Cardiolek-320

Iodixanol, Calcium chloride dihydrate, Trometamol, Sodium chloride, Edetate calcium disodium.

Each ml contains: Iodixanol USP 652 mg (Eq. to 320 mg organically bound Iodine), Calcium Chloride Dihydrate BP 0.04 mg, Trometamol BP 1.20 mg, Sodium Chloride BP 1.11 mg, Edetate Calcium Disodium USP 0.10 mg, Water For Injection BP q.s.

Pharmacology: Pharmacodynamics: 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, no significant deviation from preinjection values has been found. The few changes observed in the laboratory parameters were minor and considered to be no clinical importance.
Iodixanol induces only minor effects on renal function in patients. In diabetic patients with serum creatinine levels of 1.3-3.5 mg/dl, Iodixanol use resulted in 3% of patients experiencing a rise in creatinine of ≥0.5 mg/dl and 0% of the patients with a rise of ≥1.0 mg/dl. The release of enzymes (alkaline phosphatase and N-acetyl-s-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. Iodixanol is also well tolerated by the kidney.
Cardiovascular parameters such as LVEDP, LVSP, heart rate and QT-time as well as femoral blood flow were less influenced after iodixanol than after other contrast media, where measured.
Pharmacokinetics: Iodixanol is rapidly disturbed 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 I/kg b.w), indicating that Iodixanol is distributed in the extracellular volume only.
No metabolites have been detected. The protein binding is less than 2%.
The mean elimination half-life is approximately 2 hours. Iodixanol is excreted mainly through the kidneys by glomerular filtration.
Approximately 80% of the administered dose is recovered un-metabolized in the urine within 4 hours and 97% within 24 hours after intravenous injection. 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.
Toxicology: Preclinical Safety Data: Not Applicable.

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.

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, intra-arterial and intrathecal use.
The following dosages may serve as a guide. The doses given for intra-arterial use are for single injections that may be repeated. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Elderly: As for other adults.

Overdosage 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 (t½ ~ 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.

Hypersensitivity to Iodixanol or any components of its formulation.
Manifested thyrotoxicosis.

Special precautions for use of non-ionic contrast media in general: 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 iodixanol 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.
Patients using beta blockers may present with atypical symptoms of hypersensitivity which may be misinterpreted as a vagal reaction.
Non-ionic contrast media have less effect on the coagulation system in vitro, compared to ionic contrast media. When performing vascular catheterization procedures one should pay meticulous attention to the angiographic technique and flush the catheter frequently (e.g. with heparinised saline) so as to minimise the risk of procedure-related thrombosis and embolism.
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.
Care should also be taken in patients with serious cardiac disease and pulmonary hypertension as they may develop haemodynamic changes or arrhythmias.
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.
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 paraproteinemia (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.
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/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 is normal.
Abnormal serum creatinine/renal function: Metformin should be stopped and the contrast medium examination delayed for 48 hours. Metformin should only be restarted if renal function/serum creatinine is unchanged.
In emergency cases where renal function is impaired or unknown, the physician should evaluate the risk/ benefit of the contrast medium examination, and precautions should be implemented: Metformin should be stopped, patient hydrated, renal function monitored and patient observed for symptoms of lactic acidosis.
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 because there is no evidence that haemodialysis protects patients with impaired renal function from contrast medium induced nephropathy.
The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis. In patients with phaeochromocytoma undergoing interventional procedures, alpha blockers should be given as prophylaxis to avoid a hypertensive crisis. Special care should be exercised in patients with hyperthyroidism. Patients with multinodular goiter may be at risk of developing hyperthyroidism following injection of iodinated contrast media. One should also be aware of the possibility of inducing transient hypothyroidism in premature infants receiving contrast media.
Extravasation of Iodixanol has not been reported, but it is likely that Iodixanol 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.
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.
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 during the first 24 hours following intrathecal procedure.

Pregnancy and lactation: The safety of Iodixanol 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.
The degree of excretion into human milk is not known, although expected to be low. Breast feeding should be discontinued prior to administration of Iodixanol and should not be recommenced until at least 24 hours after.

Listed as follows are possible side effects in relation with radiographic procedures which include the use of iodixanol. Undesirable effects associated with iodixanol 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.
Intravascular administration: Blood and lymphatic system disorders: Thrombocytopenia.
Immune system disorders: Hypersensitivity, Anaphylactoid reaction, anaphylactoid shock.
Psychiatric disorders: Agitation, anxiety, Confusional state.
Nervous system disorders: Headache, Dizziness, Cerebrovascular accident, sensory abnormalities including taste disturbance, amnesia, paraesthesia, syncope. Coma, motor dysfunction, disturbance in consciousness, convulsion, transient contrast induced encephalopathy (including hallucination), tremor.
Eye disorders: Transient cortical blindness, visual impairment.
Cardiac disorders: Arrhythmia (including bradycardia, tachycardia), myocardial infarction, Cardiac arrest, Cardiac failure, Ventricular hypokinesia, myocardial ischaemia, cardio-respiratory arrest, conduction abnormalities, coronary artery thrombosis, angina pectoris, spasm of coronary arteries.
Vascular disorders: Flushing, Hypotension, Hypertension, ischaemia, Arterial spasm, thrombosis, thrombophlebitis, shock.
Respiratory, thoracic and mediastinal disorders: Cough, Dyspnoea, Pulmonary oedema, respiratory arrest, respiratory failure.
Gastrointestinal disorders: Nausea, vomiting, Abdominal pain/discomfort, Acute pancreatitis, pancreatitis aggravated, salivary gland enlargement.
Skin and subcutaneous system disorders: Rash, pruritus, urticaria, angioedema, erythema, 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: Back pain, muscle spasm, Arthralgia.
Renal and urinary disorders: Impairment of renal function including acute renal failure.
General disorders and administration site conditions: Feeling hot, chest pain, Pain, discomfort, shivering (chills), pyrexia, administration site reactions including extravasation, Feeling cold, asthenic conditions (e.g. malaise, fatigue).
Injury, poisoning and procedural complications: 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 infective meningitis should also be considered.
Immune system disorders: Hypersensitivity, including anaphylactic/anaphylactoid reactions.
Nervous system disorders: Headache (may be severe and lasting), Dizziness, transient contrast induced encephalopathy (including amnesia, hallucinations, confusion).
Gastrointestinal disorders: Vomiting, Nausea.
Musculoskeletal and connective tissue disorders: Muscle spasm.
General disorders and administration site conditions: Shivering, pain at injection site.
Hysterosalpingography (HSG): Immune system disorders: Hypersensitivity.
Nervous system disorders: Headache.
Gastrointestinal disorders: Abdominal pain, Nausea, Vomiting.
Reproductive system and breast disorders: Vaginal haemorrhage.
General disorders and administration site conditions: Pyrexia, Shivering, injection site reaction.
Arthrography: Immune system disorders: Hypersensitivity, including anaphylactic/anaphylactoid reactions.
General disorders and administration site conditions: Injection site pain, Shivering.
Examination of the GI tract: Immune system disorders: Hypersensitivity, including anaphylactic/anaphylactoid reactions.
Gastrointestinal disorders: Diarrhoea, abdominal pain, nausea, Vomiting.
General disorders and administration site reaction: Shivering.

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.
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).
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 medium 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.

Incompatibilities: No incompatibility has been found. However, CARDIOLEK should not be directly mixed with other drugs. A separate syringe should be used.

Store below 30°C. Protect from light and secondary X-rays. Do not freeze.
Shelf Life: 2 years.

Radiographic & Diagnostic Agents

V08AB09 - iodixanol ; Belongs to the class of watersoluble, nephrotropic, low osmolar preparations used as X-ray contrast media.

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