DOTAGRAF

What it is

DOTAGRAF is a solution for injection containing gadoteric acid 0.5 mM/mL. Gadoteric acid is a complex of the paramagnetic ion gadolinium oxide with tetraxetan (DOTA; 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid). DOTAGRAF is a sterile, preservative-free, clear, colourless to yellow solution for injection free of visible particles and packaged in glass vials or bottles for intravenous injection.

Approved indications

— Contrast enhancement for 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. The lowest effective dose should be used, and the dose should be calculated based on the patient's body weight and should not exceed the recommended dose per kilogram of body weight. DOTAGRAF is intended for intravenous administration only.

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 < 30 mL/min/1.73 m²), or acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. DOTAGRAF 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. Gadoteric acid must not be used intrathecally, as serious, life-threatening and fatal cases with primarily neurological reactions (such as coma, encephalopathy, seizures) have been reported with intrathecal use, and gadoteric acid should be strictly administered via intravenous injection. Gadolinium accumulates in the brain after multiple administrations of gadolinium-based contrast agents, with increased signal intensity on non-contrast T1 weighted images of the brain observed after multiple administrations in patients with normal renal function, and gadolinium detected in brain tissue particularly in the dentate nucleus and globus pallidus. To minimise potential risks associated with gadolinium accumulation in the brain, 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 DOTAGRAF, including life-threatening events, which 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, are independent of the dose, can occur after even the first dose, and are often unpredictable.

Contraindications

DOTAGRAF 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

DOTAGRAF was first listed on the ARTG on 19 October 2022 with five registered variants: gadoteric acid 2.79 g/10 mL solution for injection vial (ARTG 351770), 4.19 g/15 mL solution for injection vial (ARTG 371170), 5.59 g/20 mL solution for injection vial (ARTG 371171), 16.76 g/60 mL solution for injection bottle (ARTG 371172), and 27.93 g/100 mL solution for injection bottle (ARTG 371173).