Cyclosporine Ophthalmic Emulsion - Uses, Dosage, and Side Effects

Overview:

Cyclosporine ophthalmic emulsion has been approved by the United States Food and Drug Administration. Cyclosporine is categorized under immunosuppressants.

Cyclosporine has been used to treat certain eye conditions like keratoconjunctivitis sicca (dryness of conjunctiva and cornea) and vernal keratoconjunctivitis (an allergic eye condition). It increases tear production in the eye during these keratoconjunctivitis conditions, which causes dry eyes.

What Are Dry Eyes?

A dry eye is a multifactorial condition that occurs when tears cannot lubricate the eyes and are not adequate and stable. Many reasons can cause dry eyes. Dry eyes can cause damage to the eye surface. In the United States, dry eyes have affected five to thirty percent of the population. Dry eyes affect the quality of life, and their symptoms impair daily activities such as driving, reading, or watching television.

Symptoms of Dry Eyes:

• A burning or scratching sensation in the eye.

• Stringy mucus around the eyes.

• Redness of the eye.

• Sensitivity to light.

• Blurred vision.

• Watery eyes.

Causes of Dry Eyes:

• Tear film dysfunctioning can be due to hormone changes, autoimmune diseases, inflamed eyelids, and allergic eye disease.

• Decreased tear production related to aging, Sjogren's syndrome, or other conditions like lupus and scleroderma or any medications leading to decreased tears.

• Increased tear evaporation can occur related to vitamin A deficiency and less blinking.

How Does Cyclosporine Emulsion Work for Dry Eyes?

The ophthalmic Cyclosporine increases tear production by decreasing eye infection and swelling to allow the tear to produce.

Mechanism of Action of Cyclosporine:

Cyclosporine is an immunosuppressant medication. It affects the immune system by interfering with the production of T-cells. Cyclosporine enters the cytoplasm of the T-cells and binds to Cyclophilin. The binding complex of Cyclosporine affects T-cells by blocking the action of Calcineurin and preventing de-phosphorylation. It also affects the mitochondria and epithelial cell death by blocking mitochondrial permeability transition pore opening. Cyclosporine also activates the Fas/FasL and caspase.

Dosage:

Dosage Form - Solution and emulsion.

Dose Strength - 0.05 milligram per milliliter.

• Single-use vials - Each vial contains 0.4 milliliters of Cyclosporine.

• Multidose vials - Each bottle contains 5.5 milliliters of Cyclosporine.

Dose Restriction - Cyclosporine should be instilled in each eye twice daily (after every 12 hours).

Special Considerations:

• Allergies - The patient should always inform the doctor about allergies, if any. Allergies to food items, dyes, preservatives, or animals are involved in it.

• Pediatrics - The safety and efficacy of Cyclosporine are not established in children below the age of four.

• Geriatric - Safety and efficacy have not been established in older people. The medical conditions have varied the results.

• Breastfeeding Mothers - No relevant results determine infants' risks while using Cyclosporine in breastfeeding mothers.

For Patients:

What Are Cyclosporines?

Cyclosporine is an immunosuppressant medicine that comes in the form of eye drops used to increase tear production by decreasing the inflammation of the eye.

What Is the Use of Cyclosporine Ophthalmic Emulsion?

Cyclosporine ophthalmic emulsion is primarily used to treat dry eyes. Dry eyes can be due to lower tear production or some other conditions like Sjogren syndrome or medications. This medicine increases the production of tears and hence lowers the inflammation and swelling of the eye.

How Is This Medicine Used?

The ophthalmic eye drops of Cyclosporine come in solution or emulsion forms. A solution is a liquid, and an emulsion combines two unmixed liquids. The medicine is to be instilled in each eye twice a day. The timings of instilling the eye drops in the eyes should be the same every day. The instructions given by the doctor should be followed, and do not use more or less medicine; use as much as recommended by the doctor.

How to Instill Medicine to the Eye?

There are a few steps to delivering the medicine into the eye. They are as follows:

• Wash the hands thoroughly with soap and water.

• Follow the instructions given above the package.

• When using an emulsion form, turn over the bottle until the liquid inside looks white.

• Remove the cap of the bottle.

• Do not touch the dropper tip against the eye.

• Tilt the head back and pull the lower eyelid with the index finger to form the pocket of the eyelid.

• Hold the dropper with the other hand and keep it near the eye without touching it.

• Look up and subsequently squeeze the dropper over the stretched lower eyelid.

• The patient should close their eyes for two to three minutes.

• Do not blink the eye or squeeze the eyelids.

• Place pressure over the inner eyelid junction near the nose.

• Wipe out the extra liquid from the face and then wash the hands.

What Are the Important Points While Using Cyclosporine?

• Use the exact amount of dose as recommended by the doctor.

• It is exclusively for eye use only.

• Do not swallow or apply it to the skin.

• Do not touch the dropper to the eye.

• If eye lubricant or artificial tear is used, then use it 15 minutes before or after Cyclosporine.

• It should not be delivered while the lens is still inserted in the eyes.

• Please keep it away from the children and pets.

What Should a Doctor Know Before Prescribing Cyclosporine?

Inform the doctor before the doctor recommends Cyclosporine:

• If the patient is allergic to Cyclosporine.

• If the patient is planning for pregnancy or pregnant.

• If the patient is breastfeeding the child.

• If the patient is suffering from any medical conditions.

• If the patient is taking any medications or vitamins.

• If the patient is an alcoholic or tobacco chewer or inhaler.

What Diet Should Patients Follow While Taking Medicine?

There is no special diet required. The patient can continue with a regular diet. However, if the doctor recommends a supplement diet, the patient should have it.

When to Take Missed Dose?

Instill the missed dose as soon as remembered. However, if the time is near the following amount, skip the missed dose and have the next dose. Do not double the dose.

What Should Patients Do in case of an Overdose of Cyclosporine?

Although it is not so dangerous to overdose on Cyclosporine, do not take it unnecessarily or intentionally; instead, use the recommended dosage as suggested by the doctor.

What Are the Side Effects of Cyclosporine?

Side effects of Cyclosporine are:

• Burning.

• Itchiness.

• Redness.

• Pain in the eye.

• Eyelid swelling.

• Eye discharge.

• Headache.

• Feeling that something is present in the eye.

Severe side effects that require immediate doctor attention are:

• Itching.

• Face, throat, eye, and tongue swelling.

• Shortness of breath.

How to Store and Dispose of the Medicine?

The storage of medication should be in a closely tight container. It is stored at room temperature, away from excess heat and moisture. Place the container away from the children. It is very important to keep it away from children and pets.

The unrequited medicine is disposed of in special ways so that others cannot consume it unknowingly. The take-back programs are the best way to dispose of the medicine, instead of disposing of it in the garbage or flushing it in the toilet.

For Doctors:

Formulation of Cyclosporine:

• Cyclosporine is poorly soluble in water.

• Its ophthalmic Cyclosporine is formed by a homogenous emulsion of glycerin (2.2 percent), castor oil (1.25 percent), polysorbate 80 (1.00 percent), carbomer copolymer type A (0.05), purified water, and sodium hydroxide for pH adjustment.

• Cyclosporine is not found in the blood after it has been treated in the patients. A few patients who have delivered one percent are detected with a lesser blood concentration in the body.

Mechanism of Cyclosporine:

Cyclosporine is an immunosuppressant medication. It affects the immune system by interfering with the production of T-cells. Cyclosporine enters the cytoplasm of the T-cells and binds to cyclophilin. The binding complex of Cyclosporine affects T-cells by blocking the action of calcineurin and preventing de-phosphorylation. It also affects the mitochondria and epithelial cell death by blocking mitochondrial permeability transition pore opening. Cyclosporine also activates the Fas/FasL and caspase.

Indication of Cyclosporine:

The indication of Cyclosporine ophthalmic emulsion is to increase tear production in patients with dry eye conditions. It is an immunosuppressant.

How to Use Cyclosporine?

Steps to use Cyclosporine

• First, wash your hands properly.

• Rotate the bottle of vials gently, do not shake it.

• Open the eye by stretching the lower eyelid gently with index fingers to make a space.

• Drop the medicine into the space without touching the dropper tip.

• Do not blink; instead, close your eyes gently.

• Immediately after using the eye drops, wash your hands.

• If the patient is using the artificial tear (lubricant eye drops), after putting the artificial tears, make the patient wait for 15 minutes before putting the Cyclosporine eye drops into the eyes.

Dosing:

The dose of the medicine will be different for different patients. The single vial dose is given once a day. In contrast, the multi-vial is offered twice a day.

The amount of the medicine depends upon the strength of the treatment.

The number of doses taken in a day, the time allowed between the doses, and the length of the time taken for a medicine depend upon the patient's medical condition for which Cyclosporine is recommended.

To Increase Tear Production:

• For Ophthalmic Emulsion Dosage:

Adults and children under 16 and older are recommended one drop in the affected eye twice a day every 12 hours.

• For Ophthalmic Solution Dosage Form:

Adults are recommended one drop in the affected eye twice a day, and the doctor decides the children's dose.

To Treat Keratoconjunctivitis:

• For Ophthalmic Emulsion Dosage:

Adults and children four years of age and older are recommended one drop in the affected eye four times a day means morning, noon, afternoon, and evening.

The doctor decides on children's doses under age four.

Precautions While Using Cyclosporine:

• Avoid wearing contact lenses while using the medicine. Wait for 15 minutes after using the drug before returning the contact lens.

• Do not contaminate or touch the tip of the vial.

• Avoid eye injury or damage.

Cyclosporine Interactions:

Many drugs interact with Cyclosporine. They are:

• Betaxolol ophthalmic.

• Carteolol ophthalmic.

• Dexamethasone ophthalmic.

• Difluprednate ophthalmic.

• Fluocinolone ophthalmic.

• Levobetaxolol ophthalmic.

• Levobunolol ophthalmic.

• Prednisolone ophthalmic.

• Medrydone ophthalmic.

• Timolol ophthalmic.

• Triamcinolone ophthalmic.

• Rimexolone ophthalmic.

Contraindication of Cyclosporine:

• Hypersensitivity - If the patient suffers from any hypersensitivity reaction, the doctor should not recommend Cyclosporine.

Special Considerations -

• Allergies- If the patient has any allergies, they can be related to food, dye, or medicine. The doctor should know it before he recommends Cyclosporine.

• Pediatric Patients - Children below the age of 16 are not recommended for Cyclosporine, as no data or results have been determined in children below 16.

• Geriatric Patients - In the older population, Cyclosporine can not show useful results as in others because of the medical conditions of the older people.

• Pregnancy - No data and results were established in pregnant women related to Cyclosporine.

• Breastfeeding Mothers- The results on breastfeeding mothers related to Cyclosporine are not evaluated. The risks associated with infants are unknown.

Clinical Studies of Cyclosporine for Dry Eyes:

1. Cyclosporine for the Treatment of Moderate to Severe Dry Eyes: Survey study with 5884 patients with a controlled group with one-third reported decreased symptom severity by one week and two-thirds by three weeks. There were improvements in the objectives and subjective metrics. The use of emulsion has shown uniform superiority to vehicles in improving two signs of corneal staining and dry eyes—Schirmer scores in randomized vehicle-controlled trials, with three out of four studies using emulsion placebo. In vehicle studies, Cyclosporine was better than vehicle control, improving ocular dryness. Taking an average of the particular symptom or sign that improved was not consistent between the studies. Chen et al. found Cyclosporine emulsion was superior with improved ocular dryness, total dry eye score, foreign body sensation, Schirmer scoring, and corneal staining. Baiza-Duran et al. presented aqueous Cyclosporine was superior with improvement to ocular dryness, photophobia, and ocular fatigue. Sall et al. found Cyclosporine emulsion to improve blurry vision only. Stevenson et al. compared various Cyclosporine emulsion concentrations (0.05, 0.1, 0.2, 0.4 percent) to the vehicle and found the highest concentration, 0.4 percent, superior to the Schirmer scores. All Cyclosporine concentrations, when compared to vehicles, were fine with respect to gritty sensation, and most (0.05, 0.02, 0.4 percent) improved ocular dryness. On seeing the Cyclosporine efficacy over the dry eye treatments, Cyclosporine emulsion worked the same as vitamin A in the dry eye population. Cyclosporine has improved the symptoms in other populations with aqueous-based Cyclosporine suspensions to aqueous vehicles.

2. Cyclosporine for the Treatment of Severe Dry Eye: Cyclosporine efficacy was evaluated in severely dry eye conditions like Sjogren syndrome radiation-associated, Stevens-Johnson syndrome, trachoma, and graft versus host disease. Dastjerdi et al. presented 22 patients with severe dry eye who failed to improve after twice dosing. Among them, 15 patients showed improvements with frequent dosing (three to four times daily). One hundred eighty-three patients improved 0.1 percent aqueous Cyclosporine by more than 0.05 percent aqueous Cyclosporine. Cyclosporine emulsion showed decreased dry eye symptoms.

3. Cyclosporine for the Treatment of Post-refractive Surgery and Contact Lens-Associated Dry Eyes: Two studies have been performed on the effects of Cyclosporine emulsion after refractive surgery. A retrospective study of 40 patients showed faster baseline symptoms in Cyclosporine emulsion-treated eyes. Prospective study of 21 patients with better results in the Cyclosporine emulsion-treated group. The contact lens study showed positive results of Cyclosporine emulsion with improved symptoms.

4. Long-Term Effects of Cyclosporine Emulsion 0.05 for Dry Eye Treatment: Study conducted in patients treated with Cyclosporine emulsion for one year. It demonstrated the maintenance of effects with the once-daily dosing after stable treatment with twice-daily dosing for one year. In eight patients, it was reported that long-term resolution of chronic dry eye symptoms after long-term Cyclosporine use.

5. Cyclosporine Has Higher Doses for Treating Dry Eye: Although 0.1 percent of Cyclosporine is found safe for long-term use. The effectiveness is 0.05 and 0.1 percent doses. The studies favor the 0.05 dose by a randomized controlled study using Cyclosporine emulsion, which says 0.05 is significantly better than 0.1 percent for even the control of blurry visions. However, some studies find no differences between randomized controlled studies using various Cyclosporine emulsions concentrations (0.05, 0.1, 0.2, 0.4 percent). They report that 0.1 percent of Cyclosporine performs most consistently overall, while 0.05 percent of Cyclosporine showed the most consistent symptom improvement.