Gadofosveset Trisodium

Pronunciation: GAD-oh-FOS-ve-set trye-SOE-dee-um
Class: Diagnostic aid

Trade Names

Ablavar
- Injection, solution 244 mg/mL (0.25 mmol/mL)

Pharmacology

Binds to serum albumin, increasing the magnetic resonance relaxivity of gadofosveset and decreasing the relaxation time (T1) of water protons, resulting in an increase in signal intensity (brightness) of blood.

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Pharmacokinetics

Absorption

Mean plasma concentration was 0.43 and 0.24 mmol/L at 3 min and 1 h postinjection, respectively.

Distribution

Vd is 148 mL/kg. Protein binding ranges from 79.8% to 87.4%. Mean half-life of distribution phase is approximately 0.48 h.

Metabolism

Not metabolized.

Elimination

83.7% eliminated in the urine; 4.7% in the feces. Elimination half-life is 16.3 h. Cl is 6.57 mL/h/kg.

Special Populations

Renal Function Impairment

Cl decreases substantially as renal function decreases. AUC increased 1.75-fold in patients with moderate (CrCl 30 to 50 mL/min) and 2.25-fold in patients with severe renal impairment (CrCl less than 30 mL/min). The elimination half-life increased from 19 h in healthy subjects to 49 h in patients with moderate and 70 h in patients with severe renal impairment.

Hepatic Function Impairment

The pharmacokinetics and plasma protein binding were not significantly influenced by moderate hepatic impairment.

Elderly

Age had no meaningful effect on the pharmacokinetics of gadofosveset.

Gender

Gender had no meaningful effect on the pharmacokinetics of gadofosveset.

Hemodialysis

Gadofosveset is removed by hemodialysis using high-flux filters.

Indications and Usage

For use as a contrast agent in magnetic resonance angiography to evaluate aortoiliac occlusive disease in adults with known or suspected peripheral vascular disease.

Contraindications

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

Dosage and Administration

Adults

IV bolus 0.12 mL/kg (0.03 mmol/kg) over a period of up to 30 sec, followed by a 25 to 30 mL saline flush.

Renal function impairment

If no satisfactory diagnostic alternatives are available, administer at a dose of 0.01 to 0.02 mmol/kg in patients with moderate to severe renal impairment (glomerular filtration rate [GFR] less than 60 mL/kg/m ² ).

General Advice

• Vials are for single use only and should be used immediately upon opening. Discard any unused portion.
• Do not use gadofosveset solution if it is discolored or if particulate matter is present.
• Do not mix IV medications or parenteral solutions with gadofosveset. Do not administer any other medications in the same IV line simultaneously with gadofosveset.
• To assess the initial distribution within the arterial system, begin dynamic imaging immediately upon injection. Begin steady-state imaging after dynamic imaging has been completed, generally 5 to 7 min following administration.

Storage/Stability

Store between 59° and 86°F. Protect from light and freezing.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Vasodilation (3%); hypertension (1%).

CNS

Headache (4%); paresthesia (3%); dizziness, excluding vertigo (1%).

GI

Nausea (4%); dysgeusia (2%).

Local

Injection-site bruising, venipuncture-site bruise (2%).

Miscellaneous

Pruritus (5%); burning sensation (2%); feeling cold (1%).

Precautions

Warnings Nephrogenic systemic fibrosis Gadolinium-based contrast agents increase the risk of nephrogenic systemic fibrosis (NSF) in patients with impaired elimination of the drugs and may result in fatal or debilitating fibrosis affecting the skin, muscle, and internal organs. Avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with noncontrast-enhanced MRI or other modalities Risk for NSF appears highest among patients with chronic, severe kidney disease (GFR less than 30 mL/min per 1.73 m 2 ) or acute kidney injury. For patients at highest risk for NSF, do not exceed the recommended dose. Allow a sufficient period of time for elimination of the drug from the body prior to readministration.

Monitor Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests prior to administration. Consider follow-up renal function assessments for patients with a history of renal dysfunction. Consider baseline and follow-up ECGs in patients at high risk for arrhythmias due to QTc prolongation. Closely observe patients with a history of drug reactions, asthma, allergy, or other hypersensitivity disorders during and for several hours after gadofosveset administration for signs and symptoms of anaphylactoid and/or anaphylaxis reactions.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

May cause anaphylactoid and/or anaphylactic reactions, including life-threatening or fatal reactions.

Acute renal failure

Acute renal failure requiring dialysis or worsening renal function has occurred with the use of other gadolinium agents in patients with renal insufficiency.

QTc prolongation

Small increases have occurred and were not associated with arrhythmias or symptoms.

Overdosage

Symptoms

None well documented.

Patient Information

• Instruct patients to inform their health care provider if they are pregnant or breast-feeding; if they have a history of allergic reaction to contrast media, a history of bronchial asthma or allergic respiratory disorder, kidney and/or liver disease, heart rhythm disturbance, or cardiac disease; if they recently received a gadolinium-based contrast agent; or if they are taking any prescription or OTC medicines.
• Inform patients that gadolinium-based contrast agents increase the risk of NSF in patients with severe renal insufficiency or acute renal insufficiency of any severity due to hepato-renal syndrome or in the perioperative setting of liver transplantation. Instruct patients to contact their health care provider if they develop burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness of the joints with trouble moving, bending, or straightening of the arms, hands, legs, or feet; pain deep in the hip bones or ribs; or muscle weakness.
• Inform patients that they may experience reactions at the injection site, such as redness, mild and transient burning or pain or feeling of warmth or coldness, itching, or nausea.

Copyright © 2009 Wolters Kluwer Health.