Vasovist (Page 2 of 4)

5.2 Hypersensitivity Reactions

VASOVIST 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 VASOVIST 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 VASOVIST administration. Have emergency resuscitative equipment available prior to and during VASOVIST administration.

5.3 Acute Renal Failure

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 VASOVIST [see Clinical Pharmacology (12.3) ].

5.4 QTc Prolongation and Risk for Arrhythmias

In clinical trials, a small increase (2.8 msec) in the average change from baseline in QTc was observed at 45 minutes following VASOVIST 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 VASOVIST 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 VASOVIST administration. If VASOVIST is administered to these patients, consider follow-up electrocardiograms and risk reduction measures (e.g., patient counseling or intensive electrocardiography monitoring) until most VASOVIST has been eliminated from the blood. In patients with normal renal function, most VASOVIST was eliminated from the blood by 72 hours following injection [see Clinical Pharmacology (12.3) ].

6 ADVERSE REACTIONS

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

6.1 Clinical Studies Experience

Anaphylaxis and anaphylactoid reactions were the most common serious reactions observed following VASOVIST injection administration [see Warnings and Precautions (5.2) ].

In all clinical trials evaluating VASOVIST with MRA, a total of 1,676 (1379 patients and 297 healthy subjects) were exposed to various doses VASOVIST. The mean age of the 1379 patients who received VASOVIST was 63 years (range 18 to 91 years); 66% (903) were men and 34% (476) were women. In this population, there were 80% (1100) Caucasian, 8% (107) Black, 12% (159) Hispanic, 1% (7) Asian, and < 1% (6) patients of other racial or ethnic groups. Table 2 shows the most common adverse reactions (≥1%) experienced by subjects receiving VASOVIST at a dose of 0.03 mmol/kg.

Table 2 Common Adverse Reactions in 802 Subjects Receiving VASOVIST at 0.03 mmol/kg
Preferred Term n (%)
Pruritis 42 (5)
Headache 33 (4)
Nausea 33 (4)
Vasodilatation 26 (3)
Paresthesia 25 (3)
Injection site bruising 19 (2)
Dysgeusia 18 (2)
Burning sensation 17 (2)
Venipuncture site bruise 17 (2)
Hypertension 11 (1)
Dizziness (excluding vertigo) 8 (1)
Feeling cold 7 (1)

6.2 Post-marketing Experience

Because post-marketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The profile of adverse reactions identified during the post-marketing experience outside the United States was similar to that observed during the clinical studies experience.

7 DRUG INTERACTIONS

Following injection, VASOVIST binds to blood albumin and has the potential to alter the binding of other drugs that also bind to albumin. No drug interaction reactions were observed in clinical trials. Consider the possibility of VASOVIST interaction with concomitantly administered medications that bind to albumin. An interaction may enhance or decrease the activity of the concomitant medication [see Clinical Pharmacology (12.3) ].

7.1 Warfarin

In a clinical trial of 10 patients receiving a stable dose of warfarin, a single dose of VASOVIST (0.05 mmol/kg) did not alter the anticoagulant activity of warfarin as measured by the International Normalized Ratio (INR).

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of VASOVIST in pregnant women. In animal studies, pregnant rabbits treated with gadofosveset trisodium at doses 3 times the human dose (based on body surface area) experienced higher rates of fetal loss and resorptions. Because animal reproduction studies are not always predictive of human response, only use VASOVIST during pregnancy if the diagnostic benefit justifies the potential risks to the fetus.

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 VASOVIST, their overall exposure was significantly higher than that achieved with a single dose administered to humans.

8.3 Nursing Mothers

It is not known whether gadofosveset is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when VASOVIST is administered to a woman who is breastfeeding. The risks associated with exposure of infants to gadolinium-based contrast agents in breast milk are unknown. Limited case reports indicate that 0.01 to 0.04% of the maternal gadolinium dose is excreted in human breast milk. Studies of other gadolinium products have shown limited gastrointestinal absorption. These studies were conducted with gadolinium products with shorter half-lives than VASOVIST. Avoid VASOVIST administration to women who are breastfeeding unless the diagnostic information is essential and not obtainable with non-contrast MRA.

Less than 1% of gadofosveset at doses up to 0.3 mmol/kg was secreted in the milk of lactating rats.

8.4 Pediatric Use

The safety and effectiveness of VASOVIST in patients under 18 years of age have not been established. The risks associated with VASOVIST administration to pediatric patients are unknown and insufficient data are available to establish a dose. Because VASOVIST is eliminated predominantly by the kidneys, pediatric patients with immature renal function may be at particular risk for adverse reactions.

8.5 Geriatric Use

In clinical trials, no overall differences in safety and efficacy were observed between subjects 65 years and older and younger subjects. Whereas current clinical experience has not identified differences in responses between elderly and younger patients, greater susceptibility to adverse experiences of some older individuals cannot be ruled out.

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