Source: Health Products and Food Branch (CA) Revision Year: 2019
ZYMAR is contraindicated in individuals who have shown hypersensitivity to gatifloxacin, to other quinolones, or to any of the components in this medication. (See DOSAGE FORMS, STRENGTH AND COMPOSITION).
NOT FOR INJECTION INTO THE EYE. FOR TOPICAL OPHTHALMIC USE ONLY.
ZYMAR should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
ZYMAR contains the preservative benzalkonium chloride (see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
Contact of the tip of the bottle with the eye or surrounding structures may lead to eye injury and contamination of the eye drops.
The use of gatifloxacin with other products may lead to drug interactions. For established or potential drug interactions (see DRUG INTERACTIONS).
As with all topical ophthalmic drugs, there is a potential for a systemic reaction.
As with any ocular medication, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinery.
If an allergic reaction to gatifloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.
Hypersensitivity reactions including anaphylactic reaction, dyspnea, rash, Stevens-Johnson syndrome and urticaria have been reported in association with ZYMAR (see ADVERSE REACTIONS).
Systemic quinolones have been associated with hypersensitivity reactions, even following a single dose.
In patients receiving systemic quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.
As with all antibiotics, serious and sometimes fatal events, some due to hypersensitivity and some due to uncertain etiology, have been reported in patients receiving systemic quinolone therapy. These events may be severe and generally occur following administration of multiple doses. Clinical manifestations may include one or more of the following: fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis, interstitial nephritis; acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.
Tendon inflammation and rupture may occur with systemic fluoroquinolone therapy including gatifloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids. Treatment with ZYMAR should be discontinued at the first sign of tendon inflammation.
As with other members of the quinolone class, gatifloxacin has caused arthropathy and/or chondrodysplasia in juvenile rats and dogs when given systemically. (See TOXICOLOGY, Special Toxicity Studies).
Arthrotoxic and osteotoxic potential of ZYMAR was not assessed in animals.
Patients should not wear contact lenses while they have signs and symptoms of bacterial conjunctivitis. ZYMAR contains the preservative benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses.
Prescribing ZYMAR in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of drug-resistant organisms.
As with other anti-infectives, prolonged use of ZYMAR may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
There are no adequate and well-controlled studies of ZYMAR in pregnant women. This drug should not be used in pregnant women unless, in the physician’s opinion, the potential benefit to the mother justifies the potential risk to the fetus. ZYMAR solution has not been studied in pregnant animals. Oral and intravenous studies in pregnant animals indicate that gatifloxacin crosses the placenta and that reproductive and fetal effects occur at doses of 150 mg/kg/day, which cause maternal toxicity (see TOXICOLOGY).
It is not known whether gatifloxacin is excreted in human milk, although gatifloxacin has been shown to be excreted in the breast milk of rats. Because gatifloxacin may be excreted in human milk, a decision should be made either to discontinue nursing or to discontinue the administration of ZYMAR, taking into account the importance of ZYMAR therapy to the mother and the possible risk to the infant.
The safety and efficacy of ZYMAR in infants below the age of one year have not been established. ZYMAR ophthalmic solution has been used to treat conjunctivitis in 14 infants between 1-2 years of age and 47 children between 3-12 years of age.
No overall differences in safety or effectiveness have been observed between elderly and younger patients.
In clinical studies 364 patients were treated with ZYMAR for up to 5 days. Treatment-related adverse events were reported for 14.6% (53/364) of patients. The most frequently reported treatment-related adverse events occurring in 0.5% to 5% of patients treated with gatifloxacin are listed below:
Table 1. Percent of Patients in Phase 3 Trials with Treatment-Related Adverse Events Reported by 0.5% to 5% of Patients in the Active Treatment Arm:
| Body System Preferred Term | Gatifloxacin N=364 |
|---|---|
| Ocular | |
| Superficial punctate keratitis | 4.4% |
| Eye irritation | 1.9% |
| Dry eye | 1.6% |
| Eyelid oedema | 1.4% |
| Lacrimation increased | 1.4% |
| Visual acuity reduced | 1.1% |
| Eye pain | 0.8% |
| Conjunctivitis papillary | 0.8% |
| Eye discharge | 0.5% |
| Other (Non Ocular) | |
| Erythema | 0.8% |
| Dermatitis, contact | 0.5% |
| Taste disturbance | 1.4% |
| Rhinorrhea | 0.5% |
| Edema | 0.5% |
Other treatment-related adverse events occurring in less than 0.5% of patients included, conjunctival disorder, conjunctivitis, chemosis, conjunctival cyst, conjunctival hemorrhage, corneal deposits, eye disorder, photophobia, subepithelial opacities, blurred vision, dermatitis, generalized urticaria, nausea, sore throat, sneezing, dizziness, and iritis.
ZYMAR was discontinued due to an adverse event, either related or unrelated to the drug, in 1.6% (6/364) of patients.
The following additional adverse reactions have been identified during postmarketing use of gatifloxacin ophthalmic solution 0.3% in clinical practice. Because postmarketing reporting of these reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions.
Eye Disorders: blepharitis allergic, corneal disorder, corneal ulcer, endophthalmitis, eye edema (including corneal and conjunctival edema), eye redness, eye pruritus, keratoconjunctivitis, macular edema, uveitis.
Rare cases of corneal melts and perforation have been reported in patients with multiple confounding factors including preexisting large corneal ulcer, corneal thinning, undiagnosed dacryocystitis, and use of multiple topical medications. Thus, it is difficult to determine the relationship of the events to ZYMAR.
In one case, an elderly female with chronic conjunctivitis due to methicillin-resistant Staphylococcus aureus and a history of dacrocystitis, reported corneal perforation. This patient was using multiple concomitant antibiotics and had demonstrated evidence of a corneal defect associated with the infection prior to using ZYMAR and continued using ZYMAR during a successful post operative repair healing period.
Immune System Disorders: anaphylactic reactions, angioneurotic edema (including pharyngeal, oral or facial edema), hypersensitivity, pruritus allergic, rash, Stevens-Johnson syndrome.
Nervous System Disorders: headache, paraesthesia oral, tinnitus, tremor.
Respiratory, Thoracic and Mediastinal Disorders: dyspnea.
Specific drug interaction studies have not been conducted with ZYMAR ophthalmic solution. Limited information is available on the concurrent use of ZYMAR with other ophthalmic products.
Interactions with drugs have not been established.
Probenecid:
Systemic administration of gatifloxacin (single oral 200 mg dose) with probenecid (500 mg BID x 1 day) resulted in a 42% increase in AUC and 44% longer half-life of gatifloxacin.
Digoxin:
Overall, only modest increases in Cmax and AUC of digoxin were noted (12% and 19%, respectively) in 8 of 11 healthy volunteers who received concomitant administration of gatifloxacin (400 mg oral tablet, once daily for 7 days) and digoxin (0.25 mg orally, once daily for 7 days). In 3 of 11 subjects, however, a significant increase in digoxin concentrations was observed. In these 3 subjects, digoxin Cmax increased by 18%, 29%, and 58% while digoxin AUC increased by 66%, 104%, and 79%, and digoxin clearance decreased by 40%, 51%, and 45%.
Systemic studies have also shown that gatifloxacin is chelated by polyvalent ions, such as iron, magnesium, zinc and aluminum.
No significant pharmacokinetic interactions occur when cimetidine, midazolam, theophylline, warfarin, or glyburide is administered concomitantly with oral gatifloxacin.
Interactions with food have not been established.
Interactions with herbal products have not been established.
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