Data from FDA - Curated by Toby Galbraith - Last updated 21 February 2017

Indication(s)

1 INDICATIONS AND USAGE 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 [see Clinical Studies (14)].

ABLAVAR Injection is a gadolinium-based contrast agent 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.

(1)

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Advisory information

contraindications
4 CONTRAINDICATIONS History of a prior allergic reaction to a gadolinium-based contrast agent. History of a prior allergic reaction to a gadolinium-based contrast agent (4).
Adverse reactions

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Nephrogenic systemic fibrosis [see Warnings and Precautions (5.1)] Hypersensitivity reactions [see Warnings and Precautions (5.2)] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug can not be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The most common (>2 %) adverse reactions are pruritis, headache, nausea, vasodilatation, and paresthesia (6.1, 6.2) To report SUSPECTED ADVERSE REACTIONS, contact Lantheus Medical Imaging, Inc. at 1-978-667-9531/1-800-362-2668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Anaphylaxis and anaphylactoid reactions were the most common serious reactions observed following ABLAVAR injection administration [see Warnings and

Precautions (5.2)].

In all clinical trials evaluating ABLAVAR with MRA, a total of 1,676 (1379 patients and 297 healthy subjects) were exposed to various doses ABLAVAR.

The mean age of the 1379 patients who received ABLAVAR 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 ABLAVAR at a dose of 0.03 mmol/ kg.

Table 2 Common Adverse Reactions in 802 Subjects Receiving Ablavar 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.

Usage information

Dosing and administration

2 DOSAGE AND ADMINISTRATION Administer ABLAVAR Injection by an intravenous bolus, manually or by power injection, at a dose of 0.12 mL/kg body weight (0.03 mmol/ kg) over a period of time up to 30 seconds followed by a 25-30 mL normal saline flush.

(2.1) Imaging is performed in two stages, the dynamic stage which begins immediately following ABLAVAR Injection and the steady-state stage, which begins following dynamic imaging; generally 5 to 7 minutes after ABLAVAR Injection.

(2.2) 2.1 Dosing Guidelines Administer ABLAVAR as an intravenous bolus injection, manually or by power injection, at a dose of 0.12 mL/kg body weight (0.03 mmol/ kg) over a period of time up to 30 seconds followed by a 25-30 mL normal saline flush.

(See Table 1 for weight-adjusted dose volumes).

TABLE 1.

Weight-Adjusted Volumes for the 0.03 mmol/ kg Dose Body Weight Volume Kilograms (kg) Pounds (lb) Milliliters (mL) 40 88 4.8 50 110 6.0 60 132 7.2 70 154 8.4 80 176 9.6 90 198 10.8 100 220 12.0 110 242 13.2 120 264

14.4 130 286 15.6 140 308 16.8 150 330 18.0 160 352 19.2 Inspect the ABLAVAR vial visually for particulate matter and discoloration prior to administration.

Do not use the solution if it is discolored or particulate matter is present.

ABLAVAR is intended for single use only and should be used immediately upon opening.

Discard any unused portion of the ABLAVAR vial.

Do not mix intravenous medications or parenteral nutrition solutions with ABLAVAR. Do not administer any other medications in the same intravenous line simultaneously with ABLAVAR. 2.2 Imaging Guidelines ABLAVAR imaging is completed in two stages: the dynamic imaging stage and the steady-state imaging stage.

Both stages are essential for adequate evaluation of the arterial system, and dynamic imaging always precedes steady-state imaging.

During interpretation of the steady-state images, ABLAVAR within the venous system may limit or confound the detection of arterial lesions.

To assess the initial distribution of

ABLAVAR

within the arterial system, begin dynamic imaging immediately upon injection.

Begin steady state imaging after dynamic imaging has been completed, generally 5 to 7 minutes following ABLAVAR administration.

At this time point, ABLAVAR is generally distributed throughout the blood.

In clinical trials, steady-state imaging was completed within approximately one hour following ABLAVAR injection.

Use in special populations

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. There are no adequate and well-controlled studies of ABLAVAR 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 ABLAVAR 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 ABLAVAR, 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 ABLAVAR 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 ABLAVAR. Avoid ABLAVAR administration to women who are breastfeeding unless the diagnostic information is essential and not obtainable with non-contrast MRA.

In animal studies, 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 ABLAVAR in patients under 18 years of age have not been established.

The risks associated with ABLAVAR administration to pediatric patients are unknown and insufficient data are available to establish a dose.

Because ABLAVAR 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 can not be ruled out.

Pregnancy and lactation

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 ABLAVAR 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 ABLAVAR. Avoid ABLAVAR administration to women who are breastfeeding unless the diagnostic information is essential and not obtainable with non-contrast MRA.

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

Interactions

7 DRUG INTERACTIONS Following injection, ABLAVAR 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 ABLAVAR 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 ABLAVAR (0.05 mmol/ kg) did not alter the anticoagulant activity of warfarin as measured by the International Normalized Ratio (INR).

More information

Category Value
Authorisation number NDA021711
Orphan designation No
Product NDC 11994-012
Date Last Revised 11-03-2015
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder Lantheus Medical Imaging, Inc.
Warnings

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/1.73 m2), 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 [see Warnings and Precautions (5.1)].

WARNING:

NEPHROGENIC SYSTEMIC FIBROSIS (NSF) See full prescribing information for complete boxed warning.

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.

The risk for NSF appears highest among patients with: chronic, severe kidney disease (GFR < 30 mL/min/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 for chronically reduced renal function (e.g. age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing (5.1)

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