use of this drug in any particular patient is recommended only when the severity
of the clinical condition justifies the aggressive measures associated with
this type of therapy.
Endrate (Edetate Disodium Injection, USP) is a sterile, nonpyrogenic,
concentrated solution of edetate disodium in water for injection which as
a result of a pH adjustment with sodium hydroxide contains varying amounts
of disodium and trisodium salts. After dilution, it is administered by intravenous
Each mL contains edetate disodium, anhydrous
150 mg. May contain sodium hydroxide for pH adjustment. pH is 7.0 (6.5 to
Edetate disodium is classified as a clinical chelating
agent for emergency lowering of serum calcium in hypercalcemia.
solution contains no bacteriostat, antimicrobial agent or buffer (except for
pH adjustment) and is intended only for use (after dilution) as a single-dose
infusion. When smaller doses are required, the unused portion should be discarded.
Disodium, USP is chemically designated disodium (ethylenedinitrilo) tetraacetate
dihydrate, a white crystalline powder soluble in water. It is also described
as the disodium salt of ethylenediamine tetraacetic acid (EDTA) and has the
following structural formula:
Edetate Disodium Injection, USP forms chelates with the cations
of calcium and many divalent and trivalent metals. Because of its affinity
for calcium, edetate disodium will produce a lowering of the serum calcium
level during intravenous infusion. Slow infusion over a protracted period
may cause mobilization of extracirculatory calcium stores. Edetate disodiumexerts a negative inotropic effect upon the heart.
intravenous administration, the chelate formed is excreted in the urine with
50% appearing in 1 hour and over 95% in 24 hours.
disodium likewise forms chelates with other polyvalent metals and produces
increases in urinary excretion of magnesium, zinc and other trace elements.
It does not form a chelate with potassium but may reduce the serum level and
increase urinary loss of potassium.
INDICATIONS AND USAGE
Endrate (Edetate Disodium Injection, USP) is indicated in
selected patients for the emergency treatment of hypercalcemia and for the
control of ventricular arrhythmias associated with digitalis toxicity.
Endrate (Edetate Disodium Injection, USP) is contraindicated
in anuric patients. It is not indicated for the treatment of generalized arteriosclerosis
associated with advancing age.
See warning statement, page 1.
intravenous infusion or attainment of high serum concentration of edetate
disodium may cause a precipitous drop in the serum calcium level and many
result in fatality. Toxicity appears to be dependent upon both total dosage
and speed of administration. The rate of administration and dosage should
not exceed that indicated in DOSAGE AND ADMINISTRATION.
of its irritant effect on the tissues and because of the danger of serious
side effects if administered in the undiluted form, Endrate (Edetate Disodium
Injection, USP) should be diluted before infusion. See DOSAGE AND ADMINISTRATION.
After the infusion of edetate disodium, the
patient should remain in bed for a short time because of the possibility of
The possibility of an adverse
effect on myocardial contractility should be considered when administering
the drug to patients with heart disease. Caution is dictated in the use of
this drug in patients with limited cardiac reserve or incipient congestive
Edetate Disodium Injection, USP therapy should
be used with caution in patients with clinical or subclinical potassium deficiency
states. In such cases it is advisable to perform serum potassium blood levels
for possible hypokalemia and to monitor ECG changes.
possibility of hypomagnesemia should be kept in mind during prolonged therapy.
with edetate disodium has been shown to cause a lowering of blood sugar and
insulin requirements in patients with diabetes who are treated with insulin.
not use unless solution is clear and container is intact. Discard unused portion.
Renal excretory function should be assessed prior to treatment.
Periodic BUN and creatinine determinations and daily urinalysis should be
performed on patients receiving this drug.
the possibility of inducing an electrolyte imbalance during treatment with
edetate disodium, appropriate laboratory determinations and studies to evaluate
the status of cardiac function should be performed. Repetition of these tests
is recommended as often as clinically indicated, particularly in patients
with ventricular arrhythmia and those with a history of seizure disorders
or intracranial lesions. If clinical evidence suggests any disturbance of
liver function during treatment, appropriate laboratory determinations should
be performed and withdrawal of the drug may be required.
Drug/Laboratory Test Interactions
The oxalate method of determining serum calcium tends to
give low readings in the presence of edetate disodium; modification of this
method, as by acidifying the sample or use of a different method may be required
for accuracy. The least interference will be noted immediately before a subsequent
dose is administered.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Definitive statements cannot be made due to insufficient
data and conflicting information.
Pregnancy Category C.
Animal reproduction studies have not been conducted with
Edetate Disodium Injection. It is also not known whether Edetate Disodium
Injection can cause fetal harm when administered to a pregnant woman or can
affect reproduction capacity. Edetate Disodium Injection should be given to
a pregnant woman only if clearly needed.
The safety of this product in nursing mothers has not been
Safety and effectiveness in pediatric patients have not been
Clinical studies of Endrate® did not include sufficient
numbers of patients aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical experience has
not identified differences in responses between elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, reflecting
the greater frequency of decreased hepatic, renal, or cardiac function, and
of concomitant disease or other drug therapy.
is known to be substantially excreted by the kidney, and the risk of toxic
reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function,
care should be taken in dose selection, and it may be useful to monitor renal
Gastrointestinal symptoms such as nausea, vomiting and diarrhea
are fairly common following administration of this drug. Transient symptoms
such as circumoral paresthesia, numbness and headache and a transient drop
in systolic and diastolic blood pressure may occur. Thrombophlebitis, febrile
reactions, hyperuricemia, anemia, exfoliative dermatitis and other toxic skin
and mucous membrane reactions have been reported.
and damage to the reticuloendothelial system with hemorrhagic tendencies have
been reported with excessive dosages.
Because of the possibility that Edetate Disodium Injection,
USP may produce a precipitous drop in the serum calcium level, a source of
calcium replacement suitable for intravenous administration (such as calcium
gluconate) should be instantly available at the bedside before edetate disodium
is administered. Extreme caution is dictated in the use of intravenous calcium
in the treatment of tetany, especially in digitalized patients because the
action of the drug and the replacement of calcium ions may produce a reversal
of the desired digitalis effect.
DOSAGE AND ADMINISTRATION
Edetate Disodium Injection, USP is administered by intravenous
infusion only after dilution.
Adults: The recommended daily dosage is 50 mg/kg of body weight
to a maximum dose of 3 g in 24 hours. The dose, calculated by body weight,
should be diluted in 500 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride
Injection, USP. The intravenous infusion should be regulated so that three
or more hours are required for completion and the cardiac reserve of the patient
is not exceeded. A suggested regimen includes five consecutive daily doses
followed by two days without medication, with repeated courses as necessary
to a total of 15 doses.
Parenteral drug products should
be inspected visually for particulate matter and discoloration prior to administration,
whenever solution and container permit. See PRECAUTIONS.
may be incompatible with the reconstituted (diluted) solution required for
intravenous infusion. Consult with pharmacist, if available. When introducing
additives, use aseptic technique, mix thoroughly and do not store.
Endrate (Edetate Disodium Injection, USP) is supplied in
20 mL (3 g) ampuls, List No. 6940.
Store at 25°C
(77°F) with excursions permitted between 15° to 30°C (59°