Drug Interaction:
DOTAREM does not interfere with serum and plasma calcium measurements
determined by colorimetric assays. Specific drug interaction studies with
DOTAREM have not been conducted.
Indication:
DOTAREM (gadoterate meglumine) Injection for intravenous use
Initial U.S. Approval: 2013
WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)
See full prescribing information for complete boxed warning
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.
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
Drug Name- Dotarem
Active Ingredient - Gadoterate meglumine
For use in magnetic resonance imaging (MRI) of the brain, spine and
associated tissues of patients ages 2 years and older
Indication-
MRI of brain, spine and other tissues
Approved by FDA on 20-3-2013 (Ref- FDA approved List- 2013)
FIXED DOSE COMBINATIONS APPROVED BY DCG(I)
FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
Gadoteric acid 27.93 gm+ 23-10-2002
Megalunine 9.76gm each 100ml IV injection
Magnetic imaging dianostics investigation including
MR angiography
Adverse Reaction:
The most frequent (. 0.2%) adverse reactions in clinical studies were nausea,
headache, injection site pain, injection site coldness, and burning sensation.
Contra-Indications:
CONTRAINDICATIONS
Clinically important hypersensitivity reactions to DOTAREM.
WARNINGS AND PRECAUTIONS
Nephrogenic Systemic Fibrosis has occurred in patients with impaired
elimination of GBCAs. Higher than recommended dosing or repeat
dosing appear to increase the risk.
Hypersensitivity: Anaphylactoid/anaphylactic reactions with
cardiovascular, respiratory or cutaneous manifestations, ranging from
mild to severe, including death, have uncommonly occurred. Monitor
patients closely for need of emergency cardiorespiratory support.
Dosages/ Overdosage Etc:
Indication-
MRI of brain, spine and other tissues
INDICATIONS AND USAGE
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 abnormal vascularity.
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.
DOSAGE FORMS AND STRENGTHS
DOTAREM Injection 0.5 mmol/mL contains 376.9 mg/mL of gadoterate
meglumine and is available in vials and pre-filled syringes.
Patient Information:
PATIENT COUNSELING INFORMATION
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
the drugs.
2. 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.
3. Common Adverse Reactions
Inform patients that they may experience:
Reactions along the venous injection site, such as mild and transient burning o
pain or feeling of warmth or coldness at the injection site.
4. Side effects of headache, nausea, abnormal taste and feeling hot.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Gadoterate is a paramagnetic molecule that develops a magnetic moment
when placed in a magnetic field. The magnetic moment enhances the relaxation
rates of water protons in its vicinity, leading to an increase in signal intensity
(brightness) of tissues.
2. Pharmacokinetics
The pharmacokinetics of total gadolinium following an intravenously administered
0.1 mmol/kg dose of DOTAREM in normal subjects conform to a one-compartment
open-model with a mean elimination half-life (reported as mean Ib SD) of about
1.4 0.2 hr and 2.0 0.7 hr in female and male subjects, respectively.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies with DOTAREM conducted in
pregnant women. Limited published human data on exposure to other GBCAs during
pregnancy did not show adverse effects in exposed neonates.
DOTAREM should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
2. Nursing Mothers
It is not known whether DOTAREM 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.
Because many drugs are excreted in human milk, exercise caution when DOTAREM
is administered to a nursing woman.
3. Pediatric Use
The safety and efficacy of DOTAREM at a single dose of 0.1 mmol/kg have been
established in pediatric patients from 2 to 17 years of age. No dosage adjustment
according to age is necessary in this population
The safety and efficacy of DOTAREM have not been established in pediatric patients
below 2 years of age. GFR does not reach adult levels until 1 year of age
4.Geriatric Use
In clinical studies of DOTAREM, 900 patients were 65 years of age and over,
and 312 patients were 75 years of age and over. No overall differences in safety
or efficacy were observed between these subjects and younger subjects.
In general, 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.
Manufacturer Details