Bromfenac

S01B - Antiinflammatory agents ATC S01BC11 Small molecule approved 1997 Topical Natural product Withdrawn

JFDA label: REELAC Eye Drops

Mechanism of Action

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase 1 and 2, which results in decreased formation of prostaglandin precursors.

Indications

Approved

Postoperative ocular inflammation/pain

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Hypersensitivity to bromfenac, or any component of the formulation Absolute
There are no contraindications listed in the manufacturer’s labeling. Documentation of allergenic cross-reactivity for nonsteroidal anti-inflammatory drugs (NSAIDs) is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Common Headache

Blood and lymphatic system disorders (1)

Not Known Prolonged bleeding time

Eye disorders (10)

Common abnormal sensation in eyes · Anterior chamber inflammation · conjunctival hyperemia · eye irritation · eye pain · eye pruritus · eye redness · iritis · ocular hypertension · vitreous opacity

General disorders and administration site conditions (1)

Not Known Wound healing impairment

Dosing

Source: Lexicomp

Postoperative ocular inflammation/pain: Ophthalmic (0.07%): Instill 1 drop into affected eye(s) once daily beginning 1 day prior to cataract surgery and continue on the day of surgery and for 14 days postoperatively. Ophthalmic (0.075%): Instill 1 drop into affected eye(s) twice daily beginning 1 day prior to cataract surgery and continue on the day of surgery and for 14 days postoperatively. Ophthalmic (0.09% once daily formulation): Instill 1 drop into affected eye(s) once daily beginning 1 day prior to cataract surgery and continue on the day of surgery and for 14 days postoperatively Ophthalmic (0.09% twice-daily formulation): Instill 1 drop into affected eye(s) twice daily beginning 24 hours after cataract surgery and continue through the first 14 days postoperatively.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.

Warnings & Precautions

Source: Lexicomp

Aspirin/NSAID sensitivity

Use with caution in patients with previous sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs, including patients who experience bronchospasm, asthma, rhinitis, or urticaria following NSAID or aspirin therapy.

Corneal effects

May cause keratitis. Continued use may cause severe corneal adverse effects, including corneal thinning, erosion, perforation, or ulceration; may result in loss of vision. Discontinue use in patients with evidence of corneal epithelial damage.

Delayed healing

Healing time may be slowed or delayed. Use with caution in patients receiving concomitant topical steroid therapy due to an increased risk for healing problems. Disease-related concerns:

Bleeding disorders

Use with caution in patients with a predisposition to bleeding (bleeding tendencies or medications which interfere with coagulation). Increased intraocular bleeding (including hyphema) has been reported following surgery.

Diabetes

Use with caution in patients with diabetes mellitus; may be at risk of corneal adverse events, potentially resulting in loss of vision.

Ocular disease

Use with caution in patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, ocular surface disease, or repeat ocular surgeries (within a short timeframe); may be at risk of corneal adverse events, potentially resulting in loss of vision.

Rheumatoid arthritis

Use with caution in patients with rheumatoid arthritis; may be at risk of corneal adverse events, potentially resulting in loss of vision. Special populations:

Postsurgical patients

To minimize the risk of infection following surgery of both eyes, two separate bottles of eye drops (one for each eye) should be used; instruct patients not to use the same bottle for both eyes. Dosage form specific issues:

Benzalkonium chloride

May contain benzalkonium chloride as a preservative.

Sulfites

May contain sulfites, which may cause allergic-type reactions in susceptible individuals. Other warnings/precautions:

Contact lenses

Contact lenses should be removed prior to instillation (bromfenac drops contain benzalkonium chloride which may be adsorbed by contact lens); may be reinserted after 10 minutes.

Duration of therapy

Use for more than 1 day prior to surgery or for 14 days beyond surgery may increase risk and severity of corneal adverse events.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies. Exposure to nonsteroidal anti-inflammatory drugs late in pregnancy may lead to premature closure of the ductus arteriosus and may inhibit uterine contractions; some manufacturers recommend avoiding use in late pregnancy.

Lactation

It is not known if bromfenac is excreted in breast milk. The manufacturer recommends that caution be exercised when administering bromfenac to nursing women. According to one manufacturer, the decision to breast-feed during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Chemistry & Properties

Formula	C15H12BrNO3
Molecular weight	334.17 g/mol
IUPAC name	2-[2-amino-3-(4-bromobenzoyl)phenyl]acetic acid
CAS	91714-94-2
PubChem CID	60726
InChIKey	`ZBPLOVFIXSTCRZ-UHFFFAOYSA-N`
logP	2.89 (XLogP 3.3)
Polar surface area	80.39 Å²
H-bond acceptors / donors	3 / 2
Drug-likeness (QED)	0.67
Lipinski violations	0

SMILES

Nc1c(CC(=O)O)cccc1C(=O)c1ccc(Br)cc1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Inhibitor	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	—

Receptor binding (top 1)

Target	Action	Affinity
COX-1 (PTGS1)	Inhibitor	pIC50 8.1

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Acalabrutinib	major
Apixaban	major
Betrixaban	major
Cabozantinib	major
Dalteparin	major
Dasatinib	major
Deferasirox	major
Desirudin	major
Diatrizoate	major
Drotrecogin alfa	major
Edoxaban	major
Enoxaparin	major
Everolimus	major
Fondaparinux	major
Ibritumomab tiuxetan	major
Ibrutinib	major
Iohexol	major
Iopamidol	major
Iopromide	major
Iothalamic acid	major
Ioversol	major
Ioxilan	major
Leflunomide	major
Methotrexate	major
Omacetaxine mepesuccinate	major
Panobinostat	major
Ponatinib	major
Prasugrel	major
Ramucirumab	major
Regorafenib	major
Rivaroxaban	major
Sirolimus	major
Tacrolimus	major
Temsirolimus	major
Teriflunomide	major
Tositumomab (I-131)	major
Vorapaxar	major
Warfarin	major
Acetylsalicylic acid	moderate
Alteplase	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
REELAC Eye Drops	Ophthalmic Solution 0.1035 g/100 ml	5 ml	شركة عمان للصناعات الدوائية / Amman Pharmaceutical Indusries / General	4.960