Wednesday, October 19, 2016

IOMERON 300





1. Name Of The Medicinal Product



Iomeron 300, solution for injection


2. Qualitative And Quantitative Composition



Contains 61.24% w/v of iomeprol equivalent to 30% iodine or 300mg 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


venography



angiogardiography and left ventriculography



cerebral arteriography



visceral arteriography



digital subtraction angiography



computed tomography enhancement



urography



ERCP



dacryocystography



sialography



fistulography



galactography



myelography



4.2 Posology And Method Of Administration

























peripheral arteriography




adults



children




10 - 90ml *



* *




venography




adults




10 - 100ml*



max 250ml



10 - 50ml upper extremity



50 - 100ml lower extremity




angiocardiography and left ventriculography




adults



children




30 - 80ml max 250ml



* *




cerebral arteriography




adults



children




5 - 12ml *



3 - 7ml or * *




visceral arteriography




adults



 



children




5 - 50ml* or according to type of examination;



max 250ml



* *




digital subtraction angiography



intra arterial



visceral



 



 



peripheral



 



intravenous




 



 



adults



 



 



adults



 



adults




 



 



2 - 20ml per artery*



aorta 25-50ml*



both 250ml max



5 - 10ml per artery*



max 250ml



30 - 60ml*



max 250ml




computed tomography



brain



 



body



 



 



urography intravenous



 



 



 



arthrography



ERCP



dacryocystography



sialography



fistulography



galactography



myelography




 



adults



children



adults



 



children



adults



neonates



babies



children



adults



adults



adults



adults



adults



adults



adults




 



50 - 150ml



* *



40 - 150ml



max 250ml



* *



50 - 150ml



3 - 4.8ml/kg



2.5 - 4ml



1 - 2.5ml/kg or *



1 - 10ml



12 - 30ml



3 - 8ml



1 - 3ml



1 - 50ml



0.2 - 1.5ml



10 - 15ml by lumbar injection



* Repeat as necessary



* * According to body size and age



In elderly patients the lowest effective dose should be used.



In myelography, lower doses may be used for lumbar or thoracic studies and higher doses for cervical or total columnar studies. Regardless of the nature of the myelographic study, Iomeron should be injected slowly over 1-2 minutes.



The X ray can be taken up to 60 minutes following injection. Post myelographic CT of the spinal column should be delayed for approximately four hours to allow dilution and clearance of excessive contrast.



4.3 Contraindications



Proven or suspected hypersensitivity to iodine containing preparations of this type.



Intrathecal concomitant administration of corticosteroids with contrast media is contraindicated.



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:




















































Effect




Major Symptoms




Primary Treatment




Vasomotor effect




warmth




reassurance




 




nausea/vomiting




 




Cutaneous




scattered hives




H1 -antihistamines




 




severe urticaria




H2 -antihistamines




Bronchospastic




wheezing




oxygen




 




 




Beta-2-agonist inhalers




Anaphylactoid




angioedema




oxygen




reaction




urticaria




iv fluids




 




bronchospasm




adrenergics (iv epinephrine)




 




hypotension




Inhaled beta-2-adrenergics




 




 




antihistamines (H1-and H2- blockers)




 




 




corticosteroids




Hypotensive




hypotension




iv fluids




Vagal reaction




hypotension




iv fluids




 




bradycardia




iv atropine



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 thrombosis, phlebitis, severe ischaemic 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, in particular before re-examining the patient with 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 reinstituted only after renal function has been re-evaluated and found to be normal (see section 4.5 - Interaction with 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.



Following intrathecal use, the patient should rest with the head and the chest elevated for 1 hour and be kept well hydrated. Thereafter, he/she may ambulate carefully, but bending down must be avoided. If remaining in bed, the head and chest should be kept elevated for 6 hours. Patients, suspected of having a lower seizure threshold should be observed during this period.



Children: Infants up to 1 year, especially the new-born, 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).



Epidural and intrathecal corticosteroids should never be concurrently administered when iodinated contrast media are used, because corticosteroids may promote and affect the signs and symptoms of arachnoiditis (see section 4.3 Contraindications).



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.



After intrathecal administration, it is recommended that the patient should wait 24 hours before driving or operating machinery.



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




















































































System Organ Class




Adverse Reactions


   


 




Common



(>1/100, <1/10)




Uncommon



(>1/1,000, <1/100)




Rare



(>1/10,000,<1/1,000)




Not known



( cannot be estimated from the available clinical trial data)




Blood and lymphatic system disorders




 



 

 


thrombocytopenia




Immune system disorders




 



 


Anaphylactic/anaphylactoid reactions



 


Psychiatric Disorders




 




Agitation



 


anxiety




Nervous System Disorders




Headache




Dizziness, paralysis




Tremor, confusion, loss of consciousness, visual field defect, syncope, aphasia, convulsions, coma




taste abnormality, dysarthria, parasthesia, cerebral oedema, hypoxic encephalopathy, transient ischaemic attack, meningitis, somnolence.




Eye disorders



 

 

 


transient blindness, conjunctivitis, increased lacrimation, visual disturbance, photopsia, photophobia.




Cardiac Disorders



 


Bradycardia, tachycardia




Cyanosis




cardiac arrest, myocardial infarction, cardiac failure, angina pectoris, pulmonary oedema, arrhythmias including extrasystoles, ventricular or atrial fibrillation, atrioventricular block




Vascular Disorders *




Pallor




Hypertension, hypotension




Vasodilatation, circulatory collapse




shock, flushing, thrombosis




Respiratory, Thoracic and Mediastinal Disorders



 


Dyspnoea, nasal congestion, laryngeal oedema



 


respiratory arrest, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, stridor, rhinitis, cough, sneezing, laryngospasm, pharyngeal oedema, hypoxia, dysphonia




Gastrointestinal Disorders




Nausea




Vomiting



 


acute pancreatitis, diarrhea, abdominal pain, salivary hypersecretion, dysphagia, ileus




Skin and Subcutaneous Tissue Disorders



 


Rash, erythema, wheals, pruritus, sweating increased



 


angioneurotic oedema, urticaria, dermatitis, eczema, mucocutaneous syndromes **




Musculoskeletal and Connective Tissue Disorders



 


Back pain




Muscle spasms




muscle weakness




Renal and Urinary Disorders



 

 


Renal failure, oliguria, proteinuria



 


General Disorders and Administration Site Conditions




Injection site warmth and pain




Chest pain, rigors, injection site haemorrhage, pyrexia




Asthenia




oedema, malaise, feeling of warmth, chills, pain, injection site reaction ***




Investigations



 

 


Blood creatinine increased




abnormal electrocardiogram, abnormal liver function tests










*



 




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 Iomeron.




***




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



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/intrathecal 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).



Following intrathecal administration to animals, iomeprol is completely cleared from the CSF and passes into the plasma compartment.



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)



18920/0004



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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