After healing of keratitis the treatment should be continued for at least 3 days.

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1 Summary of Product Characteristics 1. Name of the Medicinal Product Virupos Active ingredient: Aciclovir 2. Qualitative and Quantitative Composition: 1 g of ointment contains Aciclovir 30 mg 3. Pharmaceutical Form Eye Ointment 4. Clinical Particulars 4.1 Therapeutic Indications Keratitis caused by herpes simplex virus 4.2 Posology and Method of Administration Apply a strip of about 1 cm of eye ointment 5 times daily every 4 hours into the conjunctival sac. By closing the eye lids and moving the eyes the eye ointment is distributed on the surface of the eye. After healing of keratitis the treatment should be continued for at least 3 days. 4.3 Contraindications Virupos should not be applied in hypersensitivity against aciclovir- or valaciclovircontaining drugs. During a herpes infection of the cornea and its treatment with Virupos contact lenses should not be worn. 4.4 Special Warnings and Special Precautions for Use None.

2 4.5 Interactions with Other Medicaments and Other Forms of Interaction Not known. 4.6 Pregnancy and Lactation In patients who applied aciclovir-containing eye ointment several times a day no aciclovir could be detected in plasma. In pregnancy and lactation Virupos may be applied according to the instructions of the physician. 4.7 Effects on Ability to Drive and Use Machines Vision will be impaired when applying Virupos. Therefore, special care should be taken while driving or operating machinery or working without stable footing because reaction time may be delayed. 4.8 Side Effects Immediately after application of the eye ointment a slight, quickly subsiding burning may occur. In single cases prolonged treatment (more than 14 days) may cause superficial inflammatory reactions of the lower border of the cornea and the adjoining conjunctiva (keratoconjunctivitis punctata). This may not lead to a termination of therapy and will be cured without aftereffect. In very rare cases hypersensitivity reactions of the acute type with angioedema were reported. 4.9 Overdose Overdosing or intoxications are not to be expected when Virupos is used properly. 5. Pharmacological Properties 5.1 Pharmacodynamic Properties ATC-Code: S01AD03 Acyclovir is a pharmacologically inactive substance which penetrates preferentially into cells infected by herpes simplex virus (HSV) or varicella zoster virus (VZV). Only there the substance becomes effective as an antiviral agent because the HSV - or VZV - thymidine kinase acts as an activating catalyst. Thymidine kinase is an enzyme which the virus needs for replication and which is only found in infected host cells.

3 The antiviral action is due to the following mechanisms: 1. Aciclovir penetrates to a higher degree into cells infected by herpes simplex virus. 2. Aciclovir is phosphorylated to the monophosphate by the virale thymidine kinase which is found in these cells. 3. The conversion is continued to the triphosphate by the help of other kinases of the host cell. 4. Aciclovir triphosphate is incorporated into virale DNA instead of desoxyguanosintriphosphate by the help of virale polymerase to which the affinity is fold higher than to the human polymerase. 5. Because of the differences in the chemical structure no other nucleotid can be taken up to Aciclovir triphosphate so that the DNA chain is broken off. With this, the replication of the virus is stopped. These steps cause a very effective reduction of the virusreplication. In a Plaque-Reduction-Test in HSV-infected Vero-cells an ED 50 of 0.1 µmol Aciclovir/l was determined whereas an ED 50 of 300 µmol Aciclovir/l was necessary to inhibit the growth of non-infected Vers-cells. Withit Aciclovir has a therapeutic index of In-vitro-efficacy: Very sensitive: Herpes simplex virus Typ I and II, Varicella-Zoster-Virus sensitive: Epstein-Barr-Virus partly sensitive or resistant: Cytomegalie-Virus resistant: RNS Virus, Adenovirus, pox virus 5.2 Pharmacokinetic Properties After application of a 3 % aciclovir-containing eye ointment about 7.5 µmol/l of the active ingredient were determined in aqueous humor. This concentration is multiple higher than the concentration which is necessary for reaching antiviral activity against herpes simplex virus. Therefore even intraocular infections by herpes simplex could be treated successfully with aciclovir-containing eye ointment. After therapy with aciclovir-containing eye ointment ( 5 times daily for 14 days) no active ingredient could be determined in plasma (limit of detection 0.01 µmol/l). Concentrations of aciclovir in the blood after application of aciclovir-containing eye ointment could not be determined. 5.3 Preclinical safety data Investigations to the local tolerability of the eye ointment: Eye ointments containing 1%, 3% and 6% aciclovir were tested in comparison to ointment basis and isotonic solution of sodium chloride on healthy rabbit eyes to investigate the possibility of eye irritations. Test substances were applied into the conjunctival sac of the rabbit eye 5 times a day in a period of 1.5 hours for 21 days.

4 No significant histologic and microscopic changes in the different test groups could be observed. Changes of the fundus also did not occur. Other investigations were not conducted with this pharmaceutical form, because the resorbed amount of active substance did not lead to detectable blood levels (see also section 5.2 Pharmacokinetic properties). 6. Pharmaceutical Particulars 6.1 Other ingredients White petrolatum 6.2 Incompatibilities Not known 6.3 Shelf life The duration of stability is 3 years. Virupos should not be used beyond the expiration date (imprinted on the packaging carton). After first use Virupos should be used only for one month. 6.4 Special Precautions for Storage Virupos should not be stored above 25 C. 6.5 Nature and Contents of Container Tube with 4.5 g of eye ointment 6.6 Instruction for Use/Handling As a general rule, contact with the eye or skin surface should be avoided during the application of eye ointment. Open the tube, lean the head back slightly, and apply an one cm strip of ointment into the conjunctival sac. Close the eyes slowly. After use, close the tube carefully!

5 7. Name or Style and Permanent Address or Registered Place of Business of the Marketing Authorisation Holder URSAPHARM Arzneimittel GmbH & Co. KG Industriestraße 35 D Saarbrücken Telephone: Germany - (0) Telefax: Scientific Affairs Germany - (0) Administration/Sales Germany - (0) Production/Purchase Germany - (0) Marketing Authorisation Number N.N. 9. Date of First Authorisation/Renewal of the Authorization N.N. 10. Date of (partial) Revision of the text May 2006