FML FORTE

Fluorometholone is a synthetic fluorinated corticosteroid that is structurally related to progesterone. It is indicated for treating corticosteroid-responsive allergic and inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. Fluorometholone is one of three ophthalmic corticosteroids preferred for long-term treatment because it is less likely to increase intraocular pressure. Fluorometholone was approved by the FDA in July 1982.

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Ophthalmic Administration
-Administer topically to the eye; do not administer by any other route.
-Wash hands before and after use.
-Tilt patient's head back slightly and pull the lower eyelid down to form a pouch. Try not to touch the tip of the dropper to the eye, fingertips, or any other surface. Squeeze the prescribed number of drops into the pouch. Have patient close the eye gently to spread the drops.
-Administer doses at regular intervals.
-Administer ophthalmic solutions or suspensions prior to applying eye ointments. Allow 5-10 minutes between different ocular product applications.
-To prevent infection of the eyes, do not share any eye products or other personal care items with other patients.

Ophthalmic corticosteroids can cause ocular hypertension after 1-6 weeks of use. In a small study, the average time to produce an increase in intraocular pressure demonstrated by fluorometholone was significantly longer than dexamethasone; however, the final magnitude of the increase was equivalent for both drugs. Once the medication is discontinued, ocular pressures usually reverse to normal within a few weeks. With long term administration, open-angle glaucoma can occur. Intraocular pressure should be checked frequently during treatment. Other adverse effects include glaucoma with optic nerve damage, visual impairment with acuity and field defects, and posterior subcapsular cataract formation. Following prolonged topical administration (more than two years), other corticosteroids have caused posterior subcapsular cataracts that do not regress when the drug is withdrawn.

Like other corticosteroids, fluorometholone can reduce host resistance to secondary ocular infection (bacterial, fungal and viral); acute purulent infections may be masked or exacerbated. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion should be considered in any persistent corneal ulceration. In diseases that cause thinning of the cornea or sclera, topical steroids have been known to cause perforation. Delayed or impaired wound healing has also been reported.

Ocular irritation, including transient stinging and burning, may occur upon instillation of fluorometholone, especially when using the ointment or the 0.25% suspension. Allergic reactions, ocular inflammation or swelling, rash (unspecified), blurred vision, ocular pain, ocular discharge, increased lacrimation, blepharedema, foreign body sensation, ocular pruritus, conjunctival hyperemia, and blepharitis have all been reported with use.

Although systemic effects are extremely uncommon ophthalmic fluorometholone administration, it should be noted that there have been rare occurrences of systemic hypercorticoidism after use of topical dermatologic steroids applied to the skin. Corticosteroid-containing preparations have also been reported to cause acute anterior uveitis and perforation of the globe. Conjunctivitis, keratoconjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids. If any of these reactions occur, ophthalmic fluorometholone should be considered. Systemic absorption can be limited by compression of the lacrimal sac on administration of ophthalmic suspensions.

In some instances, given appropriate anti-infective treatment concurrently, ocular corticosteroids can be used to limit serious ocular damage.

Fluorometholone is contraindicated in most viral diseases of the cornea and conjunctiva, including acute superficial herpes simplex virus epithelial keratitis, varicella, and viral infection. Patients with other active herpes infection of the eye (stromal keratitis or uveitis) should not receive fluorometholone unless in conjunction with antiviral therapy. Persons with a history of herpes infections should be prescribed ocular corticosteroids with caution. In addition, the use of ocular corticosteroids may exacerbate the severity of many viral infections of the eye.

Fluorometholone is contraindicated in mycobacterial infection and fungal infection of the eye or ocular structures. Depending on the severity and the use of concurrent anti-infective agents, bacterial infections of the eye may also preclude use of fluorometholone. The use of the ointment may be more prone to retard corneal healing.

Fluorometholone preparations are contraindicated in anyone with known hypersensitivity to the drug or components of the individual preparations. Patients who wear contact lenses should be aware that benzalkonium chloride, a preservative in many of the fluorometholone products, can be absorbed by soft contact lenses. Patients wearing soft contact lenses should wait >= 15 minutes before inserting their lenses.

Because fluorometholone has resulted in increased intraocular pressures in some individuals, this drug should be used cautiously in patients with glaucoma. If any patient receives this drug beyond 10 days, intraocular pressure should be monitored.

Fluorometholone is classified in FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, fluorometholone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether ophthalmic administration of fluorometholone results in sufficient systemic absorption to produce detectable quantities in breast milk; but pharmacokinetic studies indicate that systemic absorption after ophthalmic administration of fluorometholone is limited and therefore unlikely that a significant amount of drug would be excreted into breast-milk. The drug is likely compatible with breast-feeding. To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

The safety and efficacy of fluorometholone preparations in neonates, infants and children < 2 years have not been established.

For the treatment of corticosteroid-responsive ophthalmic disorders including allergic conjunctivitis, ocular burns or trauma due to corneal injury resulting from chemical, thermal or penetration trauma, giant papillary conjunctivitis (GPC), keratitis, postoperative ocular inflammation, vernal keratoconjunctivitis, and chronic anterior uveitis:
Ophthalmic dosage (Flarex 0.1% ophthalmic suspension):
Adults: 1 to 2 drops in the affected eye(s) 4 times daily; may increase dose to 2 drops in the affected eye(s) every 2 hours for the first 24 to 48 hours. Reevaluate if no improvement after 2 weeks.
Ophthalmic dosage (FML Liquifilm 0.1% or 0.25% ophthalmic solution):
Adults: 1 drop in the affected eye(s) 2 to 4 times daily; may increase dose to 1 drop in the affected eyes every 4 hours for the first 24 to 48 hours. Reevaluate if no improvement after 2 days. Withdraw treatment by gradually decreasing dose in chronic conditions.
Children and Adolescents 2 to 17 years: 1 drop in the affected eye(s) 2 to 4 times daily; may increase dose to 1 drop in the affected eyes every 4 hours for the first 24 to 48 hours. Reevaluate if no improvement after 2 days. Withdraw treatment by gradually decreasing dose in chronic conditions.
Ophthalmic dosage (0.1% ointment):
Adults: 0.5 inch ribbon in the affected eye(s) 1 to 3 times daily; may increase dose to 0.5 inch ribbon in the affected eye(s) every 4 hours for the first 24 to 48 hours. Reevaluate if no improvement after 2 days. Withdraw treatment by gradually decreasing dose in chronic conditions.
Children and Adolescents 2 to 17 years: 0.5 inch ribbon in the affected eye(s) 1 to 3 times daily; may increase dose to 0.5 inch ribbon in the affected eye(s) every 4 hours for the first 24 to 48 hours. Reevaluate if no improvement after 2 days. Withdraw treatment by gradually decreasing dose in chronic conditions.

Maximum Dosage Limits:
Corticosteroid dosage must be individualized and is highly variable depending on the nature and severity of the disease and on patient response. Renewal of fluorometholone prescriptions beyond 20 ml of ophthalmic suspension or 8 grams of ophthalmic ointment should be made by only after re-examination with the aid of magnification.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

There are no drug interactions associated with Fluorometholone products.

Ocular topical corticosteroids exert anti-inflammatory activity against inciting agents of mechanical, chemical or immunological nature. The exact mechanism in ocular disease remains to be elucidated. Corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. These lipocortins are postulated to control the biosynthesis of mediators of inflammation, especially prostaglandins and leukotrienes, via inhibiting the release of the precursor molecule arachadonic acid. In ocular medicine, these actions inhibit edema, capillary dilatation, migration of leukocytes, fibrin and collagen deposition, and scar formation associated with inflammation. Ocular application of corticosteroids also results in potentiation of epinephrine vasoconstriction, decreased macrophage movement, and stabilization of lysosomal membranes. Corticosteroids are able to increase intraocular pressures, the degree of which is related to the relative potency of the agent employed, as well as the concentration of the agent and the release from the pharmaceutical vehicle. Decreases in vascularization and scarring make these agents useful in limiting tissue damage in chemical and thermal exposures.

Pharmacokinetics:
Fluoromethalone is administered via the ophthalmic route. Like most ophthalmic corticosteroids, fluoromethalone is absorbed through the aqueous humor, and distributes into the local tissues. Minimal systemic absorption occurs. Fluorometholone has lower systemic penetration activity than other ocular steroids, such as dexamethasone. The low overall doses used in ophthalmic administration usually circumvent the appearance of clinical evidence of systemic absorption. Metabolism of the ocular corticosteroids occurs locally. Ophthalmic ointments will have a lower metabolic clearance rate than solutions or suspensions due to product formulation and contact times.