Ultravist 300 Injection

Ultravist 300 Injection is used for: Not for intrathecal use. Iopromide 240 mg Iodine/mL: Contrast enhancement in computerised tomography (cranial computerised tomography), arteriography and venography including intraarterial digital subtraction angiography; intravenous urography, examination of other body cavities (e.g. arthrography, hysterosalpingography). Iopromide 300 mg Iodine/mL: Contrast enhancement in computerised tomography, arteriography and venography including intravenous/intraarterial digital subtraction angiography; intravenous urography, visualisation of body cavities (e.g. arthrography). Iopromide 370 mg Iodine/mL: Contrast enhancement in computerised tomography, arteriography including intravenous digital subtraction angiography; and especially angiocardiography; intravenous urography, visualisation of body cavities (e.g. arthrography)

Iopromide should be administered by trained health care professionals only. Ensure adequate resuscitation equipment is available when performing radiographic procedures. Contrast media which are warmed to body temperature 37°C) before administration are better tolerated and can be injected more easily because of reduced viscosity Ensure the patient is well hydrated before and after administration of iopromide as for other contrast media. Dosage and strength used vary depending on the type of examination and the route of administration. Usually the same iodine concentration and volume is used as for other iodinated radio-contrast media in current use. Intravenous urography: ADULT: The minimum dose is 0.8 mL/kg body weight Iopromide-370 (1 mL/kg Iopromide-300 or 1.3 mL/kg Iopromide-240). These doses should provide adequate filling of the ureters. It may be necessary to increase the dose in individual cases. Computerised tomography: Cranial CT: The following dosages are recommended for cranial CT: Iopromide-240: 1.5-2.5 mL/kg body weight Iopromide-300: 1-2 mL/kg body weight Iopromide-370: 1-1.5 mL/kg body weight Whole-body CT: For whole-body computerised tomography, the doses of contrast medium and the rates of administration depend on the organs under investigation, the diagnostic problem and, in particular, the different scan and image-reconstruction times of the scanners in use. Angiography: The dosage depends on the age, weight, cardiac output and general condition of the patient, the clinical problem, examination technique and the nature and volume of the vascular region to be investigated Digital subtraction angiography (DSA): By IV injection, 30-60 mL Iopromide-300 or 370 as a bolus (flow-rate: 8-12 mL/second into the cubital vein; 10-20 mL/second into the vena cava) is recommended for high-contrast demonstrations of the great vessels, of the pulmonary arteries and of the arteries of the neck, head, kidneys and extremities. Intra-arterial digital subtraction angiography requires smaller volumes and lower iodine concentrations than the intravenous technique. Patients with hepatic impairment No dosage adjustment is necessary in patients with hepatic impairment. Elderly: When administered to elderly patients, the possibility of reduced renal function (leading to reduced clearance) should be considered

Intravenous urography: The poor concentrating ability of the immature nephron of infantile kidneys necessitates the use of relatively high doses of contrast medium, i.e. for Iopromide-300: Neonates: 4.0 mL/kg body weight Babies: 3.0 mL/kg body weight Small children: 1.5 mL/kg body weight NOTE: Young infants (age < 1 year) and especially newborns are susceptible to electrolyte imbalance and haemodynamic alterations. Care should be taken regarding the dose of contrast medium to be given, the technical performance of the radiological procedure and the patient status

Renal reactions/dosing: Since iopromide is excreted almost exclusively in an unchanged form via the kidneys, the elimination of iopromide is prolonged in patients with renal impairment. In order to reduce the risk of additional contrast media-induced renal impairment in patients with pre-existing renal impairment, the minimum possible dose should be used in these patients Patients with pre-existing renal impairment and diabetes mellitus are particularly at risk of developing contrast induced nephropathy (CIN) or acute renal failure following the administration of iodinated contrast media. Dehydration, advanced age and vascular disease are other risk factors. Preventive measures include: - Identification of high-risk patients - Ensuring adequate hydration. If necessary, by maintaining an IV infusion from before the procedure until the contrast medium has been cleared by the kidneys. - Avoiding additional strain on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, arterial clamping, renal arterial angioplasty, or major surgery, until the contrast medium has been cleared. - Dose reduction to a minimum. - Postponing a repeat contrast medium examination until renal function returns to pre-examination levels. Patients on haemodialysis may receive contrast media for radiological procedures. Correlation of the time of contrast media injection with the haemodialysis session is unnecessary

Important Dosage and Administration Instructions: Iopromide should be administered by trained health care professionals only. Use sterile technique for all handling and administration of iopromide for intravascular and intrathecal administration. Patients will tolerate a contrast medium better if it is warmed to body (37°C) or room temperature, which lowers the viscosity. Iopromide solution should be inspected visually for particulate matter, discolouration and the integrity of the container prior to administration. It should only be used if clear and within the normal colourless to pale yellow range. Do not use if particulate matter or discolouration is present. Do not mix iopromide injection with, or inject in intravenous lines containing, other drugs or total nutritional admixtures. Use the lowest dose necessary to obtain adequate visualization. Individualize the volume, strength, and rate of administration of iopromide injection. Consider factors such as age, body weight, vessel size, blood flow rate within the vessel, anticipated pathology, degree and extent of opacification required, structures or area to be examined, disease processes affecting the patient, and equipment and technique to be employed. Avoid extravasation when administering iopromide injection intravascularly, especially in patients with severe arterial or venous disease. Hydrate patients before and after intravascular administration of iopromide injection. Iopromide injection contains no antimicrobial agent. Use only once and discarded any residue. Intrathecal Administration: Rate of injection: Injection should be made slowly over 1 to 2 minutes Repeat procedures: If sequential or repeat examinations are required, a suitable interval of time between administrations should be observed to allow for normal clearance of the drug from the body; at least 48 hours should be allowed before repeat examination; however, whenever possible, 5 to 7 days is recommended. If computerized tomographic (CT) myelography follows myelography, delay imaging several hours to allow the degree of contrast to decrease. Pharmaceutical Precautions: Solutions are usually sterilized by autoclaving and contain no preservatives. Unused portions must be discarded. Iohexol solution is sensitive to light and therefore should be protected from exposure

General: Hypersensitivity to iopromide, its excipients or other iodine-containing compounds; History of serious reaction to iopromide. Avoid use in patients with thyrotoxicosis, anuria or decompensated cardiac insufficiency. Hysterosalpingography must not be performed during pregnancy or in the presence of acute inflammatory processes in the pelvic cavity. ERCP (endoscopic retrograde cholangiopancreatography) is contraindicated in acute pancreatitis. Serum creatinine indicating moderate to severe renal impairment Not indicated for intrathecal use Pregnancy Intravascular use: IV administration of iodinated contrast agents should be avoided in certain procedures e.g., Carotid angiography during the progressive period of stroke; Coronary arteriography in the first 4 weeks after myocardial infarction; Presence of infection or open injury in or near the region to be examined

GENERAL Iopromide should be administered by trained health care professionals only and facilities should be available for emergency treatment of severe reaction to the contrast medium. After parenteral administration, patient should be monitored for at least 30 to 60 minutes since severe delayed reactions may occur. Hydration: Patients should be well hydrated prior to and following iopromide administration as for other contrast media. Patient may need to be hydrated intravenously until excretion of the contrast medium is complete. The risk of dehydration leading to acute renal failure is higher in patients with multiple myeloma, diabetes mellitus, polyuria, oliguria, hyperuricaemia, as well as to infants, small children and elderly patients. Preventive measures against acute renal failure following contrast medium administration (see under Renal impairment below). Anxiety: Pronounced states of excitement, anxiety and pain may increase the risk of side effects or intensify contrast medium-related reactions. Care should be taken to minimise the state of anxiety in such patients. Risk of contamination: Even invisible damage caused to the container during storage or transit may result in contamination. Before using check visually and do not use if precipitates or particulate matter observed or contents not clear or discoloured. The container once opened has to be used immediately. Any unused portion of contrast medium remaining in the container must be discarded. Hypersensitivity reactions: Iopromide can be associated with anaphylactic/hypersensitivity or other idiosyncratic reactions characterised by cardiovascular, respiratory and cutaneous manifestations such as mild respiratory distress, reddening of the skin (erythema), urticaria, itching or facial oedema. Serious events such as angioedema, subglottic oedema, bronchospasm and allergic shock are rare. The risk of hypersensitivity reactions is higher in case of: - previous reaction to contrast media - history of bronchial asthma or other allergic disorders. However, such reactions are irregular and unpredictable in nature. Anaphylactic/anaphylactoid reactions ranging from mild to severe reactions including shock are possible. Most of these reactions occur within 30 minutes of administration. However, delayed reactions (after hours to days) may occur. In the event of a severe hypersensitivity reaction, patients with cardiovascular disease are more susceptible to serious or even fatal outcomes. PRECAUTIONARY RECOMMENDATIONS ON HYPERSENSITIVITY - Sensitivity testing using a small test dose of contrast medium is not recommended, as it has no predictive value. Furthermore, sensitivity testing itself has occasionally led to serious and even fatal hypersensitivity reactions. - Before any contrast medium is injected, the patient should be questioned for a history of allergy (e.g. seafood allergy, hay fever, hives), sensitivity to iodine or to radiographic media and bronchial asthma as the reported incidence of adverse reactions to contrast media is higher in patients with these conditions. - Premedication with antihistamines and/or glucocorticoids may be considered in patients with an allergic disposition (see above). If premedication is given, a corticosteroid regimen is recommended. Note that contrast media and prophylactic agents should not be administered together. - Patients with bronchial asthma are at special risk of having bronchospasms or a hypersensitivity reaction. Patients who experience hypersensitivity reactions to iopromide while simultaneously taking beta blockers may be resistant to treatment effects of beta agonists. - If hypersensitivity reactions occur, administration of the contrast medium must be discontinued immediately. - Irrespective of the quantity and type of administration, even mild allergic symptoms may be the first signs of a serious anaphylactoid reaction requiring treatment. - For this reason, iodinated contrast media should only be employed in medical environments where emergency treatment is available, i.e. the necessary equipment and medications, physicians with sufficient clinical experience, as well as trained assisting medical staff. - It must therefore be possible to initiate immediate emergency measures for all patients in order to treat a serious reaction, and to maintain direct access to the requisite emergency drugs and emergency surgical kit. - The patient should be observed for at least 30 minutes after the end of administration; Most of these reactions occur within 30 minutes of administration. However, delayed reactions (after hours to days) may occur. Severe cutaneous adverse reactions: Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administration of iopromide to patients with a history of a severe cutaneous adverse reaction to iodinated contrast media. Intravascular: Meticulous intravascular administration technique is required with both ionic and non-ionic contrast media, particularly during angiographic procedures, to minimize thromboembolic events. Extravasation: Extravasation of contrast media may on rare occasions give rise to local pain, and oedema, which usually recedes without sequelae. However, inflammation and even tissue necrosis have been seen. Elevating and cooling the affected site are recommended as routine measures. Surgical decompression may be necessary in cases of compartment syndrome. Renal impairment: Temporary renal failure may occur in rare cases PREVENTIVE MEASURES AGAINST ACUTE RENAL FAILURE FOLLOWING CONTRAST MEDIUM ADMINISTRATION INCLUDE: - Identifying high-risk patients, e.g. patients with a history of renal disease, pre-existing renal insufficiency, previous renal failure after contrast medium administration, diabetes mellitus with nephropathy, volume depletion, multiple myeloma, age greater than 60 years, advanced vascular disease, paraproteinaemia, severe and chronic hypertension, gout, patients receiving large or repeated doses. - Ensuring adequate hydration in all patients before contrast medium administration, preferably by maintaining intravascular infusion before and after the procedure and until the contrast medium has been cleared by the kidneys. - Avoiding additional strain on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, arterial clamping, renal arterial angioplasty, major surgery, etc., until the contrast medium has been cleared. - Postponing a new contrast medium examination until renal function returns to pre-examination levels. Patients on dialysis, if without residual renal function, may receive iopromide for radiological procedures as iodinated contrast media are cleared by the dialysis process. Severe liver dysfunction: In the case of severe renal insufficiency, the coexistence of severe hepatic dysfunction can seriously delay contrast medium excretion, possibly necessitating haemodialysis Thyroid dysfunction: Contrast media may induce hyperthyroidism and thyrotoxic crisis especially in patients with known or suspected hyperthyroidism or goitre. Testing of thyroid function prior to iopromide administration and/or preventive thyroid medication may be considered in patients with known or suspected hyperthyroidism. Cardiovascular disease: Patients with significant cardiac disease or severe coronary artery disease are at an increased risk of developing clinically relevant haemodynamic changes and dysrhythmia. In patients with valvular disease and pulmonary hypertension, contrast medium administration may lead to pronounced haemodynamic changes. Reactions involving ischaemic ECG changes and major dysrhythmia are more common in older patients and in those with pre-existing cardiac disease. The intravascular injection of contrast media may precipitate pulmonary oedema in patients with heart failure Thromboembolic events: Non-ionic contrast media usually cause low interference with normal physiological function and therefore, have less anticoagulant activity in vitro than ionic media. Serious thromboembolic events have been reported during angiographic procedures with both ionic and non-ionic contrast media, the risk being higher with non-ionic agents. Clotting may occur when blood remains in contact with syringes containing iodinated contrast media. Other risk factors may include: - length of procedure, - number of injections, - catheter and syringe material, - underlying disease state, and - concomitant medication. Preventive measures include: - careful angiographic technique - flush the catheter frequently with physiological saline (if possible with the addition of heparin) - minimise the length of the procedure so as to minimise the risk of procedure-related thrombosis and embolism Central nervous system disorders: Factors which increase blood brain barrier permeability facilitate the passage of the contrast medium into cerebral tissue and thereby increasing the risk of CNS reactions. Such factors may include acute cerebral infarction, acute intracranial haemorrhage, and other conditions involving blood brain barrier damage, cerebral oedema or acute demyelination. Intracranial tumours or metastases and a history of epilepsy may increase the incidence of convulsive seizures after administration of iopromide. Caution should be exercised in situations in which there may be reduced seizure threshold, such as a previous history of seizures and the use of certain concomitant medication. Vasospasm and subsequent cerebral ischaemic phenomena may be caused by intraarterial injections of iopromide. Patients with symptomatic cerebrovascular diseases, recent stroke or frequent transient ischaemic attacks have an increased risk of neurological complications. Pregnancy and lactation: Pregnancy: Iopromide is classified as FDA Pregnancy Category B. Animal studies performed on rats and rabbits have demonstrated no harm to the use of up to 100 times the recommended human dose (Shaw and Potts, 1985). No studies have been performed in pregnant women. Manufacturer recommends to avoid during pregnancy (see under Contra-indications) Nursing mothers: The amount of Iopromide excreted in breast milk has not been determined but is probably small because of its high hydrophilicity. The use of Iopromide in nursing mothers should be made considering the importance of the drug to the mother

Recommendations on the use of Iopromide in Pregnancy & Lactation: The use of iodine-containing contrast media should be avoided during pregnancy especially after 12 weeks’ gestation because of their potential impact on the fetal thyroid gland and should be limited to unavoidable circumstances. However, no mutagenic or teratogenic effects have been associated with their use during pregnancy (Schaefer et al., 2015; Tremblay et al., 2012). The risk of exposure of the infant through breastmilk must be borne in mind when making the decision to use iodine-containing contrast media. Other alternative diagnostic methods should be explored. When the use of iodine-containing contrast agent is unavoidable, many manufacturers recommend that breastfeeding should be temporarily discontinued for 24-48 hours especially in infants younger than 2 months. This has been considered as unnecessary as available evidence suggest that it is safe to continue breastfeeding. However, the amount of iopromide secreted into the breastmilk is much lower than the dose utilized for infants and is therefore, unlikely to cause any adverse effects (Schaefer et al., 2015; Tremblay et al., 2012). ESUR (European Society of Urogenital Radiology) Guidelines on the Use of Iodine-Based Contrast Agents during Pregnancy & Lactation (Contrast Media Safety Committee, 2018): In exceptional circumstances, when radiographic examination is essential, iodine-based contrast media may be given to the pregnant female. Following administration of iodine-based contrast media to the mother during pregnancy, thyroid function should be checked in the neonate during the first week Breastfeeding may be continued normally when iodine-based contrast media is given to the mother References: 1. Contrast Media Safety Committee. (2018). ESUR Guidelines on contrast agents (10th version). European Society of Urogenital Radiology. http://www.esur.org/fileadmin/content/2019/ESUR_Guidelines_10.0_Final_Version.pdf 2. Schaefer, C., Peters, P., & Miller, R. K. (2015). Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment (Third Edition). Academic Press. 3. Tremblay, E., Thérasse, E., Thomassin-Naggara, I., & Trop, I. (2012). Quality Initiatives: Guidelines for Use of Medical Imaging during Pregnancy and Lactation. RadioGraphics, 32(3), 897–911. https://doi.org/10.1148/rg.323115120

Iopromide should not be directly mixed with other drugs. A separate syringe should be used, and the injection needle should be flushed between administrations of iopromide and other drugs. Metformin: Use of contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin. Discontinue metformin before iopromide administration and for 48 hours after the procedure. Ensure renal function is within normal limits before restarting metformin. Medications that lower the seizure threshold, such as phenothiazine derivatives, MAO inhibitors, CNS stimulants, and antipsychotics: Discontinue use at least 48 hours before iopromide administration and for 24 hours after the procedure. Consider prophylactic antiepileptics. Beta blockers: Patients using beta blockers may present with atypical symptoms of anaphylaxis which may be misinterpreted as a vagal reaction. Patients who experience hypersensitivity reactions while taking a beta-blocker may be resistant to treatment effects of beta agonists Interluekin-2: Patients treated with interleukin-2 less than two weeks previously have been associated with an increased risk of delayed reactions (flu-like symptoms or skin reactions). Laboratory tests: All iodinated contrast media may interfere with tests on thyroid function, thus the iodine-binding capacity of the thyroid may be reduced for up to several weeks. High concentrations of contrast media in serum and urine can interfere with laboratory tests for bilirubin, proteins or inorganic substances (e.g. iron, copper, calcium and phosphate). These substances should therefore not be assayed on the day of examination

Side effects of Iopromide : Contrast media generally have similar adverse effect profiles, but the incidence tends to be higher with the high-osmolality agents. Osmolality depends on the iodine concentration and for a given iodine content, this is highest for the ionic monomers and lowest for non-ionic dimers. The adverse reactions are broadly classified as non-renal and renal. See the Therapeutic Notes for details and ESUR (European Society of Urogenital Radiology) recommendations for management of these adverse reactions. Non-renal adverse reactions: Acute adverse reactions occur within 1 hour of contrast medium injection; usually mild to moderate. Common minor adverse reactions include rash, pain at the injection site, nausea, vomiting, and minor hemodynamic changes, which are all usually self-limiting. Acute severe reactions are usually anaphylactic or anaphylactoid and the risk is usually greatest in patients with asthma, atopy, or a previous reaction to an iodinated contrast agent. Delayed adverse reactions to intravascular iodine-based contrast medium occur 1 h to 1 week after contrast medium injection and are similar in type to other drug-induced eruptions. Maculopapular rashes, erythema, swelling and pruritus are most common. Most skin reactions are mild to moderate and self-limiting. Contrast induced nephropathy (CIN) is a condition in which a decrease in renal function occurs within 3 days of the intravascular administration of a contrast media, causing acute kidney injury and possibly, renal failure. Risk factors include patients with pre-existing renal disease, advanced age, advanced vascular disease, heart failure, dehydration, diabetes mellitus, concomitant use of nephrotoxic agents or diuretics, multiple myeloma/paraproteinemia, or large doses or multiple doses of iodinated contrast media. Adequately hydrate patients prior to and following administration to minimize the risk

Ultravist 300 623.4mg/ml Injection manufactured by SCHERING AG. Its generic name is Iopromide. Ultravist 300 is availble in United Arab Emirates. Farmaco UAE drug index information on Ultravist 300 Injection is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.