Summary of medicine characteristics - VISIPAQUE INJECTION 270 MG I/ML
1 NAME OF THE MEDICINAL PRODUCT
VISIPAQUE 270 mg I/ml
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
| Active ingredient | Strength | Content pr. ml. |
| lodixanol (INN) | 270 mg I/ml | 550 mg equiv. 270 mg I |
Iodixanol is a non-ionic, dimeric, hexaiodinated, water-soluble X-ray contrast medium. Pure aqueous solutions of iodixanol in all clinical relevant concentrations have a lower osmolality than whole blood and the corresponding strengths of the non-ionic monomeric contrast media. VISIPAQUE is made isotonic with normal body fluids by addition of electrolytes. The osmolality and viscosity values of VISIPAQUE are as follows:
| Concentration | Osmolality * mOsm/kg H2O | Viscosity (mPa-s) | |
| 37°C | 20°C | 37°C | |
| 270 mg I/ml | 290 | 11.3 | 5.8 |
* Method: Vapour – pressure osmometry.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection.
VISIPAQUE is supplied ready to use as clear, colourless to pale yellow aqueous solutions.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
X-ray contrast medium for cardioangiography, cerebral angiography (conventional), peripheral arteriography (conventional), abdominal angiography (i.a.DSA), urography, venography, CT-enhancement. Lumbar, thoracic and cervical myelography. Arthrography, hysterosalpingography (HSG) and studies of the gastrointestinal tract. In children it is used for cardioangiography, urography, CT-enhancement and studies of the upper gastrointestinal tract.
4.2 Posology and method of administration
The dosage may vary depending on the type of examination, the age, weight, cardiac output and general condition of the patient and the technique used. Usually approximately the same iodine concentration and volume is used as with other iodinated X-ray contrast media in current use, but adequate diagnostic information has also been obtained in some studies with iodixanol injection with somewhat lower iodine concentration. Adequate hydration should be assured before and after administration as for other contrast media. The product is for intravenous, intraarterial and intrathecal use, and for use in body cavities.
The following dosages may serve as a guide. The doses given for intra-arterial use are for single injections that may be repeated.
| Indi cati on/Investigati on | Concentration | Volume |
| Intra-arterial use | ||
| Arteriographies Adults Selective cerebral Aortography Peripheral Selective visceral i.a. DSA | 270/320(1) mg I/ml 270/320 mg I/ml 270/320 mg I/ml 270 mg I/ml | 5 – 10 ml per inj 40 – 60 ml per inj. 30 – 60 ml per inj. 10 – 40 ml per inj. |
| Cardioangiography Adults Left ventricle and aortic root inj. Selective coronary arteriography Children | 320 mg I/ml 320 mg I/ml 320 mg I/ml | 30 – 60 ml/inj. 4 – 8 ml/inj. Depending on age, weight and pathology (recommended max total dose 10 ml/kg) |
(1) Both strengths are documented, but 270 mg I/ml is recommended in most cases.
| Indication/Investigation | Concentration | Volume |
| Intravenous use | 270/320 mg I/ml 270/320 mg I/ml 270/320 mg I/ml | 40 – 80 ml(2) 2 – 4 ml/kg 2 – 3 ml/kg All doses depending on age, weight and pathology (max. 50 ml). |
| Urography Adults Children < 7 kg Children > 7 kg | ||
| Venography Adults 270 mg I/ml 50 – 150 ml/leg | ||
| CT-enhancement Adults CT of the head CT of the body Children CT of the head and body | 270/320 mg I/ml 270/320 mg I/ml 270/320 mg I/ml | 50 – 150 ml 75 – 150 ml 2–3 ml/kg up to 50 ml (in a few cases up to 150 ml may be given) |
| Intrathecal use | 270 mg I/ml or 320 mg I/ml 270 mg I/ml or 320 mg I/ml | 10 – 12 ml(3) 10 ml(3) 10 – 12 ml(3) 10 ml(3) |
| Lumbar and thoracic myelography (lumbar injection) Cervical myelography (cervical or lumbar injection) | ||
(2) 80 ml may be exceeded in selected cases.
(3) To minimize possible adverse reactions a total dose of 3.2 g iodine should not be
exceeded.
| Indication/Investigation | Concentration | Volume |
| Use in body cavities | 270 mg I/ml 270 mg I/ml | The dosage must be adjusted individually to allow optimal visualisation 1 – 15 ml 5 – 10 ml The recommended dose may be exceeded several times due to e.g. backflow into the vagina (up to 40 ml has been studied). |
| Adults Arthrography Hysterosalpingography (HSG) | ||
| Gastrointestinal studies | 320 mg I/ml 320 mg I/ml 320 mg I/ml 320 mg I/ml 270/320 mg I/ml | 80 – 200 ml has been studied 10 – 200 ml has been studied 20 – 200 ml has been studied 5 ml/kg b.w.10–240 ml has been studied 30 – 400 ml has been studied |
| Oral use Adults Small bowel follow through Oesophagus Stomach Children Rectal use Children |
For elderly patients, patients with hepatic and/or renal impairment, the usual/proposed doses for adults can be used.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients. Manifest thyrotoxicosis.
4.4 Special warnings and precautions for use
Special precautions for use of non-ionic contrast media in general:
Hypersensitivity:
A positive history of allergy, asthma, or untoward reactions to iodinated contrast media indicates a need for special caution. Premedication with corticosteroids or histamine H1 and H2 antagonists might be considered in these cases.
The risk of serious reactions in connection with use of VISIPAQUE is regarded as remote. However, iodinated contrast media may provoke anaphylactoid reactions or other manifestations of hypersensitivity. A course of action should therefore be planned in advance, with necessary drugs and equipment available for immediate treatment, should a serious reaction occur. It is advisable always to use an indwelling cannula or catheter for quick intravenous access throughout the entire X-ray procedure.
The possibility of hypersensitivity including serious, life-threatening, fatal anaphylactic/ anaphylactoid reactions should always be considered. The majority of serious undesirable occur within the first 30 minutes. Late onset (that is 1 hour or more after application) hypersensitivity reactions can occur.
Patients should be observed for at least 30 minutes after administration of VISIPAQUE.
Patients using beta blockers may present with atypical symptoms of hypersensitivity which may be misinterpreted as a vagal reaction.
Coagulopathy:
Non-ionic, iodinated contrast media inhibit blood coagulation in vitro less than ionic contrast media._Clotting has been reported when blood remains in contact with syringes containing contrast media including non-ionic media. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.
Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angio-cardiographic procedures with both ionic and nonionic contrast media. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications, may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended, including close attention to guide wire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinized saline solutions, and minimizing the length of the procedure.) so as to minimize the risk of procedure-related thrombosis and embolism.
Advanced life support facilities should be readily available.
Care should be taken in patients with homocystinuria. (Risk for thromboembolism).
Hydration
Adequate hydration should be assured before and after contrast media administration. This applies especially to patients with multiple myeloma, diabetes mellitus, renal dysfunction, as well as to infants, small children and elderly patients. Young infants (age < 1 year) and especially neonates are susceptible to electrolyte disturbance and haemodynamic alterations.
Cardio-circulatory reactions
Care should also be taken in patients with serious cardiac disease and pulmonary hypertension as they may develop haemodynamic changes or arrhythmias. Rarely severe life-threatening reactions and fatalities of cardiovascular origin such as cardiac-, cardio-respiratory arrest and myocardial infarction have occurred.
CNS disturbances
Encephalopathy has been reported with the use of iodixanol (see section 4.8). Contrast encephalopathy 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 of iodixanol, and generally resolves within days.
The product should be used with caution in patients with conditions that disrupt the integrity of the blood brain barrier (BBB), potentially leading to increased permeability of contrast media across the BBB and increasing the risk of encephalopathy. Patients with acute cerebral pathology, tumours or a history of epilepsy are predisposed for seizures and merit particular care. Also alcoholics and drug addicts have an increased risk for seizures and neurological reactions. In regard to intravascular application care should be taken in patients with acute stroke or acute intracranial bleeding, in patients with altered blood brain barrier, cerebral oedema or acute demyelinisation.
If contrast encephalopathy is suspected, administration of iodixanol should be discontinued and appropriate medical management should be initiated.
Renal reactions
Major risk factor for contrast medium-induced nephropathy is underlying renal dysfunction.
Diabetes mellitus and the volume of iodinated contrast medium administered are contributing factors in the presence of renal dysfunction. Additional concerns are dehydration, advanced arteriosclerosis, poor renal perfusion and the presence of other factors that may be nephrotoxic, such as certain medications or major surgery.
To prevent acute renal failure following contrast media administration, special care should be exercised in patients with pre-existing renal impairment and diabetes mellitus as they are at risk. Patients with paraproteinemias (myelomatosis and Waldenstrom’s macroglobulinemia) are also at risk.
Preventive measures include:
– Identification of high risk patients
– Ensuring adequate hydration. If necessary by maintaining an i.v. 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 reducing to a minimum.
– Postponing a repeat contrast medium examination until renal function returns to pre-examination levels.
Iodinated contrast agents can be used by patients on haemodialysis as the agents are removed by the dialysis process.
Diabetic patients receiving metformin:
There is a risk of the development of lactic acidosis when iodinated contrast agents are administered to diabetic patients treated with metformin, particularly in those with impaired renal function. To prevent lactic acidosis, the serum creatinine level should be measured in diabetic patients treated with metformin prior to intravascular administration of iodinated contrast media
Normal serum creatinine (<130umol/litre)/normal renal function: Administration of metformin should be stopped at the time of administration of contrast medium and not resumed for 48 hours unless renal function/serum creatinine remains in the normal range.
Abnormal serum creatinine (>130umol/litre)/impaired renal function: Metformin should be stopped and the contrast medium examination delayed for 48 hours. Metformin should only be restarted if renal function is not diminished (if serum creatinine is not increased) compared to pre-contrast values.
Emergency cases: In emergency cases where renal function is impaired or unknown, the
physician should evaluate the risk/benefit of the contrast medium examination, and the following precautions should be implemented: Metformin should be stopped. The patient should be fully hydrated prior to contrast medium administration and for 24 hours afterwards. Renal function (e.g. serum creatinine), serum lactic acid and blood pH should be monitored. A pH< 7.25 or a lactic acid level of >5 mmol/litre are indicative of lactic acidosis. The patient should be observed for symptoms of lactic acidosis. These include vomiting, somnolence, nausea, epigastric pain, anorexia, hyperpnoea, lethargy, diarrhoea and thirst.
Impaired renal and hepatic function
Particular care is required in patients with severe disturbance of both renal and hepatic function as they may have significantly delayed contrast medium clearance. Patients on haemodialysis may receive contrast media for radiological procedures. Correlation of the time of contrast media injection with the haemodialysis session is unnecessary.
Myasthenia gravis
The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis.
Phaeochromocytoma
In patients with phaeochromocytoma undergoing interventional procedures, alpha blockers should be given as prophylaxis to avoid a hypertensive crisis.
Disturbances in thyroid function
Patients at risk of thyrotoxicosis should be carefully evaluated before any use of iodinated contrast medium.
Special care should be exercised in patients with hyperthyroidism.
Patients with multinodular goitre may be at risk of developing hyperthyroidism following injection of iodinated contrast media.
Paediatric population
One should also be aware of the possibility of inducing transient hypothyroidism in premature infants receiving contrast media.
Thyroid function should be checked in neonates during the first week of life, following administration of iodinated contrast agents to the mother during pregnancy. Repeat testing of thyroid function is recommended at 2 to 6 weeks of age, particularly in low birth weight newborn or premature newborn.
See also section 4.6.
Extravasation
It is likely that VISIPAQUE due to its isotonicity gives rise to less local pain and extravascular oedema than hyperosmolar contrast media. In case of extravasation, elevating and cooling the affected site is recommended as routine measures. Surgical decompression may be necessary in cases of compartment syndrome.
Observation-time
After contrast medium administration the patient should be observed for at least 30 minutes, since the majority of serious side effects occur within this time. However, experience shows that hypersensitivity reactions may appear up to several hours or days post injection. The patient should remain in the hospital environment (but not necessarily the radiology department) for one hour after the last injection, and should return to the radiology department if any symptoms develop.
Intrathecal use
Following myelography the patient should rest with the head and thorax elevated by 20° for one hour. Thereafter he/she may ambulate carefully but bending down must be avoided. The head and thorax should be kept elevated for the first 6 hours if remaining in bed. Patients suspected of having a low seizure threshold should be observed during this period. Outpatients should not be completely alone for the first 24 hours.
Hysterosalpingography
Hysterosalpingography should not be performed during pregnancy or in the presence of acute pelvic inflammatory disease (PID).
4.5 Interaction with other medicinal products and other forms of interaction
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.
Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin (see section 4.4).
Patients treated with interleukin-2 less than two weeks prior to an iodinated contrast medium injection have an increased risk for delayed reactions (flu-like symptoms or skin reactions).
There is some evidence that use of beta blockers is a risk factor for anaphylactoid reactions to X-ray contrast media (severe hypotension has been seen with X-ray contrast media on beta blocker therapy).
4.6 Fertility, Pregnancy and lactation
Pregnancy:
The safety of VISIPAQUE for use in human pregnancy has not been established. An evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to reproduction, development of the embryo or fetus, the course of gestation and peri- and postnatal development.
Since, wherever possible, radiation exposure should be avoided during pregnancy, the benefits of any X-ray examination, with or without contrast media, should be carefully weighed against the possible risk. The product should not be used in pregnancy unless benefit outweighs risk and it is considered essential by the physician.
Thyroid function should be checked in neonates during the first week of life, following administration of iodinated contrast agents to the mother during pregnancy.
Repeat testing of thyroid function is recommended at 2 to 6 weeks of age, particularly in low birth weight newborn or premature newborn.
Breast-feeding:
Contrast media are poorly excreted in human breast milk and minimal amounts are absorbed by the intestine. Breast feeding may be continued normally when iodinated contrast media are given to the mother.
4.7 Effects on ability to drive and use machines
No studies on the ability to drive or use machines have been performed. However, it is not advisable to drive a car or use machines for one hour after the last injection or during the first 24 hours following intrathecal examination (see section 4.4).
4.8 Undesirable effects
Below are listed possible side effects in relation with radiographic procedures which include the use of VlSIPAQUE.
Undesirable effects associated with Visipaque are usually mild to moderate and transient in nature. Serious reactions as well as fatalities are only seen on very rare occasions, these may include acute-on-chronic renal failure, acute renal failure, anaphylactic or anaphylactoid shock, hypersensitivity reaction followed by cardiac reactions (Kounis’ syndrome), cardiac or cardio-respiratory arrest and myocardial infarction. Cardiac reaction may be promoted by the underlying disease or the procedure.
Hypersensitivity reactions may present as respiratory or cutaneous symptoms like dyspnoea, rash, erythema, urticaria, pruritus, skin reactions angioneurotic oedema, hypotension, fever, laryngeal oedema, bronchospasm or pulmonary oedema.
In patients with autoimmune diseases cases of vasculitis and SJS-like syndrome were observed.
They may appear either immediately after the injection or up to a few days later. Hypersensitivity reactions may occur irrespectively of the dose and mode of administration and mild symptoms may represent the first signs of a serious anaphylactoid reaction/shock.
Administration of the contrast medium must be discontinued immediately and, if necessary, specific therapy instituted via the vascular access. Patients using beta blockers may present with atypical symptoms of hypersensitivity which may be misinterpreted as a vagal reaction. A minor transient increase in serum creatinine is common after iodinated contrast media, but is usually of no clinical relevance.
The frequencies of undesirable effects are defined as follows:
Very common (>1/10), common ((>1/100 to < 1/10), uncommon(((>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
The listed frequencies are based on internal clinical documentation and published studies, comprising more than 48,000 patients.
Intravascular administration:
Blood and lymphatic system disorders
Not known: Thrombocytopenia
Immune system disorders:
Uncommon: Hypersensitivity
Not known: Anaphylactoid reaction, anaphylactoid shock;
Psychiatric disorders:
Very rare: Agitation, anxiety
Not known: Confusional state
Nervous system disorders:
Uncommon: Headache
Rare: Dizziness
Very rare: Cerebrovascular accident, sensory abnormalities including taste disturbance, amnesia, paraesthesia, syncope.
Not known: Coma, motor dysfunction, disturbance in consciousness, convulsion, transient contrast induced encephalopathy (including hallucination), tremor.
Eye disorders:
Very rare: Transient cortical blindness, visual impairment
Cardiac disorders:
Rare: Arrhythmia (including bradycardia, tachycardia), myocardial infarction
Very rare: Cardiac arrest
Not known: Cardiac failure, Ventricular hypokinesia, myocardial ischaemia, cardiorespiratory arrest, conduction abnormalities, coronary artery thrombosis, angina pectoris, spasm of coronary arteries..
Vascular disorders:
Uncommon: Flushing
Rare: Hypotension
Very rare: Hypertension, ischaemia
Not known: Arterial spasm, thrombosis, thrombophlebitis, shock.
Respiratory, thoracic and mediastinal disorders:
Rare: Cough
Very rare: Dyspnoea
Not known: Pulmonary oedema, respiratory arrest, respiratory failure.
Gastrointestinal disorders:
Uncommon: Nausea, vomiting
Very rare: Abdominal pain/discomfort
Not known: Acute pancreatitis, pancreatitis aggravated, salivary gland enlargement
Skin and subcutaneous system disorders
Uncommon: Rash, pruritus, urticaria
Very rare: angioedema, erythema
Not known: Bullous dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, drug eruption, dermatitis allergic, skin exfoliation
Musculoskeletal and connective tissue disorders:
Very rare: Back pain, muscle spasm
Not known: Arthralgia
Renal and urinary disorders:
Very rare: Impairment of renal function including acute renal failure
General disorders and administration site conditions:
Uncommon: Feeling hot, chest pain.
Rare: Pain, discomfort, shivering (chills), pyrexia, administration site reactions including extravasation
Very rare: Feeling cold, asthenic conditions (e.g. malaise, fatigue)
Injury, poisoning and procedural complications:
Not known: Iodism
Intrathecal administration:
Undesirable effects following intrathecal use may be delayed and present some hours or even days after the procedure. The frequency is similar to lumbar puncture alone.
Meningeal irritation giving photophobia and meningism and frank chemical meningitis have been observed with other non-ionic contrast media. The possibility of an infective meningitis should also be considered.
Immune system disorders:
Not known: Hypersensitivity, including anaphylactic/ anaphylactoid reactions
Nervous system disorders:
Uncommon: Headache (may be severe and lasting)
Not known: Dizziness, transient contrast induced encephalopathy (including amnesia, hallucinations, confusion)
Gastrointestinal disorders:
Uncommon: Vomiting
Not known: Nausea
Musculoskeletal and connective tissue disorders:
Not known: Muscle spasm
General disorders and administration site conditions:
Not known: Shivering, pain at injection site
Hysterosalpingography (HSG):
Immune system disorders:
Not known: Hypersensitivity
Nervous system disorders:
Common: Headache
Gastrointestinal disorders:
Very common: Abdominal pain
Common: Nausea
Not known: Vomiting
Reproductive system and breast disorders:
Very common: Vaginal haemorrhage
General disorders and administration site conditions:
Common: Pyrexia
Not known: Shivering, injection site reaction
Arthrography:
Immune system disorders:
Not known: Hypersensitivity, including anaphylactic/ anaphylactoid reactions
General disorders and administration site conditions:
Common: Injection site pain
Not known: Shivering
Examination of the GI tract:
Immune system disorders:
Not known: Hypersensitivity, including anaphylactic/ anaphylactoid reactions
Gastrointestinal disorders:
Common: Diarrhoea, abdominal pain, nausea
Uncommon: Vomiting
General disorders and administration site reaction
Not known: Shivering
Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at the website: www.mhra.gov.uk/yellowcard.
4.9 Overdose
4.9 OverdoseOverdosage is unlikely in patients with a normal renal function. The duration of the procedure is important for the renal tolerability of high doses of contrast media (t./2 ~ 2 hours). In the event of accidental overdosing, the water and electrolyte losses must be compensated by infusion. Renal function should be monitored for at least the next 3 days. If needed, haemodialysis may be used to remove iodixanol from the patient's system. There is no specific antidote, treatment of overdose is symptomatic.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: X-ray contrast medium, iodinated ATC code: V08A B09
The organically bound iodine absorbs radiation in the blood vessels/tissues when it is injected.
For most of the haemodynamic, clinical-chemical and coagulation parameters examined following intravenous injection of iodixanol in healthy volunteers, no significant deviation from preinjection values has been found. The few changes observed in the laboratory parameters were minor and considered to be of no clinical importance.
VISIPAQUE induces only minor effects on renal function in patients. In 64 diabetic patients with serum creatinine levels of 115 – 308 |amoi/L, VISIPAQUE use resulted in 3% of patients experiencing a rise in creatinine of > 44.2 |amol/L and 0% of the patients with a rise of > 88.4 ^mol/L.The release of enzymes (alkaline phosphatase and N-acetyl-B-glucosaminidase) from the proximal tubular cells is less than after injections of non-ionic monomeric contrast media and the same trend is seen compared to ionic dimeric contrast media. VISIPAQUE is also well tolerated by the kidney.
5.2 Pharmacokinetic properties
Iodixanol is rapidly distributed in the body with a mean distribution half-life of approximately 21 minutes. The apparent volume of distribution is of the same magnitude as the extracellular fluid (0.26 l/kg b.w.), indicating that iodixanol is distributed in the extra-cellular volume only.
No metabolites have been detected. The protein binding is less than 2%.
The mean elimination half-life is approximately 2 hours in normal adults. In infants the elimination of iodixanol is prolonged (t^ approx. 4 hours in newborns). lodixanol is excreted mainly through the kidneys by glomerular filtration. Approximately 80% of the administered dose is recovered unmetabolized in the urine within 4 hours and 97% within 24 hours after intravenous injection in healthy volunteers. Only about 1.2% of the injected dose is excreted in faeces within 72 hours. The maximum urinary concentration appears within approximately 1 hour after injection.
No dose dependent kinetics has been observed in the recommended dose range.
After intrathecal administration the half-life of iodixanol is prolonged reflecting the rate of elimination from the central nervous system compartment into systemic circulation. The apparent elimination half-life varies, but with a mean value around 12 hours.
5.3 Preclinical safety data
5.3 Preclinical safety dataNon-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
The following excipients are included:
Trometamol, sodium chloride, calcium chloride, sodium calcium edetate, hydrochloric acid (pH adjustment) and water for injections.
The pH of the product is 6.8–7.6
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. A separate syringe should be used.
6.3 Shelf life
The shelf life is 3 years.
In-use shelf-life: Chemical and physical in-use stability for the iodixanol solution in the 500 ml polypropylene bottles has been demonstrated for 24 hours at 25°C.
6.4 Special precautions for storage
Keep the container in the outer carton. The product in glass containers and 40, 50, 75, 100, 150, 175, 200 and 500 ml in polypropylene bottles can be stored for up to 1 month at 37 °C, protected from light.
6.5 Nature and contents of container
Glass containers:
The product is filled in injection vials (20 ml) and infusion bottles (50, 75, 100, and 200 ml). The glass vials/bottles containers are made of colourless highly resistant borosilicate glass (Ph.Eur. Type I), closed with black chlorobutyl rubber stoppers (Ph.Eur. Type I), and sealed with complete tear off caps with coloured plastic “flip-off” tops.
Polypropylene bottles:
The product is filled in polypropylene bottles. The bottles of 50, 75, 100, 150, 175, 200 and 500 ml are closed with chlorobutyl rubber stoppers (Ph.Eur. Type I) and supplied with a screw cap which is provided with a tamper proof ring.
The product is supplied as:
Glass containers:
270 mg I/ml:________________________
10 vials of 20 ml
10 bottles of 50 ml
10 bottles of 75 ml
1 bottle of 100 ml, 10 bottles of 100 ml
1 bottle of 200 ml, 6 bottles of 200 ml
320 mg I/ml:________________________
10 vials of 20 ml
10 bottles of 50 ml
1 bottle of 100 ml, 10 bottles of 100 ml
1 bottle of 200 ml, 6 bottles of 200 ml
Polypropylene Containers:
270 mg I/ml:
BBottles with rubber stopper and plastic screw cap:
1 bottle of 50 ml, 10 bottles of 50 ml
1 bottle of 75 ml, 10 bottles of 75 ml
1 bottle of 100 ml, 10 bottles of 100
1 bottle of 150 ml, 10 bottles of 150
1 bottle of 175 ml, 10 bottles of 175
1 bottle of 200 ml, 10 bottles of 200
6 bottles of 500 ml (multi-dose) 320 mg I/ml:
Bottles with rubber stopper and plastic screw cap:
1 bottle of 50 ml, 10 bottles of 50 ml
1 bottle of 75 ml, 10 bottles of 75 ml
1 bottle of 100 ml, 10 bottles of 100 ml
1 bottle of 150 ml, 10 bottles of 150 ml
1 bottle of 175 ml, 10 bottles of 175 ml
1 bottle of 200 ml, 10 bottles of 200 ml
6 bottles of 500 ml (multi-dose)
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
6.6 Special precautions for disposalLike all parenteral products, Visipaque should be inspected visually for particulate matter, discolouration and the integrity of the container prior to use.
Visipaque may be warmed to body temperature (37°C) before administration. Any unused product or waste material should be disposed of in accordance with local requirements.
Glass vials/bottles and polypropylene bottles up to 200 ml
The product should be drawn into the syringe immediately before use.
For single use only, any unused portions must be discarded.
Polypropylene bottles of 500 ml
Chemical and physical in-use stability for the iodixanol solution in the 500 ml polypropylene bottles has been demonstrated for 24 hours at 25°C. From a microbiological point of view, the product should be used immediately after opening. If not used immediately after opening, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at temperatures below 25°C, unless opening has taken place under controlled and validated aseptic conditions.
The 500 ml contrast medium bottles should only be used in connection with auto injectors/pumps approved for this volume.
A single piercing procedure should be used.
Remove the plastic screw cap by tearing off the pull ring.
After cleaning the stopper with a pad soaked in sporicidal solution followed by a pad soaked in alcohol, puncture the stopper with the needle.
The line running from the auto injector/pump to the patient must be exchanged after each patient.
Any unused portions of the contrast medium remaining in the bottle and all connecting tubes must be discarded after 24 hours.
Instructions from the manufacturer of the auto injector/pump must be followed.
7 MARKETING AUTHORISATION HOLDER
GE Healthcare AS
Nycoveien 1–2
P.O. Box 4220 Nydalen
NO-0401 OSLO
NORWAY
LOCAL REPRESENTATIVE
GE Healthcare Ltd.
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
Telephone: 1494 544 000
Telefax: 1494 542 266