INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ULTRAVIST

SCHEDULING STATUS:
S2

PROPRIETARY NAME
(and dosage form):

ULTRAVIST

ULTRAVIST 300 20 mL
ULTRAVIST 300 50 mL
ULTRAVIST 300 75 mL
ULTRAVIST 300 100 mL
ULTRAVIST 300 200 mL
ULTRAVIST 370 50 mL
ULTRAVIST 370 100 mL
ULTRAVIST 370 200 mL

Non-ionic contrast medium

COMPOSITION
Ultravist 300
1 mL contains 0,623 g
iopromide (5-methoxyacetylamino-2,4,6-triiodisophthalic acid-(2,3-dihydroxy-N-methylpropyl)-(2,3-dihydroxypropyl)-diamide), in aqueous solution.

Ultravist 370
1 mL contains 0,769 g iopromide in aqueous solution.

  Ultravist 300 Ultravist 370
Iodine concentration (mg/mL)         300         370
Iodine content (g) per                
        vial of 20 mL         6,0 -
        bottle of 50 mL         15,0         18,5
        bottle of 75 mL         22,5         -
        bottle of 100 mL         30,0         37,0
        bottle of 200 mL         60,0         74,0
Contrast medium concentration                
        (mg/mL)         623         69
Contrast medium content (g) per                
        vial of 20 mL         12,5         -
        bottle of 50 mL         31,2         38,4
        bottle of 75 mL         46,8         -
        bottle of 100 mL         62,3         76,9
        bottle of 200 mL         124,6         153,8
Viscosity (mPa.s or cP)                
        at 20°C         8,7         20,1
        at 37°C         4,6         9,5
Osmotic pressure at 37°C                
        (MPa)         1,59         2,02
        (atm)         15,7         19,9
Osmolality at 37°C (osm/kg H2O)         0,61         0,77

PHARMACOLOGICAL CLASSIFICATION
A. 28 Contrast media.

PHARMACOLOGICAL ACTION
Ultravist 300 and Ultravist 370 are non-ionic contrast media with low osmotic pressure.
Following intravascular administration, iopromide is very rapidly distributed in the extracellular space. It is unable to cross the blood-brain barrier but a small amount does cross the placental barrier (rabbit). Plasma protein binding with a concentration of 1,2 mg I/mL plasma is 0,9 + 0,2%. The contrast medium is first of all rapidly distributed, the half-life being 3 minutes, while the elimination half-life in patients with normal kidney function is approximately 2 hours, irrespective of the size of the dose. Under the doses recommended for diagnostic purposes, filtration of iopromide is exclusively glomerular. Renal excretion is approximately 18% of the dose within 30 minutes post injection, approximately 60% within 3 hours post injection and 92% within 24 hours post injection. No metabolites were demonstrable in man following administration of the clinically relevant doses of iopromide.

INDICATIONS
Ultravist 300
Contrast enhancement in computerised tomography (CT), cerebral angiography (intraarterial), thoracic and abdominal aortography, intravenous digital subtraction angiography (DSA), intravenous urography, phlebography of the extremities, venography, arteriography, visualisation of body cavities (eg arthrography, hysterosalpingography, fistulography) with the exception of myelography, cerebral ventriculography, cisternography.

Ultravist 370
Especially angiocardiography, arteriography, contrast enhancement in computerised tomography (CT), intravenous digital subtraction angiography (DSA), intravenous urography, visualisation of body cavities (eg arthrography, fistulography) with the exception of myelography, cerebral ventriculography, cisternography.

CONTRA-INDICATIONS
Hyperthyroidism.
Not to be administered to patients who are allergic to iodine.
Hysterosalpingography must not be performed during pregnancy or in the presence of acute inflammatory processes in the pelvic cavity.
The safety of Ultravist in pregnancy has not been established. Ultravist should not be used during pregnancy.

WARNINGS
Not to be used in myelography, cerebral ventriculography and cisternography.
Fatal reactions have been associated with the administration of water-soluble contrast media. It is therefore of the utmost importance that a course of action be carefully planned in advance for the treatment of serious reactions, and that adequate and appropriate facilities and personnel be readily available in case of a severe reaction. Patients should be observed for a possible severe reaction during and for at least 30-60 minutes after administration.

DOSAGE AND DIRECTIONS FOR USE
        General information
Patients must present themselves in a fasted but 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 emptied 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, fruits, dark and fresh bread and all kinds of uncooked vegetables. On the day before the examination, patients should refrain from eating after 6 pm. Moreover, it would be appropriate to administer a laxative in the evening.
In babies and young children, however, prolonged fasting and the administration of a laxative before the examination are contra-indicated.
Patients may tolerate the contrast medium better if it is warmed to body temperature.
Intravascular administration of contrast media should, if possible, be done with the patient lying down. After the administration the patient should be kept under observation for at least 30 minutes, since experience shows that the majority of all severe incidents occur within this time.
Ultravist should not be drawn into the syringe or the infusion bottle attached to the infusion set until immediately before use. Contrast medium solution in vials, not used in one examination session must be discarded.
Vials containing contrast medium solutions are not intended for the withdrawal of multiple doses. The rubber stopper should never be pierced more than once. The use of cannulas with a long tip and a diameter of maximally 18 G is recommended for piercing the stopper and drawing up the contrast medium (dedicated withdrawal cannulas with a side hole are particularly suitable).

        Intravenous urography
O        Dosage
Adults
The total dose of 1 mL Ultravist 300, or 0,8 mL Ultravist 370/kg body weight should not be exceeded.
Children
The physiologically poor concentrating ability of the still immature nephron of infantile kidneys demands relatively higher doses of contrast medium, eg with the use of Ultravist 300.
Neonates
1,2 g I/kg body weight, corresponding to 4,0 mL/kg body weight.
Babies
1,0 g I/kg body weight, corresponding to about 3,0 mL/kg body weight.
Small children
0,5 g I/kg body weight, corresponding to about 1,5 mL/kg body weight.

O        Filming times
When the above dosage guidelines are observed and Ultravist 300/370 is injected over 1 or 2 minutes, the renal parenchyma is usually opacified 3-5 minutes and the renal pelvis with the urinary tract 8-15 minutes after the start of the examination. The earlier time should be chosen for younger patients and the later time for older patients.

        Computerised tomography (CT)
O        Cranial CT
The following dosage is recommended for cranial computerised tomography:
Ultravist 300: 1,0 –max 1,5 mL/kg body weight.
Ultravist 370: 1,0 –max 1,5 mL/kg body weight.
O        Whole body CT
In the whole body computerised tomography, the necessary doses of contrast medium and the rates of administration depend on the organs under investigation, diagnostic problem and, in particular, the different scan and image reconstruction times of the scanners in use. The infusion should be preferred for slow scanners and the injection for fast scanners.

        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. When comparable iodine concentrations are used, the necessary dose usually corresponds to that of the previously used ionic contrast media.
O        Suggested dosages
Phlebography of the extremities 40-80 mL Ultravist 300
Cerebral angiography                
  Aortic arch angiography 50-80 mL Ultravist 300
  Carotid angiography 30-40 mL Ultravist 300
  Selective angiography 6-15 mL Ultravist 300
Thoracic aortography 50-80 mL Ultravist 300
Abdominal aortography 40-60 mL Ultravist 300
Angiography of the extremities 
Upper extremities 
  Arteriography 8-12 mL Ultravist 300
  Venography 15-30 mL Ultravist 300
Lower extremities 
  Arteriography 20-30 mL Ultravist 300
  Venography 30-60 mL Ultravist 300
Angiocardiography 
Selective, in individual cardiac cavities 40-60 mL Ultravist 370
Coronarangiography 5-8 mL Ultravist 370

        Digital subtraction angiography (DSA)
Intravenous DSA
Based on experience with ionic contrast media, the intravenous injection of 30-60 mL Ultravist 300/370 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. The period of time for which the contrast medium is in contact with the wall of the veins can be reduced by injecting 20-40 mL isotonic sodium chloride as a bolus immediately afterwards.
Intraarterial DSA
Intraarterial digital subtraction angiography requires smaller volumes and lower iodine concentrations than the intravenous technique. The more selective the angiography is, the lower the dose of contrast medium can be. The method is therefore recommended for patients with impaired renal function. The values used in conventional angiography for bolus concentration, bolus volume and flow rate can be reduced for intraarterial digital subtraction angiography.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
The need for examination needs particularly careful consideration in patients with hypersensitivity to iodinated contrast media, severe impairment of hepatic or renal function, cardiac and circulatory insufficiency, pulmonary emphysema, very poor general condition, advanced cerebral arteriosclerosis, diabetes of long standing, cerebral spasmodic conditions, latent hyperthyroidism, bland nodular goitre and multiple myeloma.
Patients with an allergic disposition suffer more frequently than others 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.
In patients with multiple myeloma, diabetes of long standing, polyuria, oliguria or gout, in babies, small children and in patients in a very poor general state of health, fluid intake should not be restricted even before the use of low-osmolar contrast media.
Premedication with alpha-receptor blockers is recommended in phaeochromocytoma patients because of the risk of blood pressure crises.
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.
Vascular pain may also be expected with administration of non-ionic contrast media of high iodine concentrations because of their high osmolality.
Hypersensitivity
Hypersensitivity reactions to the contrast medium including shock cannot be ruled out. Even relatively mild effects (eg itching of the skin, sneezing, violent yawning, coughing fits), which occur regardless of the amount of contrast medium administered, can indicate incipient shock. Administration of the contrast medium must then be terminated immediately and - if necessary - specific therapy initiated intravenously (cf "Suggestions for the management of life-threatening acute hypersensitivity reactions or acute anaphylaxis after administration of contrast media"). In the case of intravenous administration, use of a flexible indwelling catheter is therefore recommended.
Precautionary measures against contrast medium reactions consist of being prepared for immediate therapy. This involves the timely provision of assured vascular access for any therapeutic measures and the ready availability of appropriate medicines, an endotracheal tube and a respirator (cf "Suggestions for the management of life-threatening acute hypersensitivity reactions or acute anaphylaxis after administration of contrast media").
Tolerance and side effects
Side effects such as a sensation of heat, headache, reddening of the skin, nausea and vomiting may occur. However, they quickly disappear after the administration.
Only in isolated cases does the paravenous administration of Ultravist lead to marked tissue reactions.
Suggestions for the management of life-threatening acute hypersensitivity reactions or acute anaphylaxis after administration of contrast media
Give adrenaline solution 1 mL of 1:1000 concentration (1 mg) subcutaneously. Repeat if necessary 5-10 minutes later. If the patient does not respond immediately give 0,1-0,4 mL of 1:1000 concentration diluted in 10 mL physiological saline intravenously SLOWLY.
Maintain an open airway. An emergency tracheostomy may be necessary. Positive pressure oxygen administration may be required.
In the event of urticaria or angio-oedema, administer adrenaline subcutaneously followed by an antihistamine intravenously (eg diphenhydramine hydrochloride 20 mg).
For prolonged or severe reactions give hydrocortisone sodium succinate 250 mg or methylprednisolone sodium succinate 100 mg intravenously over 30 seconds after adrenaline and the antihistamine.
Aminophylline injection 250-500 mg should be given slowly intravenously in the presence of bronchospasm.
Intravenous fluids may be required to correct hypovolemia.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
With overdosage, the symptoms described under "Side effects and special precautions" may occur which should be treated according to the recommended procedures to be adopted in incidents after the administration of contrast media.

IDENTIFICATION
Clear, sterile, pyrogen-free solution.

PRESENTATION
Ultravist 300: Vials of 20 mL
                Bottles of 50, 75, 100 and 200 mL
Ultravist 370: Bottles of 50, 100 and 200 mL

STORAGE INSTRUCTIONS
To be stored in original packs at room temperature (below 30°C). Protect from light, heat and secondary X-rays. For shelf-life, refer to the imprint on the pack. Keep out of reach of children.

REGISTRATION NUMBERS
Ultravist 300 20 mL vial:         V/28/175
Ultravist 300 50 mL bottle:         V/28/176
Ultravist 300 75 mL bottle:         28/28/0642
Ultravist 300 100 mL bottle:         V/28/177
Ultravist 300 200 mL bottle:         33/28/0082
Ultravist 370 50 mL bottle:         V/28/178
Ultravist 370 100 mL bottle:         V/28/179
Ultravist 370 200 mL bottle:         28/28/0643

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Schering (Pty) Ltd
(Reg No: 1964/009072/07)
106 Sixteenth Road
Randjespark
Midrand        1685
P O Box 5278
Halfway House        1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT
2 December 1998

SCHERING (PTY) LTD
(Reg No 1964/009072/07)
Subsidiary of
Schering AG        Germany

Updated on this site: March 2004
Current: January 2005
Source: Pharmaceutical Industry

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