Bystage

This medicinal product is for diagnostic use only.

X-ray contrast medium for injection, particularly in digital subtraction angiography.

Route of administration

In digital subtraction angiography:

- Intra-ventricular

- Intra-arterial

Posology

Bystage 150: DOSAGE SCHEDULE

The dosage must be adapted to the examination, the age, body weight, cardiac output, renal function, general condition of the patient and the technique used. Usually the same iodine concentration and volume are used with other iodinated x-ray contrast in current use.

Method of administration

As with all contrast media, the lowest dose necessary to obtain adequate visualisation should be used.

Non-ionic contrast media have less anti-coagulant activity in-vitro than ionic media. Meticulous attention should therefore be paid to angiographic technique. Non-ionic media should not be allowed to remain in contact with blood in the syringe and intravascular catheters should be flushed frequently, to minimise the risk of clotting, which rarely has led to serious thromboembolic complications after procedures. Factors such as length of procedure, catheter and syringe material, underlying disease state, and concomitant medications may contribute to the development of thromboembolic events. Therefore, meticulous angiographic techniques are recommended including close attention to guide wire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinized saline solutions, and minimizing the length of the procedure.

As experience shows that warmed contrast media are better tolerated, the contrast medium should be warmed up to body temperature before administration.

No other drugs or contrast media should be mixed with the iopamidol solution for injection.

Digital subtraction angiography

For cardiac imaging the contrast medium may be administered intra-arterially by selective catheterisation to provide subtracted images. Bystage 340 and 370 injected intravenously either centrally or peripherally is also recommended for use in this modality.

Hypersensitivity to the active ingredient iopamidol or to any of the excipients.

Diagnostic procedures which involve the use of any radiopaque medium should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed.

Appropriate facilities should be available for coping with any complication of the procedure, as well as for emergency treatment of severe reaction to the contrast medium itself.

During the examination an intravenous route for emergency treatment in the event of a reaction is required.

After the administration of the contrast medium, competent personnel, drugs and equipment for emergency resuscitation must be available for at least 30 minutes..

Caution during injection of contrast media is necessary to avoid extravasation.

Local tissue irritation can occur as an event of perivascular infiltration of the contrast media.

In patients who are known epileptics or have a history of epilepsy, anticonvulsant therapy should be maintained before and following myelographic procedures.- Interaction with medicaments and other forms of interaction).

Patients must be sufficiently hydrated before and after radiographic procedures. Patients with severe functional impairment of the liver or myocardium, myelomatosis, diabetes, polyuria or oliguria, hyperuricemia, infants, elderly patients and patients with severe systemic disease should not be exposed to dehydration.

Fluid intake should not be limited and any abnormalities of fluid or electrolyte balance should be corrected prior to use of this hypertonic solution.

Patients with paraproteinaemia of Waldenström, with multiple myeloma or severely compromised hepatic and renal impairment are also more at risk: in these cases adequate hydration is recommended after contrast medium administration.

Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when injected intravenously and intra-arterially. To prevent crises in patients with sickle cell disease adequate hydration should be assured and a minimal volume of low concentration should be used.

Patients with congestive heart failure should be observed for several hours following the procedure to detect delayed haemodynamic disturbances, which may be associated with a transitory increase in the circulating osmotic load..

In patients undergoing angiocardiographic procedures special attention should be paid to the status of the right heart and pulmonary circulation. Right heart insufficiency and pulmonary hypertension may precipitate bradycardia and systemic hypotension, when the organic iodine solution is injected. Right heart angiography should be carried out only when absolutely indicated.

During intracardiac and/or coronary arteriography, ventricular arrhythmias may infrequently occur.

Caution should be exercised in performing iodinated contrast-enhanced examinations in patients with, or with suspicion of, hyperthyroidism or autonomously functioning thyroid nodule(s), as thyroid storms have been reported following administration of iodinated contrast media.

Bystage should be used with caution in patients with hyperthyroidism. It is possible that hyperthyroidism may recur in patients previously treated for Graves' disease.

In patients scheduled for thyroid examination with a radioactive iodine tracer, one must take into consideration that iodine uptake in the thyroid gland will be reduced for several days (up to two weeks) after dosing with an iodinized contrast medium that is eliminated through the kidneys.

Patients with phaeochromocytoma may develop severe hypertensive crisis following intravascular Iopamidol. Pre-medication with α-receptor blockers is recommended.

In angiographic procedures, the possibility of dislodging plaque or damaging or perforating the vessel wall should be considered during catheter manipulation and contrast medium injection. Test injections to ensure proper catheter placements are recommended.

In examinations of the aortic arch the tip of the catheter should be positioned carefully to avoid hypotension, bradycardia and CNS injury due to excess pressure transmitted from the injector pump to the brachiocephalic branches of the aorta.

Angiography should be avoided whenever possible in patients with homocystinuria due to an increased risk of thrombosis and embolism.

In patients undergoing peripheral angiography, there should be pulsation in the artery into which the X-ray contrast medium will be injected. In patients with thromboangiitis obliterans or ascending infections in combination with serious ischemia the angiography should be performed, if at all, with special caution.

In patients undergoing venography, special caution should be exercised in patients with suspected phlebitis, serious ischaemia, local infections, or a complete venous occlusion.

Serious neurological events have been observed following direct injection of contrast media into cerebral arteries or vessels supplying the spinal cord or in angiocardiography due to inadvertent filling of the carotids.

Bystage should be administered with caution in elderly patients, in patients with symptomatic cerebrovascular diseases, recent stroke, or frequent TIA, altered permeability of the blood-brain barrier, increased intracranial pressure, suspicion of intracranial tumour, abscess or hematoma/hemorrhage, history of convulsive disorder, chronic alcoholism or multiple sclerosis. Patients with these conditions have an increased risk of neurological complications.

Vasospasm and subsequent cerebral ischemic phenomena may be caused by intra-arterial injections of contrast media.

Intrathecal administration

An accurate evaluation of the risk/benefit ratio is needed if from clinical history there is a previous history of epilepsy or in the presence of blood in the cerebrospinal fluid or presence of local or systemic infection where bacteremia is likely.

The contrast medium should be removed as much as possible in case of spinal fluid blockage.

Use in Special Populations

Newborns, children

Infants (age<1year), and especially newborns are particularly susceptible to electrolyte imbalances and haemodynamic alterations. Care should be taken regarding the dosage to be used, the details of the procedure, and the patient's status.

When examining small children or babies, do not limit fluid intake before administering a hypertonic contrast solution. Also, correct any existing water and electrolyte imbalance.

In paediatric roentgenology, one should proceed with great caution when injecting the contrast medium into the right heart chambers of cyanotic neonates with pulmonary hypertension and impaired cardiac function.

In neonates, and particularly in premature neonates, it is recommended that tests of thyroid function (typically TSH and T4), should be checked 7-10 days and 1 month after the administration of iodinated contrast media because of the risk of hypothyroidism due to iodine overload.

Elderly

The elderly are at special risk of reactions due to reduced physiological functions, especially when high dosage of contrast medium is used. Myocardial ischemia, major arrhythmias and premature ventricular complexes are more likely to occur in these patients. The probability of acute renal insufficiency is higher in these patients.

Women of child-bearing potential

X-ray examination of women should if possible be conducted during the pre-ovulation phase of the menstrual cycle and should be avoided during pregnancy.

Appropriate investigations and measures should be taken when exposing women of child-bearing potential to any X-ray examination, whether with or without contrast medium.

There is no known effect on the ability to drive and operate machines. However, because of the risk of early reactions, driving or operating machinery is not advisable for one hour following the last injection.

The use of iodinated contrast media may cause untoward side effects. They are usually mild to moderate and transient in nature. However, severe and life threatening reactions sometimes leading to death have been reported.

Anaphylaxis (anaphylactoid reactions/hypersensitivity) may manifest with: mild localized or more diffuse angioneurotic oedema, tongue oedema, laryngospasm or laryngeal oedema, dysphagia, pharyngitis and throat tightness, pharyngolaryngeal pain, cough, conjunctivitis, rhinitis, sneezing, feeling hot, sweating increased, asthenia, dizziness, pallor, dyspnoea, wheezing, bronchospasm, and moderate hypotension. Skin reactions may occur in the form of various types of rash, diffuse erythema, diffuse blisters, urticaria, and pruritus. These reactions, which occur irrespective of the dose administered and the route of administration, may represent the first signs of incipient state of shock. Administration of the contrast medium must be discontinued immediately and - if necessary - specific treatment initiated via a venous access.

Following intravascular administration, in most cases reactions occur within minutes of dosage. However, delayed reactions, usually involving skin, may occur, mostly within 2-3 days, more rarely within 7 days, after the administration of the contrast medium.

More severe reactions involving the cardiovascular system such as vasodilatation with pronounced hypotension, tachycardia, dyspnoea, agitation, cyanosis and loss of consciousness progressing to respiratory and/or cardiac arrest may result in death. These events can occur rapidly and require full and aggressive cardio-pulmonary resuscitation.

Primary circulatory collapse can occur as the only and/or initial presentation without respiratory symptoms or without other signs or symptoms outlined above.

Intravascular administration -Adults

The adverse reactions are classified by System Organ Class and frequency, using the following convention: Very common (>1/10), Common (>1/100 to < 1/10), Uncommon (>1/1,000 to < 1/100), Rare (>1/10,000 to < 1/1,000), Very rare (< 1/10,000), not known (cannot be estimated from the available data)

* Cardiac reactions may occur as consequences of the coronary catheterization procedural hazard: these complications include coronary artery thrombosis and coronary artery embolism.

** As with other iodinated contrast media, very rare cases of muco-cutaneous syndromes, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome) and erythema multiforme, have been reported following the administration of Iopamidol

*** Injection site pain and swelling may occur. In the majority of cases it is due to extravasation of contrast medium. These reactions are usually transient and result in recovery without sequelae. However, inflammation and even skin necrosis have been seen on very rare occasions. In isolated reports extravasation led to the development of compartment syndrome

Intravascular administration - Pediatric Population

Frequency type and severity of adverse reactions in children are similar to those in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard.

Dosages exceeding the specific package insert dose are not recommended, as they might lead to life-threatening adverse effects.

If needed, haemodialysis can be used to eliminate Iopamidol from the body. Treatment of overdosage is directed toward the support of all vital functions and prompt institution of symptomatic therapy.

Intravascular

In the event of accidental intravascular overdose in humans, the water and electrolyte losses must be compensated by infusion. Renal function should be monitored for at least three days.

Iopamidol is contrast medium belonging to the new generation of non-ionic compound whose solubility is due to the presence of hydrophilic substitutes in the molecule. This results in a solution of low osmolality when compared with ionic media.

Iopamidol has been shown to be effective as an X-ray contrast medium in neuroradiology, angiography, venography, arthrography, urography, cerebral angiography and left ventriculography and coronary arteriography. Its toxicity particularly cardiac and CNS toxicity are less than those of ionic contrast media.

The pharmacokinetics of Iopamidol conform to an open two compartment pharmacokinetic model with first order elimination.

Distribution volume is equivalent to extracellular fluid.

Elimination is almost completely through the kidneys. Less that 1% of the administered dose has been recovered in the faeces up to 72 hours after dosing. Elimination is rapid; up to half the administered dose may be recovered in the urine in the first two hours of dosing.

There is no evidence of biotransformation.

Serum protein binding is negligible.

No adverse effects can be predicted from animal toxicology studies other than those documented from human use of Iopamidol.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products

Discard if the solution is not clear of particulate matter.

Exceptionally, the event of crystallisation of Bystage could occur. It has been shown that such a phenomenon is caused by a damaged or defective container and therefore the product should not be used in this case.

The bottle, once opened, must be used immediately.

Any unused medicinal product or waste material should be disposed off in accordance with local requirements.

Bystage, as other iodinated contrast media, can react with metallic surfaces containing copper (e.g. brass), therefore the use of equipment, in which the product comes into direct contact with such surfaces, should be avoided.