GADOVIST

What it is

Gadovist 1.0 is a paramagnetic contrast agent for magnetic resonance imaging containing gadobutrol, a neutral (non-ionic) complex consisting of gadolinium (III) and the macrocyclic ligand dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol). Gadovist 1.0 is available as a 1.0 mmol/mL solution for injection. This medicinal product is for diagnostic use only.

Approved indications

Gadovist 1.0 is indicated in adults and children including full-term newborns for: — Contrast enhancement in cranial and spinal magnetic resonance imaging (MRI). — Contrast enhancement in whole body MRI including head and neck region, thoracic space, breast, abdomen (pancreas, liver and spleen), pelvis (prostate, bladder and uterus), retroperitoneal space (kidney), extremities and musculoskeletal system. — Use in first–pass MRI studies of cerebral perfusion. — Contrast enhancement in magnetic resonance angiography (CE MRA). — Contrast enhancement in cardiac MRI including assessment of rest and pharmacological stress perfusion and delayed enhancement.

Dosing overview

A single intravenous injection of 0.1 mmol Gadovist 1.0 per kg body weight is recommended for adults, with a total maximum amount of 0.3 mmol per kg body weight not to be exceeded, and the lowest dose that provides sufficient enhancement for diagnostic purposes should be used. For children of all ages including full-term newborns, the recommended dose is 0.1 mmol Gadovist 1.0 per kg body weight for all indications.

Key safety warnings

Gadolinium-based contrast agents increase the risk of nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m²), or acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. NSF is a debilitating and sometimes fatal disease affecting the skin, muscle, and internal organs. Gadovist 1.0 can be associated with anaphylactoid/hypersensitivity or other idiosyncratic reactions, and the risk of hypersensitivity reactions is higher in case of previous reaction to contrast media, history of bronchial asthma, or history of allergic disorders. Most of these reactions occur within half an hour of administration; therefore post-procedure observation of the patient is recommended. Acute respiratory distress syndrome (ARDS) has been reported in patients administered Gadovist 1.0 and may be characterised by severe hypoxaemia requiring oxygen support and mechanical ventilation, with onset of respiratory distress within <30 minutes to 24 hours after Gadovist 1.0 administration. 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 has been detected in brain tissue after multiple exposures, particularly in the dentate nucleus and globus pallidus. To minimize 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.

Contraindications

Gadovist 1.0 should not be administered to patients with known hypersensitivity to any of the ingredients. Gadobutrol must not be used intrathecally, as serious, life-threatening and fatal cases, primarily with neurological reactions (e.g. coma, encephalopathy, seizures), have been reported with intrathecal use.

Regulatory history

Gadovist 1.0 was first approved on 2 December 1998. The initial ARTG registrations comprised Gadovist 1.0 gadobutrol 4.5354 g/7.5 mL injection syringe and 9.0708 g/15 mL injection vial, both first listed on 1998-12-02. Additional presentations were added to the ARTG: 6.0472 g/10 mL injection syringe (2000-01-17), 3.0236 g/5 mL injection syringe (2000-01-17), 1.2094 g/2 mL solution for injection vial (2018-03-16), and 39.307 g/65 mL injection vial (2024-05-09).