Zioptan

Mechanism Of Action

Tafluprost acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is believed to reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown at this time.

Pharmacokinetics

Following instillation, tafluprost is absorbed through the cornea and is hydrolyzed to the biologically active acid metabolite, tafluprost acid. Following instillation of one drop of the 0.0015% solution once daily into each eye of healthy volunteers, the plasma concentrations of tafluprost acid peaked at a median time of 10 minutes on both Days 1 and 8. The mean plasma Cmax of tafluprost acid were 26 pg/mL and 27 pg/mL on Day 1, and Day 8, respectively. The mean plasma AUC estimates of tafluprost acid were 394 pg*min/mL and 432 pg*min/mL on Day 1 and 8, respectively.

Tafluprost, an ester prodrug, is hydrolyzed to its biologically active acid metabolite in the eye. The acid metabolite is further metabolized via fatty acid β-oxidation and phase II conjugation.

Mean plasma tafluprost acid concentrations were below the limit of quantification of the bioanalytical assay (10 pg/mL) at 30 minutes following topical ocular administration of tafluprost 0.0015% ophthalmic solution.

Clinical Studies

In clinical studies up to 24 months in duration, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 23 to 26 mm Hg who were treated with ZIOPTAN® dosed once daily in the evening demonstrated reductions in intraocular pressure at 3 and 6 months of 6 to 8 mmHg and 5 to 8 mmHg, respectively.

Zioptan is a prescription medication used to treat open-angle glaucoma or ocular hypertension. Zioptan belongs to a group of drugs called prostaglandin analogs, which work by helping excess fluid drain from the eye, lowering the pressure in the eye.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• any other eyedrops
• bematoprost (Lumigan, Latisse)
• latanoprost (Xalatan)

This is not a complete list of Zioptan drug interactions. Ask your doctor or pharmacist for more information.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Zioptan there are no specific foods that you must exclude from your diet when receiving Zioptan.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Ocular hypotensive agent; fluorinated analog of prostaglandin F2α (PGF2α).1 8 9

• Importance of not exceeding once daily dosing; more frequent administration may decrease IOP-lowering effect of tafluprost.1

• Importance of administering tafluprost ophthalmic solution immediately after opening single-use container and discarding any unused portion immediately after administration.1

• Risk of permanent increased brown pigmentation of the iris; risk of darkening of the skin around the eyes (eyelid), which may be reversible after discontinuance of tafluprost.1

• Risk of changes in eyelashes and vellus hair.1 Potential for disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth if only one eye is treated.1 Eyelash changes are usually reversible after discontinuance of tafluprost.1

• Importance of patients informing a clinician if they develop a new ocular condition (e.g., trauma, infection), experience a sudden decrease in visual acuity, have ocular surgery or experience ocular reactions (particularly conjunctivitis and eyelid reactions).1

• Importance of administering different topical ophthalmic preparations at least 5 minutes apart.1

• Importance of following instruction on proper storage of cartons, unopened foil pouches, and opened foil pouches.1 (See Storage under Stability.) Importance of noting the date the foil pouch was opened in the space provided on the pouch and of discarding unused containers after 28 days.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Women of childbearing potential should use effective contraceptive methods during tafluprost therapy.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

In the U.S.

• Zioptan

Available Dosage Forms:

• Solution

Therapeutic Class: Antiglaucoma

Pharmacologic Class: Prostaglandin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Because of tafluprost's toxicity, use in children is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tafluprost eye drops in the elderly.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Eye lens is missing (aphakia) or
• Eyes lens is torn—Use with caution. May cause more side effects.

• Eye pigmentation (extra color in the eye) or
• Iritis (eye inflammation) or
• Macular edema (swelling in the back of the eye) or
• Uveitis (eye inflammation)—Use with caution. May make these conditions worse.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Blurred vision
• burning, dry, or itching eyes
• decreased vision
• eye discharge or excessive tearing
• eye pain
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache
• stinging or irritation of the eye

• Cough
• darker color of the eyelashes
• dry eyes
• increased growth of the eyelashes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to treat glaucoma.
• It is used to lower high eye pressure.

Pregnancy

Pregnancy Category C.

Teratogenic effects: In embryo-fetal development studies in rats and rabbits, tafluprost administered intravenously was teratogenic. Tafluprost caused increases in post-implantation losses in rats and rabbits and reductions in fetal body weights in rats. Tafluprost also increased the incidence of vertebral skeletal abnormalities in rats and the incidence of skull, brain and spine malformations in rabbits. In rats, there were no adverse effects on embryo-fetal development at a dose of 3 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid that were 343 times the maximum clinical exposure based on Cmax. In rabbits, effects were seen at a tafluprost dose of 0.03 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid during organogenesis that were approximately 5 times higher than the clinical exposure based on Cmax. At the no-effect dose in rabbits (0.01 mcg/kg/day), maternal plasma levels of tafluprost acid were below the lower level of quantification (20 pg/mL).

In a pre- and postnatal development study in rats, increased mortality of newborns, decreased body weights and delayed pinna unfolding were observed in offsprings. The no observed adverse effect level was at a tafluprost intravenous dose of 0.3 mcg/kg/day which is greater than 3 times the maximum recommended clinical dose based on body surface area comparison.

There are no adequate and well-controlled studies in pregnant woman. Although animal reproduction studies are not always predictive of human response, Zioptan should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Women of childbearing age/potential should have adequate contraceptive measures in place.

Nursing Mothers

A study in lactating rats demonstrated that radio-labeled tafluprost and/or its metabolites were excreted in milk. It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zioptan is administered to a nursing woman.

Pediatric Use

Use in pediatric patients is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

Geriatric Use

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

An overdose of Zioptan is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medication.