Source: European Medicines Agency (EU) Revision Year: 2012 Publisher: GE Healthcare AS, Nycoveien 1-2, P.O. Box 4220 Nydalen, NO-0401, OSLO, Norway
Pharmacotherapeutic group: Paramagnetic MRI contrast medium
ATC Code: V08CA05
Mangafodipir is a chelate containing the metal manganese – which has paramagnetic properties and is responsible for the contrast enhancement effect in MRI – and the ligand 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 mangafodipir 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 mangafodipir facilitates the detection of liver lesions in patients with such lesions.
TESLASCAN is isotonic with blood and normal body fluids.
An uncontrolled observational study assessed the use of mangafodipir in the radiological assessment of infant patients with suspected bilary atresia. 23 consecutive patients aged 24-139 days (mean 69 days) with prolonged jaundice and lightened stool colour in whom bilary atresia had not been ruled out underwent MR cholangiography with contrast. The dose of mangafodipir used was 5 μmol/kg. No safety concerns arose from this study, although the numbers were too small to be useful in this regard.
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.
Non-clinical 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 liver toxicity (cholangiohepatitis) 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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