1. Name Of The Medicinal Product
Iomeron 400, solution for injection
2. Qualitative And Quantitative Composition
Contains 81.65% w/v of iomeprol equivalent to 40% iodine or 400mg iodine/ml.
For excipients, see 6.1.
3. Pharmaceutical Form
Solution for injection.
4. Clinical Particulars
4.1 Therapeutic Indications
X-ray contrast medium used for:
peripheral arteriography
aortography
angiocardiography and left ventriculography
coronary arteriography
visceral arteriography
digital subtraction angiography
computed tomography enhancement
urography
dacryocystography
sialography
fistulography
galactography
4.2 Posology And Method Of Administration
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digital subtraction angiography
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computed tomography
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urography
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* Repeat as necessary
* * According to body size and age
In elderly patients the lowest effective dose should be used.
The X ray can be taken up to 60 minutes following injection.
4.3 Contraindications
Proven or suspected hypersensitivity to iodine containing preparations of this type.
4.4 Special Warnings And Precautions For Use
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:
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From: Bush WH; The Contrast Media Manual; Katzburg RW Ed.; Williams and Wilkins; Baltimore 1992; Chapter 2 p 23
In consideration of possible complications, the patient should be kept under observation for at least 60 minutes after the administration.
Extreme caution during injection of contrast media is necessary to avoid extravasation.
Special care is required when investigations are performed in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection or a totally obstructed artero-venous system.
Any severe disorders of water and electrolyte balance must be corrected prior to administration. Adequate hydration must be ensured particularly in patients with multiple myeloma, paraproteinaemia, 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.
Care should be taken in severe cardiac disease particularly heart failure and coronary artery disease. Reactions 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. In these cases the risks associated with the catheterization procedure are increased. 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.
A combination of severe hepatic and renal impairment delays excretion of the contrast medium therefore such patients should not be examined unless absolutely necessary.
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.
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.
Treatment with drugs that lower the seizure threshold such as analgesics and anti-emetics of the phenotiazine class neuroleptics and antidepressants should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure.
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 facilitates the passage of contrast medium into cerebral tissue possibly leading to CNS 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 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.
Anticonvulsant therapy should not be discontinued. A normal diet should be maintained until the patient refrains from eating 2 hours before the procedure.
Non ionic contrast media have less antiocoagulant 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 a syringe, and intravascular catheters should be flushed frequently to minimise the risk of clotting which, rarely, has led to serious thromboembolic complications.
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.
In diabetic patients with diabetic nephropathy, , under treatment with metformin and with moderate renal impairment (eGFR between 30 and 60 mL/min/1.73 m2), metformin should be stopped at the time of, or prior to the procedure and withheld for 48 hours subsequent to the procedure and re-instituted only after renal function has been re-evaluated and found to be normal (see section 4.5 - Interaction with other medicaments and other forms of interaction).
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.
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.
Elderly: There is special risk of reactions involving the circulatory system such that myocardial ischaemia, major arrhythmias and extrasystoles are more likely to occur. A combination of neurological disturbances and vascular pathologies present a serious complication. The probability of acute renal insufficiencies is higher in these people.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Use of the product may interfere with tests for thyroid function. Vasopressor agents should not be administered prior to iomeprol.
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 4.4 - Special warnings and special precautions for use).
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).
4.6 Pregnancy And Lactation
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.
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.
As a precautionary measure, breast-feeding should be discontinued prior to the administration of iomeprol and should not be recommenced until at least 24 hours after the administration of the contrast medium.
4.7 Effects On Ability To Drive And Use Machines
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.
4.8 Undesirable Effects
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.
After intra-thecal administration most side effects occur some hours (3 to 6 hours) after the procedure, due to the distribution of the contrast medium in the cerebro-spinal fluid (CSF) circulation from the site of administration to the intravascular space. Most reactions usually occur within 24 hours after injection.
After injection of an iodinated contrast media in body cavities, the majority of the reactions occur some hours after the contrast administration due to the slow absorption from the area of administration.
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 following adverse reactions have been reported with iomeprol. Adverse reactions from clinical trials have been included with an indication of the frequency. Adverse reactions from spontaneous reporting are included with the frequency “not known”.
Administration by intravascular and intrathecal routes
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Administration to body cavities.
Hypersensitivity reactions are rare, generally mild and in the form of dermatitis. However, the possibility of severe anaphylactoid reactions cannot be excluded.
After injection into body cavities, local pain may occur.
4.9 Overdose
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.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
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.
5.2 Pharmacokinetic Properties
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).
5.3 Preclinical Safety Data
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.
6. Pharmaceutical Particulars
6.1 List Of Excipients
trometamol
hydrochloric acid
water for injection
6.2 Incompatibilities
No other drug should be mixed with the contrast medium.
6.3 Shelf Life
Five years
6.4 Special Precautions For Storage
Store below 30°C
Protect from light
6.5 Nature And Contents Of Container
Colourless Type I glass ampoules and colourless Type I or Type II glass bottles with rubber/aluminium cap.
Quantities of 10, 20, 30, 50, 75, 100, 150, 200 or 250 ml of solution.
6.6 Special Precautions For Disposal And Other Handling
Bottles containing contrast media solution are not intended for the withdrawal of multiple doses. The rubber stopper should never be pierced more than once. The use of proper withdrawal cannulas for piercing the stopper and drawing up the contrast medium is recommended.
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 contrast medium should not be drawn into the syringe until immediately before use. Withdrawal of contrast agents from their containers should be accomplished under aseptic conditions with sterile syringes. Sterile techniques must be used with any spinal puncture or intravascular injection, and with catheters and guidewires. If non-disposable equipment is used, scrupulous care should be taken to prevent residual contamination with traces of cleansing agents.
It is desirable that solutions of contrast media for intravascular and intrathecal use should be at body temperature when injected.
Any residue of contrast medium in the syringe must be discarded. Solutions not used in one examination session or waste material, such as the connecting tubes, should be disposed in accordance with local requirements.
7. Marketing Authorisation Holder
Bracco U.K. Ltd,
Bracco House, Mercury Park,
Wycombe Lane, Wooburn Green,
Buckinghamshire HP10 OHH
8. Marketing Authorisation Number(S)
18920/0006
9. Date Of First Authorisation/Renewal Of The Authorisation
11 December 1992/ 29 December 1998
10. Date Of Revision Of The Text
20 September 2011
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