Ikervis

Ikervis

ciclosporin

Manufacturer:

Santen

Distributor:

DKLL
Full Prescribing Info
Contents
Ciclosporin.
Description
One mL of emulsion contains 1 mg of ciclosporin.
Action
Pharmacotherapeutic Group: Ophthalmologicals, other ophthalmologicals. ATC Code: S01XA18.
Pharmacology: Pharmacodynamics: Mechanism of Action: Ciclosporin (also known as ciclosporin A) is a cyclic polypeptide immunomodulator with immunosuppressant properties. It has been shown to prolong survival of allogeneic transplants in animals and significantly improved graft survival in all types of solid organ transplantation in man.
Ciclosporin has also been shown to have an anti-inflammatory effect. Studies in animals suggest that ciclosporin inhibits the development of cell-mediated reactions. Ciclosporin has been shown to inhibit the production and/or release of pro-inflammatory cytokines, including interleukin 2 (IL-2) or T-cell growth factor (TCGF.) It is also known to up-regulate the release of anti-inflammatory cytokines. Ciclosporin appears to block the resting lymphocytes in the G0 or G1 phase of the cell cycle. All available evidence suggests that ciclosporin acts specifically and reversibly on lymphocytes and does not depress haematopoiesis or has any effect on the function of phagocytic cells.
In patients with dry eye disease, a condition that may be considered to have an inflammatory immunological mechanism, following ocular administration, ciclosporin is passively absorbed into T-lymphocyte infiltrates in the cornea and conjunctiva and inactivates calcineurin phosphatase. Ciclosporin-induced inactivation of calcineurin inhibits the dephosphorylation of the transcription factor NF-AT and prevents NF-AT translocation into the nucleus, thus blocking the release of pro-inflammatory cytokines such as IL-2.
Pharmacokinetics: Formal pharmacokinetic studies have not been conducted in humans with IKERVIS.
Blood concentrations of IKERVIS were measured using a specific high-pressure liquid chromatography-mass spectrometry assay. In 374 patients from the two efficacy studies, plasma concentrations of ciclosporin were measured before administration and after 6 months (SICCANOVE study and SANSIKA study) and 12 months of treatment (SANSIKA study). After 6 months of ocular instillation of IKERVIS once per day, 327 patients had values below the lower limit of detection (0.050 ng/mL) and 35 patients were below the lower limit of quantification (0.100 ng/mL). Measurable values not exceeding 0.206 ng/mL were measured in eight patients, values considered to be negligible. Three patients had values above the upper limit of quantification (5 ng/mL) however they were already taking oral ciclosporin at a stable dose, which was allowed by the studies' protocol. After 12 months of treatment, values were below the low limit of detection for 56 patients and below the low limit of quantification in 19 patients. Seven patients had measurable values (from 0.105 to 1.27 ng/mL), all considered to be negligible values. Two patients had values above the upper limit of quantification, however they were also on oral ciclosporin at a stable dose since their inclusion in the study.
Indications/Uses
Treatment of severe keratitis in adult patients with dry eye disease, which has not improved despite treatment with tear substitutes.
Dosage/Direction for Use
IKERVIS treatment must be initiated by an ophthalmologist or a healthcare professional qualified in ophthalmology.
Posology: Adults: The recommended dose is one drop of IKERVIS once daily to be applied to the affected eye(s) at bedtime. Response to treatment should be reassessed at least every 6 months.
If a dose is missed, treatment should be continued on the next day as normal. Patients should be advised not to instill more than one drop in the affected eye(s).
Elderly patients: The elderly population has been studied in clinical studies. No dose adjustment is required.
Patients with renal or hepatic impairment: The effect of IKERVIS has not been studied in patients with hepatic or renal impairment. However, no special considerations are needed in these populations.
Paediatric population: There is no relevant use of IKERVIS in children and adolescents aged below 18 in the treatment of severe keratitis in adult patients with dry eye disease, which has not improved despite treatment with tear substitutes.
Method of administration: Ocular use.
Precautions to be taken before administering the medicinal product: Patients should be instructed to first wash their hands.
Prior to administration, the single-dose container should be gently shaken.
For single use only. Each single-dose container is sufficient to treat both eyes. Any unused emulsion should be discarded immediately.
Patients should be instructed to use nasolacrimal occlusion and to close the eyelids for 2 minutes after instillation, to reduce the systemic absorption. This may result in a decrease in systemic undesirable effects and an increase in local activity.
If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 15 minutes apart. IKERVIS should be administered last.
Overdosage
A topical overdose is not likely to occur after ocular administration. If overdose with IKERVIS occurs, treatment should be symptomatic and supportive.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Active or suspected ocular or peri-ocular infection.
Special Precautions
IKERVIS has not been studied in patients with a history of ocular herpes and should therefore be used with caution in such patients.
Contact lenses: Patients wearing contact lenses have not been studied. Careful monitoring of patients with severe keratitis is recommended. Contact lenses should be removed before instillation of the eye drops at bedtime and may be reinserted at wake-up time.
Concomitant therapy: There is limited experience with IKERVIS in the treatment of patients with glaucoma. Caution should be exercised when treating these patients concomitantly with IKERVIS, especially with beta-blockers which are known to decrease tear secretion.
Effects on the immune system: Medicinal products, which affect the immune system, including ciclosporin, may affect host defences against infections and malignancies.
Co-administration of IKERVIS with eye drops containing corticosteroids could potentiate the effects of IKERVIS on the immune system.
Excipient: IKERVIS contains cetalkonium chloride which may cause eye irritation.
Effects on the Ability to Drive and Use Machines: IKERVIS has moderate influence on the ability to drive and use machines.
This medicinal product may induce temporary blurred vision or other visual disturbances which may affect the ability to drive or use machines.
Patients should be advised not to drive or use machines until their vision has cleared.
Fertility: There is no data on the effects of IKERVIS on human fertility.
No impairment of fertility has been reported in animals receiving intravenous ciclosporin.
Women of childbearing potential/contraception in females: IKERVIS is not recommended in women of childbearing potential not using effective contraception.
Use In Pregnancy & Lactation
Use in Pregnancy: There is no data from the use of IKERVIS in pregnant women.
Studies in animals have shown reproductive toxicity following systemic administration of ciclosporin at exposure considered sufficiently in excess of the maximum human exposure indicating little relevance to the clinical use of IKERVIS.
IKERVIS is not recommended during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus.
Use in Lactation: Following oral administration, ciclosporin is excreted in breast milk. There is insufficient information on the effects of ciclosporin in newborns/infants. However, at therapeutic doses of ciclosporin in eye drops, it is unlikely that sufficient amounts would be present in breast milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from IKERVIS therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Adverse Reactions
Summary of the safety profile: In four clinical studies including 532 patients who received IKERVIS and 398 who received an IKERVIS vehicle (control), IKERVIS was administered at least once a day in both eyes, for up to one year. The most common adverse reactions were eye pain (19%), eye irritation (17.8%), lacrimation (6.2%), ocular hyperaemia (5.5%) and eyelid erythema (1.7%) which were usually transitory and occurred during instillation.
The majority of adverse reactions reported in clinical studies with the use of IKERVIS were ocular, and mild to moderate in severity.
Tabulated list of adverse reactions: The following adverse reactions listed below were observed in clinical studies. They are ranked according to system organ class and classified according to the following convention: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), or not known (cannot be estimated from the available data). (See Table.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Instillation site pain was a frequently reported local adverse reaction associated with the use of IKERVIS during clinical trials. It is likely to be attributable to ciclosporin.
One case of severe epithelial erosion of the cornea identified as corneal decompensation by the investigator resolved without sequeleae was reported.
Patients receiving immunosuppressive therapies, including ciclosporin, are at increased risk of infections.
Both generalised and localised infections can occur. Pre-existing infections may also be aggravated.
Cases of infections have been reported uncommonly in association with the use of IKERVIS.
Drug Interactions
No interaction studies have been performed with IKERVIS.
Combination with other medicinal products that affect the immune system: Co-administration of IKERVIS with eye drops containing corticosteroids could potentiate the effects of ciclosporin on the immune system.
Storage
Do not store above 30°C. Protect from light.
Do not freeze.
After opening of the aluminium pouches, the single-dose containers should be kept in the pouches in order to protect from light and avoid evaporation. Any opened individual single-dose container with any remaining emulsion should be discarded immediately after use.
ATC Classification
S01XA18 - ciclosporin ; Belongs to the class of other ophthalmologicals .
Presentation/Packing
Eye drops 1 mg/mL (milky white emulsion) x 6 x 5's.
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