(gad oh FOS ve set)
Contrast medium used in magnetic resonance angiography (MRA) to evaluate or better define aortoiliac occlusive disease
Hypersensitivity to gadofosveset, any gadolinium-based contrast agent, or any component of the formulation
Gadolinium-based contrast agents increase the risk of nephrogenic systemic fibrosis (NSF) in patients with impaired elimination of the drugs. In these patients, avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with noncontrast-enhanced magnetic resonance imaging (MRI) or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle, and internal organs.
The risk for NSF appears highest among patients with chronic, severe kidney disease (glomerular filtration rate [GFR] <30 mL/minute per 1.73 m2) or acute kidney injury.
Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk of chronically reduced renal function (eg, >60 years, hypertension, diabetes), estimate the GFR through laboratory testing.
For patients at highest risk for NSF, do not exceed the recommended gadofosveset dose. Allow a sufficient period of time for elimination of the drug from the body prior to readministration.
MRA: IV: 0.03 mmol/kg (0.12 mL/kg )
Refer to adult dosing.
Dose adjustment is not recommended; however, use with caution. Risk for NSF development increases as renal function decreases.
Hemodialysis: If administered to patients already receiving hemodialysis, consider prompt hemodialysis following exposure (eg, within 3 hours) (Kuo, 2007). Data has shown hemodialysis enhances gadolinium elimination with average gadolinium excretory rates of 78%, 96%, and 99% in the first to third hemodialysis sessions, respectively (Kuo, 2007; Okada, 2001).
Peritoneal dialysis: Likely to be less efficient at clearing gadolinium (Joffe, 1998; Kuo, 2007).
No dosage adjustment provided in manufacturer 's labeling. Limited data suggest pharmacokinetics of gadofosveset in patients with hepatic disease do not differ substantially.
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.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Ablavar: 244 mg/mL (10 mL, 15 mL)
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Baseline ECG if risk factors for QTc 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); patients should be monitored for at least 1 hour after administration of gadofosveset.
1% to 10%:
Cardiovascular: Vasodilatation (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% (Limited to important or life-threatening): Acute renal failure, anaphylactoid reaction, anaphylaxis, nephrogenic systemic fibrosis (NSF/NFD), prolonged Q-T interval on ECG
Cl 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).
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: [U.S. 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 30-59 mL/minute/1.73 m2) and little, if any, in patients with mild, chronic renal disease (GFR 60-89 mL/minute/1.73 m2). NSF, a potentially fatal disease, affects the skin, muscle, and internal organs and can occur days to months after exposure. All patients should be screened for renal dysfunction prior to administration; estimate GFR in patients at risk for chronic renal disease (diabetes, 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.
- QTc prolongation: Rare cases of QTc 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 QTc 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 QTc prolongation (eg, underlying cardiac disease, concurrent medications). Patients should be monitored for at least 1 hour after the administration of gadofosveset.
Disease-related concerns:
- Hypoalbuminemia: Elimination of gadofosveset may be quicker in patients with decreased levels of serum albumin.
- 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.
- Sickle cell anemia: In in vitro studies, deoxygenated sickle erythrocytes align perpendicular to a magnetic field; the enhancement of magnetic moment by contrast agents may potentiate this alignment possibly resulting in vaso-occlusive complications in vivo. Use in patients with sickle cell anemia or other hemoglobinopathies has not been studied.
Concurrent drug therapy issues:
- Contrast agents: Safety and efficacy have not been studied for the use of gadofosveset in conjunction with other contrast agents (eg, iodine-containing, gadolinium based). Use caution in patients who have received iodine-containing agents within 72 hours or other gadolinium-based agents within 24 hours prior to gadofosveset administration.
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Adverse events were observed in some animal reproduction studies. Gadnolinium-based contrast agents cross the placenta; in general, their use in pregnant women is controversial (ACOG 2016). Use should be avoided unless critical for the care of the mother or fetus, and it is not prudent to wait until after pregnancy. Agents with a low risk for development of nephrogenic systemic fibrosis should be used at the lowest effective dose (ACR 2015).
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.
Vdss: 148 ‚ ± 16 mL/kg
Negligible
Urine (84% as unchanged drug); feces (~5%)
~15 minutes
~1 hour
~16 hours; moderate renal impairment: 49 hours; severe renal impairment: 70 hours
80% to 87% (predominantly to albumin)
- 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 (urinary retention, blood in urine, change in amount of urine passed, weight gain), severe dizziness, passing out, arrhythmia, or tachycardia (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.