Gadobutrol

1 mmol/kg). Refer to Table 1 to determine the volume to be administered. 2 Administration Guidelines • Gadobutrol injection is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium based contrast agents, resulting in a lower volume of administration.

Use Table 1 to determine the volume to be administered. • Use sterile technique when preparing and administering gadobutrol injection. MRI of the Central Nervous System • Administer gadobutrol injection as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second.

• Follow gadobutrol injection with a normal saline flush to ensure complete administration of the contrast. • Post contrast MRI can commence immediately following contrast administration. MRI of the Breast • Administer gadobutrol injection as an intravenous bolus by power injector, followed by a normal saline flush to ensure complete administration of the contrast.

• Start image acquisition following contrast administration and then repeat sequentially to determine peak intensity and wash-out. MR Angiography Image acquisition should coincide with peak arterial concentration, which varies among patients.

5 mL/second, followed by a 30 mL normal saline flush at the same rate to ensure complete administration of the contrast. Pediatric patients • Administer gadobutrol injection by power injector or manually, followed by a normal saline flush to ensure complete administration of the contrast.

Cardiac MRI • Administer gadobutrol injection through a separate intravenous line in the contralateral arm if concomitantly providing a continuous infusion of a pharmacologic stress agent. 05 mmol/kg) body weight at rest. • Administer gadobutrol injection via a power injector at a flow rate of approximately 4 mL/second and follow each injection with a normal saline flush of 20 mL at the same flow rate.

3 Drug Handling • Visually inspect gadobutrol injection for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged.

• Do not mix gadobutrol injection with other medications and do not administer gadobutrol injection in the same intravenous line simultaneously with other medications because of the potential for chemical incompatibility. Vials • Draw gadobutrol injection into the syringe immediately before use.

2 )] . 3 )] . 4 )] . 5 )] . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The adverse reactions described in this section reflect gadobutrol injection exposure in 7,713 subjects (including 184 pediatric patients, ages 0 to 17 years) with the majority receiving the recommended dose. 5% patients of other ethnic groups.

The average age was 56 years (range from 1 week to 93 years). Overall, approximately 4% of subjects reported one or more adverse reactions during a follow-up period that ranged from 24 hours to 7 days after gadobutrol injection administration.

Adverse reactions associated with the use of gadobutrol injection were usually mild to moderate in severity and transient in nature. 1% subjects who received gadobutrol injection. 1% in subjects who received gadobutrol injection include: hypersensitivity/anaphylactic reaction, loss of consciousness, convulsion, parosmia, tachycardia, palpitation, dry mouth, malaise and feeling cold.

2 Postmarketing Experience The following additional adverse reactions have been identified during postmarketing use of gadobutrol injection or other GBCAs. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Cardiac arrest • Nephrogenic Systemic Fibrosis (NSF) • Hypersensitivity reactions (anaphylactic shock, circulatory collapse, respiratory arrest, bronchospasm, cyanosis, oropharyngeal swelling, laryngeal edema, blood pressure increased, chest pain, angioedema, conjunctivitis, hyperhidrosis, cough, sneezing, burning sensation, and pallor) • Respiratory, Thoracic, and Mediastinal Disorders: Acute respiratory distress syndrome, pulmonary edema • General Disorders and Administration Site Conditions: Adverse reactions with variable onset and duration have been reported after GBCA administration These include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems .

5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions: Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have occurred. Monitor patients closely during and after administration of gadobutrol injection.

3 ) • Acute Respiratory Distress Syndrome: For Patients demonstrating respiratory distress after administration, assess oxygen requirement and monitor for worsening respiratory function. 4 ) • Gadolinium Retention: Gadolinium is retained for months or years in brain, bone, and other organs.

1 Risk Associated with Intrathecal Use Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of Gadobutrol injection have not been established with intrathecal use.

2 )] . 2 Nephrogenic Systemic Fibrosis GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of gadobutrol injection among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.

73m 2 ) as well as patients with acute kidney injury. 73m 2 ). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. 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.

4 CONTRAINDICATIONS Gadobutrol injection is contraindicated in patients with history of severe hypersensitivity reactions to gadobutrol injection. History of severe hypersensitivity reaction to gadobutrol injection ( 4 )