GADOPENTETATE DIMEGLUMINE- gadopentetate dimeglumine injection
Alvogen, Inc
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.
� Do not administer gadopentetate dimeglumine to patients with:
? chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), or
? acute kidney injury (see CONTRAINDICATIONS).
� 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.
Do not exceed the recommended gadopentetate dimeglumine 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).
DESCRIPTION
Gadopentetate dimeglumine Injection is the N-methylglucamine salt of the gadolinium complex of diethylenetriamine pentaacetic acid, and is an injectable contrast medium for magnetic resonance imaging (MRI). Gadopentetate dimeglumine Injection is provided as a sterile, clear, colorless to slightly yellow aqueous solution for intravenous injection.
Gadopentetate dimeglumine Injection is a 0.5-mol/L solution of 1-deoxy-1-(methylamino)-D-glucitol dihydrogen [N,N-bis[2-[bis(carboxymethyl)amino]ethyl] glycinato(5-)]gadolinate(2-)(2:1) with a molecular weight of 938, an empirical formula of C28 H54 GdN5 O20 , and has the following structural formula:
Chemical Structure
(click image for full-size original)
Each mL contains 469.01 mg gadopentetate dimeglumine, 0.99 mg meglumine, 0.40 mg diethylenetriamine pentaacetic acid and water for injection. Gadopentetate dimeglumine Injection contains no antimicrobial preservative.
Gadopentetate dimeglumine Injection has a pH of 6.5 to 8.0. Pertinent physicochemical data are noted below:
PARAMETER
Osmolality (mOsmol/kg water)
at 37� C
1,960
Viscosity (CP)
at 20� C
4.9
at 37� C
2.9
Density (g/mL)
at 25� C
1.195
Specific Gravity
at 25� C
1.208
Octanol: H2 O Coefficient
at 25� C, pH7 log Pow = - 5.4
Gadopentetate dimeglumine Injection has an osmolality 6.9 times that of plasma which has an osmolality of 285 mOsmol/kg water. Gadopentetate dimeglumine Injection is hypertonic under conditions of use.
CLINICAL PHARMACOLOGY
Pharmacokinetics
The pharmacokinetics of intravenously administered gadopentetate dimeglumine in normal subjects conforms to a two compartment open-model with mean distribution and elimination half-lives (reported as mean � SD) of about 0.2 � 0.13 hours and 1.6 � 0.13 hours, respectively.
Upon injection, the meglumine salt is completely dissociated from the gadopentetate dimeglumine complex. Gadopentetate is exclusively eliminated in the urine with 83 � 14% (mean � SD) of the dose excreted within 6 hours and 91 � 13% (mean � SD) by 24 hours, post-injection. There was no detectable biotransformation or decomposition of gadopentetate dimeglumine.
The renal and plasma clearance rates (1.76 � 0.39 mL/min/kg and 1.94 � 0.28 mL/min/kg, respectively) of gadopentetate are essentially identical, indicating no alteration in elimination kinetics on passage through the kidneys and that the drug is essentially cleared through the kidney. The volume of distribution (266 � 43 mL/kg) is equal to that of extracellular water and clearance is similar to that of substances which are subject to glomerular filtration.
In vitro laboratory results indicate that gadopentetate does not bind to human plasma protein. In vivo protein binding studies have not been done.