Magnevist - Action And Clinical Pharmacology
Magnevist was developed as a contrast agent for diagnostic
use in magnetic resonance imaging (MRI). Gadolinium is a
rare earth element. Its ion (Gd++ has 7 unpaired electrons
and, therefore, shows paramagnetic properties. Gd++has a
strong effect on the hydrogen-proton spin-lattice relaxation
time (T1), which causes the observed contrast enhancement
in MRI scans. By chelation of Gd++with diethylenetriamine
pentaacetic acid (DTPA), a strongly paramagnetic, well-tolerated,
stable complex (gadopentetate dimeglumine salt) is obtained.
The free gadolinium ion is unsuitable for clinical use
due to high toxicity, however, the metal chelate is metabolically
inert. The organic component of the chelate is not measurably
metabolized and the metal does not dissociate. After i.v.
injection of Magnevist, the meglumine ion completely dissociates
from the gadopentetate. The hydrophylic chelate is distributed
only in the extracellular water and does not cross the intact
blood-brain barrier. Gadopentetate is excreted unchanged
in the urine. It is rapidly eliminated by the kidneys with
a clearance identical to that of inulin (no tubular reabsorption).
Pharmacokinetics: The pharmacokinetic profile of i.v. administered
Magnevist in normal subjects conforms to a 2 compartment
open model with a mean distribution half-life of about 0.2
hours and a mean elimination half-life of about 1.6 hours.
Approximately 80% of the dose was excreted in the urine
within 6 hours and 93% within 24 hours post injection of
a 0.1 mmol/kg dose. Excretion in the feces amounted to <0.1%
over 5 days. There was no detectable biotransformation,
dissociation or decomposition of gadopentetate.
Magnevist has no pharmacodynamic effect when administered
as indicated with the exception of slightly increased plasma
Magnevist - Indications And Clinical Uses
By i.v. injection, for contrast enhancement during cranial
and spinal MRI investigations in adults and children, to
detect lesions associated with abnormal vascularity, or
those thought to alter the blood-brain barrier.
Magnevist - Contra-Indications
Should not be administered to patients who are known or
suspected of being hypersensitive to it.
Magnevist - Manufacturers' Warnings In Clinical States
The decision to use Magnevist must be made after careful
evaluation of the risk-benefit in patients with a history
of allergic disposition or bronchial asthma, since experience
shows that these patients suffer more frequently than others
from hypersensitivity reactions.
In very rare cases anaphylactoid reactions, including anaphylactic
shock, may occur after i.v. injection of Magnevist. It is
important for prompt action in the event of such incidents
to be familiar with the practice of emergency measures.
To permit immediate countermeasures to be taken in emergencies,
appropriate drugs and instruments (e.g., endotracheal tube
and ventilator) should be readily available.
Deoxygenated sickle cell erythrocytes have been shown in
in vitro studies to align perpendicular to a magnetic field
which may result in vaso-occlusive complications in vivo.
The enhancement of magnetic moment by Magnevist may possibly
potentiate sickle erythrocyte alignment. Magnevist in patients
with sickle cell anemia and other hemoglobinopathies has
not been studied.
No studies have been conducted in children with severe
renal or hepatic dysfunction, clinically unstable or uncontrolled
hypertension, or in premature infants.
MRI procedures which involve the use of Magnevist by injection
should be carried out by physicians who have the prerequisite
training and a thorough knowledge of the particular procedure
to be performed.
Magnevist - Precautions
General: Magnevist is to be administered strictly by i.v.
injection. It will cause tissue irritation and pain if administered
extravascularly or if it leaks interstitially.
A sweet taste may be experienced briefly by patients receiving
a bolus injection of Magnevist i.v.
Hemolytic States: Magnevist alters red blood cell morphology
resulting in transient, slight, extravascular (splenic)
hemolysis with increased serum iron and total bilirubin
levels. Although this effect was of no clinical significance
during clinical trials, caution is advised in patients with
hepatic disease and/or hemolytic states.
Convulsive States: While there is no evidence suggesting
that Magnevist directly precipitates convulsion, the possibility
that it may decrease the convulsive threshold in susceptible
patients cannot be ruled out. Precautionary measures should
be taken with patients predisposed to seizure, e.g., close
monitoring and availability of injectable anticonvulsants
Pregnancy: There are no studies on the use of Magnevist
in pregnant women. Magnevist should not be used during human
pregnancy unless the potential benefit justifies the potential
risk to the fetus.
Lactation: Transfer of Magnevist into the milk of lactating
mothers can occur. Thus breast-feeding should be interrupted
for 24 hours postadministration of Magnevist and the milk
discarded during this period.
Geriatrics: No special precautions are required for elderly
Magnevist- Adverse Reactions
General: Most adverse reactions develop soon after injection,
however the possibility of delayed reactions cannot be ruled
out. The most frequently reported adverse reactions following
administration of Magnevist are shown in Table I.
Adverse reactions occurred in 11 of 319 (3.4%) pediatric
patients receiving Magnevist in clinical trials (headache,
vasodilatation, dizziness, diarrhea, ear pain, tachycardia,
fever, edema, seizure, vomiting, nausea and urticaria).
This adverse reaction profile is consistent with the adverse
reaction profile observed in adults.
Magnevist will cause tissue irritation and pain if administered
Transient increases or decreases in blood pressure may
occur after the administration of Magnevist. These changes
are generally of little consequence although 3 clinically
significant cases of hypotension have occurred 2 to 6 hours
after Magnevist injection. A relationship to the contrast
medium could not be determined, however caution should be
exercised by the patient when driving or operating machinery.
Serious or severe adverse effects associated with Magnevist
have been rare in clinical experience. Postmarketing anaphylactic
reactions have been reported, but are very rare. Convulsions
were reported in 3 patients with a history of seizures.
Laboratory Changes: Reversible mild elevations over baseline
in serum iron and total bilirubin occur in most patients
after receiving Magnevist. These changes do not appear to
be clinically relevant. Other disturbances in laboratory
values (transient increases in liver function tests) have
not been associated with the use of Magnevist.
Adverse Drug Reaction Profile: The following adverse reactions,
listed according to body system, have been reported after
administration of Magnevist.
Cardiovascular: hypotension, vasodilatation, pallor, phlebitis,
nonspecific ECG changes, substernal pain, angina.
CNS: headache, dizziness, agitation, paresthesia, tinnitus,
visual field defect, convulsions, hyperesthesia.
Gastrointestinal: nausea, vomiting, gastrointestinal distress,
stomach pain, thirst, increased salivation, taste abnormality.
Respiratory: dry mouth, throat irritation, rhinorrhea,
wheezing, sneezing, laryngismus, cough, dyspnea/apnea.
Cutaneous/Mucous Membranes: rash, sweating, urticaria,
Miscellaneous: injection site discomfort (coldness, burning,
warmth, pain), teeth pain, generalized weakness, fever,
localized edema, tiredness, anaphylactoid reactions (characterized
by cardiovascular, respiratory and cutaneous symptoms),
Laboratory Tests: transient elevation of serum iron and
The following other adverse events were reported. A causal
relationship has neither been established nor refuted.
Cardiovascular: hypertension, tachycardia, syncope, death
related to myocardial infarction or other undetermined causes.
CNS: diplopia, migraine, anxiety, drowsiness, nystagmus,
Gastrointestinal: constipation, diarrhea, anorexia.
Cutaneous/Mucous Membranes: facial edema, erythema, epidermal
Miscellaneous: localized pain (back, ear, eye).
Magnevist - Symptoms And Treatment Of Overdose
Symptoms and Treatment: In the event of inadvertent overdosage
or in the case of severely impaired renal function, Magnevist
can be removed from the body by extracorporeal hemodialysis.
Magnevist - Dosage And Administration
Special preparation of the patient for examination with
gadopentetate meglumine is not required; however, precautionary
measures should be taken with patients predisposed to seizure,
e.g., close monitoring and availability of injectable anticonvulsants
(see Precautions). The usual safety rules for MRI (e.g.,
exclusion of ferromagnetic vascular clips) must be observed.
Young children, infants and neonates may require sedation
prior to undergoing an MRI examination, in order to eliminate
The following dosage guidelines apply to adults and children
(including neonates and infants):
Recommended Dose: 0.2 mL/kg (0.1 mmol/kg).
Route of Administration: i.v. (into a large vein, if possible).
Rate of Administration: 10 mL/min or as a bolus injection
at 10 mL/15 sec.
Maximum Total Dose: 20 mL.
To ensure complete injection of the contrast medium, the
injection should be followed by a 5 mL normal saline flush.
If strong clinical suspicion of an intracranial or intraspinal
lesion persists, despite a normal MRI scan, the diagnostic
yield of the examination may be increased by giving another
injection of Magnevist equivalent to the original total
dose within 30 minutes and performing MRI again.
Magnevist should not be drawn into the syringe until immediately
before use. Any unused portion must be discarded upon completion
of the procedure.
T1-weighted scanning sequences are particularly suitable
for contrast-enhanced examinations.
Magnevist has been shown to be effective in a wide range
of field strengths (0.14 to 1.5 Tesla).
Important Note: The imaging procedure should be completed
within 1 hour since optimal contrast is generally observed
in cranial investigations within 27 minutes following injection
of Magnevist and in spinal investigations during the early
postadministration phase (10 to 30 minutes).
In neonates and infants, optimal CNS contrast has been
observed to persist for several hours after Magnevist administration.