ACIVIR Eye Ointment (Acyclovir 3%)

Table of Content

Composition

Aciclovir IP………………….3.0% w/w

Benzalkonium chloride IP….0.01% w/w

In a sterile ointment base…q.s.

Dosage Form

Ophthalmic ointment

Pharmacology

Pharmacodynamics

Aciclovir is an antiviral agent which is highly active in vitro against herpes simplex (HSV) types I and II, but its toxicity to mammalian cells is low. However, the relationship between in vitro sensitivity of herpes viruses to aciclovir and clinical response to therapy has yet to be established.

Aciclovir needs to be phosphorylated to the active compound, aciclovir triphosphate, in order to become active against the virus. Such conversion is very limited in normal cells and in addition cellular DNA polymerase is not very sensitive to the active compound. However, in infected cells HSV or VZV-coded thymidine kinase facilitates the conversion of aciclovir to aciclovir monophosphate which is then converted to aciclovir triphosphate by cellular enzymes. Aciclovir triphosphate acts as an inhibitor of, and substrate for, herpes-specified DNA polymerase, preventing further viral DNA synthesis without affecting normal cellular processes.

Pharmacokinetics

Aciclovir is rapidly absorbed from the ophthalmic ointment through the corneal epithelium and superficial ocular tissues, achieving significant antiviral concentrations in the aqueous humor. However, trace quantities are detectable in the urine. These levels are not therapeutically significant. It has not been possible by existing methods to detect aciclovir in the blood after topical application to the eye. In animal studies, however, low levels of aciclovir could be detected in blood after topical application to the eye.

Indications

Treatment of herpes simplex keratitis.

Dosage and Administration

Topical administration to the eye

Adults

1cm ribbon of ointment should be placed inside the lower conjunctival sac five times a day at approximately four hourly intervals, omitting the night time application. Treatment should continue for at least 3 days after healing is complete.

Children

As for adults.

Use in the elderly

As for adults.

Contraindications

Aciclovir ophthalmic ointment is contraindicated in patients with a known hypersensitivity to aciclovir or valaciclovir or any of the ingredients included in the formulation.

Warnings and Precautions

General

FOR OPHTHALMIC USE ONLY.

Patients should be informed that transient, mild stinging immediately following application may occur. Patients should avoid wearing contact lenses when using ACIVIR ophthalmic ointment.

Resistant strains have been isolated in vitro and in animals following treatment with aciclovir. HSV strains resistant in vitro to aciclovir have also been isolated from immune compromised as well as immuno-competent patients receiving Aciclovir for Herpes simplex infections. Therefore the potential for the development of resistant HSV strains in patients treated with aciclovir should be borne in mind. The relationship between in vitro sensitivity of herpes viruses to aciclovir and clinical response to therapy has yet to be established.

Effect on Ability to Drive and Use Machines

Eye ointments can affect visual ability and therefore caution is advised when driving or using machines.

Drug Interactions

No clinically significant interactions have been identified.

Pregnancy

Pregnancy Category B3

There have been no adequate and well controlled studies concerning the safety of aciclovir in pregnant women. Only small amounts are absorbed following application to the eye. ACIVIR eye ointment should not be used during pregnancy unless the benefits to the patient clearly outweigh the potential risks to the foetus.

Lactation

Limited human data show that aciclovir does not pass into breast milk following systemic administration. Aciclovir should only be administered to nursing mothers if the benefits to the mother outweigh the potential risks to the baby.

However, the dosage received by the nursing infant following maternal use of aciclovir eye ointment would be insignificant.

Undesirable Effects

Transient mild stinging immediately following administration occurs in a proportion of patients.

Superficial punctate keratopathy occurs somewhat more frequently but healing has occurred, without apparent sequelae, following the completion of a course of treatment of dendritic ulcers. Blepharitis has been reported in patients on aciclovir ophthalmic ointment.

Sensitivity reactions have been reported but are uncommon.

The following have also been reported but may be disease-related: mild hyperaemia, discharge, lid oedema and erythema, epithelial microcysts and conjunctivitis.

Adverse reactions are listed below by MedDRA body system organ class and by frequency.

The frequency categories used are:

Very common ≥ 1/10,

Common 1/100 and < 1/10,

Uncommon ≥ 1/1,000 and <1/100,

Rare 1/10,000 and <1/1,000,

Very rare <1/10,000

Clinical trial data have been used to assign frequency categories to adverse reactions observed during clinical trials with aciclovir 3% ophthalmic ointment. Due to the nature of the adverse events observed, it is not possible to determine which events were related to the administration of the drug and which were related to the disease. Spontaneous reporting data has been used as a basis for allocating frequency for those events observed post-marketing.

Immune system disorders

Very rare: Immediate hypersensitivity reactions including angioedema and urticaria.

Eye disorders

Very common: Superficial punctate keratopathy.

This did not necessitate an early termination of therapy and healed without apparent sequelae.

Common: Transient mild stinging of the eye occurring immediately following application, conjunctivitis.

Rare: Blepharitis.

Postmarketing

There have been very rare reports of immediate hypersensitivity reactions including angiodema with topical aciclovir.

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product.

Overdosage

No untoward effects would be expected if the entire contents of the tube containing 135 mg of aciclovir were to be ingested orally. However, the accidental, repeated overdose of oral aciclovir, over several days, has resulted in gastrointestinal effects (nausea and vomiting) and neurological effects (headache and confusion). Aciclovir is dialysable by haemodialysis.

Incompatibility

None known.

Shelf-Life

3 years

Storage and Handling Instructions

Store below 25oC

Packaging Information

ACIVIR Eye Ointment: Tube of 5 gm

Information for Patients

Patients should avoid wearing contact lenses when using aciclovir ophthalmic ointment.

Patients should be informed that transient mild stinging immediately following application may occur.

 

Last updated: June 2018

Last reviewed: June 2018