USA

DOTAREM® (gadoterate meglumine) Injection

       

IMPORTANT SAFETY INFORMATION

The possibility of serious or life-threatening anaphylactoid/anaphylactic reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, should be considered. Monitor patients closely for need of emergency cardiorespiratory support.  In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. 

Please consult full Prescribing Information for DOTAREM® including boxed WARNING contained within this website.

To report SUSPECTED ADVERSE REACTIONS, contact GUERBET LLC at 1-877-729-6679 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

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PHYSICAL CHARACTERISTICS

(Please see Prescribing Information)

Osmolality
mOsm/kg H2O

Viscosity
mPa*s at 20°C

Viscosity
mPa*s at 37°C

Thermodynamic Stability
Log Ktherm*

Thermodynamic Stability
Log Kcond† at pH 7.4

Kinetic
Stability
(Dissociation Half-life)
T1/2 at pH 1.0 at 25°C

Dotarem®

1350

3.4

2.4

25.6

19.3

> 338 h

* Log Ktherm = absolute thermodynamic stability constant
† Log Kcond = conditional thermodynamic stability constant depending on pH

INDICATIONS

DOTAREM is a gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (2 years of age and older) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or anormal vascularity.

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PACKAGING


Dotarem  (gadoterate meglumine) Injection, 0.5 mmol/mL 

10 mL vials in a shrink wrapped package of 10 (NDC 67684-2000-1)

15 mL vials in a shrink wrapped package of 10 (NDC 67684-2000-2)

20 mL vials in a shrink wrapped package of 10 (NDC 67684-2000-3)

100 mL vials in a shrink wrapped package of 6 (NDC 67684-2000-4)

10 mL pre-filled syringe in a shrink wrapped package of 5 (NDC 67684-2000-5)

15 mL pre-filled syringe in a shrink wrapped package of 5 (NDC 67684-2000-6)

20 mL pre-filled syringe in a shrink wrapped package of 5 (NDC 67684-2000-7)

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Pharmacy Bulk Package: NOT FOR DIRECT INFUSION

PRESCRIBING INFORMATION

Dotarem Injection 0.5 mmol/mL contains 376.9 mg/mL of gadoterate meglumine, and is available in vials, pre-filled syringes, and a Pharmacy Bulk Package. Please see Prescribing Information

DOTAREM Prescribing Information

For additional product related questions, please contact a Medical Liaison.

DOSAGE AND ADMINISTRATION

Adult and pediatric patients: The recommended dose of DOTAREM is 0.2 mL/kg (0.1 mmol/kg) body weight administered as an intravenous bolus injection at a flow rate of approximately 2 mL/second for adults and 1-2 mL/second for pediatric patients. The dose is delivered by manual or power injection.

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CONTRAINDICATIONS

History of clinically important hypersensitivity reactions to DOTAREM [see Warnings and Precautions].

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WARNINGS

Nephrogenic Systemic Fibrosis

                                               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/1.73m2), 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 (for example, age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing (5.1).
  • For patients at highest risk for NSF, do not exceed the recommended DOTAREM dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration [see Warnings and Precautions (5.1)].--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

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 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 DOTAREM administration to Guerbet LLC (1-877-729-6679) 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 (e.g., 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 the 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 DOTAREM 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.

Hypersensitivity Reactions

Anaphylactic and anaphylactoid reactions have been reported with DOTAREM, involving cardiovascular, respiratory, and/or cutaneous manifestations. Some patients experienced circulatory collapse and died. In most cases, initial symptoms occurred within minutes of DOTAREM administration and resolved with prompt emergency treatment.

Before DOTAREM 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 DOTAREM. 

Administer DOTAREM only in situations where trained personnel and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in resuscitation. 

During and following DOTAREM administration, observe patients for signs and symptoms of hypersensitivity reactions.

Acute Kidney Injury

In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging. Screen all patients for renal impairment by obtaining a history and/or laboratory tests. Consider follow-up renal function assessments for patients with a history of renal dysfunction.

Extravasation and Injection Site Reactions

Ensure catheter and venous patency before the injection of DOTAREM. Extravasation into tissues during DOTAREM administration may result in tissue irritation.

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ADVERSE REACTIONS

The most frequent (≥ 0.2%) adverse reactions in clinical studies were nausea, headache, injection site pain, injection site coldness, and burning sensation.

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ORDERING INFORMATION

For U.S. customers only. To request a sample or to order products please contact an Imaging Sales Specialist. Please contact Guerbet's Corporate office or an appropriate subsidiary if you are located outside the U.S.

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REIMBURSEMENT INFORMATION

For U.S. Reimbursement Information, please see attached information for Hospital Outpatient settings and Freestanding/Independent Diagnostic Testing Facility (IDTF) settings.

For further assistance, please contact DOTAREM Reimbursement Support at 1-855-368-2736, Monday–Friday, 7 am–7 pm ET.

DOTAREM® is a registered trademark of Guerbet LLC, and is available by prescription only.

Legal Copyright 2014 Guerbet