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Vidarabine (Ophthalmic)


VA CLASSIFICATION
Primary: OP203

Commonly used brand name(s): Vira-A.

Other commonly used names are
arabinoside and ara-A .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiviral (ophthalmic)—

Indications

Accepted

Keratitis, herpes simplex virus (treatment) or
Keratoconjunctivitis, herpes simplex virus (treatment)—Ophthalmic vidarabine is indicated in the treatment of acute keratoconjunctivitis and recurrent epithelial keratitis caused by herpes simplex virus (HSV), types 1 and 2. {01}

—Vidarabine also may be indicated in patients with superficial herpetic keratitis who do not respond to idoxuridine or who develop ocular toxicity or hypersensitivity to idoxuridine.

Unaccepted
Vidarabine is not indicated for the treatment of infections caused by RNA viruses or adenoviruses, in other infections (bacterial, fungal, chlamydial), or in nonviral trophic ulcers.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    285.26

Mechanism of action/Effect:

Vidarabine is phosphorylated intracellularly to arabinosyl adenosine monophosphate (ara-AMP) or the triphosphate (ara-ATP). These cause preferential inhibition of viral DNA polymerase, inhibition of virus-induced ribonucleotide reductase, or inhibition of other virus-specific enzymes involved in DNA synthesis that are more sensitive to inhibition than the corresponding host cell enzymes. This inhibition prevents lengthening of the DNA chain. Vidarabine may also be incorporated into both mammalian and viral DNA.

Absorption:

Systemic absorption is unlikely following ocular administration even when nasolacrimal secretions are swallowed, since vidarabine is rapidly deaminated in the gastrointestinal tract.

Distribution:

Because of low solubility, trace amounts of vidarabine and its metabolite, ara-hx, can be detected in the aqueous humor only if there is a corneal epithelial defect. When the cornea is intact, trace amounts of the metabolite only are found in the aqueous humor.

Biotransformation:

Vidarabine is rapidly deaminated by adenosine deaminase to arabinosyl hypoxanthine (ara-hx). Ara-hx is the primary metabolite, which also has antiviral activity, although much less than vidarabine. Vidarabine and arabinosyl hypoxanthine may act synergistically to inhibit DNA viral replication.


Precautions to Consider

Carcinogenicity/Tumorigenicity

Chronic studies in mice given vidarabine intramuscularly have shown that vidarabine causes a statistically significant increase in hepatic tumors in female mice and renal neoplasia in male mice.

Chronic studies in rats given vidarabine intramuscularly have shown that intestinal, testicular, and thyroid neoplasia occurred more frequently in rats given vidarabine than in control animals. Male rats given doses of 50 mg per kg of body weight (mg/kg) per day and female rats given doses of 30 mg/kg per day showed statistically significant increases in the incidence of thyroid adenomas. {02}

Mutagenicity

In vitro studies have shown that vidarabine may be incorporated into mammalian DNA and may induce mutations in mammalian cells (mouse L5178Y cell line). The in vivo dominant lethal assay in mice, although not as conclusive, has shown some evidence that vidarabine may cause mutagenic effects in male germ cells.

In vitro studies also have shown that vidarabine causes chromosome breaks and gaps when added to human leukocytes. {02}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. The possibility of embryonic or fetal damage in pregnant women is remote, since the ophthalmic dose of vidarabine is small, vidarabine is relatively insoluble, and ocular penetration of vidarabine is very low.

Studies in rats and rabbits have shown that vidarabine given parenterally is teratogenic. Fetal abnormalities have been reported in rabbits that had 10% vidarabine ointment applied to 10% of the body surface during organogenesis. There were no fetal abnormalities reported when the ointment was applied to only 2 to 3% of the body surface, a dose that greatly exceeds the total recommended human ophthalmic dose.

FDA Pregnancy Category C. {02}

Breast-feeding

It is not known whether vidarabine, applied ophthalmically, is absorbed systemically and distributed into breast milk. However, it is unlikely, since the ophthalmic dose of vidarabine is small, vidarabine is relatively insoluble, ocular penetration of vidarabine is very low, and vidarabine is rapidly deaminated in the gastrointestinal tract even when nasolacrimal secretions are swallowed. {02}

Pediatrics

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

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 vidarabine

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



Those indicating need for medical attention only if they continue or are bothersome
Incidence not reported
    
Feeling of something in the eye
    
lacrimal punctal stenosis or occlusion (excess flow of tears)





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

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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to vidarabine

Proper use of this medication
Proper administration technique for ophthalmic ointment

» Not using 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
Blurred vision after application of ophthalmic ointments

Importance of keeping appointments with physician; checking with physician if symptoms become worse

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


Side/adverse effects
Signs of potential side effects, especially hypersensitivity or increased sensitivity of eyes to light


General Dosing Information
Vidarabine may be administered concurrently with antibiotics (gentamicin, erythromycin, and chloramphenicol) and corticosteroids (prednisolone and dexamethasone). Corticosteroids can accelerate the spread of viral infections and usually are contraindicated alone {02} in superficial herpes simplex virus keratitis. However, corticosteroids may be used concurrently with vidarabine in the treatment of herpes simplex infections. Vidarabine should be continued for a few days after the corticosteroid has been discontinued.

Treatment should usually not be continued for more than a total of 21 days or for more than 3 to 5 days after healing is complete. However, chronic or particularly difficult infections may require a longer treatment period. Too frequent administration may result in small, punctate defects in the cornea.


Ophthalmic Dosage Forms

VIDARABINE OPHTHALMIC OINTMENT USP

Usual adult and adolescent dose
Ophthalmic antiviral
Topical, to the conjunctiva, a thin strip (approximately 1.25 cm) of ointment every three hours (five times a day). {04} Treatment should be continued until the cornea is completely re-epithelialized. Dose then may be reduced to 1.25 cm of ointment two times a day for an additional seven days. {03}


Usual pediatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


3% (monohydrate) (each gram of ophthalmic ointment contains 30 mg of vidarabine monohydrate, equivalent to 28.11 mg of anhydrous vidarabine) (Rx) [Vira-A{03}]

Canada—


3% (monohydrate) (each gram of ophthalmic ointment contains 30 mg of vidarabine monohydrate, equivalent to 28.11 mg of anhydrous vidarabine) (Rx) [Vira-A{05}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

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



Revised: 07/01/1993



References
  1. Indications Index review, 1986.
  1. Vira-A package insert (PD—US), PDR 1988: 1601.
  1. Vira-A package insert (PD—US), PDR Ophthalmology 1993: 309.
  1. Vira-A package insert (PD—US), Rev 3/81, Rec 3/89.
  1. Vira-A package insert (PD—Canada), CPS 1992: 1249.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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