Gadofosveset

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous [preservative free]:

Ablavar: 244 mg/mL (10 mL [DSC], 15 mL [DSC])

Pharmacology

Mechanism of Action

Gadofosveset is a gadolinium-containing paramagnetic agent that reversibly binds to albumin in the plasma. Exposure to an external magnetic field induces a large local magnetic field in exposed blood vessels. This local magnetism disrupts water protons in the vicinity, resulting in a change in proton density and spin characteristics, which can be detected by the imaging device. The binding of gadofosveset to albumin prolongs the period of time gadofosveset resides intravascularly, enhances T1 relaxivity up to 10 times greater than nonprotein bound gadolinium chelates and provides a longer imaging window.

Pharmacokinetics/Pharmacodynamics

Distribution

V_dss: 148 ± 16 mL/kg

Metabolism

Negligible

Excretion

Urine (79% to 94% as unchanged drug); feces (~5%)

Onset of Action

5 to 7 minutes

Duration of Action

~1 hour

Half-Life Elimination

16.3 ± 2.6 hours; moderate renal impairment: 49 hours; severe renal impairment: 70 hours

Protein Binding

80% to 87% (predominantly to albumin)

Use in Specific Populations

Special Populations: Renal Function Impairment

Clearance decreases substantially as renal function decreases. AUC increased 1.75-fold in patients with moderate (CrCl 30 to 50 mL/minute) and 2.25-fold in patients with severe renal impairment (CrCl <30 mL/minute).

Use: Labeled Indications

Angiography imaging: Contrast medium agent used in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease in adults with known or suspected peripheral vascular disease.

Contraindications

History of prior hypersensitivity to any gadolinium-based contrast agent.

Dosage and Administration

Dosing: Adult

Angiography imaging: IV: 0.03 mmol/kg (0.12 mL/kg).

Dosing: Geriatric

Refer to adult dosing.

Administration

IV: Administer as an intravenous bolus injection over a period up to 30 seconds through a dedicated IV line separate from other medications. Flush line with 25-30 mL NS after administration to ensure complete injection of medium. Imaging should be completed within 1 hour of injection.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze. Protect from light. Use immediately after opening.

Drug Interactions

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Adverse Reactions

1% to 10%:

Cardiovascular: Vasodilation (3%), hypertension (1%)

Central nervous system: Headache (4%), paresthesia (3%), burning sensation (2%), dizziness (1%), sensation of cold (1%)

Dermatologic: Pruritus (5%)

Gastrointestinal: Nausea (4%), dysgeusia (2%)

Local: Bruising at injection site (2%)

<1%, postmarketing, and/or case reports: Acute renal failure, anaphylactoid reaction, anaphylaxis, nephrogenic systemic fibrosis (NSF/NFD), prolonged Q-T interval on ECG

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity, including anaphylactic reactions (rare), may occur; appropriate equipment (eg, ventilator) and emergency medications (eg, epinephrine) should be available during use. Delayed reactions may also occur (within several hours of administration). Patients with a history of allergic reactions and/or bronchial asthma may be at an increased risk for developing hypersensitivity reactions; use caution in these patients.
• Nephrogenic systemic fibrosis: [US Boxed Warning]: Gadolinium-based contrast agent (GBCA) exposure may increase the risk for nephrogenic systemic fibrosis (NSF) in patients with renal impairment; avoid use unless GBCA enhanced imaging is essential for diagnostic purposes. The risk is highest in patients with acute kidney injury or chronic, severe renal disease (GFR <30 mL/minute/1.73 m²). The risk appears lower in patients with moderate, chronic renal disease (GFR 30 to 59 mL/minute/1.73 m²) and little, if any, in patients with mild, chronic renal disease (GFR 60 to 89 mL/minute/1.73 m²). NSF, a potentially fatal disease, affects the skin, muscle, and internal organs. All patients should be screened for renal dysfunction prior to administration; estimate GFR in patients at risk for chronic renal disease (diabetes, chronic hypertension, age >60 years). In patients at risk of NSF, do not exceed the recommended dosage and allow sufficient time (ie, several half-lives) for elimination prior to readministration (avoidance of readministration is preferred). In patients receiving hemodialysis, consider prompt initiation of hemodialysis following administration.
• QT_c prolongation: Rare cases of QT_c prolongation have been observed with gadofosveset use. Data from pooled safety studies have demonstrated that the administration of gadofosveset resulted in minimal changes to the QT_c interval as compared to placebo (means of 2.8 msec and 3.2 msec respectively). Consider baseline and follow up ECG in patients at increased risk of arrhythmias due to QT_c prolongation (eg, underlying cardiac disease, concurrent medications). Patients should be monitored for at least 1 hour after the administration of gadofosveset.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment. Dose-dependent worsening of renal function or acute renal failure has occurred in patients with renal insufficiency following use of other gadolinium agents, generally within 48 hours following administration. Dosage reductions may be necessary. Evaluate renal function in patients with renal impairment prior to use; consider follow-up monitoring.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Baseline ECG if risk factors for QT_c prolongation/torsade de pointes; baseline electrolytes (including potassium, calcium and magnesium); screen for renal impairment (all patients); baseline renal function in patients at risk of NSF and follow-up evaluation with renal dysfunction; signs of hypersensitivity (during and for several hours after procedure); short- and long-term monitoring of signs and symptoms of NSF/NFD (eg, burning, itching, swelling, hardening and/or tightening of skin, joint stiffness, deep hip or rib bone pain, muscle weakness, limited range of motion, and/or yellowed/raised spots on whites of eye).

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Gadolinium-based contrast agents may cross the placenta (ACOG 723 2017; ACR 2018).

Use of gadolinium-based contrast agents in pregnancy is controversial and should be limited. A gadolinium-based contrast agent may be considered for use in pregnancy if it will significantly improve diagnostic performance and is expected to improve fetal or maternal outcome (ACOG 723 2017). In addition, use should only be considered if information needed from the study cannot be acquired without using a contrast agent and cannot be deferred until after delivery. Agents with a low risk for development of nephrogenic systemic fibrosis should be used at the lowest effective dose (ACR 2018).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience injection site irritation, itching or nausea. Have patient report immediately to prescriber signs of nephrogenic systemic fibrosis (skin burning, itching, swelling, or scaling; red or dark spots on the skin; hard or tight skin; stiff joints; muscle weakness; hip or rib pain; difficulty moving, bending, or straightening arms, hands, legs, or feet), signs of kidney problems (unable to pass urine, blood in urine, change in amount of urine passed, weight gain), severe dizziness, passing out, arrhythmia, or fast heartbeat (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.