Iomeron 400, solution for injection, multi-dose container

Contains 81.65% w/v of Iomeprol equivalent to 40% iodine or 400 mg iodine/ml.

For the full list of excipients, see section 6.1.

Solution for injection.

A clear colourless to pale yellow solution supplied in glass multi-dose container.

X-ray contrast medium used for computed tomography enhancement, including CTA (CT Angiography).

computed tomography

* According to body size and age

In elderly patients the lowest effective dose should be used.

Hypersensitivity to the active substance or any of the excipients.

In consideration of possible complications, the patient should be kept under observation for at least 30 minutes after the examination.

Extreme caution during injection of contrast media is necessary to avoid extravasation.

A normal diet should be maintained until the patient refrains from eating 2 hours before the procedure.

Hydration

Any severe disorders of water and electrolyte balance must be corrected prior to administration. Adequate hydration must be ensured particularly in patients with diabetes mellitus, polyuria, oliguria and hyperuricaemia; also in babies, small children and the elderly. Rehydration prior to use of Iomeprol is recommended in patients with sickle cell disease.

Special population

Hypersensitivity to iodinated contrast media, allergic predisposition

A positive history of allergy, asthma or untoward reaction during previous similar investigations indicates a need for extra caution since, as with other contrast media, this product may provoke anaphylaxis or other manifestations of allergy with nausea, vomiting, dyspnoea, erythema, urticaria and hypotension. The benefits should clearly outweigh the risks in such patients and appropriate resuscitative measures should be immediately available. The primary treatments are as follows:

From: Bush WH; The Contrast Media Manual; Katzburg RW Ed.; Williams and Wilkins; Baltimore 1992; Chapter 2 p 23

The risk of bronchospasm-inducing reactions in asthmatic patients is higher after contrast media administration, especially in patients taking beta-blockers.

Hypersensitivity testing

In patients with suspected or known hypersensitivity to contrast media, sensitivity test doses are not recommended, as severe or fatal reactions to contrast media are not predictable from sensitivity test.

Myelomatosis or paraproteinaemias are conditions predisposing to renal impairment following CM administration. The benefits of the use of a contrast-enhanced procedure should be carefully weighed against the possible risk. Adequate hydration and monitoring of renal function are recommended after CM administration.

Cardiovascular diseases

Care should be taken in patients with severe cardiac disease particularly heart failure and coronary artery disease. Cardiac manifestations may include pulmonary oedema, haemodynamic changes, ischaemic ECG changes and arrhythmias. In severe, chronic hypertension the risk of renal damage following administration of a contrast medium is increased.

The product should be used with caution in patients with hyperthyroidism or goitre. Use may interfere with thyroid function tests.

The administration of iodinated contrast media may aggravate myasthenia signs and symptoms.

CNS Disorders

Particular care is needed in patients with acute cerebral infarction, acute intracranial haemorrhage and any conditions involving damage to the blood brain barrier, brain oedema or acute demyelination. Convulsive seizures are more likely in patients with intracranial tumours or metastases or with a history of epilepsy.

Neurological symptoms related to cerebrovascular diseases, intracranial tumours/metastases or degenerative or inflammatory pathologies may be exacerbated.

There is an increased risk of transient neurological complications in patients with symptomatic cerebrovascular disease eg stroke, transient ischaemic attacks. Cerebral ischaemic phenomena may be caused by intravascular injection.

Anticonvulsant therapy should not be discontinued.

In acute and chronic alcoholism the increase in blood brain barrier permeability facilitates the passage of the contrast medium into cerebral tissue possibly leading to CMS disorders. There is a possibility of a reduced seizure threshold in alcoholics.

In patients with a drug addiction there is also the possibility of a reduced seizure threshold.

Patients with phaeochromocytoma may develop severe, occasionally uncontrollable hypertensive crises during intravascular administration. Premedication with an alpha and beta receptor blocker is recommended in these patients. Pronounced excitement, anxiety and pain can cause side effects or intensify reaction to the contrast medium. A sedative may be given.

Renal failure

In patients with moderate to severe impairment of renal function, attention should be paid to renal function parameters before re-examining the patient with a contrast media.

Preventive measures include:

- identification of high-risk patients;

- ensuring adequate hydration before CM administration, preferably by maintaining i.v. infusion before and during the procedure and until the CM has been cleared by the kidneys;

- avoiding whenever possible, the administration of nephrotoxic drugs or major surgery or procedure such as renal angioplasty, until the CM has been cleared;

A combination of severe hepatic and renal impairment delays excretion of the contrast medium therefore such patients should not be examined unless absolutely necessary.

Diabetes mellitus

Care should be taken in renal impairment and diabetes. In these patients it is important to maintain hydration in order to minimise deterioration in renal function.

The presence of renal damage in diabetic patients is one of the factors predisposing to renal impairment following contrast media administration. This may precipitate lactic acidosis in patients who are taking metformin (see section 4.5 - Interaction with medicaments and other forms of interaction).

Children: Infants up to 1 year, especially the newborn, are particularly susceptible to electrolyte imbalance and haemodynamic alterations. Care should be taken regarding the dosage used.

Transient hypothyroidism may occur in neonates when the mother or the neonate has received an iodinated contrast agent. Thyroid function tests (usually TSH and T4) are recommended in neonates 7-10 days and 1 month after exposure to Iomeron especially in preterm neonates.

Elderly:

The elderly are at special risk of reactions due to reduced physiological functions, especially when high dosage of contrast media is used. A combination of neurological disturbances and vascular pathologies present a serious complication. The probability of acute renal insufficiencies is higher in these people.

Intravascular administration should be performed if possible with the patient lying down. The patient should be kept in this position and closely observed for at least 30 minutes after the procedure since the majority of severe incidents occur with this time.

Use of the product may interfere with tests for thyroid function. Vasopressor agents should not be administered prior to Iomeprol.

Treatment with drugs that lower the seizure threshold such as certain neuroleptics (MAO inhibitors, tricyclic antidepressants), analeptics, and anti-emetics and phenothiazine derivatives should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure.

It has been reported that cardiac and/or hypertensive patients under treatment with diuretics, ACE-inhibitors, and/or beta blocking agents are at higher risk of adverse reactions when administered iodinated contrast media.

Beta-blockers may impair the response to treatment of bronchospasm induced by contrast medium.

Patients with normal renal function can continue to take metformin normally. In diabetic patients with diabetic nephropathy, under treatment with metformin and with moderate renal impairment, metformin should be stopped at the time of, or prior to, the procedure and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal. In emergency patients in whom renal function is either impaired or unknown, the physician shall weigh out risk and benefit of an examination with a contrast medium and take precautions. Metformin should be stopped from time of contrast medium administration. After the procedure the patient should be monitored for signs of lactic acidosis. Metformin should be restarted 48 hours after contrast medium if serum creatinine/eGFR is unchanged from the pre-imaging level.

Allergy-like reactions to contrast media are more frequent and may manifest as delayed reactions in patients treated with immuno-modulators, like Interleukin-2 (IL-2).

Women of childbearing potential

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.

Pregnancy

Animal studies have not indicated any harmful effects with respect to the course of pregnancy or on the health of the unborn or neonate. The safety of Iomeprol in human pregnancy however has not been established. Therefore avoid in pregnancy unless there is no safer alternative.

Since, wherever possible, exposure to radiation should be avoided during pregnancy, the benefits of any X-ray examination, whether with or without contrast material, should for this reason alone be carefully weighed against the possible risk

Breastfeeding

No human data exist concerning the excretion of Iomeprol in breast milk. Animal studies have demonstrated that the excretion of Iomeprol in breast milk is similar to that of other contrast agents and that these compounds are only minimally absorbed by the gastrointestinal tract of the young. Adverse effects on the nursing infant are therefore unlikely to occur.

Stopping breastfeeding is unnecessary.

There is no known effect on the ability to drive and operate machines.

General

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. In most cases, reactions occur within minutes of dosing but at times reactions may occur at later time.

Anaphylaxis (anaphylactoid/hypersensitivity reactions) may manifest with various symptoms, and rarely does any one patient develop all the symptoms. Typically, in 1 to 15 min (but rarely after as long as 2 h), the patient complains of feeling abnormal, agitation, flushing, feeling hot, sweating increased, dizziness, increased lacrimation, rhinitis, palpitations, paresthesia, pruritus, sore throat and throat tightness, dysphagia, cough, sneezing, urticaria, erythema, mild localised oedema, angioneurotic oedema and dyspnoea due to glottic/laryngeal/pharyngeal oedema and/or spasm manifesting with wheezing, and bronchospasm.

Nausea, vomiting, abdominal pain, and diarrhoea are also reported.

These reactions, which can occur independently of the dose administered or the route of administration, may represent the first signs of circulatory collapse.

Administration of the contrast medium must be discontinued immediately and, if needed, appropriate specific treatment urgently initiated via venous access.

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.

The adverse reactions reported in clinical trials among 4,903 adult patients and from post-marketing surveillance are represented in the tables below by frequency and classified by MedDRA system organ class.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Adult patients involved in clinical trials with intravascular administration of Iomeprol were 4,515.

Adults

* Since the reactions were not observed during clinical trials with 4515 patients, best estimate is that their relative occurrence is rare ( ≥1/10,000 to <1/1000).

The most appropriate MedDRA term is used to describe a certain reaction and its symptoms and related conditions.

** Injection site reactions comprise injection site pain and swelling. In the majority of cases they are due to extravasation of contrast medium. These reactions are usually transient and result in recovery without sequelae. Cases of extravasation with inflammation, skin necrosis and even development of compartment syndrome have been reported.

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

Paediatric patients

There is limited experience with paediatric patients. The clinical trial paediatric safety database comprises 167 patients.

The Iomeprol safety profile is similar in children and 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 or search for MHRA Yellow Card in the Google Play or Apple App Store

The effects of overdose on the pulmonary and cardiovascular systems may become life-threatening. Treatment consists of support of the vital functions and prompt use of symptomatic therapy. Iomeprol does not bind to plasma or serum proteins and is therefore dialyzable.

ATC code: V08AB10

Iomeprol is a low osmolality, non-ionic organic molecule with radio-opacity conferred by an iodine content of 49% of the molecular weight. It is formulated for use as an intravascular/intracavitary contrast medium in concentrations of up to 400mg iodine per ml. Even at this concentration the low viscosity allows delivery of high doses through thin catheters.

The pharmacokinetics of intravascularly administered Iomeprol are similar to those of other iodinated contrast media and conform to a two-compartment model with a rapid distribution and a slower elimination phase. In healthy subjects, the mean distribution and elimination half-lives of Iomeprol were 0.5 hours and 1.9 hours respectively.

Distribution volume is similar to that of extra cellular fluid. There is no significant serum protein binding and Iomeprol is not metabolized.

Elimination is almost exclusively through the kidneys (90% of the dose recovered in the urine within 96 hours of its administration) and is rapid (50% of an intravascularly administered dose within 2 hours).

Pre-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction.

Results from studies in rats, mice and dogs demonstrate that Iomeprol has an acute intravenous or intra-arterial toxicity similar to that of the other non-ionic contrast media, as well as a good systemic tolerability after repeated intravenous administrations in rats and dogs.

trometamol

hydrochloric acid

water for injection

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

Five years

The maximum use time after a bottle stopper has been pierced is 10 hours.

Store below 30°C

Protect from light

Colourless type I glass bottles with chlorobutylrubber stopper/aluminium cap containing 500 ml of solution.

Boxes of 1, 5 and 6 bottles.

Before use, examine the product to assure that the container and closure have not been damaged. Do not use the solution if it is discolored or particulate matter is present. The stopper should be pierced only once. The use of proper withdrawal cannulas for piercing the stopper and drawing up the contrast medium is recommended.

Multi-dose containers should be used only in conjunction with an automatic injector which has been approved for multipatient use.

After each patient, the connector between the injector and the patient should be replaced. All other devices should be replaced following the injector manufacturer's instructions. In any case, strictly follow the manufacturer's instructions.

Any unused product or waste material should be disposed of in accordance with local requirements

Bracco U.K. Ltd,

Unit 15, Valley Business Centre,

Gordon Road, High Wycombe,

Buckinghamshire HP13 6EQ,

United Kingdom

PL 18920/0043

14/11/2018

March 2020