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רופא בעלון ללרופא בטיחות) בעלון )מידע בטיחות החמרה (( מידע על החמרה הודעה על הודעה ))05.2013 05.2013 (מעודכן (מעודכן 8.07.2015 תאריך שם תכשיר באנגלית ומספר הרישום Iomeron 300 (103-45-28521-11) Iomeron 350 (103-46-28522-11) Iomeron 400 (103-47-28523-11) שם בעל הרישום דקסל בע"מ ! טופס זה מיועד לפרוט ההחמרות בלבד ההחמרות המבוקשות טקסט חדש טקסט נוכחי פרק בעלון Indication Hypersensitivity to the active substance or any of the excipients. Hypersensitivity to the active principle and to any of its ingredients. Intravascular administration There are no precise and absolute contraindications to the use of non-ionic uroangiographic contrast media. Investigations of the female genitalia are contraindicated in suspected or confirmed pregnancy and in cases of acute inflammation. Intravascular administration There are no precise and absolute contraindications to the use of non-ionic uroangiographic contrast media. Investigations of the female genitalia are contraindicated in suspected or confirmed pregnancy and in cases of acute inflammation. Intrathecal administration Concomitant administration of Iomeprol with corticosteroids is contraindicated (see Interactions). Due to overdose considerations, immediate repeat myelography in the event of technical failure is contraindicated. Contraindications Intrathecal administration Concomitant administration of Iomeprol with corticosteroids is contraindicated (see Interactions). Precautions for use Due to overdose considerations, immediate repeat myelography in the event of technical failure is contraindicated. Precautions for use a. In relation to the patient: Hydration - Any severe disorders of water and electrolyte balance should must be corrected prior to administration. Especially in patients with multiple myeloma, diabetes mellitus, polyuria, oliguria, hyperuricemia, as well as in neonate, children and elderly patients adequate hydration must be ensured before examination. Rehydration prior to use of iomeprol is recommended in patients with sickle cell disease. a. In relation to the patient: Hydration - Any severe disorders of water and electrolyte balance should be corrected. Especially in patients with multiple myeloma, diabetes mellitus, polyuria, oliguria, hyperuricemia, as well as in neonate, children and elderly patients adequate hydration must be ensured before examination. Dietary advice - If not otherwise recommended Precautions for Use Dietary advice - If not otherwise recommended by the physician, a normal diet and adequate fluid intake is maintained during the day preceding the examination. However, patients should avoid eating or drinking during the two hours preceding the X-ray examination. Pre-medication - In pheochromocytoma patients, premedication with alpha and beta receptor blockers is recommended, because of the risk of blood pressure crises. Hypersensitivity - 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 risk of bronchospasm-inducing reactions in asthmatic patients is higher after contrast media administration, especially in patients taking beta-blockers. In patients with an allergic disposition, known hypersensitivity to iodinated contrast media and a history of asthma, pre-medication with antihistamines and/or corticoids is recommended to prevent possible anaphylactoid reactions. 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. Anxiety - Pronounced states of excitement, anxiety and malaise pain may cause or potentiate contrast related reactions. In these cases, a sedative may be given. Concomitant medication – 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, analgesics, antiemetics and phenotiazine derivatives should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure. Anticonvulsant therapy must not be discontinued and should be administered in optimal dosage. 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. 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). b. In relation to the imaging procedure: Coagulation, catheter manipulation - A property of nonionic contrast media is the extremely low interference with normal physiological functions. Non-ionic contrast media have less anti-coagulant activity in-vitro than ionic media. by the physician, a normal diet and adequate fluid intake is maintained during the day preceding the examination. However, patients should avoid eating or drinking during the two hours preceding the X-ray examination. Pre-medication - In pheochromocytoma patients, pre-medication with alpha-receptor blockers is recommended because of the risk of blood pressure crises. Hypersensitivity - In patients with an allergic disposition, known hypersensitivity to iodinated contrast media and a history of asthma, premedication with antihistamines and/or corticoids is recommended to prevent possible anaphylactoid reactions. Anxiety - Pronounced states of excitement, anxiety and malaise may cause or potentiate contrast related reactions. In these cases, a sedative may be given. Concomitant medication - Treatment with drugs that lower the seizure threshold such as neuroleptics, analgesics, antiemetics, and phenotiazine derivatives should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure. Anticonvulsant therapy must not be discontinued and should be administered in optimal dosage. b. In relation to the imaging procedure: Coagulation, catheter manipulation - A property of non-ionic contrast media is the extremely low interference with normal physiological functions. Non-ionic contrast media have less anti-coagulant activity in-vitro than ionic media. Medical and paramedical personnel performing vascular catheterization procedures should be aware of this and pay meticulous attention to the angiographic technique so as to minimize the risk of procedure-related thrombosis and embolism, including catheter flushing with physiological saline solution (if necessary with heparin added). Observation of the patient Intravascular administration of contrast media should be performed, whenever possible, with the patient lying down. The patient should be kept under observation for at least 30 minutes after the administration. Hypersensitivity testing - Reactions to contrast media are not predictable from sensitivity test. Extravasation - Extreme caution during injection of contrast media is necessary to avoid extravasation. This is especially important in patients with severe arterial or venous disease Medical and paramedical personnel performing vascular catheterization procedures should be aware of this and pay meticulous attention to the angiographic technique. so as to minimize the risk of procedure-related thrombosis and embolism, including catheter flushing with physiological saline solution (if necessary with heparin added). 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. Observation of the patient Intravascular administration of contrast media should be performed, whenever possible, with the patient lying down. The patient should be kept under observation for at least 30 minutes after the administration. Hypersensitivity testing - Reactions to contrast media are not predictable from sensitivity test. Extravasation - Extreme caution during injection of contrast media is necessary to avoid extravasation. This is especially important in patients with severe arterial or venous disease. c. In relation to the contrast medium: Single use - 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 cannulae for piercing the stopper and drawing up the contrast medium is recommended. The contrast medium should not be drawn into the syringe until immediately before use and should not be diluted. Solutions not used in one examination session or waste material, such as the connecting tubes, should be disposed. Any residue of contrast medium in the syringe must be discarded. Bottles of 500 ml should be used in conjunction with an injector system. After each patient examination, the connecting tubes (to the patient) and relevant disposable parts should be disposed because could be contaminated with blood. At the end of the sessions, the left over solution in the bottle and in the connecting tubes as well as any disposable parts of the injector system should be discarded. Any additional instructions from the respective equipment manufacturer must also be adhered to. Incompatibilities with other drugs - Contrast media should never be admixed with any other drug to avoid incompatibility. Thyroid function tests - Administration of iodinated contrast media reduces thyroid-targeted radioisotopeuptake by the thyroid tissue for a period of at least two weeks. The results of “Protein Binding Iodine” and “radioactive iodine uptake” studies may not reflect thyroid function accurately for up to two weeks following administration of iodinated contrast media. When such tests should be performed, it is advisable to use T3 resin uptake and total or free thyroxine (T4) assays. Oral cholecystographic agents - Recent literature has revealed no evidence of interactions of renally-excreted c. In relation to the contrast medium: Single use - 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 cannulae for piercing the stopper and drawing up the contrast medium is recommended. The contrast medium should not be drawn into the syringe until immediately before use and should not be diluted. Solutions not used in one examination session or waste material, such as the connecting tubes, should be disposed. Any residue of contrast medium in the syringe must be discarded. Bottles of 500 ml should be used in conjunction with an injector system. After each patient examination, the connecting tubes (to the patient) and relevant disposable parts should be disposed because could be contaminated with blood. At the end of the sessions, the left over solution in the bottle and in the connecting tubes as well as any disposable parts of the injector system should be discarded. Any additional instructions from the respective equipment manufacturer must also be adhered to. Incompatibilities with other drugs - Contrast media should never be admixed with any other drug to avoid incompability. Thyroid function tests - Administration of iodinated contrast media reduces thyroidtargeted radioisotope-uptake by the thyroid tissue for a period of at least two weeks. The results of “Protein Binding Iodine” and “radioactive iodine uptake” studies may not reflect thyroid function accurately for up to two weeks following administration of iodinated contrast media. When such tests should be performed, it is advisable to use T3 resin uptake and total or free thyroxine (T4) assays. Oral cholecystographic agents - Recent literature has revealed no evidence of interactions of renally-excreted contrast media with oral cholecystographic contrast media. Laboratory tests - High concentrations of contrast media in serum and urine can interfere with laboratory test results of bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium, phosphate). contrast media with oral cholecystographic contrast media. Laboratory tests - High concentrations of contrast media in serum and urine can interfere with laboratory test results of bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium, phosphate). Special warnings Consideration of possible serious side effects, the use of iodinated contrast media should be limited to cases for which there is a precise need for a contrast examination. The need should be evaluated on the basis of the clinical status of the patient, in particular in relation to history of pathologies of the cardiovascular, renal and/or hepatobiliary systems. The use of contrast media should be avoided in case of Waldenstroem's paraproteinemia, and multiple myeloma and of advanced hepato and/or renal diseases. Cardioangiographic diagnostic procedures that involve the use of any radiopaque contrast media should be carried out in hospitals where appropriate emergency facilities and personnel trained in life support is readily available. After any other contrast-enhanced X-ray procedures, competent personnel and adequate emergency facilities should be available (AMBU, oxygen, antihistaminics, vasoconstrictors, cortisonics, etc.) in the radiology departments of public or private clinics. Special care should be taken when venography is performed in patients with suspected thrombosis, phlebitis, severe ischaemic disease, local infection or a totally obstructed artero-venous system. Use in: New-borns, children -Young infants aged less than one year, new-borns in particular, are highly 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. Pregnancy - Animal studies do not indicate any teratogenic or foetotoxic effects. As with other non-ionic contrast media, there are no adequate and well-controlled studies in pregnant women to confirm no harmful affect also in human beings. Therefore avoid in pregnancy unless there is no safer alternative. Wherever possible, radiation exposure, either with or without contrast media use, should be avoided during pregnancy and its benefit accurately weighted against the possible risks. Nursing women - Iodinated contrast media are poorly excreted in human breast milk and from experience it appears there should be no damage to the breast-fed baby. Stopping breastfeeding is unnecessary. However, as a cautionary 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. Women Of Child-Bearing 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. Special warnings a) General for all administration routes Consideration of possible serious side effects, the use of iodinated contrast media should be limited to cases for which there is a precise need for a contrast examination. The need should be evaluated on the basis of the clinical status of the patient, in particular in relation to history of pathologies of the cardiovascular, renal and/or hepatobiliary systems. The use of contrast media should be avoided in case of Waldenstroem's paraproteinemia, and multiple myeloma and of advanced hepato and/or renal diseases. Cardioangiographic diagnostic procedures that involve the use of any radiopaque contrast media should be carried out in hospitals where appropriate emergency facilities and personnel trained in life support is readily available. After any other contrast-enhanced X-ray procedures, competent personnel and adequate emergency facilities should be available (AMBU, oxygen, antihistaminics, vasoconstrictors, cortisonics, etc.) in the radiology departments of public or private clinics. Special care should be taken in patients with suspected thrombosis, phlebitis, severe ischemia, local infection or arterovenous obstruction. Use in: New-borns, children -Young infants aged less than one year, new-borns in particular, are highly 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. Pregnancy - Animal studies do not indicate any teratogenic or foetotoxic effects. As with other non-ionic contrast media, there are no adequate and well-controlled studies in pregnant women to confirm no harmful affect also in human beings. Wherever possible, radiation exposure, either with or without contrast media use, should be avoided during pregnancy and its benefit accurately weighted against the possible risks. Nursing women - Iodinated contrast media are poorly excreted in human breast milk and from experience it appears there should be no damage to the breast-fed baby. Special warnings Elderly - The elderly are at special risk of reactions to contrast media especially when high dosage of contrast medium is used. Myocardial ischemia, major arrhythmias and extrasystoles are more likely to occur in these patients. The higher probability of neurological diseases and severe vascular disease represents an aggravating factor. Probability of acute renal insufficiency is higher in these subjects. In elderly patients the lowest effective dose should be used. Use in patients with particular pathological conditions: Hypersensitivity to iodinated contrast media Hypersensitivity or a previous history of a reaction to iodinated contrast media increase the risk of recurrence of a severe reaction even with non-ionic media. Allergic predisposition - It is generally agreed that adverse reactions to iodinated contrast media are more common in patients having a history of allergy such as hay fever, hives and food allergy. Asthmatic patients – These patients are at higher risk of bronchospasm and related events after contrast media administration. Hyperthyroidism, nodular goitre - The product should be used with caution in patients with hyperthyroidism or goitre. The small amount of free inorganic iodide that may be present in contrast media, might have some effects on thyroid function: these effects appear more evident in patients with latent or overt hyperthyroidism or goitre. Thyroid storms have been reported following administration of iodinated contrast media. Use may interfere with thyroid function tests. Effect on ability to drive and use machinery – No data is available. However, given the rare possibility of delayed adverse reactions to contrast media, driving or using machinery should be avoided for 24 hours following the administration. Renal failure - Pre-existing renal impairment may predispose to acute renal dysfunction following contrast media administration. Preventive measures include: identification of high-risk patients; ensuring adequate hydration before contrast medium administration, preferably by maintaining i.v. infusion before and during the procedure and until the contrast medium 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 contrast medium has been cleared; postponing a new contrast agent examination until renal function returns to pre-examination levels. Patients on dialysis may receive contrast media which are easily dialysable such is the case with iomeprol. 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. Diabetic nephropathy The presence of renal damage in diabetic patients may predispose to renal impairment However, as a cautionary measure, breastfeeding 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. Women Of Child-Bearing 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. Elderly - The elderly are at special risk of reactions to contrast media especially when high dosage of contrast medium is used. Myocardial ischemia, major arrhythmias and extrasystoles are more likely to occur in these patients. The higher probability of neurological diseases and severe vascular disease represents an aggravating factor. Probability of acute renal insufficiency is higher in these subjects. Use in patients with particular pathological conditions: Hypersensitivity to iodinated contrast media - Hypersensitivity or a previous history of a reaction to iodinated contrast media increase the risk of recurrence of a severe reaction even with non-ionic media. Allergic predisposition - It is generally agreed that adverse reactions to iodinated contrast media are more common in patients having a history of allergy such as hay fever, hives and food allergy. Asthmatic patients – These patients are at higher risk of bronchospasm and related events after contrast media administration. Hyperthyroidism, nodular goitre -The small amount of free inorganic iodide that may be present in contrast media, might have some effects on thyroid function: these effects appear more evident in patients with latent or overt hyperthyroidism or goitre. Thyroid storms have been reported following administration of iodinated contrast media. Effect on ability to drive and use machinery – No data is available. However, given the rare possibility of delayed adverse reactions to contrast media, driving or using machinery should be avoided for 24 hours following the administration. Intraarterial and intravenous administration Use in patients with special pathological conditions Renal failure - Pre-existing renal impairment may predispose to acute renal dysfunction following contrast media administration. Preventive measures include: identification of high-risk patients; ensuring adequate hydration following intravascular contrast medium administration. This may precipitate lactic acidosis in patients who are taking biguanides metformin. As a precaution, biguanides should be stopped 48 hours prior to the administration of the contrast medium. Antidiabetic treatment with biguanides should be reinstated only after renal function has been regained. 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. Patients with normal renal function can continue to take metformin normally. Multiple myeloma, Waldestroem’s paraproteinaemia The use of the product is generally contraindicated. It is noteworthy that Myelomatosis or paraproteinaemias are conditions predisposing to renal impairment following contrast medium administration. The benefits of the use of a contrast-enhanced procedure should be carefully weighted against the possible risk. Adequate hydration and monitoring of renal function are recommended after CM administration. Pheochromocytoma - These patients may develop severe hypertensive crises (at times uncontrollable) during radiological procedures with contrast media (see also premedication). Sickle cell disease - Contrast media may promote sickling in individuals who are homozigous for sickle cell disease. Adequate hydration is recommended. Myasthenia gravis - The administration of iodinated contrast media may aggravate myasthenia signs and symptoms. Severe liver and renal dysfunction - Generally, contrast media use is contraindicated Indeed., Combination of severe hepatic and renal impairment can delay contrast medium excretion, hence predisposing to increased risk of untoward reactions. therefore such patients should not be examined unless absolutely necessary. Severe cardiovascular disease - There is an increased risk of severe reactions in individuals with severe cardiovascular disease and particularly in those with heart failure and coronary artery disease. Intravascular contrast medium injection may precipitate pulmonary oedema in patients with manifest or incipient heart failure, whereas administration in pulmonary hypertension and valvular heart diseases, may lead to pronounced haemodynamic changes. Ischaemic ECG changes and major arrhythmias are before contrast medium administration, preferably by maintaining i.v. infusion before and during the procedure and until the contrast medium 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 contrast medium has been cleared; postponing a new contrast agent examination until renal function returns to pre-examination levels. Patients on dialysis may receive contrast media which are easily dialysable such is the case with iomeprol. Diabetes mellitus - Diabetic nephropathy may predispose to renal impairment following intravascular contrast medium administration. This may precipitate lactic acidosis in patients who are taking biguanides. As a precaution, biguanides should be stopped 48 hours prior to the administration of the contrast medium. Antidiabetic treatment with biguanides should be re-instated only after renal function has been regained. Multiple myeloma, Waldestroem’s paraproteinaemia - The use of the product is generally contraindicated. It is noteworthy that myelomatosis or paraproteinaemias are conditions predisposing to renal impairment following contrast medium administration. Adequate hydration is recommended. Pheochromocytoma - These patients may develop severe hypertensive crises (at times uncontrollable) during radiological procedures with contrast media. Sickle cell disease - Contrast media may promote sickling in individuals who are homozigous for sickle cell disease. Adequate hydration is recommended. Myasthenia gravis - The administration of iodinated contrast media may aggravate myasthenia signs and symptoms. Severe liver and renal dysfunction Generally, contrast media use is contraindicated Indeed, combination of severe hepatic and renal impairment can delay contrast medium excretion, hence predisposing to increased risk of untoward reactions. Severe cardiovascular disease - There is an increased risk of severe reactions in individuals with severe cardiovascular disease and particularly in those with heart failure and coronary artery disease. Intravascular contrast medium injection may precipitate pulmonary oedema in patients with manifest or incipient heart failure, whereas administration in pulmonary hypertension and valvular heart commonest in elderly patients and in those with preexisting cardiac disease: their frequency and severity appear to be related to the severity of cardiac impairment. Severe and chronic hypertension may increase the risk of renal damage following contrast medium administration and the risks associated with the catheterization procedure. Cardiovascular diseases - 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. CNS disorders - Particular care should be paid in patients with acute cerebral infarction, acute intracranial haemorrhage, and conditions involving blood-brain-barrier (BBB) damage, brain oedema and acute demyelination. The presence of intracranial tumors or metastases and a history of epilepsy may increase the probability of the occurrence of convulsions. Neurological symptoms due to degenerative, inflammatory or neoplastic cerebrovascular pathologies may be exacerbated by contrast medium administration. Vasospasm and consequent Cerebral ischaemic phenomena may be caused by intravascular injections of contrast medium. Patients with symptomatic cerebrovascular diseases, e.g. recent stroke or frequent TIA (transient ischaemic attack) have an increased risk of transient neurological complications. Alcoholism - Acute and chronic alcoholism have been proven both experimentally and clinically to increase BBB permeability. This facilitates the passage of iodinated agents the contrast medium into the cerebral tissue, possibly leading to CNS disorders. Alcoholism may reduce seizure threshold. Drug addiction - Also the abuse of drugs may reduce seizure threshold. Effect on ability to drive and use machinery - There is no known effect on the ability to drive and operate machines. diseases, may lead to pronounced haemodynamic changes. Ischaemic ECG changes and major arrhythmias are commonest in elderly patients and in those with pre-existing cardiac disease: their frequency and severity appear to be related to the severity of cardiac impairment. Severe and chronic hypertension may increase the risk of renal damage following contrast medium administration and the risks associated with the catheterization procedure. CNS disorders - Particular care should be paid in patients with acute cerebral infarction, acute intracranial haemorrhage, and conditions involving blood-brain-barrier (BBB) damage, brain oedema and acute demyelination. The presence of intracranial tumors or metastases and a history of epilepsy may increase the probability of the occurrence of convulsions. Neurological symptoms due to degenerative, inflammatory or neoplastic cerebrovascular pathologies may be exacerbated by contrast medium administration. Vasospasm and consequent ischaemic phenomena may be caused by intravascular injections of contrast medium. Patients with symptomatic cerebrovascular diseases, recent stroke or frequent TIA (transient ischaemic attack) have an increased risk of transient neurological complications. Alcoholism - Acute and chronic alcoholism have been proven both experimentally and clinically to increase BBB permeability. This facilitates the passage of iodinated agents into the cerebral tissue, possibly leading to CNS disorders. Alcoholism may reduce seizure threshold. Drug addiction - Also the abuse of drugs may reduce seizure threshold. 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, more serious reactions up to anaphylactoid shock, with possible fatal outcome, may occur. In most cases reactions occur within minutes of dosing up. However, reactions may manifest also later on up to 24 hours from the injection, depending on the administration route. 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, lacrimation increased, rhinitis, palpitations, paraesthesia, pruritus, head throbbing, pharyngolaryngeal pain and throat tightness, dysphagia, cough, sneezing, urticaria, erythema, mild localised oedema, angioneurotic oedema and dyspnoea owing to tongue glottic and /laryngeal/ pharyngeal oedema and/or laryngospasm manifesting with wheezing and bronchospasm. Nausea, vomiting, abdominal pain, and diarrhoea are less common 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 anaphylactic reactions involving the cardiovascular system, such as vasodilatation, with pronounced hypotension, reflex 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. Blood and lymphatic system disorders Immune system disorders Frequency unknown* Thrombocytopenia Frequency unknown* Anaphylactoid reaction Psychiatric disorders Frequency unknown* Anxiety, Confusional state Undesirable Effects General The use of iodinated contrast media may cause untoward side effects. They are usually mild to moderate. However, more serious reactions up to anaphylactoid shock, with possible fatal outcome, may occur. In most cases reactions occur within minutes of dosing up. However, reactions may manifest also later on up to 24 hours from the injection, depending on the administration route. 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, lacrimation increased, rhinitis, palpitations, paraesthesia, pruritus, head throbbing, pharyngolaryngeal pain and throat tightness, dysphagia, cough, sneezing, urticaria, erythema, and mild localised oedema or angioneurotic oedema and dyspnoea owing to tongue and laryngeal oedema and/or laryngospasm manifesting with wheezing and bronchospasm. Nausea, vomiting, abdominal pain, and diarrhoea are less common. 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 anaphylactic reactions involving the cardiovascular system, such as vasodilatation, with pronounced hypotension, reflex 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. From clinical trials Adverse experiences reported among patients treated with Iomeprol during clinical trials are shown below. Adverse events Eye disorders Cardiac disorders Frequency unknown* Uncommon (≥1/1000 to <1/100) Rare (≥1/10,000 to <1/1000) Frequency unknown* Vascular disorders Nervous system disorders Uncommon (≥1/1000 to <1/100) Rare (≥1/10,000 to <1/1000) Frequency unknown* Blindness transient, Visual disturbance, Conjunctivitis, Lacrimation increased, Photopsia Bradycardia, tachycardia, hypertension, hypotension Bradycardia, tachycardia Vasodilatation, cyanosis, circulatory collapse Cardiac arrest, Myocardial infarction, Cardiac failure, Angina pectoris, Arrhythmia, Ventricular or atrial fibrillation, Atrioventricular block, Extrasystoles, Palpitations, Cyanosis Hypertension Hypotension Common (≥1/100 to <1/10) Circulatory collapse or shock, Hot flush, Flushing, Pallor Asthenia, syncope, headache Uncommon (≥1/1000 to <1/100) Headache, dizziness, paralysis, agitation Rare (≥1/10,000 to <1/1000) Presyncope Tremor, muscle spams, confusion, loss of consciousness, visual field defect, aphasia, convulsions, coma Frequency unknown* Coma, Transient ischaemic attack, Paralysis, Syncope, Convulsions, Loss of Cardiovascular (mainly after cardiovascular procedures/ Uncommon Bradycardia , tachycardia, hypertension, hypotension Rare Vasodilatation, cyanosis, circulatory collapse interventions) Nervous System Common Uncommon Rare Gastrointestinal system Asthenia, syncope, headache Dizziness, paralysis, agitation Tremor, muscle spasms, confusion, loss of consciousness, visual field defect, aphasia, convulsions, coma Common Nausea Uncommon Vomiting Common Dyspnoea, nasal congestion, laryngeal oedema Skin and Subcutaneous Tissue Uncommon Wheals, pruritus, rash General Common Injection site warmth and pain, pallor Respiratory system Uncommon Renal and Urinary Disorders Back pain, chest pain, rigors, injection site haemorrhage, pyrexia, sweating increased Rare Anaphylactoid reaction (characterized by cardiovascular, respiratory and cutaneous symptoms) Rare Renal insufficiency, oliguria, proteinuria, blood creatinine increased Some of these events may occur as a consequence of the procedure. Post Marketing Surveillance The following undesirable effects have been Gastrointestinal disorders Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Frequency unknown* Respiratory, thoracic and mediastinal disorders Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Frequency unknown* Skin and subcutaneous tissue disorders Uncommon (≥1/1000 to <1/100) Rare (≥1/10,000 to <1/1000) Frequency unknown* General disorders and administration site conditions Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) consciousness, Dysarthria, Paraesthesia, Amnesia, Somnolence, Taste abnormality Nausea reported during post- marketing in <3/10,000 patients. Intravascular and intra-thecal administration: - Nausea, vomiting Diarrhoea, Abdominal pain, Salivary hypersecretion, Dysphagia, Salivary gland enlargement - Dyspnea, nasal congestion, laryngeal oedema Dyspnoea Respiratory arrest, Acute respiratory distress syndrome (ARDS), Pulmonary oedema, Laryngeal oedema, Pharyngeal oedema, Bronchospasm, Asthma, Cough, Hyperventilation, Pharynx discomfort, Laryngeal discomfort, Rhinitis, Dysphonia Wheals, Erythema, Urticaria, Pruritus rash Rash Angioedema Cold sweat Sweating increased Injection site warmth and pain, pallor Feeling hot Back pain, Chest pain, Injection site - - - - - General: shock, malaise, fatigue, hot flushes, flushing, cold sweat, coldness local, taste abnormality, thirst, injection site reaction. Nervous system: hyperkinetic syndrome, encephalopathy, paralysis, oculomotor nerve paralysis, paraesthesia, dysarthria, dizziness, dysphonia, faecal incontinence, brain oedema, Cardiovascular: cardiac arrest, myocardial infarction, angina pectoris, extrasystoles, arrhythmia, ventricular or atrial fibrillation, tachycardia, palpitations, atrioventricular block, electrocardiogram abnormal, ST segment elevation. Respiratory: respiratory arrest, pulmonary oedema, acute respiratory distress syndrome (ARDS), bronchospasm, asthma, pharyngeal oedema, laryngeal stridor, rhinitis, cough, hyperventilation, hypoxia, pharynx and/or laryngeal discomfort. Skin and subcutaneous tissue disorders: angioneurotic oedema, eczema, urticaria, wheals cold sweat Vascular (extracardiac): cerebrovascular disorder, transient ischaemic attack. Gastrointestinal disorders: pancreatitis acute, ileus, diarrhea, abdominal pain, salivary hypersecretion, dysphagia. Urogenital: urinary incontinence, blood urea increased. Senses: parosmia Eye disorders: blindness transient, visual disturbance, conjunctivitis, lacrimation increased, photopsia, photophobia. Musculoskeletal: arthralgia, muscle stiffness. Psychiatric disorders: amnesia, anorexia, anxiety, somnolence. Liver and biliary system: liver function tests abnormal. Platelets, bleeding and coagulation: thrombocytopenia. Administration to body cavities Blood amylase increase is common following ERCP (Endoscopic retrograde cholangiopancreatography). Rare cases of pancreatitis have been described. The reactions reported in cases of arthrography and fistulography usually represent irritative manifestations superimposed on pre-existing warmth and pain rigors, injection site haemorrhage,, pyrexia, sweating increased Rare (≥1/10,000 to <1/1000) Frequency unknown* Musculoskeletal and connective tissue disorder Renal and urinary disorders Rare (≥1/10,000 to <1/1000) Frequency unknown Rare (≥1/10,000 to <1/1000) Frequency unknown Investigations Rare (≥1/10,000 to <1/1000) Frequency unknown Asthenia, Rigors, Pyrexia Anaphylactoid reaction (characterized by cardiovascular, respiratory and cutaneous symptoms) Injection site reaction**, Coldness local, Fatigue, Malaise, Thirst Back pain Arthralgia Renal insufficiency, oliguria, proteinuria, blood creatinine increased Renal failure Blood creatinine increased Electrocardiogram ST segment elevation, Electrocardiogram abnormal * 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. Coronary artery thrombosis and coronary artery embolism have been reported as a complication of coronary catheterization procedures. Vasospasm and consequent ischaemia have been observed during intra-arterial injections of contrast medium, in conditions of tissue inflammation. Generalised hypersensitivity reactions are rare, generally mild and in the form of skin reactions. However, the possibility of severe anaphylactoid reactions cannot be excluded. (See beginning of chapter “Undesirable effects” ). As with other iodinated contrast media, pelvic pain and malaise may occur after hysterosalpingography. Compliance with the instruction contained in the package insert reduces the risk of untoward effects. It is important to inform the physician or the pharmacist of any untoward effect, even if not mentioned in this package insert. particular after coronary and cerebral angiography often procedurally related and possibly triggered by the tip of the catheter or excess catheter pressure. 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. Some of these events may occur as a consequence of the procedure. Post marketing surveillance and intra-thecal administration: - Nervous system: hyperkinetic syndrome, encephalopathy, oculomotor nerve paralysis, dizziness, faecal incontinence, brain oedema, - Cardiovascular: tachycardia, - Respiratory: laryngeal stridor, hypoxia, - Skin and subcutaneous tissue disorders: angioneurotic oedema, eczema, urticaria, wheals, - Vascular (extracardiac): cerebrovascular disorder, - Gastrointestinal disorders: pancreatitis acute, ileus, - Urogenital: urinary incontinence, blood urea increased. - Senses: parosmia - Eye disorders: photophobia. - Musculoskeletal: muscle stiffness. - Psychiatric disorders: anorexia, - Liver and biliary system: liver function tests abnormal. - Platelets, bleeding and coagulation: Administration to body cavities Blood amylase increase is common following ERCP (Endoscopic retrograde cholangiopancreatography). Rare cases of pancreatitis have been described. The reactions reported in cases of arthrography and fistulography usually represent irritative manifestations superimposed on pre-existing conditions of tissue inflammation. Generalised hypersensitivity reactions are rare, generally mild and in the form of skin reactions. However, the possibility of severe anaphylactoid reactions cannot be excluded. (See beginning of chapter “Undesirable effects” ). As with other iodinated contrast media, pelvic pain and malaise may occur after hysterosalpingography. Compliance with the instruction contained in the package insert reduces the risk of untoward effects. It is important to inform the physician or the pharmacist of any untoward effect, even if not mentioned in this package insert.