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SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT KORTOS Cream 2. QUALITY AND QUANTITATIVE COMPOSITION Active ingredients: 1g of Kortos Cream contains: 5 mg of hydrocortisone acetate 25 mg of benzocaine

100 mg of benzalkonium chloride 20 mg of bismuth subgallate Excipients:

For a full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM Cream 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Kortos Cream is used for the symptomatic treatment of acute hemorrhoids, anal fissure and anal pruritus. 4.2. Posology and method of administration Kortos Cream is applied to the anorectal area once or twice a day, unless advised otherwise by a physician. Kortos Cream may be used concomitantly with Kortos Suppositories in the presence of internal hemorrhoids. 4.3. Contraindications Kortos Cream should not be used in case of contraindication in patients with known hypersensitivity to any of the components. Kortos Cream should not be used in the presence of tuberculosis of rectum and anal region, fungal infections and during living virus vaccinations because of hydrocortisone acetate in composition. Due to the risk of systemic side effects, it should be used with caution in patients with peptic ulcer, osteoporosis, psychosis, severe psychoneurosis, diabetes, congestive heart failure, chronic renal failure and in elderly patients. However the amount of hydrocortisone acetate of the preparation and its rectal absorption rate are low.

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4.4. Special warning and precautions for use It should not be used during the first trimester of pregnancy, because of the possibility of systemic effects of the corticosteroid. Kortos Cream should not be applied to children. Usage of Kortos Cream longer than 7 days is not recommended. 4.5. Interaction with other medicinal products and other forms of interactions: Kortos Cream is applied for local effect. Drug interactions may only occur in case of significant systemic absorption. 4.6. Pregnancy and lactation Pregnancy category is C. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemic corticosteroids are excreted in breast milk in amounts that do not have harmful effects on infants. however, topical corticosteroids should be used with caution by nursing mothers.

4.7. Effects on ability to drive and use machines No effects on ability to drive and use machines. 4.8. Undesirable effects Systemic and local side effects due to the corticosteroid should be borne in mind. These side effects include: increased secretion of gastric acid, and peptic ulcer reactivation, retention of water and sodium (edema), loss of potassium, increase in arterial pressure in hypertensive patients, decrease of glucose tolerance. During prolonged use, Cushing's syndrome, osteoporosis, psychic disordes, acne and inhibition of surrenal cortex may result. Kortos Cream is applied to anorectal tissue for local effects. It has been reported that 26% of hydrocortisone acetate, which is administered by the rectal route in the form of suppositories, is absorbed. However, absorption may vary in abraded or inflamed surfaces. During prolonged use of high dosages of Kortos Cream, an amount which is high enough to cause systemic effects, may be absorbed. Hydrocortisone may delay the healing of wounds. Local side effects : Telangiectasia, mucosal athropy, irritation, dryness, folliculitis, hypopigmentation, secondary infection or allergic contact dermatitis. 4.9. Overdose and treatment If accidental ingestion takes place, nausea, vomiting, gastric pain and diarrhea may be observed. Swallowed cream can be taken back by gastric lavage. Purgatives may be used. For supportive treatment, oxygen and if methaemoglobinaemia occurs i.v. methylene blue may be used. Bed rest is recommended. There is no specific antidote for Kortos Cream.

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5. PHARMACOLOGICAL PROPERTIES 5.1. Pharmacodynamic properties Kortos cream contains drugs that perform antiinflammatory, antipruritic, astringent, local antibacterial and local anesthetic actions. Bismuth subgallate is an astringent agent and used in anodermal diseases. Benzocaine exerts its local anesthetic effects especially on mucous membranes. Benzalkonium chloride (1%) is a superfacial antiseptic and particularly effective against Gram positive and Gram negative bacteria, fungi and yeasts including Candida albicans. Hydrocortisone acetate is a highly effective anti-inflammatory. It has antiphlogistic, antipruritic and vasoconstrictive effects. It prevents edema and itching in a short time. 5.2. Pharmacokinetic properties: Hydrocortisone acetate may be absorbed from intact skin, if skin is inflamed absorption of hydrocortisone acetate may increase. Because of the low water solubility of benzocaine, it is barely absorbed and systemic toxicity is rarely seen. Bismuth subgallate is a water-insoluble salt. It increases mucus secretion and prevents acide diffusion. Benzalkonium chloride has rapid and long-lasting effects. 5.3. Preclinical safety data In a preclinical study, after the injections of hydrocortisone acetate into posttraumatized Achilles tendon of the adult male rat, it was demonstrated that hydrocortisone acetate had no deleterious effect on the rat biomechanically or histologically. In another preclinical study, it was demonstrated that after infiltration of hydrocortisone into rabbit calcaneal tendons, necrosis of collagen produced at the site of injection and corticosteroid injection delays the repair of lesion on the tendon. Transport rate was determined by an in vivo endoscopic method in rabbit tracheas. the ciliary beat activity (frequency) and the mucociliary transport rate were not significantly affected by 0.02% of benzalkonium chloride, whereas they were completely halted by 0.05% of benzalkonium chloride. In a study, fifty-six rabbits were treated with 4 topical anesthetics and the onset time of all anesthetic agents was within 1 minute; however, bupivacaine and lidocaine produced significantly longer action than procaine or benzocaine. Corneal sensation, corneal toxicity, and corneal epithelial healing time were measured. No significant corneal epithelial time and corneal toxicity were observed.

In another study with 40 Wistar rats, two standard wounds (3.5mm x 2 mm) were made using a biopsy punch on the back of each animal. Test wounds were filled with bismuth subgallate

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and control wounds with 0.9% saline.. There were no significant histological differences between test and control according to the qualitative evolution of the granulation tissue morphology. It was concluded that bismuth subgallate is biocompatible to the healing tissue, and did not interfere with the normal development of wound healing. 6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients Dimeticone 200 Liquid paraffin White petrolatum (vaseline) Cetyl alcohol Span 60 Compritol 888 ATO Tween 60 Potassium dihhdrogen phosphate Sorbitol (70% solution) Water 6.2. Incompatibilities

No incompatibilities have been reported.

6.3. Shelf life

24 months 6.4. Special precautions for storage

Store at room temperature below 25C. 6.5. Nature and contents of container

Laminated polyfoil tubes Package size: 30 g 6.6. Instructions for use and handling, and disposal No special requirements. 7. MARKETING AUTHORISATION HOLDER Embil la Sanayii Ltd. ti. Merkez Mahallesi Birahane Sok. No:28 ili-stanbul 8. MARKETING AUTHORISATION NUMBER(S) 184/ 3

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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorization: 11.08.1997 10. KBN YENLENME TARH