Besifloxacin

S01A - Antiinfectives ATC S01AE08 Small molecule approved 2009 Topical

JFDA label: Besivance 0.6%

Mechanism of Action

Inhibits both DNA gyrase and topoisomerase IV. DNA gyrase is an essential bacterial enzyme required for DNA replication, transcription, and repair. Topoisomerase IV is an essential bacterial enzyme required for decatenation during cell division. Inhibition effect is bactericidal.

Indications

Approved

Bacterial conjunctivitis

Contraindications

Source: Lexicomp

There are no contraindications listed in the manufacturer's labeling 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

Eye disorders (5)

Common blurred vision · Conjunctival erythema · eye irritation · eye pain · eye pruritus

Dosing

Source: Lexicomp

Bacterial conjunctivitis: Ophthalmic: Instill 1 drop into affected eye(s) 3 times daily (4 to 12 hours apart) for 7 days

(For additional information see "Besifloxacin: Pediatric drug information") Bacterial conjunctivitis: Children ≥1 year and Adolescents: Ophthalmic: Refer to adult dosing.

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

Hypersensitivity reactions

Severe hypersensitivity reactions, including anaphylaxis, have occurred with systemic quinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.

Superinfection

Prolonged use may result in fungal or bacterial superinfection. Discontinue use and initiate alternative therapy if superinfection occurs. Special populations:

Contact lens wearers

Contact lenses should not be worn during treatment of ophthalmic infections. Dosage form specific issues:

Ophthalmic solution

For topical ophthalmic use only. Do not inject ophthalmic solution subconjunctivally or introduce directly into the anterior chamber of the eye.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in some animal reproduction studies. Systemic concentrations of besifloxacin following ophthalmic administration are low. If ophthalmic agents are needed during pregnancy, the minimum effective dose should be used in combination with punctual occlusion for 3 to 5 minutes after application to decrease potential exposure to the fetus (Samples 1988).

Lactation

It is not known if besifloxacin is excreted into breast milk. The manufacturer recommends that caution be exercised when administering besifloxacin to nursing women.

Chemistry & Properties

Formula	C19H21ClFN3O3
Molecular weight	393.85 g/mol
IUPAC name	7-[(3R)-3-aminoazepan-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
CAS	141388-76-3
PubChem CID	10178705
InChIKey	`QFFGVLORLPOAEC-SNVBAGLBSA-N`
logP	3.14 (XLogP 1.1)
Polar surface area	88.56 Å²
H-bond acceptors / donors	5 / 2
Drug-likeness (QED)	0.84
Lipinski violations	0

SMILES

N[C@@H]1CCCCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2Cl)C1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.742 h
Volume of distribution	1.701 L/kg
Protein binding	45.6%
BBB penetrant	No

Transporters

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

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Besivance	Solution 0.6 %	5 ml	Petra Drug Store	9.050