Vasovist

957.86000

976.11312

V08CA

278.77000

-4.48880

1.1224 g/mL at 25 °C

954.8ºC

531.3ºC

0mmHg at 25°C

Osmolarity: 825 mOsmol/kg water at 37 °C

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including gadofosveset trisodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

IDENTIFICATION: Gadofosveset 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. HUMAN EXPOSURE AND TOXICITY: In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following Ablavar administration; no increase was observed at 24 and 72 hours. A QTc change of 30 to 60 msec from baseline was observed in 39/702 (6%) patients at 45 min following Ablavar administration. At this time point, 3/702 (0.4%) patients experienced a QTc increase of > 60 msec. These QTc prolongations were not associated with arrhythmias or symptoms. In patients at high risk for arrhythmias due to QTc prolongation (e.g., concomitant medications, underlying cardiac conditions) consider obtaining baseline electrocardiograms to help assess the risks for Ablavar administration. If Ablavar is administered to these patients, consider follow-up electrocardiograms and risk reduction measures (e.g., patient counseling or intensive electrocardiography monitoring) until most Ablavar has been eliminated from the blood. In patients with normal renal function, most Ablavar was eliminated from the blood by 72 hours following injection. Ablavar may cause anaphylactoid and/or anaphylactic reactions, including life-threatening or fatal reactions. In clinical trials, anaphylactoid and/or anaphylactic reactions occurred in two of 1676 subjects. Common adverse reactions in 802 subjects receiving Ablavar at 0.03 mmol/kg are pruritis headache, nausea, vasodilatation, paresthesia injection site bruising, dysgeusia, burning sensation, venipuncture site bruise, hypertension, dizziness (excluding vertigo), feeling cold. ANIMAL STUDIES: Developmental or Reproductive Toxicity/ In reproductive studies, pregnant rats and rabbits received gadofosveset trisodium at various doses up to approximately 11 (rats) and 21.5 (rabbits) times the human dose (based on body surface area). The highest dose resulted in maternal toxicity in both species. In rabbits that received gadofosveset trisodium at 3 times the human dose (based on body surface area), increased post-implantation loss, resorptions, and dead fetuses were observed. Fetal anomalies were not observed in the rat or rabbit offspring. Because pregnant animals received repeated daily doses of ABLAVAR, their overall exposure was significantly higher than that achieved with a single dose administered to humans.

Following intravenous injection, gadofosveset binds reversibly to endogenous serum albumin resulting in longer vascular residence time than non-protein binding contrast agents. The binding to serum albumin also increases the magnetic resonance relaxivity of gadofosveset and decreases the relaxation time (T1) of water protons resulting in an increase in signal intensity (brightness) of blood.

In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following Ablavar administration; no increase was observed at 24 and 72 hours. A QTc change of 30 to 60 msec from baseline was observed in 39/702 (6%) patients at 45 min following Ablavar administration. At this time point, 3/702 (0.4%) patients experienced a QTc increase of > 60 msec. These QTc prolongations were not associated with arrhythmias or symptoms. In patients at high risk for arrhythmias due to QTc prolongation (e.g., concomitant medications, underlying cardiac conditions) consider obtaining baseline electrocardiograms to help assess the risks for Ablavar administration. If Ablavar is administered to these patients, consider follow-up electrocardiograms and risk reduction measures (e.g., patient counseling or intensive electrocardiography monitoring) until most Ablavar has been eliminated from the blood. In patients with normal renal function, most Ablavar was eliminated from the blood by 72 hours following injection.|Ablavar may cause anaphylactoid and/or anaphylactic reactions, including life-threatening or fatal reactions. In clinical trials, anaphylactoid and/or anaphylactic reactions occurred in two of 1676 subjects. If anaphylactic or anaphylactoid reactions occur, stop ABLAVAR Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after ablavar administration. Have trained personnel and emergency resuscitative equipment available prior to and during ablavar administration. If such a reaction occurs stop ablavar and immediately begin appropriate therapy.|In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred with the use of other gadolinium agents. The risk of renal failure may increase with increasing dose of gadolinium contrast. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. Consider follow-up renal function assessments for patients with a history of renal dysfunction. No reports of acute renal failure were observed in clinical trials of ABLAVAR.

In animal studies, less than 1% of gadofosveset at doses up to 0.3 mmol/kg was secreted in the milk of lactating rats.

This medicinal product is for diagnostic use only.Ablavar is indicated for contrast-enhanced magnetic resonance angiography (CE-MRA) for visualisation of abdominal or limb vessels in adults only, with suspected or known vascular disease.

Ablavar 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.

/BOXED WARNING/ WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF) Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted 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 (GFR < 30 mL/min/1.73m sq), or acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. For patients at highest risk for NSF, do not exceed the recommended ABLAVAR dose and allow a sufficient period of time for elimination of the drug from the body prior to re-administration.|In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred with the use of other gadolinium agents. The risk of renal failure may increase with increasing dose of gadolinium contrast. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. Consider follow-up renal function assessments for patients with a history of renal dysfunction. No reports of acute renal failure were observed in clinical trials of ABLAVAR.|In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following Ablavar administration; no increase was observed at 24 and 72 hours. A QTc change of 30 to 60 msec from baseline was observed in 39/702 (6%) patients at 45 min following Ablavar administration. At this time point, 3/702 (0.4%) patients experienced a QTc increase of > 60 msec. These QTc prolongations were not associated with arrhythmias or symptoms. In patients at high risk for arrhythmias due to QTc prolongation (e.g., concomitant medications, underlying cardiac conditions) consider obtaining baseline electrocardiograms to help assess the risks for Ablavar administration. If Ablavar is administered to these patients, consider follow-up electrocardiograms and risk reduction measures (e.g., patient counseling or intensive electrocardiography monitoring) until most Ablavar has been eliminated from the blood. In patients with normal renal function, most Ablavar was eliminated from the blood by 72 hours following injection.|Ablavar may cause anaphylactoid and/or anaphylactic reactions, including life-threatening or fatal reactions. In clinical trials, anaphylactoid and/or anaphylactic reactions occurred in two of 1676 subjects. If anaphylactic or anaphylactoid reactions occur, stop ABLAVAR Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after ablavar administration. Have trained personnel and emergency resuscitative equipment available prior to and during ablavar administration. If such a reaction occurs stop ablavar and immediately begin appropriate therapy.|For more Drug Warnings (Complete) data for Gadofosveset trisodium (9 total), please visit the HSDB record page.

Substances used to allow enhanced visualization of tissues. (See all compounds classified as Contrast Media.)

Gadofosveset is eliminated primarily in the urine, with between 79% and 94% (mean of 83.7%) of an injected dose recovered in the urine. Of the total gadofosveset recovered in urine, 94% is recovered within the first 72 hours. A small portion of gadofosveset dose is recovered in feces (approximately 4.7%).|The mean volume of distribution at steady state for gadofosveset was 148 +/- 16 mL/kg, roughly equivalent to that of extracellular fluid. A significant portion of circulating gadofosveset is bound to plasma proteins, predominantly albumin. At 0.05, 0.5, 1 and 4 hours after injection of 0.03 mmol/kg the plasma protein binding of gadofosveset ranges from 79.8 to 87.4%.|The pharmacokinetics of intravenously administered gadofosveset conforms to a two-compartment open model with mean plasma concentrations (reported as mean +/-SD) of 0.43 +/- 0.04 mmol/L at 3 minutes post-injection, and 0.24 +/- 0.03 mmol/L at one hour post-injection. The mean half-life of the distribution phase is 0.48 +/- 0.11 hours and the mean half-life of the elimination phase is 16.3 +/- 2.6 hours. The mean total clearance of gadofosveset is 6.57 +/- 0.97 mL/h/kg following the administration of 0.03 mmol/kg.|In animal studies, less than 1% of gadofosveset at doses up to 0.3 mmol/kg was secreted in the milk of lactating rats.

Gadofosveset does not undergo measurable metabolism in humans.

The mean half-life of the distribution phase is 0.48 +/- 0.11 hours and the mean half-life of the elimination phase is 16.3 +/- 2.6 hours.

ABLAVAR Injection has been administered to humans up to a dose of 0.15 mmol/kg (5 times the clinical dose). No ABLAVAR overdoses were reported in clinical trials. In the event of an overdose, direct treatment toward the support of all vital functions and prompt institution of symptomatic therapy. Gadofosveset has been shown to be removed by hemodialysis using a high flux dialysis procedure.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following Ablavar administration; no increase was observed at 24 and 72 hours. A QTc change of 30 to 60 msec from baseline was observed in 39/702 (6%) patients at 45 min following Ablavar administration. At this time point, 3/702 (0.4%) patients experienced a QTc increase of > 60 msec. These QTc prolongations were not associated with arrhythmias or symptoms. In patients at high risk for arrhythmias due to QTc prolongation (e.g., concomitant medications, underlying cardiac conditions) consider obtaining baseline electrocardiograms to help assess the risks for Ablavar administration. If Ablavar is administered to these patients, consider follow-up electrocardiograms and risk reduction measures (e.g., patient counseling or intensive electrocardiography monitoring) until most Ablavar has been eliminated from the blood. In patients with normal renal function, most Ablavar was eliminated from the blood by 72 hours following injection.|/SIGNS AND SYMPTOMS/ Ablavar may cause anaphylactoid and/or anaphylactic reactions, including life-threatening or fatal reactions. In clinical trials, anaphylactoid and/or anaphylactic reactions occurred in two of 1676 subjects. If anaphylactic or anaphylactoid reactions occur, stop ABLAVAR Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after ablavar administration. Have trained personnel and emergency resuscitative equipment available prior to and during ablavar administration. If such a reaction occurs stop ablavar and immediately begin appropriate therapy.|/SIGNS AND SYMPTOMS/ Common adverse reactions in 802 subjects receiving Ablavar at 0.03 mmol/kg are pruritis headache, nausea, vasodilatation, paresthesia injection site bruising, dysgeusia, burning sensation, venipuncture site bruise, hypertension, dizziness (excluding vertigo), feeling cold. /from table/|/EPIDEMIOLOGY STUDIES/ The institutional review board approved this retrospective study in which data in the electronic incident reporting system were searched. A total of 194, 400 intravenous administrations of linear ionic GBCAs were assessed for the incidence of adverse reactions and risk factors from 1 January 2007 to 14 January 2014. The severity of reactions (mild, moderate, and severe), patient type (outpatients, inpatients, and emergency), examination type, and treatment options were also investigated. RESULTS: In total, 204/194400 (0.1%) patients (mean age 45.7 +/- 14.9) showed adverse reactions, consisting of 6/746 (0.80%), 10/3200 (0.31%), 14/6236 (0.22%) and 174/184218 (0.09%), for gadofosveset trisodium, gadoxetate disodium, gadobenate dimeglumine, and gadopentetate dimeglumine, respectively. An overall significant difference was found between different GBCAs regarding the total number of reactions (p < 0.0001). When comparing the GBCAs together, significant differences were found between gadofosveset trisodium versus gadopentetate dimeglumine (p < 0.0001), gadofosveset trisodium versus gadobenate dimeglumine (p = 0.0051), gadoxetate disodium versus gadopentetate dimeglumine (p < 0.0001) and gadopentetate dimeglumine versus gadobenate dimeglumine (p = 0.0013). Rate of reaction was higher in females (F: 146/113187, 0.13%/M: 58/81213, 0.07%; p < 0.0001). Rate of reactions was higher in outpatient (180/158885, 0.11%), emergency (10/10413, 0.10%), and inpatients (14/25102, 0.05%), respectively (p < 0.0001). Most of the patients had mild symptoms 171/204 (83.8%). Abdomen-pelvis, liver, and thoracic examinations had highest rates of reactions (0.17 versus 0.16 versus 0.15). CONCLUSION: The overall rate of adverse reaction to GBCAs was 0.1%. The rates of reactions were highest in gadofosveset trisodium with (0.80%), followed by gadoxetate disodium (0.31%), gadobenate dimeglumine (0.22%) and gadopentetate dimeglumine (0.09%).

gadofosveset

Ablavar is a sterile solution for intravenous injection containing 244 mg/mL (0.25 mmol/mL) gadofosveset trisodium.

Human drugs -> Ablavar (previously Vasovist) -> EMA Drug Category|Contrast media -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients