Gatifloxacin

S01A - Antiinfectives ATC S01AX21 Small molecule approved 1999 Oral Parenteral Topical Withdrawn

JFDA label: Gatistar

Mechanism of Action

Inhibitor of DNA gyrase — DNA gyrase inhibitor; Inhibitor of Topoisomerase IV — Topoisomerase IV inhibitor

Target	Action	Gene / class
DNA gyrase efficacy	INHIBITOR
Topoisomerase IV efficacy	INHIBITOR

Indications

Approved

Conjunctivitis

Off-label

Bacterial keratitis

Contraindications

Source: Lexicomp

Hypersensitivity to gatifloxacin, other quinolones, or any component of the formulation 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

Metabolism and nutrition disorders (1)

Common Chemosis

Gastrointestinal disorders (1)

Common Dysgeusia

Eye disorders (13)

Common Conjunctival hemorrhage · conjunctival irritation · conjunctivitis (worsening) · decreased visual acuity · dry eye syndrome · eye discharge · eye irritation · eye pain · eye redness · eyelid edema · increased lacrimation · keratitis · papillary conjunctivitis

Dosing

Source: Lexicomp

Bacterial conjunctivitis: Ophthalmic: Zymar [Canadian product]: Days 1 and 2: Instill 1 drop into affected eye(s) every 2 hours while awake (maximum: 8 times/day). Days 3 to 7: Instill 1 drop into affected eye(s) 4 times/day while awake. Zymaxid: Day 1: Instill 1 drop into affected eye(s) every 2 hours while awake (maximum: 8 times/day). Days 2 to 7: Instill 1 drop into affected eye(s) 2 to 4 times/day while awake. Bacterial keratitis (off-label use): Ophthalmic: Instill 1 drop into affected eye(s) every 1 hour around the clock until healing begins (usually 48 to 72 hours); dosing frequency is then gradually reduced until the ulcer is completely healed, at which point, treatment can be discontinued (Parmar 2006; Shah 2010). One suggested tapering regimen is as follows: Days 3 to 6: Instill 1 drop into affected eye(s) every 2 hours around the clock; Days 7 to 9: Instill 1 drop into affected eye(s) every 2 hours while awake; Day 9 and on: Instill 1 drop into affected eye(s) every 6 hours and continue at this frequency until complete healing of ulcer (Shah 2010). Note: For central or severe keratitis, a loading dose of instillation every 5 to 15 minutes for the first 30 to 60 minutes may be considered (AAO 2013).

(For additional information see "Gatifloxacin: 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

Hypersensitivity reactions, including anaphylactic reactions, angioedema (including pharyngeal, laryngeal, or facial edema), dyspnea, urticaria, and itching, have been reported (even following a single dose) with topical ophthalmic gatifloxacin. Rare cases of Stevens-Johnson syndrome were also reported. If an allergic reaction occurs, discontinue use.

Superinfection

Prolonged use may result in fungal or bacterial superinfection. If superinfection is suspected, institute appropriate alternative therapy. Special populations:

Contact lens wearers

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

Appropriate use

For topical ophthalmic use only. Do not inject ophthalmic solution subconjunctivally or introduce directly into the anterior chamber of the eye (may cause corneal endothelial cell injury).

Pregnancy & Lactation

Pregnancy

Systemic concentrations of gatifloxacin following ophthalmic administration are below the limit of quantification. 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 gatifloxacin is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother.

Chemistry & Properties

Formula	C19H22FN3O4
Molecular weight	375.4 g/mol
IUPAC name	1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
CAS	112811-59-3
PubChem CID	5379
InChIKey	`XUBOMFCQGDBHNK-UHFFFAOYSA-N`
logP	1.98 (XLogP -0.7)
Polar surface area	83.8 Å²
H-bond acceptors / donors	6 / 2
Drug-likeness (QED)	0.85
Lipinski violations	0

SMILES

COc1c(N2CCNC(C)C2)c(F)cc2c(=O)c(C(=O)O)cn(C3CC3)c12

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)OATP1A2 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Abarelix	major
Abiraterone	major
Acarbose	major
Acetohexamide	major
Albiglutide	major
Alimemazine	major
Alogliptin	major
Aminolevulinic acid	major
Anagrelide	major
Apalutamide	major
Arsenic trioxide	major
Astemizole	major
Betamethasone	major
Bicalutamide	major
Bosutinib	major
Bupropion	major
Cabozantinib	major
Canagliflozin	major
Ceritinib	major
Chloroquine	major
Chlorpropamide	major
Cilostazol	major
Cisapride	major
Clarithromycin	major
Crizotinib	major
Dapagliflozin	major
Dasatinib	major
Daunorubicin	major
Daunorubicin (liposomal)	major
Deflazacort	major
Degarelix	major
Dexamethasone	major
Dicoumarol	major
Dolasetron	major
Doxepin	major
Doxepin (topical)	major
Doxorubicin	major
Doxorubicin (liposomal)	major
Dulaglutide	major
Empagliflozin	major

Showing 40 of 100+.

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Gatistar	Solution as Sesquihydrate 0.3 %	5 ml	Nabulsi Drug Store	2.890
Zymaxid Ophthalmic Solution	Ophthalmic Solution 5 mg/ml	2.5 ml	Arab Company for Medical & Agricultural Products	6.060