Consumer medicine information

Cequa

Ciclosporin

BRAND INFORMATION

Brand name

Cequa

Active ingredient

Ciclosporin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cequa.

What is in this leaflet

This leaflet answers some common questions about CEQUA eye drops. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking CEQUA against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What CEQUA eye drops are used for

CEQUA is used to treat a condition known as 'keratoconjunctivitis sicca' which is also known as 'dry eye'. When you have this condition, your tear glands do not produce enough tears and your eyes can become dry, red and irritated.

Your doctor will give you CEQUA if you have this condition and treatment with tear substitute medicines alone have not worked.

CEQUA belongs to a group of medicines called immunosuppressants. It works by reducing inflammation and increasing tear production so that your eyes are better lubricated.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

CEQUA is not addictive.

CEQUA is available only with a doctor's prescription.

CEQUA is not expected to affect your ability to drive a car or operate machinery.

There is not enough information to recommend the use of this medicine for children under the age of 18 years.

Before you use CEQUA eye drops

When you must not use it

Do not use CEQUA if you have an allergy to:

  • any medicine containing ciclosporin
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use this medicine if you are pregnant.

Do not use this medicine if you have an eye infection or think you may have an eye infection.

Do not use this medicine if you have a cancer of the eye or around the eye.

Possible effects of CEQUA on a developing baby have not been studied and are unknown.

Do not breast-feed if you are taking this medicine. Possible effects of CEQUA on a breast-feeding baby have not been studied and are unknown.

Do not give this medicine to a child under the age of 18 years. Safety and effectiveness in children younger than 18 years have not been established.

Do not use CEQUA after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking CEQUA, talk to your doctor.

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you use contact lenses as you must not use CEQUA while you are wearing contact lenses. Your contact lenses must be removed before you use CEQUA and may be reinserted 15 minutes after using CEQUA.

Tell your doctor if you are using artificial tears as you must not apply artificial tears at the same time as CEQUA. You can apply artificial tears 15 minutes after applying CEQUA.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start using CEQUA.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food store.

Some medicines and CEQUA may interfere with each other. These include:

  • other eye drops.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to use CEQUA eye drops

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to use

One drop of CEQUA twice daily (about 12 hours apart) into each eye. You can use other artificial tears eye drops but you should wait at least 15 minutes after applying CEQUA.

How to use it

If you are wearing contact lenses, remove them first and wait at least 15 minutes after using CEQUA before reinserting.

Detach the ampoule from the connecting plastic strip and then twist the top off the plastic ampoule.

Tilt your head back and squeeze one drop into each eye.

To avoid injury, be careful not to touch your eye with the tip of the ampoule.

Immediately discard the ampoule after each use. Do not store any opened CEQUA ampoules.

When to use it

As CEQUA should not be used more than twice a day and use should be about 12 hours apart, a morning and evening application is recommended. Using it at the same times each day may help you remember when to use it.

It does not matter if you use this medicine before or after food.

How long to use it

Continue using your medicine for as long as your doctor tells you.

This medicine helps to control your condition but does not cure it.

If you forget to use it

If it is less than about 12 hours before your next dose, skip the dose you missed and use your next dose when you are meant to.

Do not use a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

It is unlikely that you will use too much CEQUA, however, if you or anyone else has, or you or anyone else has accidentally swallowed CEQUA, telephone your doctor or the Poisons Information Centre at 13 11 26 (Australia) and 0800 764 766 (New Zealand) for advice or go to Accident and Emergency at the nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using CEQUA eye drops

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking CEQUA.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking CEQUA.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking CEQUA. It may affect other medicines used during surgery.

If you become pregnant while taking CEQUA, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking CEQUA.

Keep all your doctor's appointments so that your progress can be checked.

Things you must not do

Do not use CEQUA to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor. If you stop taking it suddenly, your condition may worsen. If possible, your doctor will reduce the amount you use each day.

Do not store any opened CEQUA ampoules.

Things to be careful of

If you are wearing contact lenses, remove them first before applying CEQUA.

To avoid injury, be careful not to touch your eye with the tip of the ampoule.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking CEQUA.

This medicine helps most people with your condition, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • pain, stinging or itchiness in your eye that persists after you add the drops to your eyes
  • persistent red or bloodshot eyes.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

If you suffer from damage to the clear layer at the front of your eye (the cornea), the phosphates in CEQUA may very rarely cause cloudy patches on your eye. Tell your doctor if you notice this.

Tell your doctor as soon as possible if you notice any of the following:

  • light sensitivity and/or blurred vision.

This could indicate a serious side effect that may require medical attention. Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using CEQUA eye drops

Storage

Keep your medicine in the foil pouch until you want to use it. The ampoules may not keep well out of the foil pouch.

Keep your medicine in a cool dry place where the temperature stays below 25°C.

Do not freeze.

Do not store your medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

CEQUA is a clear, colourless liquid in soft plastic ampoules connected in cards of 5 ampoules. Two cards are enclosed in a sealed foil pouch and there are 6 foil pouches in a carton (60 ampoules per carton).

Ingredients

Each CEQUA ampoule contains 225 micrograms of ciclosporin as the active ingredient plus the following excipients:

  • PEG-40 hydrogenated castor oil
  • octoxinol 40
  • povidone
  • dibasic sodium phosphate
  • monobasic sodium phosphate dihydrate
  • sodium chloride
  • water for injections
  • sodium hydroxide or hydrochloric acid to adjust pH.

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

This medicine is preservative free.

Supplier

CEQUA is supplied in Australia by:

Sun Pharma ANZ Pty Ltd
ABN 17 110 871 826
12 Waterloo Road
Macquarie Park Sydney NSW 2113
Telephone: 1800 726 229
Email:[email protected]

AUST R number 313780

CEQUA is sponsored in New Zealand by:

CARSL Consulting
P O Box 766
Hastings 4156

This leaflet was prepared in October 2022.

Published by MIMS February 2023

BRAND INFORMATION

Brand name

Cequa

Active ingredient

Ciclosporin

Schedule

S4

 

1 Name of Medicine

Ciclosporin.

2 Qualitative and Quantitative Composition

Cequa contains ciclosporin 900 microgram/mL as the active ingredient. It has an osmolality of 160 to 190 mOsmol/kg and a pH of 6.5-7.2.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops.
Cequa is a sterile, clear, colourless solution, practically free from visible particulates.

4 Clinical Particulars

4.1 Therapeutic Indications

Cequa is indicated to increase tear production in patients with moderate to severe keratoconjunctivitis sicca (dry eye) where prior use of artificial tears has not been sufficient.

4.2 Dose and Method of Administration

For topical ophthalmic use.
Each Cequa ampoule is for single use in one patient only.
Instill one drop of Cequa twice daily (approximately 12 hours apart) into the affected eye(s).
Response to treatment should be reassessed at least every 6 months.
Cequa can be used concomitantly with artificial tears, allowing a 15-minute interval between products. Discard the ampoule immediately after using in both eyes.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.
Active or suspected ocular or peri-ocular infection (see Section 4.4 Special Warnings and Precautions for Use).
Ocular or peri-ocular malignancies or premalignant conditions.

4.4 Special Warnings and Precautions for Use

Potential for eye injury and contamination.

To avoid the potential for eye injury and contamination, advise patients not to touch the ampoule tip to the eye or other surfaces.

Use with contact lenses.

Cequa should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of Cequa ophthalmic solution.
Patients wearing contact lenses have not been studied.
Careful monitoring of patients with severe keratitis is recommended.

Infections.

Resolve existing or suspected ocular or peri-ocular infections before initiating Cequa treatment. If an infection occurs during treatment, Cequa should be temporarily withheld until the infection has been resolved.

Effects on the immune system.

Ophthalmic medicinal products, which affect the immune system, including ciclosporin, may affect host defenses against local infections and malignancies. Therefore, regular examination of the eye(s) is recommended, e.g. at least every 6 months, when Cequa is used for long periods.

Use in the elderly.

No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.

Paediatric use.

The safety and efficacy of Cequa ophthalmic solution have not been established in paediatric patients below the age of 18.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No data available.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Male and female fertility were unaffected by ciclosporin in rats at oral doses up to 15 mg/kg/day (more than 1500 times higher than the maximum recommended human ophthalmic dose, based on body surface area-adjusted doses for a 50 kg subject).
(Category C)
There are no adequate and well-controlled studies of Cequa administration in pregnant women. Studies in animals do not indicate a likely risk of embryofetal harm with ophthalmic use of ciclosporin. No embryofetal toxicity was observed with ciclosporin at oral doses of 17 mg/kg/day in the rat and 30 mg/kg/day in the rabbit, which are approximately 1800 and 6200 times higher than the maximum recommended human ophthalmic dose (based on body surface area-adjusted doses for a 50 kg subject). Embryo- and fetotoxicity; as increased pre- and postnatal mortality, reduced fetal weight and skeletal retardations, were observed in animals at higher oral doses that were maternally toxic (30 mg/kg/day in rats and 100 mg/kg/day in rabbits). The offspring of pregnant rabbits given ciclosporin subcutaneously at 10 mg/kg/day had reduced numbers of nephrons and exhibited renal hypertrophy, systemic hypertension and progressive renal insufficiency postnatally.
 Ciclosporin blood concentrations are low following topical ocular administration of Cequa (see Section 5.2 Pharmacokinetic Properties). There is no information regarding the presence of ciclosporin in human milk following topical administration or on the effects of Cequa on the breastfed infants and milk production. While systemically absorbed ciclosporin is excreted in milk, ciclosporin blood concentrations are low following topical ocular administration of Cequa (see Section 5.2 Pharmacokinetic Properties). Adverse effects in breast-fed infants are not expected given the low level of potential exposure but cannot be excluded. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Cequa and any potential adverse effects on the breast-fed child from ciclosporin.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

OTX‐101‐2014‐001 and OTX 101‐2016‐001 pooled data.

Safety data from the two 12-week pivotal studies, where a total of 524 subjects received OTX-101 0.09% (Safety Population), were pooled to provide increased sensitivity and precision. Most subjects were treated between 9 and < 13 weeks.
Subjects in the OTX-101 0.09% group had a higher incidence of any AE (38.7% versus 27.1%) and treatment-related AEs (25.2% versus 8.6%) compared with the Vehicle group. However, OTX-101 0.09% was generally well tolerated, with most AEs (approximately 70%), including ocular AEs, considered mild and did not require treatment. The most common AE was instillation site pain (OTX-101: 21.8%, Vehicle: 4.0%).
AEs of severe intensity (1.7% vs 0.8%), and events that led to interruption (0.8% vs 0.4%) or discontinuation (4.2% vs 1.7%) of study drug were low. Serious adverse events were uncommon (1.1% in both treatment groups). One subject randomized to OTX-101 0.09% in OTX-101-2016-001 died from an unknown cause, but not considered to be related to study drug. Table 1 presents treatment-emergent adverse events (TEAEs) reported in ≥ 2% of subjects in the Safety Population.

OTX‐101‐2016‐002 safety extension study.

All 258 subjects from the phase 3 study OTX-101-2016-001 who subsequently participated in the open-label 40-week OTX-101-2016-002 extension study were treated with OTX-101 0.09%. Of these, 129 subjects had previously received OTX-101 0.09% (Group 1) and another 129 subjects received Vehicle (Group 2) during the 12-week OTX-101-2016-001 study period. At completion of the extension study, a total of 225 subjects had more than 6 months exposure to OTX-101 0.09%, including 138 subjects who had ≥ 12 months of total exposure. The overall mean duration of exposure was 10.42 months.
An analysis of AEs in the full safety population for OTX-101-2016-002 did not reveal any new findings. There were no changes to the SAE profile. Instillation site pain remained the most commonly reported AE. It was reported at a higher incidence, as expected, in subjects who had received Vehicle prior to being switched to OTX-101 0.09%.
Besides instillation site pain (22.9%), conjunctival hyperemia (10.1%), and punctate keratitis (6.2%) were the most commonly reported TEAEs. Punctate keratitis was reported by more subjects in Group 1, but it was considered unrelated to treatment in all cases but one, and the difference is attributed to the natural variability of the presentation of KCS. Table 2 presents the TEAEs reported in ≥ 2% of total subjects.
Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.

Post‐marketing experience.

Infections and infestations.

Urinary tract infection.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ciclosporin is a calcineurin inhibitor immunosuppressant agent when administered systemically. It is able to inhibit the activation of transcription factors required for T-cell activation and inflammatory cytokine production. In patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca, topical administration of ciclosporin is thought to act as a partial immunomodulator. The exact mechanism of action in treating keratoconjunctivitis sicca is not known.

Clinical trials.

Two multicentre, randomised, vehicle-controlled clinical studies treated 1,048 patients with keratoconjunctivitis sicca (OTX-101-2014-001 and OTX-101-2016-001). In both studies, compared to vehicle at Day 84, there was a statistically significant (p < 0.01) higher percentage of eyes with increases of ≥ 10 mm from baseline in Schirmer wetting. This effect was seen in approximately 17% of Cequa-treated patients versus approximately 9% of vehicle-treated patients. Table 3 presents data from the studies.

5.2 Pharmacokinetic Properties

Absorption.

Blood concentrations of ciclosporin after twice daily topical ocular administration of Cequa into each eye of healthy subjects for up to 7 days, and once on Day 8, were either not detectable or were marginally above the lower limit of assay quantitation of 0.100 nanogram/mL (range 0.101 to 0.195 nanogram/mL) for up to 2 hours after a single dose, and up to 4 hours after multiple doses.

5.3 Preclinical Safety Data

Genotoxicity.

Ciclosporin was not genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA-repair test in sperm from treated mice. An in vitro sister chromatid exchange (SCE) assay using human lymphocytes gave indications of a positive effect for ciclosporin at high concentrations.

Carcinogenicity.

Systemic carcinogenicity studies were carried out in mice and rats. A 78-week mouse study, at oral doses of 1, 4, and 16 mg/kg/day, revealed a trend for increased incidences of lymphomas at the highest dose studied. In another study with ARK mice treated with ciclosporin at 150 mg/kg in the diet, ciclosporin accelerated the development of lymphomas.
In a 24-month rat study, conducted at oral doses of 0.5, 2, and 8 mg/kg/day, no significant increase in tumour incidence was observed. Adjusted for body surface area, the highest doses without tumourigenic effect in the mouse and rat are approximately 210 and 830 times higher than the maximum recommended ophthalmic dose of ciclosporin provided by Cequa therapy.

6 Pharmaceutical Particulars

6.1 List of Excipients

PEG-40 hydrogenated castor oil, octoxinol 40, povidone, dibasic sodium phosphate, monobasic sodium phosphate dihydrate, sodium chloride, water for injections and sodium hydroxide or hydrochloric acid to adjust pH.

6.2 Incompatibilities

Cequa should not be administered to patients while they are wearing contact lenses (see Section 4.4 Special Warnings and Precautions for Use).

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Do not freeze. Store the ampoules in the original foil pouch. Protect from light.

6.5 Nature and Contents of Container

Cequa ophthalmic solution is packaged in single-use LDPE ampoules. Each ampoule contains 0.25 mL of the solution.
Cequa ampoules are packaged in cartons of 10 or 60 ampoules: 10 ampoules (2 cards of 5 ampoules) are packaged in a polyfoil aluminum pouch; 1 pouch (10s) or 6 pouches (60s) are packaged in the cartons. The carton of 10 ampoules is a sample pack only.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material can be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Ciclosporin is a white powder that is insoluble in water and freely soluble in ethanol.

Chemical structure.

Mol. Formula: C62H111N11O12.
Mol. Wt.: 1202.6.

CAS number.

59865-13-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes