DOTAREM (Page 6 of 6)

16 HOW SUPPLIED/STORAGE AND HANDLING

DOTAREM Injection is a clear, colorless to yellow solution containing 0.5 mmol/mL of gadoterate meglumine.

• DOTAREM Injection Pharmacy Bulk Package is supplied in 100 mL vials containing 100 mL of solution.

Each Pharmacy Bulk Package vial is closed with a rubber stopper and sealed with an aluminum cap and the contents are sterile. DOTAREM Pharmacy Bulk Package is packaged in a shrink wrapped package of 6, in the following configurations:

100 mL in glass vial (NDC 67684-2000-4)

DOTAREM Pharmacy Bulk Package is also packaged in a box of 6, in the following configurations:

100 mL in glass vial (NDC 67684-2001-4)

Storage

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

Should solidification occur in the vial because of exposure to the cold, bring DOTAREM to room temperature before use. If allowed to stand at room temperature for a minimum of 90 minutes, DOTAREM should return to a clear, colorless to yellow solution. Before use, examine the product to assure that all solids are dissolved and that the container and closure have not been damaged. Discard the vial if solids persist.

17 PATIENT COUNSELING INFORMATION

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).

17.1 Nephrogenic Systemic Fibrosis

Instruct patients to inform their healthcare provider if they:

1. have a history of kidney disease, or
2. have recently received a GBCA.

GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. To counsel patients at risk for NSF:

• Describe the clinical manifestations of NSF.
• Describe procedures to screen for the detection of renal impairment.

Instruct the patients to contact their physician if they develop signs or symptoms of NSF following DOTAREM administration, such as burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints with trouble moving, bending or straightening the arms, hands, legs or feet; pain in the hip bones or ribs; or muscle weakness.

17.2 Common Adverse Reactions

Inform patients that they may experience:

• Reactions along the venous injection site, such as mild and transient burning or pain or feeling of warmth or coldness at the injection site.
• Side effects of headache, nausea, abnormal taste and feeling hot.

17.3 General Precautions

• Pregnancy: Advise pregnant women of the potential risk of fetal exposure to gadoterate [see Use in Specific Populations (8.1)].
• Gadolinium Retention: Advise patients that gadolinium is retained for months or years in brain, bone, skin, and other organs in patients with normal renal function. The clinical consequences of retention are unknown. Retention depends on multiple factors and is greater following administration of linear GBCAs than following administration of macrocyclic GBCAs [see Warnings and Precautions (5.3)].

Rx Only

Guerbet LLC

821 Alexander Road, Suite 204,
Princeton, New Jersey 08540

Vials manufactured by Recipharm, France and Liebel-Flarsheim Company, USA for Guerbet

Medication Guide

DOTAREM® (doh TAH rem)
(gadoterate meglumine) Injection for intravenous use

What is DOTAREM? DOTAREM is a prescription medicine called a gadolinium-based contrast agent (GBCA). DOTAREM, like other GBCAs, is injected into your vein and used with a magnetic resonance imaging (MRI) scanner. An MRI exam with a GBCA, including DOTAREM, helps your doctor to see problems better than an MRI exam without a GBCA. Your doctor has reviewed your medical records and has determined that you would benefit from using a GBCA with your MRI exam.

What is the most important information I should know about DOTAREM? DOTAREM contains a metal called gadolinium. Small amounts of gadolinium can stay in your body including the brain, bones, skin and other parts of your body for a long time (several months to years). It is not known how gadolinium may affect you, but so far, studies have not found harmful effects in patients with normal kidneys. Rarely patients have reported pains, tiredness, and skin, muscle or bone ailments for a long time, but these symptoms have not been directly linked to gadolinium. There are different GBCAs that can be used for your MRI exam. The amount of gadolinium that stays in the body is different for different gadolinium medicines. Gadolinium stays in the body more after Omniscan or Optimark than after Eovist, Magnevist or MultiHance. Gadolinium stays in the body the least after Dotarem, Gadavist or ProHance. People who get many doses of gadolinium medicines, women who are pregnant and young children may be at increased risk from gadolinium staying in the body. Some people with kidney problems who get gadolinium medicines can develop a condition with severe thickening of the skin, muscles and other organs in the body (nephrogenic systemic fibrosis). Your healthcare provider should screen you to see how well your kidneys are working before you receive DOTAREM.

Do not receive DOTAREM if you have had a severe allergic reaction to DOTAREM.

Before receiving DOTAREM, tell your healthcare provider about all your medical conditions, including if you: have had any MRI procedures in the past where you received a GBCA. Your healthcare provider may ask you for more information including the dates of these MRI procedures. are pregnant or plan to become pregnant. It is not known if DOTAREM can harm your unborn baby. Talk to your healthcare provider about the possible risks to an unborn baby if a GBCA such as DOTAREM is received during pregnancy. have kidney problems, diabetes, or high blood pressure. have had an allergic reaction to dyes (contrast agents) including GBCAs.

What are possible side effects of DOTAREM? See “What is the most important information I should know about DOTAREM?” Allergic reactions. DOTAREM can cause allergic reactions that can sometimes be serious. Your healthcare provider will monitor you closely for symptoms of an allergic reaction. The most common side effects of DOTAREM include: nausea, headache, pain, or cold feeling at the injection site, and rash. These are not all the possible side effects of DOTAREM.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective uses of DOTAREM. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your healthcare provider for information about DOTAREM that is written for health professionals.

What are the ingredients in DOTAREM?Active ingredient: gadoterate meglumineInactive ingredients: DOTA, water for injection Manufactured by: Catalent (glass pre-filled syringes), Liebel-Flarsheim Company LLC (plastic pre-filled syringes and vials) and Recipharm (vials) for GuerbetFor more information, go to www.guerbet-us.com or call 1-877-729-6679. This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. 4/2019

Principal Package Display

DOTAREM gadoterate meglumine injection

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:67684-2000 Route of Administration Intravenous DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength gadoterate meglumine (GADOLINIUM CATION (3+)) GADOLINIUM CATION (3+) 376.9 mg in 1 mL

Inactive Ingredients Ingredient Name Strength WATER 1 mL in 1 mL

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:67684-2000-4 6 VIAL in 1 PACKAGE contains a VIAL 1 100 mL in 1 VIAL This package is contained within the PACKAGE (67684-2000-4)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA204781 04/26/2013

DOTAREM gadoterate meglumine injection

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:67684-2001 Route of Administration Intravenous DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength gadoterate meglumine (GADOLINIUM CATION (3+)) GADOLINIUM CATION (3+) 376.9 mg in 1 mL

Inactive Ingredients Ingredient Name Strength WATER 1 mL in 1 mL

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:67684-2001-4 6 VIAL in 1 PACKAGE contains a VIAL 1 100 mL in 1 VIAL This package is contained within the PACKAGE (67684-2001-4)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA204781 04/26/2013

Labeler — Guerbet LLC (037876096)

Registrant — Guerbet LLC (037876096)

Establishment
Name	Address	ID/FEI	Operations
Recipharm Monts		777990813	manufacture (67684-2000), analysis (67684-2000), pack (67684-2000), label (67684-2000)

Establishment
Name	Address	ID/FEI	Operations
Simafex		381108273	api manufacture (67684-2000), api manufacture (67684-2001), analysis (67684-2000)

Establishment
Name	Address	ID/FEI	Operations
PCAS Finland O.y		369587311	api manufacture (67684-2000), api manufacture (67684-2001), analysis (67684-2000)

Establishment
Name	Address	ID/FEI	Operations
Liebel-Flarsheim Company LLC		109024984	manufacture (67684-2001), label (67684-2001)

Revised: 04/2020 Guerbet LLC