Dotarem’s Unmatched Legacy

Guerbet’s research team designed Dotarem® (gadoterate meglumine) with a unique profile, providing the highest molecular stability to minimize the risk of gadolinium release.1

  • The first macrocyclic & ionic GBCA molecule sold in the US2
  • Patented manufacturing process3
  • More than 100 million global doses administered with zero unconfounded cases of NSF2,4,5
  • Following repeated administrations, no visible T1 signal intensity detected on non-contrast images within the brain6-10

For more information about Dotarem, please see the Full Prescribing Information and Medication Guide (also available: Spanish Version Medication Guide); Dear Health Care Provider Letter-Gadolinium Retention Letter

Physical Characteristics2

  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 Stability11 (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

Packaging

DOTAREM® Vials2

DOTAREM Prefilled Syringes2

DOTAREM Pharmacy Bulk Package Vials2

Unit of Sale

5 mL, 10 mL, 15 mL or 20 mL available in glass vials

10mL, 15 mL, or 20 mL solution available in prefilled syringes

Pharmacy Bulk Package is supplied in 100 mL 

Unit/Carton

Vials are packaged in a box of 10.

Syringes, including plunger rod, are packaged in a box of 10.

Pharmacy Bulk Package is individually packaged in a box of 6.

Wholesale Minimum Order

1 box of 10 Vials

1 box of 10 Prefilled Syringes

1 box of 6 Vials

Storage

Store at 25°C (77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see United States Pharmacopeia (USP), Controlled Room Temperature (CRT)].

Store at 25°C (77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see United StatesPharmacopeia (USP), Controlled Room Temperature (CRT)]. Prefilled syringes must not be frozen. Frozen syringes should be discarded.

Store at 25°C (77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP, Controlled Room Temperature (CRT)].

Dotarem (gadoterate meglumine) Injection, 0.5 mmol/mL

  • 5 mL in glass vials in case of 10 (NDC 67684-2001-0)
  • 10 mL in glass vials in case of 10 (NDC 67684-2001-1)
  • 15 mL in glass vials in case of 10 (NDC 67684-2001-2)
  • 20 mL in glass vials case of 10 (NDC 67684-2001-3)
  • 100 mL in glass vials in a case of 6 (NDC 67684-2001-4)
  • 10 mL in pre-filled syringe in a case of 10 (NDC 67684-3001-1)
  • 15 mL in pre-filled syringe in a case of 10 (NDC 67684-3001-2)
  • 20 mL in pre-filled syringe in a case of 10 (NDC 67684-3001-3)

Pharmacy Bulk Package: NOT FOR DIRECT INFUSION

Clinical Case Studies

as seen in Applied Radiology

D3guerbet 02 21 Neuro Figure01a

Neurological and Orbital Involvement of Systemic IgG4-related Sclerosing Disease

DOWNLOAD
D3guerbet 01 21 Figure01b

Atypical Teratoid Rhabdoid Tumor of the Oculomotor Nerve

DOWNLOAD

References

1. Frenzel, T., Lengsfeld, P., Schirmer, H., Hütter, J. and Weinmann, H., 2008. Stability of Gadolinium-Based Magnetic Resonance Imaging Contrast Agents in Human Serum at 37°C. Investigative Radiology, 43(12), pp.817-828.  
2. Dotarem [package insert]. Princeton, NJ: Guerbet LLC; January 2024.
3. Guerbet, Villepinte(FR).Process for preparing a pharmaceutical formulation of Contrast Agents. US 9,655,983 B2, 2017.  
4. Baraghini S. Number of doses Dota. 2019. 
5. deKervilerE, Maravilla K, Meder J, Naggara O, Dubourdieu C, Jullien V et al. Adverse Reactions to Gadoterate Meglumine. Investigative Radiology. 2016;51(9):544-551. 
6. RadbruchA, WeberlingL, Kieslich P, Eidel O, Burth S, Kickingereder P et al. Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent. Radiology. 2015;275(3):783-791. 
7. Radbruch A, WeberlingL, KieslichP, Hepp J, Kickingereder P, Wick W et al. Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents. Investigative Radiology. 2016;51(11):683-690. 
8. Eisele P, Alonso A, Szabo K, Ebert A, Ong M, Schoenberg S et al. Lack ofincreased signal intensity in the dentate nucleus after repeated administration of a macrocyclic contrast agent in multiple sclerosis. Medicine. 2016;95(39):e4624.
9. Radbruch A, HaaseR, KieslichP, Weberling L, Kickingereder P, Wick W et al. No Signal Intensity Increase in the Dentate Nucleus on Unenhanced T1-weighted MR Images after More than 20 Serial Injections of Macrocyclic Gadolinium-based Contrast Agents. Radiology. 2017;282(3):699-707. 
10. Tibussek D, Rademacher C, CaspersJ, TurowskiB, Schaper J, Antoch G et al. Gadolinium Brain Deposition after Macrocyclic Gadolinium Administration: A Pediatric Case-Control Study. Radiology. 2017;285(1):223-230. 
11. Hao D, Ai T, Goerner F, Hu X, Runge V, TweedleM. MRI contrast agents: Basic chemistry and safety. Journal of Magnetic Resonance Imaging. 2012;36(5):1060-1071.

*Dotarem was launched globally in 1989 and approved by the FDA for use in the US in 2013.

** Reimbursement information provided is for illustrative purposes only and does not constitute legal advice. Information provided is gathered from third party sources and is subject to change without notice due to frequently changing laws, rules and regulations. Guerbet makes no guarantee that the use of this information will prevent differences of opinion or disputes with Medicare or other third party payers as to the correct form of billing or the amount that will be paid to providers of service. The provider of service has the responsibility to determine medical necessity and to submit appropriate codes and charges for care provided. Please contact your local payers, reimbursement specialists and/or legal counsel for interpretation of coding, coverage, and payment policies. Guerbet does not promote the use of its products outside FDA-approved labeling.

 

GU05201138

Important Safety Information

WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS  (NSF)

 

Risk Associated with Intrathecal Use

Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious  adverse

reactions including death, coma, encephalopathy, and seizures. DOTAREM is not approved for

intrathecal use.

 

Nephrogenic Systemic Fibrosis

GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of DOTAREM 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 (e.g. age > 60 years, hypertension, diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.

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.

 

 

Indications and Usage

DOTAREM® (gadoterate meglumine) injection is a prescription 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 (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

 

Contraindications

History of clinically important hypersensitivity reactions to DOTAREM.

 

Warnings and Precautions

    • 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 DOTAREM have not been established with intrathecal use. DOTAREM is not approved for intrathecal use.
    • Nephrogenic Systemic Fibrosis: GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of DOTAREM among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.
    • 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.
    • 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.
    • Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by other organs (e.g. brain, skin, kidney, liver and spleen). While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible.
    • 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.
    • 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.

 

Adverse Reactions

    • In clinical trials, the most frequent adverse reactions that occurred in > 0.2% of patients who received Dotarem included: nausea, headache, injection site pain, injection site coldness and rash.
    • Serious adverse reactions in the Postmarketing experience have been reported with DOTAREM. Serious adverse reactions include but are not limited to arrhythmia, cardiac arrest, respiratory arrest, pharyngeal edema, laryngospasm, bronchospasm, coma, convulsion, and acute pancreatitis with onset within 48 hours after GBCA administration.

 

Use in Specific Populations

    • Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. Use only if imaging is essential during pregnancy and cannot be delayed.
    • Lactation: There are no data on the presence of gadoterate in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk.
    • Pediatric Use: The safety of DOTAREM has not been established in preterm neonates.  No dosage adjustment according to age is necessary in pediatric patients.
    • Geriatric Use: use of DOTAREM in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. No age-related dosage adjustment is necessary.
    • Renal Impairment: No DOTAREM dosage adjustment is recommended for patients with renal impairment.

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

 

Please see the full Prescribing Information, including the Medication Guide, for additional important safety information.