PRIMOVIST

What it is

Primovist is a magnetic resonance imaging (MRI) contrast agent containing 0.25 mmol disodium gadoxetate per 1 mL. It is supplied as a solution for injection. Primovist is a paramagnetic contrast agent for magnetic resonance imaging, with the contrast-enhancing effect mediated by gadoxetate, an ionic complex consisting of gadolinium (III) and ethoxybenzyl-diethylenetriamine-pentaacetic acid. When T1-weighted scanning sequences are used, the gadolinium ion-induced shortening of the spin-lattice relaxation time of excited atomic nuclei leads to an increase of the signal intensity and image contrast of certain tissues.

Approved indications

Primovist is indicated for use in adults for the enhancement of magnetic resonance imaging (MRI) of focal liver lesions.

Dosing overview

The recommended dose of Primovist is 0.1 mL/kg body weight (equivalent to 25 μmol/kg body weight) for adults. Primovist is administered undiluted as an intravenous bolus injection at a flow rate of about 2 mL/sec through a large-bore needle or indwelling catheter (18–20 gauge is recommended). The delayed (hepatocyte) phase imaging window lasts at least 120 minutes and is reduced to 60 minutes in patients requiring haemodialysis and in patients with elevated bilirubin values (>3 mg/dL).

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. Disodium gadoxetate can be removed from the body by haemodialysis, with about 30% of the administered dose eliminated by a single dialysis session of 3 hours starting 1 hour post injection. Elevated levels of bilirubin (>3 mg/dL or 51.3 micromol/L) or ferritin can reduce the hepatic contrast effect of Primovist. If Primovist is used in these patients, complete the magnetic resonance imaging no later than 60 minutes after Primovist administration. Primovist can be associated with anaphylactoid/hypersensitivity or other idiosyncratic reactions characterised by cardiovascular, respiratory and cutaneous manifestations and ranging to severe reactions including shock. The risk of hypersensitivity reactions is higher in patients with 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. Gadolinium accumulates in the brain after multiple administrations of gadolinium-based contrast agents. Gadolinium has been detected in brain tissue after multiple exposures, particularly in the dentate nucleus and globus pallidus. 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.

Contraindications

Primovist is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

Regulatory history

Primovist was first approved on 1 July 2004. Three variants are registered on the Australian Register of Therapeutic Goods: disodium gadoxetate 181.43 mg/mL (0.25M) in 5 mL injection vial (ARTG 102088, first listed 2004-07-01), 10 mL injection vial (ARTG 104379, first listed 2004-07-02), and 10 mL injection pre-filled syringe (ARTG 104381, first listed 2004-07-02).