For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only
Qualitative and Quantitative Composition
Aciclovir IP………………….3.0% w/w
Benzalkonium chloride IP….0.01% w/w
Dosage Form and Strength
Ophthalmic ointment of Aciclovir 3% w/w
Clinical Particulars
Therapeutic Indications
Treatment of herpes simplex keratitis.
Posology and Method of 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.
Special Warnings and Precautions for Use
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.
Drug interactions
No clinically significant interactions have been identified.
Use in Special Population
Pregnant Women
Pregnancy Category B3
A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of Aciclovir. The registry findings have not shown an increase in the number of birth defects described amongst Aciclovir exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause.
Animal studies show that aciclovir crosses the placenta readily. Aciclovir was not teratogenic in the mouse (450 mg/kg/day po), rabbit (50 mg/kg/day, sc and iv) or rat (50 mg/kg/day, sc) when dosed throughout the period of major organogenesis. In additional studies in which rats were given 3 sc doses of 100 mg/kg aciclovir on gestation day 10, fetal abnormalities, such as head and tail anomalies, were reported).
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.
Lactating Women
Limited human data show that aciclovir does not pass into breast milk following systemic administration. However, the dosage received by the nursing infant following maternal use of aciclovir ophthalmic ointment would be insignificant. Aciclovir should only be administered to nursing mothers if the benefits to the mother outweigh the potential risks to the baby.
Effects on Ability to Drive and Use Machines
Eye ointments can affect visual ability and therefore caution is advised when driving or using machines.
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.
Post-marketing
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 or you can report to Cipla Ltd. on 18002677779. By reporting side effects, you can help provide more information on the safety of this product.
Overdose
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.
Pharmacological Properties
Mechanism of Action
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.
Pharmacodynamic Properties
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.
Pharmacokinetic Properties
Aciclovir is rapidly absorbed from the ophthalmic ointment through the corneal epithelium and superficial ocular tissues, achieving significant antiviral concentrations in the aqueous humor. It has not been possible by existing methods to detect aciclovir in the blood after topical application to the eye. However, trace quantities are detectable in the urine. These levels are not therapeutically significant.
Nonclinical Properties
Animal Toxicology or Pharmacology
The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir does not pose a genetic risk to man.
Aciclovir was not found to be carcinogenic in long-term studies in the rat and the mouse.
Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses of aciclovir greatly in excess of those employed therapeutically. Two generation studies in mice did not reveal any effect of orally administered aciclovir on fertility.
Systemic administration of aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rats, rabbits or mice.
In a non-standard test in rats, foetal abnormalities were observed, but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.
Description
Aciclovir is a synthetic acyclic purine nucleoside analogue. Its chemical name is 9-((2 hydroxyethoxy)methyl)guanine. It is a white crystalline powder. Each gram of Aciclovir Ophthalmic Ointment contains 30 mg of aciclovir in white soft paraffin base (aciclovir 3 per cent).
Pharmaceutical Particulars
Incompatibilities
None known.
Shelf-Life
As on the pack
Packaging Information
ACIVIR Eye Ointment: Tube of 5 gm
Storage and Handling Instructions
Store below 25oC.
Patient Counselling Information
Patients should avoid wearing contact lenses when using ACIVIR ophthalmic ointment.
Patients should be informed that transient mild stinging immediately following application may occur.
Details of Manufacturer
Mfd. By Cipla Ltd.
Registered Office:
Cipla House, Peninsula Business Park,
Ganpatrao Kadam Marg
Lower Parel
Mumbai – 400 013, India
Details of Permission or Licence Number with Date
28A-KD/2149-A – 2017
Date of Revision
18/12/2019