Gadavist

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Nephrogenic Systemic Fibrosis

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m2) as well as patients with acute kidney injury. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30-59 mL/min/1.73m2) and little, if any, for patients with chronic, mild kidney disease (GFR 60-89 mL/min/1.73m2). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following Gadavist (gadobutrol) administration to Bayer Healthcare (1-888-842-2937) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).

Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronically reduced renal function (for example, age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing.

Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. For patients at highest risk for NSF, do not exceed the recommended Gadavist (gadobutrol) dose and allow a sufficient period of time for elimination of the drug prior to re-administration. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA in order to enhance the contrast agent's elimination. The usefulness of hemodialysis in the prevention of NSF is unknown [see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION].

Hypersensitivity Reactions

Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist administration [see ADVERSE REACTIONS].

  • Before Gadavist (gadobutrol) administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to Gadavist (gadobutrol) .
  • Administer Gadavist (gadobutrol) only in situations where trained personnel and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in resuscitation.

Most hypersensitivity reactions to Gadavist (gadobutrol) have occurred within half an hour after administration. Delayed reactions can occur up to several days after administration. Observe patients for signs and symptoms of hypersensitivity reactions during and following Gadavist (gadobutrol) administration.

Extravasation and Injection Site Reactions

Ensure catheter and venous patency before the injection of Gadavist (gadobutrol) . Extravasation into tissues during Gadavist (gadobutrol) administration may result in moderate irritation. Avoid intramuscular administration of Gadavist (gadobutrol) [see Nonclinical Toxicology].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity studies of gadobutrol have been conducted.

Gadobutrol was not mutagenic in in vitro reverse mutation tests in bacteria, in the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) test using cultured Chinese hamster V79 cells, or in chromosome aberration tests in human peripheral blood lymphocytes, and was negative in an micronucleus test in mice after intravenous injection of 0.5 mmol/kg.

Gadobutrol had no effect on fertility and general reproductive performance of male and female rats when given in doses 12.2 times the human equivalent dose (based on body surface area).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of Gadavist (gadobutrol) in pregnant women. While it is unknown if Gadavist (gadobutrol) crosses the human placenta, other gadolinium-based contrast agents (GBCAs) do cross the placenta in humans and result in fetal exposure. Limited published human data on exposure to other GBCAs during pregnancy did not show adverse effects in exposed neonates. Gadavist (gadobutrol) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Retardation of the embryonal development and embryolethality occurred in pregnant rats receiving maternally toxic doses of Gadavist (gadobutrol) ( ≥ 7.5 mmol/kg body weight) that were 12 times the human equivalent dose based on body surface area and in pregnant rabbits receiving doses ( ≥ 2.5 mmol/kg body weight) that were 8 times the recommended human dose (based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses).

Gadavist (gadobutrol) was not teratogenic when given intravenously to monkeys during organogenesis at doses up to 8 times the recommended single human dose (based on body surface area) but was embryolethal at that dose. Because pregnant animals received repeated daily doses of Gadavist (gadobutrol) , their overall exposure was significantly higher than that achieved with the standard single dose administered to humans.

Nursing Mothers

It is not known whether gadobutrol is excreted in human milk. Limited case reports on use of GBCAs in nursing mothers indicate that 0.01 to 0.04% of the maternal gadolinium dose is excreted in human breast milk. Studies have shown limited GBCA gastrointestinal absorption. Nonclinical data show that gadobutrol is excreted into breast milk in very small amounts ( < 0.1% of the dose intravenously administered) and the absorption via the gastrointestinal tract is poor (approximately 5% of the dose orally administered was excreted in the urine) [see CLINICAL PHARMACOLOGY]. In lactating rats given 0.5 mmol/kg of intravenous [153Gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the neonate via maternal milk, mostly within 3 hours after the intravenous administration. Because many drugs are excreted in human milk, exercise caution when gadobutrol is administered to a nursing woman.

Pediatric Use

The pharmacokinetics, safety and efficacy of Gadavist (gadobutrol) at a single dose of 0.1 mmol/kg have been established in children 2 to 17 years of age. No dose adjustment according to age is necessary in this population. The safety and effectiveness of Gadavist (gadobutrol) have not been established in children below two years of age. [See DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY.]

Geriatric Use

In clinical studies of Gadavist (gadobutrol) , 1377 patients were 65 years of age and over, while 104 patients were 80 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, use of Gadavist (gadobutrol) in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. No dose adjustment according to age is necessary in this population.

Renal Impairment

Prior to administration of Gadavist (gadobutrol) , screen all patients for renal dysfunction by obtaining a history and/or laboratory tests [see WARNINGS AND PRECAUTIONS]. No dosage adjustment is recommended for patients with renal impairment.

Gadavist (gadobutrol) can be removed from the body by hemodialysis [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 5/5/2011
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.


NIH talks about Ebola on WebMD