Vasovist

VASOVIST- gadofosveset trisodium injection
Bayer Healthcare, Inc.

1 INDICATIONS AND USAGE

VASOVIST is indicated for use as a contrast agent in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease [see Clinical Studies (14) ].

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Guidelines

Administer VASOVIST as an intravenous bolus injection, manually or by power injection, at a dose of 0.12 mL/kg body weight (0.03 mmol/kg) over a period of time up to 30 seconds followed by a 25-30 mL normal saline flush. (See Table 1 for weight-adjusted dose volumes).

TABLE 1. Weight-Adjusted Volumes for the 0.03 mmol/kg Dose

Body Weight		Volume
Kilograms (kg)	Pounds (lb)	Milliliters (mL)
40	88	4.8
50	110	6.0
60	132	7.2
70	154	8.4
80	176	9.6
90	198	10.8
100	220	12.0
110	242	13.2
120	264	14.4
130	286	15.6
140	308	16.8
150	330	18.0
160	352	19.2

Inspect the VASOVIST vial visually for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or particulate matter is present.

VASOVIST is intended for single use only and should be used immediately upon opening. Discard any unused portion of the VASOVIST vial.

Do not mix intravenous medications or parenteral nutrition solutions with VASOVIST. Do not administer any other medications in the same intravenous line simultaneously with VASOVIST.

2.2 Imaging Guidelines

VASOVIST imaging is completed in two stages: the dynamic imaging stage and the steady-state imaging stage. Both stages are essential for adequate evaluation of the arterial system, and dynamic imaging always precedes steady-state imaging. During interpretation of the steady-state images, VASOVIST within the venous system may limit or confound the detection of arterial lesions.

To assess the initial distribution of VASOVIST within the arterial system, begin dynamic imaging immediately upon injection. Begin steady state imaging after dynamic imaging has been completed, generally 5 to 7 minutes following VASOVIST administration. At this time point, VASOVIST is generally distributed throughout the blood. In clinical trials, steady-state imaging was completed within approximately one hour following VASOVIST injection.

3 DOSAGE FORMS AND STRENGTHS

VASOVIST is a sterile solution for intravenous injection containing 244 mg/mL (0.25 mmol/mL) gadofosveset trisodium [see How Supplied/Storage and Handling (16) ]

4 CONTRAINDICATIONS

History of a prior allergic reaction to a gadolinium-based contrast agent.

5 WARNINGS AND PRECAUTIONS

5.1 Nephrogenic Systemic Fibrosis

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/1.73m²) and in patients with acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced MRA. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a gadolinium-based contrast agent in order to enhance the contrast agent’s elimination. VASOVIST binds to blood albumin and use of a high-flux dialysis procedure is essential to optimized VASOVIST elimination in patients receiving chronic hemodialysis. The usefulness of hemodialysis in the prevention of NSF is unknown [see Boxed Warning and Clinical Pharmacology (12.3)].

Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a gadolinium-based contrast agent and the degree of renal function impairment at the time of exposure.

Post-marketing reports have identified the development of NSF following single and multiple administrations of gadolinium-based contrast agents. These reports have not always identified a specific agent. Prior to marketing of Vasovist®, where a specific agent was identified, the most commonly reported agent was gadodiamide (Omniscan^TM), followed by gadopentetate dimeglumine (Magnevist^®) and gadoversetamide (OptiMARK^®). NSF has also developed following sequential administrations of gadodiamide with gadobenate dimeglumine (MultiHance^®) or gadoteridol (ProHance^®). The number of post-marketing reports is subject to change over time and may not reflect the true proportion of cases associated with any specific gadolinium-based contrast agent.

The extent of risk for NSF following exposure to any specific gadolinium-based contrast agent is unknown and may vary among the agents. Published reports are limited and predominantly estimate NSF risks with gadodiamide. In one retrospective study of 370 patients with severe renal insufficiency who received gadodiamide, the estimated risk for development of NSF was 4% (J Am Soc Nephrol 2006; 17:2359). The risk, if any, for the development of NSF among patients with mild to moderate renal insufficiency or normal renal function is unknown.

Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent prior to any re-administration. NSF was not reported in clinical trials of VASOVIST [see Clinical Pharmacology (12) and Dosage and Administration (2)].