DOTAREM

What it is

DOTAREM is a solution for injection containing gadoteric acid 0.5 mM/mL, with each vial or bottle containing 279.32 mg/mL of gadoteric acid. Gadoteric acid is a complex of the paramagnetic ion gadolinium oxide with tetraxetan (DOTA). DOTAREM is a sterile, preservative-free, clear, colourless to yellow solution for injection packaged in glass vials or bottles for intravenous injection. Gadoteric acid has paramagnetic properties which increase contrast enhancement in MRI. Gadoteric acid shortens the longitudinal relaxation time (T1) and the transverse relaxation time (T2) of water protons in tissues where it is distributed, with the major effect at clinical doses on T1 relaxation time, resulting in increased signal intensity in T1-weighted sequences and better visualisation of abnormal structures or lesions.

Approved indications —

Intracranial and spinal lesions with abnormal blood brain barrier or abnormal vascularity in adults and children. — Whole body imaging in adults and children.

Dosing overview

The maximum recommended dose is 0.1 mmol/kg (0.2 mL/kg) for both adults and children. DOTAREM is intended for intravenous administration only. For children, it is preferable to use single-use syringes of volume adapted to the required dose for better precision of the injected volume, and in neonates and infants the required dose should be administered by hand.

Key safety warnings

Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate less than 30 mL/min/1.73 m²) or acute renal insufficiency of any severity due to hepato-renal syndrome or in the perioperative liver transplantation period. DOTAREM should only be used in patients with severe renal impairment and in patients with perioperative liver transplantation after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI. NSF is a debilitating and sometimes fatal disease affecting the skin, muscle, and internal organs. DOTAREM must not be used intrathecally. Serious, life-threatening and fatal cases, primarily with neurological reactions such as coma, encephalopathy and seizures, have been reported with intrathecal use. Gadoteric acid should be strictly administered via intravenous injection. Gadolinium accumulates in the brain after multiple administrations of gadolinium-based contrast agents. Increased signal intensity on non-contrast T1-weighted images of the brain has been observed after multiple administrations, and gadolinium has been detected in brain tissue particularly in the dentate nucleus and globus pallidus. Gadolinium accumulation is higher after repeat administration of linear than macrocyclic agents. The clinical significance of gadolinium accumulation in the brain is presently unknown. To minimise potential risks, it is recommended to use the lowest effective dose and perform a careful benefit-risk assessment before administering repeated doses. Hypersensitivity reactions can occur with DOTAREM, including life-threatening events. Hypersensitivity reactions may be either allergic or non-allergic, and can be either immediate (less than 60 minutes) or delayed (up to 7 days). Anaphylactic reactions occur immediately and can be fatal. They are independent of the dose, can occur after even the first dose and are often unpredictable.

Contraindications

DOTAREM is contraindicated in patients with hypersensitivity to gadoteric acid, meglumine or any products containing gadolinium. Contraindications related to magnetic resonance imaging include patients with pacemakers, patients with ferromagnetic vascular clips, infusion pumps, nerve stimulators, cochlear implants, or suspected intracorporal metallic foreign bodies, particularly in the eye.

Regulatory history

DOTAREM gadoteric acid 279.32 mg/mL injection was first registered on the ARTG on 11 December 2000, with initial listings for 10 mL, 15 mL, 20 mL and 5 mL vials. Pre-filled syringe formulations (10 mL, 15 mL and 20 mL) were added to the ARTG on 26 August 2010.