Jopamiron 50,0 mL Solution for injection.

JOPAMIRON is indicated for myelography, cisternography and ventriculography, for all angiographic and urographic examinations and for contrast enhancement in computerised tomography. Its properties also permit the visualisation of body cavities (e.g. arthrography, fistulography, vesiculography, endoscopic - retrograde cholangio - pancreaticography).

General Information
Patients must present themselves in a fasted and adequately hydrated state on the day of the examination. Compensation must be made for disturbances of water and electrolyte balance. This applies in particular to patients who are predisposed to such disturbances. In the case of abdominal angiography and urography, the diagnostic yield is increased if the bowels are empty of faecal matter and gas. On the two days prior to the examination patients should therefore avoid flatulent food, in particular peas, beans and lentils, salads, fruit, dark and fresh bread and all kinds of uncooked vegetables. On the day before the examination, patients should refrain from eating after 6 p.m. Moreover, it is appropriate to administer a laxative in the evening. In babies, however, prolonged fasting and the administration of a laxative before the examination are contra-indicated. Calm management of the patients and appropriate premedication will obviate pronounced states of excitement, anxiety and pain - factors known to be able to cause side - effects or intensify contrast medium - induced reactions. Sensitive patients tolerate the contrast medium better if it is warmed to body temperature, at which it is also less viscous. Intravascular administration of contrast media should, if possible, be done with the patient lying down. After the examination the patient should be kept under observation for at least 15 minutes, since the majority of all severe incidents is known to occur within this time. After myelography - in particular in the case of myelography of upper sections - the contrast medium must always as far as possible be conducted away to the lumbar region. This is achieved by moving the patient into the upright sitting position for several minutes. Afterwards, the patient should rest in bed for at least 24 hours, with the trunk in the horizontal position and the bed head tilted up by 15 degrees. Patients in whom it must be suspected that the stimulus threshold is reduced must be kept under careful observation for 8 hours.
At the first signs of hyperreactivity and particularly if epileptiform reactions should occur, appropriate countermeasures are to be taken (see section 4.8).
Posology
Adults and elderly
In angiography, deviations must possibly be made from the suggested dosages contained in Table 1, for adults of normal weight, depending on age, weight, cardiac output, general state of health, the clinical problem, examination technique, kind and volume of the region to be examined. For examination of the subarachnoid region a total iodine dose of 3 g should not be exceeded.
Pediatric population
Examinations of infants and children always require individualisation of dosages, to be chosen in the first place in relation to the region to be demonstrated, the weight and the age.
Table 1: Dosage schedule
Examination method Concentration of JOPAMIRON (mg iodine/mL) Dosage (mL)
Subarachnoid region Myeloradiculography 300 5 u2013 10
Cisternography and Ventriculography 300 3 u2013 10
Angiography Thoracic aortography 300 u2013 370 50 u2013 80
Abdominal aortography 300 u2013 370 50 u2013 80
Peripheral arteriography 300 u2013 370 30 u2013 50
Selective arteriography 300 u2013 370 Depending on the vessel
Phlebography 300 30 u2013 50
Cerebral arteriography 300 5 u2013 10
Angiocardiography Coronarography 370 8 u2013 15
Ventriculography 370 40 u2013 70
Urography 300 370 300 370 300 370 50 u2013 100 30 u2013 50 3 u2013 5 mL/kg body mass 2 u2013 4 mL/kg body mass 1 u2013 2 mL/kg body mass 1 u2013 1.5 mL/kg body mass
Intravenous urography Adults: Children up to 8 kg body mass: Children over 8 kg body mass: Computerised tomography 300 u2013 370 0.5 u2013 2 mL/kg body mass
Method of administration Intrathecal Intraventricular Intra-arterial Intravenous Intra-cisternal Intra-articular.

• Hypersensitivity to iopamidol, iodine or to any of the excipients of JOPAMIRON (see section 6.1).
• Intrathecal administration: the concomitant intrathecal administration of corticosteroids with JOPAMIRON.
• Intrathecal administration: immediate repeat myelography in the event of technical failure, to avoid overdosage.
• Cerebral fits are a relative contraindication for myelography. When the examination is carried out, all facilities to counter any convulsions which may occur must first of all be made readily available (see section 4.8).
• Manifest hyperthyroidism.
• Waldenstru00f6m's macroglobulinemia.
• Multiple myeloma.
• Severe kidney disease.
• JOPAMIRON should not be used during pregnancy (see section 4.6).

Diagnostic procedures which involve the use of any radiopaque medium should be carried out under the direction of personnel with the prerequisite training and with a thorough knowledge of the particular procedure to be performed. Appropriate facilities should be available for coping with any complication of the procedure, as well as for emergency treatment of severe reaction to the contrast medium itself. Fatal reactions have been associated with the administration of water-soluble contrast media. During the examination an intravenous route for emergency treatment in the event of a reaction is required. After the administration of the contrast medium, competent personnel, medicines and equipment for emergency resuscitation must be available for at least 30 minutes. Caution during injection of contrast media is necessary to avoid extravasation. Local tissue irritation can occur in the case of perivascular infiltration of the contrast media. In patients who are known epileptics or have a history of epilepsy, anticonvulsant therapy should be maintained before and following myelographic procedures. In some instances anticonvulsant therapy may be increased for 48 hours before the examination. General information: Particular caution must be exercised in the case of hypersensitivity to iodinated contrast media. Experience shows that patients with an allergic disposition suffer more frequently from hypersensitivity reactions. In such cases some examiners administer an antihistamine or corticoid prophylactically. However, contrast media and prophylactic agents should not be administered mixed together. The patient should also be informed that allergic reactions may develop up to several days after the procedure; in such case, a physician should be consulted. The risk of bronchospasm-inducing reactions in asthmatic patients is higher after contrast media administration, especially in patients taking beta-blockers. Patients with congestive heart failure should be observed for several hours following the procedure to detect delayed haemodynamic disturbances, which may be associated with a transitory increase in the circulating osmotic load. All other patients should be observed for at least 30 minutes after the procedure as most of the adverse events occur within this period. Pre-existing renal impairment may predispose to acute renal dysfunction following contrast media administration. In patients with impairment of renal function, the administration of potentially nephrotoxic medicines should be avoided until the contrast medium is completely excreted. In such patients, renal function parameters should be monitored after the procedure. Further administration of contrast media should be postponed until renal function has returned to its previous level. 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 biguanides (e.g. metformin, see section 4.5). As a precaution, biguanides should be stopped 48 hours prior to the contrast agent examination and reinstated only after control of renal function has been regained. Patients must be sufficiently hydrated before and after radiographic procedures. Patients with severe functional impairment of the liver or myocardium, myelomatosis, diabetes, polyuria or oliguria, hyperuricemia, infants, elderly patients and patients with severe systemic disease should not be exposed to dehydration. Fluid intake should not be limited and any abnormalities of fluid or electrolyte balance should be corrected prior to use of this hypertonic solution. To prevent crises in patients with sickle cell disease adequate hydration should be assured and a minimal volume of low concentration should be used. Thyroid storms have been reported following administration of iodinated contrast media to patients with, or with suspicion of, hyperthyroidism or autonomously functioning thyroid nodule(s) (see section 4.3). It is possible that hyperthyroidism may recur in patients previously treated for Graves' disease. Following the administration of iodinated renal contrast media, the capacity of the thyroid tissue to take up radioisotopes for diagnosing disorders of the thyroid is reduced for up to 2 weeks, and even longer in individual cases after dosing with an iodinated contrast medium that is eliminated through the kidneys. A characteristic of non-ionic contrast media is the extremely low interference with normal physiological functions. As a consequence of this, non-ionic contrast media have less anti-coagulant activity in vitro than ionic media. Medical personnel performing vascular catheterisation procedures should be aware of this and pay meticulous attention to the angiographic technique. JOPAMIRON should be used with caution in patients with hypercalcaemia and cerebral vascular disease. Vasospasm and subsequent cerebral ischemic phenomena may be caused by intra-arterial injections of contrast media. The risk associated with a particular investigation may be increased by conditions such as advanced arteriosclerosis and hypertension. The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis. On intravascular administration: In patients with severe impairment of hepatic function, cardiac and circulatory insufficiency, pulmonary emphysema, poor general health, cerebral arteriosclerosis, juvenile-type diabetes or diabetes of long standing, cerebral spasmodic conditions, the need for examination merits particularly careful consideration. Fluid intake should not be restricted before the use of JOPAMIRON in patients with juvenile-type or diabetes of long standing, polyuria, oliguria or gout or in babies, young children and marasmic patients. Compensation must be made for disturbances of water and electrolyte balance. Patients with phaeochromocytoma can develop severe hypertensive crises following intravascular JOPAMIRON administration. Premedication with u03b1-receptor blockers is recommended. Contrast induced encephalopathy: Encephalopathy has been reported with the use of JOPAMIRON (see section 4.8). This may manifest with symptoms and signs of neurological dysfunction such as headache, visual disturbance, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, coma and cerebral oedema within minutes to hours after administration and generally resolves within days. Factors which increase blood-brain barrier permeability will ease the transfer of contrast media to brain tissue and may lead to possible CNS reactions, for instance encephalopathy. If contrast encephalopathy is suspected, JOPAMIRON should not be re-administered and appropriate medical management should be initiated. Angiography: In patients undergoing angiocardiographic procedures special attention should be paid to the status of the right heart and pulmonary circulation. Special care should be exercised when this product is injected into the right heart or pulmonary artery in patients with pulmonary hypertension. Right heart insufficiency and pulmonary hypertension may precipitate bradycardia and systemic hypotension, when the organic iodine solution is injected. Right heart angiography should be carried out only when absolutely indicated. During intracardiac and/or coronary arteriography, ventricular arrhythmias may infrequently occur. In angiographic procedures, the possibility of dislodging plaque or damaging or perforating the vessel wall should be considered during catheter manipulation and contrast medium injection. Test injections to ensure proper catheter placement are recommended. Angiography should be avoided whenever possible in patients with homocystinuria due to an increased risk of thrombosis and embolism. In patients undergoing peripheral angiography, there should be pulsation in the artery into which the X-ray contrast medium will be injected. In patients with thromboangiitis obliterans or ascending infections in combination with serious ischaemia the angiography should be performed with special caution. In paediatric roentgenology, one should proceed with great caution when injecting the contrast medium into the right heart chambers of cyanotic neonates with pulmonary hypertension and impaired cardiac function. In examinations of the aortic arch the tip of the catheter should be positioned carefully to avoid hypotension, bradycardia and central nervous system (CNS) injury due to excess pressure transmitted from the injector pump to the brachiocephalic branches of the aorta. Likewise, in abdominal aortography, excess pressure from the pump may cause renal infarction, spinal cord injury, retroperitoneal bleeding, intestinal infarction and necrosis. In peripheral arteriography JOPAMIRON 370 may sometimes cause a painful reaction in the involved limb. This is usually not the case with the less concentrated solution JOPAMIRON 300. In patients undergoing venography, special caution should be exercised in patients with suspected phlebitis, serious ischaemia, local infections, or a complete venous occlusion. JOPAMIRON should be administered with caution in patients with symptomatic cerebrovascular diseases, recent stroke, or frequent transient ischemic attack (TIA), altered permeability of the blood-brain barrier, increased intracranial pressure, suspicion of intracranial tumour, abscess or haematoma/haemorrhage, history of convulsive disorder or alcoholism. Neuroradiology: The contrast medium should be removed as much as possible in case of spinal fluid blockage. Anticonvulsant therapy should be maintained before and following myelographic procedures in patients who are known to suffer from convulsions. If during the procedure a convulsive crisis occurs, it is recommended to administer intravenously diazepam or phenobarbital. Neuroleptics must be absolutely avoided, because they lower the seizure threshold. The same applies to analgesics, anti-emetics, antihistamines and sedatives of the phenothiazine group. Whenever possible, treatment with medicines should be discontinued at least 48 hours before administration of the contrast medium and not be resumed less than 12 hours after completion of the procedure, particularly in thoracic and cervical myelography and in ventriculography. Caution must also be exercised in alcoholics and drug addicts because of the possibility of a reduced stimulus threshold. Intrathecal administration: If from clinical history, there is a previous history of epilepsy or in the presence of blood in the cerebrospinal fluid or presence of local or systemic infection where bacteraemia is likely, special caution for use of JOPAMIRON is advised. After completion of direct cervical or lumbo-cervical procedures:
u2022 Raise head of table steeply (45 degree angle) for about two minutes so that the contrast medium flows towards the caudal end.
u2022 Avoid excessive and particularly active patient movement or straining, maintain the patient under close observation, quiet and in a head up position especially in the first few hours. The patient should remain supine and at bed rest during this period. Encourage the patient, if able, to take in fluids orally and eat.

Thyroid function tests: JOPAMIRON may interfere with tests for thyroid function. Following administration of JOPAMIRON, the capacity of the thyroid tissue to take up iodine is reduced for 2 u2013 6 weeks. Following administration of JOPAMIRON atypical adverse reactions e.g. erythema, fever and flu symptoms have been reported in patients treated with interleukin - 2. To prevent onset of lactic acidosis in diabetic patients under treatment with oral anti-diabetic agents of the biguanide class and with moderate renal impairment undergoing elective procedures, biguanides should be stopped 48 hours prior to the administration of the contrast medium and re-instated only after 48 hours if serum creatinine is unchanged (see section 4.4). In emergency patients in whom renal function is either impaired or unknown, it is recommended that metformin should be stopped from the 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. Cardiac and/or hypertensive patients under treatment with diuretics, ACE-inhibitors, and/or beta-blocking medicines 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. In patients receiving beta-blockers there is an elevated risk of more severe anaphylactoid reactions. Arterial thrombosis has been reported when JOPAMIRON was given following papaverine. The administration of vasopressors strongly potentiates the neurological effects of intra-arterial contrast media. Contrast media may interfere with laboratory tests for bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium, and phosphate). These substances should not be assayed during the same day following the administration of contrast media.

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. X-ray examination of women should, if possible be conducted during the pre-ovulation phase of the menstrual cycle.
Pregnancy
JOPAMIRON should not be used during pregnancy (see section 4.3). The safety of JOPAMIRON in pregnancy has not been established. Where possible, exposure to radiation should be avoided during pregnancy.
Breastfeeding
Iodine-containing X-ray contrast agents are excreted into the breast milk in low amounts. From animal experience, JOPAMIRON is non-toxic in animals after oral administration. From experience gained so far, harm to the nursing infant is unlikely to occur. Stopping breastfeeding is unnecessary.
Fertility
No data on male and female fertility are available.

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 intravascular injection. Driving or operating machinery is not advisable for 6 hours following intrathecal administration.

Skin reactions may occur in the form of various types of rash or diffuse blister formation. Side effects are usually mild to moderate and transient in nature; however, rare severe and life-threatening reactions, sometimes leading to death, have been reported. Following intravascular administration, in most cases reactions occur within minutes of dosage. However, delayed reactions, usually involving skin, may occur, mostly within 2 u2013 3 days, more rarely within 7 days, after the administration of the contrast medium. Severe cutaneous adverse reactions (SCARs), including Stevens - Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP) have been reported in association with JOPAMIRON administration (see section 4.4). After intrathecal administration, most side effects occur with a delay of some hours due to the slow absorption from the site of administration and distribution to the whole body. Reactions usually occur within 24 hours after injection.

Symptoms of overdosage
Dosages exceeding the specific package insert dose are not recommended, as they might lead to life-threatening adverse effects. With overdosage, the symptoms described under section 4.8 may occur, which should be treated according to the recommended procedures to be adopted in incidents after the administration of contrast media. If needed, haemodialysis can be used to eliminate JOPAMIRON from the body. Treatment of overdosage is directed toward the support of all vital functions and prompt institution of symptomatic therapy.
Intravascular
In the event of accidental intravascular overdose in humans, the water and electrolyte losses must be compensated by infusion. Renal function should be monitored for at least three days.
Intrathecal
Signs of intrathecal overdose may be ascending hyperreflexia or tonic-clonic spasms, up to generalised seizures, and in severe cases of central involvement, hyperthermia, stupor and respiratory depression.