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TESLASCAN 0.01 mmol/ml solution for infusion is a clear bright to dark yellow solution containing 7.57mg/ml mangafodipir trisodium equivalent to 6.91mg/ml mangafodipir.
Pharmaco-therapeutic group: Paramagnetic MRI contrast medium ATC code: V08C A05.
Mangafodipir is a chelate containing the metal manganese - which has paramagnetic properties and is responsible for the contrast enhancement effect in MRI - and the ligated fodipir (dipyridoxyl diphosphate). Manganese is preferentially taken up by normal liver parenchyma and also in the pancreas so that contrast enhancement between abnormal and normal tissue can be expected.
The effect of the product is to shorten the longitudinal relaxation time (T1) of targeted tissues during MRI, leading to an increase in signal intensity (brightness) of, for example, pancreas and liver parenchyma.
Enhancement in both organs is near maximal for up to approx. 4 hours after the end of administration. Lesion related enhancement of certain types of lesions, such as liver metastases and hepatocellular carcinomas, may be detectable for up to 24 hours. Clinical studies have demonstrated that TESLASCAN facilitates the detection of liver lesions in patients with such lesions.
TESLASCAN is isotonic with blood and normal body fluids.
Mangafodipir trisodium is metabolised (dephosphorylated) and manganese ions are released from the mangafodipir by exchange with plasma zinc (mainly) after intravenous administration. Manganese and the ligand (fodipir), which have different pharmacokinetics, are eliminated by different routes.
The mean initial plasma half-life of manganese is 20 minutes or less, with significant uptake into the liver, pancreas, kidneys and spleen. The initial plasma half-life of ligand is about 50 minutes. The volume of distribution for manganese is between 0.5 and 1.5 l/kg, and for fodipir 0.17 to 0.45 l/kg. Following its metabolism, nearly all of the ligand (fodipir) is excreted in urine within 24 hours, with negligible amounts being eliminated via the faeces, About 15-20% of the manganese is eliminated in the urine within the first 24 hours, most of the remainder is excreted in the faeces over the following 4 days.
In whole human blood in vitro, the protein binding of manganese is approximately 27%, but binding of fodipir to protein is negligible.
Contrast medium for diagnostic Magnetic Resonance Imaging (MRI) for the detection of lesions of the liver suspected to be due to metastatic disease or hepatocellular carcinomas. Detection, differentiation and diagnosis of lesions of the pancreas.
The product is for single intravenous use only as repeated dosing has not been studied. It should be administered as an intravenous infusion at the rate of 2-3 ml/min for liver imaging and at a rate of 4-6 ml/min for imaging of the pancreas.
Near maximal enhancement of the normal liver parenchyma is generally observed 15-20 minutes from start of administration and lasts for approximately 4 hours.
At the clinical dose the contrast agent has no T2-effect, and pre- and post- T2-weighted images are equivalent. The clinical use of TESLASCAN has been investigated at field strengths from 0.5 to 2.0 Tesla.
Clinical trials have not been performed to assess the safety and efficacy of repeated dosing of TESLASCAN. If considering a second injection of TESLASCAN to one patient, the pharmacokinetics of mangafodipir should be taken into consideration.
The recommended dosage is 0.5 ml/kg b.w. (5 μmol/kg b.w.). This corresponds to a dose of 35 ml for a 70 kg person. Above 100 kg body weight, 50 ml is usually sufficient to provide a diagnostically adequate contrast effect.
Pharmacokinetics in the elderly have not been investigated. However, clinical studies to date do not suggest that a dose adjustment is required.
Safety and efficacy in patients below the age of 18 have not been documented.
As for all parenteral products, vials of TESLASCAN should be visually inspected for particulate matter and the integrity of the container prior to use. Vials are intended for single use only; any unused portions must be discarded,
The required volume to be given to the patient should be determined and administered appropriately (intravenous infusion). Any excess volume should be withdrawn from the vial before infusion.
Connective tubing may be flushed with physiological saline (0.9% sodium chloride), to ensure complete administration of the contrast medium.
Pregnancy and lactation.
Hypersensitivity to the product or its constituents.
Phaeochromocytoma.
Severely reduced liver function (Child - Pugh class C), especially severe obstructive hepatobiliary disease.
Severely reduced renal function.
Rarely, hypersensitivity reactions (urticaria and other possible allergic phenomena) or anaphylactic reactions may occur. Familiarity with the practice and technique of resuscitation and treatment of anaphylaxis is essential. Appropriate drugs and instruments should be readily available.
Care should be exercised in patients with severe cardiac disease and in patients with injuries of the blood brain barrier and severe cerebral disease.
The fact that long term parenteral nutrition with manganese supplementation can cause manganese accumulation in the basal ganglia should be considered when administering TESLASCAN to patients on such treatment.
The safety of TESLASCAN in human pregnancy has not been established. TESLASCAN must not be used during pregnancy.
Prior to the administration of TESLASCAN to women of child bearing potential pregnancy should be excluded.
Experimental studies in rats have established teratogenic effects when TESLASCAN was given repeatedly during major organogenesis. TESLASCAN causes foetotoxicity and embryotoxicity in rabbits. TESLASCAN is not teratogenic in rabbits. TESLASCAN has no effect on male or female fertility in rats.
The degree of excretion into human breast milk is not known. Breast-feeding should be discontinued from administration and should not be recommenced until 14 days after administration of TESLASCAN.
Most of the adverse reactions reported were transient and of mild intensity. Those most commonly reported were: feeling of warmth/flushing, headache, nausea, vomiting, other gastrointestinal symptoms (like abdominal pain, diarrhoea, flatulence) and taste sensations. Less frequent reactions are hypersensitivity reactions (such as skin reactions, rhinitis, pharyngitis), dizziness, palpitation, chest pain, hypertension and injection associated discomfort. Rarely, visual disturbances, fever and paraesthesia have been reported. Anaphylactic reactions may occur.
Mangafodipir can cause transient increases of bilirubin and liver transaminases and transient decreases in plasma zinc.
The frequency of mild and moderate, non-serious adverse reactions, mainly transient warmth and flushing, is likely to increase if TESLASCAN is administered at a faster rate than that advised.
No specific interaction studies have been performed with TESLASCAN.
Serious adverse events have not been reported in healthy subjects with dosages up to 5 times the normal clinical dose (maximum dose investigated).
High doses of manganese can have negative inotropic and vasodilatory effects as well as effects on heart rhythm and conduction because of calcium antagonism.
Treatment of an overdose should be symptomatic and directed towards the support of vital functions. There is no antidote to this contrast medium.
Mangafodipir and its metabolites pass membranes with cut-off thresholds of 10-30 kDa and are, therefore, most probably dialysable with conventional membranes.
TESLASCAN should be stored at room temperature, below 25°C protected from light.
General Sale Medicine
TESLASCAN is supplied in packs of 1 x 50 ml and 10 x 50 ml vials.
TESLASCAN has the following physicochemical properties:
Osmolality (mosmol/kg H2O) at 37°C 290
Viscosity (mPa·s) at 20°C 1.0
Viscosity (mPa·s) at 37°C 0.7
Density (g/ml) at 20°C 1.01
Ascorbic acid, sodium chloride, sodium hydroxide and/or hydrochloric acid (pH adjustment), water for injections.
Preclinical studies reveal no special hazard for humans based on conventional studies of genotoxicity, safety pharmacology and validating kinetics and metabolism. Relevant adverse effects from repeated dose toxicity studies were as follows: Liver toxicity (cholangiohepatitis) was observed at relatively low dosages in dogs, while sufficient margins of safety were determined in rats and monkeys.
Mangafodipir is teratogenic in rats; it causes increased foetal skeletal abnormalities when given daily by intravenous injection to female rats at dosages slightly greater than clinical dosages. Embryo- and foetotoxicity has been observed in rabbits.
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26 June 2006