Fluorometholone
JFDA label: Flucon Eye Drops
Mechanism of Action
Agonist of Glucocorticoid receptor — Glucocorticoid receptor agonist
| Target | Action | Gene / class |
|---|---|---|
| Glucocorticoid receptor efficacy | AGONIST | NR3C1 |
Indications
Approved
- Ocular inflammation
Contraindications
Source: Lexicomp
- Hypersensitivity to fluorometholone, other corticosteroids, or any component of the formulation Absolute
- acute purulent untreated eye infections which may be masked/enhanced by a steroid Absolute
- mycobacterial or fungal infections of the eye Absolute
- viral diseases of the cornea and conjunctiva (including epithelial herpes simplex keratitis, vaccinia, and varicella) Absolute
Adverse Reactions
Immune system disorders (1)
Not Known Hypersensitivity reaction
Metabolism and nutrition disorders (1)
Not Known Hypercorticoidism (rare)
Gastrointestinal disorders (1)
Not Known Dysgeusia
Skin and subcutaneous tissue disorders (1)
Not Known Skin rash
Eye disorders (22)
Not Known Bacterial eye infection (secondary) · blurred vision · burning sensation of eyes · cataract · decreased visual acuity · erythema of eyelid · eye discharge · eye irritation · eye pain · eye pruritus · eyelid edema · foreign body sensation of eye · fungal eye infection (secondary) · glaucoma · increased intraocular pressure · increased lacrimation · optic nerve damage · stinging of eyes · swelling of eye · viral eye infection (secondary) · visual field defect · wound healing impairment
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Cataracts
Prolonged use of corticosteroids may result in posterior subcapsular cataract formation. Use following cataract surgery may delay healing or increase the incidence of bleb formation.
Corneal thinning
Various ophthalmic disorders, as well as prolonged use of corticosteroids, may result in corneal and scleral thinning. Continued use in a patient with thinning may result in perforation.
Glaucoma
Prolonged use of corticosteroids may result in elevated intraocular pressure (IOP) and/or glaucoma; damage to the optic nerve; and defects in visual acuity and fields of vision. Use with caution in patients with glaucoma; monitor IOP in any patient receiving treatment for ≥10 days.
Immunosuppression
Prolonged use of corticosteroids may increase the incidence of secondary infection (including fungal infections). Acute purulent ocular infections may be masked or exacerbated with use. Fungal infection should be suspected in any patient with persistent corneal ulceration who has received corticosteroids. Disease-related concerns:
Herpes simplex
Use caution in patients with history of herpes simplex; frequent slit lamp microscopy is recommended. Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:
Contact lens wearers
Some products contain benzalkonium chloride which may be adsorbed by contact lenses; remove contacts prior to administration and wait 15 minutes before reinserting. Other warnings/precautions:
Appropriate use
Patients should be re-evaluated if symptoms fail to improve after 2 to 14 days (product specific). Initial prescription and renewal of medication >20 mL (suspension) or >8 g (ointment) should be made by health care provider only after examination with the aid of magnification such as slit lamp biomicroscopy or fluorescein staining (if appropriate).
Discontinuation of therapy
In chronic conditions, withdraw therapy with gradual tapering of dose.
Pregnancy & Lactation
Pregnancy
Adverse events were observed in animal reproduction studies following use of ophthalmic fluorometholone. The extent of systemic absorption following topical application of the ophthalmic drops is not known. If ophthalmic agents are needed during pregnancy, the minimum effective dose should be used in combination with punctual occlusion to decrease potential exposure to the fetus (Samples 1988).
Lactation
Systemic corticosteroids are excreted in human milk. The extent of systemic absorption following topical application of the ophthalmic drops is not known. The manufacturer recommends that caution be exercised when administering fluorometholone to breastfeeding women.
Monitoring
| Clinical pearl | Intraocular pressure when used for ≥10 days; signs or symptoms of infection. |
|---|
Chemistry & Properties
| Formula | C22H29FO4 |
|---|---|
| Molecular weight | 376.47 g/mol |
| IUPAC name | (6S,8S,9R,10S,11S,13S,14S,17R)-17-acetyl-9-fluoro-11,17-dihydroxy-6,10,13-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one |
| CAS | 426-13-1 |
| PubChem CID | 9878 |
| InChIKey | FAOZLTXFLGPHNG-KNAQIMQKSA-N |
| logP | 2.92 (XLogP 2.0) |
| Polar surface area | 74.6 Ų |
| H-bond acceptors / donors | 4 / 2 |
| Drug-likeness (QED) | 0.74 |
| Lipinski violations | 0 |
SMILES
CC(=O)[C@@]1(O)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]21CBiology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | Yes |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2B6 | Inhibitor | — |
| CYP2C8 | Inhibitor | — |
| CYP3A4 | Inhibitor | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 1)
| Target | Action | Affinity |
|---|---|---|
| Glucocorticoid receptor (NR3C1) | Agonist | pKi 8.8 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Registered Products (4)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Fluoron Ophthalmic | Ophthalmic Solution 0.1 % | 5 ml pack varies | Amman Pharmaceutical Indusries | 0.820 |
| Fluoron Ophthalmic | Ophthalmic Solution 0.1 % | 10 ml pack varies | Amman Pharmaceutical Indusries | 1.560 |
| Flucon Eye Drops | Ophthalmic Solution 0.1 % | 5 ml | The Jordan Drugstore Co | 1.880 |
| F.M.L. | Solution 0.1 % | 5 ml | Arab Company for Medical & Agricultural Products | 2.060 |