended in the first 24 hours after the administration of radiopaque.

Effect on the ability to drive transp. cf. and fur:

It is not recommended to drive vehicles or work with any other mechanisms during the first 24 hours after intrathecal administration of contrast media.

Form release / dosage:

Solution for injection, 270 mg iodine / ml, 320 mg iodine / ml.

Packaging:

Primary packaging

For 20 and 50 ml of the preparation in a colorless glass bottle (Hev.Pharm., Type I) closed with a stopper of chlorobutyl rubber and crimped with an aluminum cap, top covered with a snapping plastic lid.

A 50 ml bottle contains a label, the lower part of which is used to suspend the bottle.

For 50, 100, 200 and 500 ml of the preparation of both dosages into a bottle of polypropylene PPM R021, sealed with a plug of chlorobutyl rubber and closed with a screwed polypropylene cover, provided with a ring for monitoring the first opening, and on top with a ring for tearing off the sealing gasket. The vial has a label, the lower part of which is used to suspend the vial.

Secondary packaging

On 10 glass or polypropylene bottles of the preparation together with the instruction for use are placed in a cardboard box.

Storage conditions:

In a place protected from light and secondary X-rays, at a temperature not exceeding 30 ° С.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N 015628/01

Date of registration:16.03.2009 / 11.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:JI Halskea LimitedJI Halskea Limited United Kingdom

Manufacturer: & nbsp

GE HEALTHCARE IRELAND Ireland

Representation: & nbspJI Halskea Nycomed Distribution Ltd.JI Halskea Nycomed Distribution Ltd.Russia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Visipac® (Visipaque®)