Idoxuridine (Ophthalmic)


VA CLASSIFICATION
Primary: OP203

Commonly used brand name(s): Herplex Liquifilm; Stoxil.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiviral (ophthalmic)—

Indications

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

Accepted

Keratitis, herpes simplex virus (treatment) or{01}{02}{03}
[Keratitis, vaccinia virus (treatment)]1{02}—Idoxuridine is indicated in the treatment of keratitis caused by herpes simplex virus (HSV) and [vaccinia virus] .

[Keratoconjunctivitis, herpes simplex virus (treatment)]1{02}—Idoxuridine is used in the treatment of keratoconjunctivitis caused by herpes simplex virus (HSV).

Unaccepted
Idoxuridine has no effect on accumulated scarring, vascularization, or progressive loss of vision that may result from the infection. It also has no effect on corneal inflammation that may follow HSV keratitis when the virus is absent, nor on adenoviral keratoconjunctivitis.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Chemically related to thymidine.
Molecular weight—
    354.10

Mechanism of action/Effect:

Idoxuridine, which closely resembles thymidine, inhibits thymidylic phosphorylase and specific DNA polymerases, which are necessary for the incorporation of thymidine into viral DNA. Idoxuridine is incorporated in place of thymidine into viral DNA, resulting in faulty DNA and the inability to infect or destroy tissue or to reproduce. Idoxuridine is incorporated into mammalian DNA as well.

Distribution:

Idoxuridine penetrates the cornea poorly and therefore is ineffective in the treatment of iritis or deep stromal infections.

Biotransformation:

Idoxuridine is rapidly inactivated by deaminases or nucleotidases.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to iodine or iodine-containing preparations may be sensitive to this medication also.

Pregnancy/Reproduction

Pregnancy—
Idoxuridine crosses the placenta. Studies in humans have not been done.

Fetal malformations in rabbits (including exophthalmos and clubbing of forelegs) and chromosomal aberrations in mice have been reported.

Breast-feeding

It is not known whether idoxuridine is distributed into breast milk. However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of this medicine have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Appropriate studies on the relationship of age to the effects of this medicine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Boric acid    (concurrent use of boric acid with idoxuridine formulations is not recommended; boric acid may interact with inactive ingredients in some idoxuridine formulations, resulting in precipitate formation; in addition, boric acid may interact with preservatives, especially higher concentrations of thimerosal, in other idoxuridine formulations, resulting in increased ocular toxicity)


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 idoxuridine

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Ophthalmologic, including slit-lamp, examinations    (may be required periodically during therapy)




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
    
Hypersensitivity (itching, redness, swelling, pain, or other sign of irritation not present before therapy)
    
increased sensitivity of eyes to light

Incidence rare
    
Corneal clouding (blurring, dimming, or haziness of vision)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Lacrimal punctal stenosis or occlusion (excess flow of tears)



Those not indicating need for medical attention
For ophthalmic ointment dosage form only
    
Blurred vision





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Idoxuridine (Ophthalmic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to idoxuridine or to iodine or iodine-containing preparations

Pregnancy—Ophthalmic idoxuridine crosses the placenta and has been shown to cause protruding eyes and deformed forelegs in rabbits. However, the medication has not been shown to cause birth defects or other problems in humans
Other medications, especially boric acid

Proper use of this medication
Proper administration technique for ophthalmic ointment and solution

» Not administering more frequently or for longer than ordered by physician

» Compliance with full course of therapy

» Proper dosing
Missed dose: Applying as soon as possible; not applying if almost time for next dose

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress

Checking with physician if no improvement within a week

Possible photophobic reactions; wearing sunglasses and avoiding prolonged exposure to bright light


Side/adverse effects
Blurred vision may occur for a few minutes after application of ophthalmic ointments

Signs of potential side effects, especially hypersensitivity, increased sensitivity of eyes to light, or corneal clouding


General Dosing Information
At night the ophthalmic ointment may be used as an adjunct to the ophthalmic solution to provide prolonged contact with the medication.

Although some manufacturers recommend a dose of 2 drops of an ophthalmic solution at appropriate intervals, the conjunctival sac will usually hold only 1 drop.

Idoxuridine may be administered concurrently with cycloplegics, antibiotics, or corticosteroids. Corticosteroids can accelerate the spread of viral infections and are usually contraindicated in superficial herpes simplex virus keratitis. However, steroids may be used concurrently with idoxuridine in the treatment of herpes simplex infections with stromal lesions, corneal edema, or iritis. Prolonged administration with corticosteroids may be required. Idoxuridine should be continued for a few days after the steroid has been discontinued.

Since idoxuridine inhibits the formation of DNA in the cornea, prolonged administration of idoxuridine alone may damage the corneal epithelium and prevent healing of the ulcers. Treatment should usually not be continued for more than 21 days total or for more than 3 to 5 days after healing is complete. However, chronic or particularly difficult infections may require up to 3 to 6 weeks of treatment. Too frequent administration may result in small punctate defects in the cornea.

Burning after application or failure to respond to treatment may suggest deterioration of the ophthalmic solution; replace with fresh solution.

Herpetic keratitis may recur if idoxuridine is discontinued before microscopic staining with fluorescein has cleared.


Ophthalmic Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

IDOXURIDINE OPHTHALMIC OINTMENT USP

Usual adult and adolescent dose
Keratitis, herpes simplex virus
Topical, to the conjunctiva, a thin strip (approximately 1 cm) of ointment every four hours (five times a day) during the day. The last dose may be administered at bedtime. Treatment should be continued until definite improvement occurs, as demonstrated by loss of staining with fluorescein.

[Keratitis, vaccinia virus]1 or
[Keratoconjunctivitis, herpes simplex virus]1
Topical, to the conjunctiva, a thin strip (approximately 1 cm) of ointment five times a day.


Usual adult prescribing limits
Up to 8 times daily.

Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


0.5% (Rx) [Stoxil]

Canada—


0.5% (Rx) [Stoxil]

Packaging and storage:
Store between 8 and 15 °C (46 and 59 °F). Store in a collapsible ophthalmic ointment tube.

Note: Some manufacturers indicate that the ointment does not require refrigeration.


Stability:
Idoxuridine is rapidly inactivated by deaminases or nucleotidases.

Auxiliary labeling:
   • Store in a cool place. May be refrigerated.
   • For the eye.
   • Continue medicine for full time of treatment.
   • Do not use more often or longer than ordered.


IDOXURIDINE OPHTHALMIC SOLUTION USP

Usual adult and adolescent dose
Keratitis, herpes simplex virus
Topical, to the conjunctiva, 1 drop every hour during the day and every two hours during the night; or 1 drop every minute for five minutes with the dosage schedule repeated every four hours day and night. Treatment should be continued until definite improvement occurs, as demonstrated by loss of staining with fluorescein. Dose may then be reduced to 1 drop every two hours during the day and every four hours during the night. {01} {03}

[Keratitis, vaccinia virus]1 or
[Keratoconjunctivitis, herpes simplex virus]1
Topical, to the conjunctiva, 1 drop every hour during the day and every two hours during the night.


Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


0.1% (Rx) [Herplex Liquifilm{03} (polyvinyl alcohol 1.4%) (benzalkonium chloride)] [Stoxil (thimerosal 1:50,000)]

Canada—


0.1% (Rx) [Herplex Liquifilm{01} (polyvinyl alcohol 1.4%) (benzalkonium chloride 0.004%)] [Stoxil (thimerosal 1:50,000)]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). Store in a tight, light-resistant container.

Stability:
Idoxuridine is rapidly inactivated by deaminases or nucleotidases. To ensure stability, the ophthalmic solution should not be mixed with other medications. Burning after application or failure to respond to treatment may suggest deterioration of the ophthalmic solution; replace with fresh solution.

Auxiliary labeling:
   • Refrigerate.
   • For the eye.
   • Continue medicine for full time of treatment.
   • Do not use more often or longer than ordered.

Note: Dispense in original unopened container.




Revised: 06/21/1993



References
  1. Herplex Liquifilm package insert (Allergan—Canada), Rev 6/90, Rec 1/91.
  1. Stoxil package insert (SKF—Canada), CPS 1988: 869.
  1. Herplex Liquifilm package insert (Allergan—US), PDR Ophthalmology 1993: 247.
Hide
(web2)