Edetate Disodium (Ophthalmic)


BAN:
Disodium edetate {01} {02}


JAN:
Disodium edetate {01}

VA CLASSIFICATION
Primary: OP900.

Some commonly used names are
disodium EDTA, edathamil disodium, ethylenediamine tetraacetic acid, and sodium edetate .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Chelating agent (ophthalmic)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

[Calcium deposits, corneal (treatment)]1—Edetate disodium is used topically to remove exogenous or endogenous calcific corneal deposits {02} {03} {04} {06} {09} {10} {11} that may cause pain or impair vision. Removal of superficial calcium deposits may improve vision, unless scarring and vascularization have occurred. {03} {10}

[Calcium hydroxide burns, in eye (treatment)]1or
[Zinc chloride injury, in eye (treatment)]1—Edetate disodium has been used as emergency treatment to decontaminate the eye after injury by zinc chloride {02} {03} and for emergency management and follow-up treatment of calcium hydroxide burns in the eye. {03}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    372.24 {01}


pH
    Edetate disodium injection: 6.5 to 7.5. {02} {04} {05} {06} {08}

Mechanism of action/Effect:

Calcium deposits, corneal—Edetate disodium forms a soluble complex with calcium ions. {02} {04} {06} {08} {10} {12} Deposits from band keratopathy and other corneal calcium deposits associated with chronic uveitis, advanced interstitial keratitis, or hypercalcemia are dissolved from the conjunctiva, corneal epithelium, and anterior layers of the stroma. {03}

Distribution:

Calcium deposits in the deep stroma are not affected. Edetate disodium is lipid-insoluble and does not penetrate the corneal epithelium. Therefore, the epithelium must be completely removed before application, unless the deposit extends to the surface. {03} {04} {10}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—Problems in humans have not been documented.

FDA Pregnancy Category C (edetate disodium injection). {08}

Breast-feeding

Problems in humans have not been documented.

Pediatrics

No information is available on the relationship of age to the effects of edetate disodium in pediatric patients.


Geriatrics


No information is available on the relationship of age to the effects of edetate disodium in geriatric patients.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to edetate disodium{08}


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Swelling of the stroma —usually with higher concentrations{03}{04}



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Stinging in the eye {03}
    
swelling of the eyelids {03}





General Dosing Information
To remove calcium deposits from the anterior layers of the stroma, a local anesthetic is administered before the procedure. {03} {10} {11} Since cocaine facilitates the removal of the corneal epithelium, it is often preferred. {03} {04}

After the complete removal of the epithelium, the edetate disodium solution is applied to the cornea {07} as a corneal bath, by continuous irrigation, {10} or by a solution-soaked pledget {03} or sponge {09} {11} for 15 to 20 minutes. {03} {04}

The eye is irrigated after the procedure with a balanced salt solution. {03} {04}

Since edetate disodium does not remove embedded calcium salts well, treatment often is {12} combined with mechanical scraping. {07}

For treatment of calcium hydroxide burns or zinc chloride injury, the eye should first be flushed with water as quickly as possible and then irrigated with edetate disodium solution for 15 minutes. Treatment for zinc chloride injury may be ineffective unless started within 2 minutes of injury. {02} {03}

In excess concentrations, {12} edetate disodium is toxic to the corneal stroma, causing swelling of the cornea and severe inflammation. To avoid overuse, only as much as is necessary should be applied for the shortest possible duration, varying from patient to patient. {07}


Ophthalmic Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications for drugs that are not commercially available in the U.S.

EDETATE DISODIUM OPHTHALMIC SOLUTION

Note: In the U.S. and Canada, edetate disodium injection [ Disotate; Endrate; GENERIC] is used to prepare the ophthalmic solution dosage form. Edetate disodium injection is not commercially available in Canada; however, it is available by emergency drug release from the Health Protection Branch.


Usual adult and adolescent dose
[Corneal calcium deposits]1 or
[Calcium hydroxide burns]1
Topical, to the cornea, a 0.35 to 1.85% {02} {03} {04} {11} (0.0094 to 0.049 molar [M]) solution as irrigation for fifteen to twenty minutes. {03} {04}

[Zinc chloride injury]1
Topical, to the cornea, a 1.7% (0.046 M) solution as irrigation for fifteen minutes. {03}


Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—
Dosage form not commercially available. Compounding required for prescriptions. {11}

Canada—
Dosage form not commercially available. Compounding required for prescriptions. {11}

Preparation of dosage form:
In a laminar air-flow hood, using aseptic technique, 1.25 mL of edetate disodium injection USP (150 mg/mL) and 8.75 mL of sterile water for irrigation USP should be placed in an empty, sterilized 10-mL dropper bottle. The ingredients should be measured using a 1-mL, a 3-mL, and a 10-mL syringe. The 1-mL syringe is used to increase accuracy in measuring the 0.25- and 0.75-mL volumes. The bottle should be shaken well to ensure proper mixing. The concentration of the resulting solution is 0.05 M {06} (1.86%).

Stability:
The solution does not contain a bacteriostatic agent and therefore should be used within 24 hours. {06}

Auxiliary labeling:
   • For the eye. {06}



Revised: 07/29/1997



References
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1997. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1996. p. 258.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 31st ed. London: The Pharmaceutical Press; 1996. p. 981-2.
  1. Drug evaluations subscription. Chicago: American Medical Association; Spring 1992. p. 4:9.
  1. AHFS Drug information 96. Bethesda, MD: American Society of Hospital Pharmacists; 1996. p. 2208-10.
  1. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopieal Convention, Inc.; 1995. p. 571.
  1. Pesko LJ. Edetate disodium ophthalmic irrigation 0.05 M. Am Druggist 1996 May: 38-9.
  1. Panel comment.
  1. Edetate disodium injection package insert (Steris—US), Rev 4/90, Rec 8/2/93.
  1. Schechter EL, Keates RH. Treatment of band keratopathy. Ophthalmic Surg 1971; 2: 75.
  1. Grant WM. New treatment for calcific corneal opacities. AMA Arch Ophthalmol 1952; 48: 681-5.
  1. Dresner MS, Spence DJ, Schanzlin DJ. Corneal and conjunctival calcifications (band keratopathy). In: Fraunfelder FT, Roy FH, editors. Current ocular therapy 3. Philadelphia: W.B. Saunders; 1990. p. 408-9, 728.
  1. Panel comment, 02/24/97.
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