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Ofloxacin (Otic)


VA CLASSIFICATION
Primary: OT101

Commonly used brand name(s): Floxin Otic.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antibacterial (otic)—

Indications

Accepted

Otitis externa (treatment)
Otitis media, acute (treatment) or
Otitis media, chronic suppurative (treatment)—Otic ofloxacin is indicated for the treatment of otitis externa (in adults and children 1 year of age and older) caused by Staphylococcus aureus and Pseudomonas aeruginosa {01}. In addition, otic ofloxacin is indicated for treatment of acute otitis media (in children 1 to 12 years of age with tympanostomy tubes) due to Staphylococcus aureus , Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , and Pseudomonas aeruginosa {01}. Otic ofloxacin is also indicated for treatment of chronic suppurative otitis media (in adults and children 12 years of age and older with perforated tympanic membranes) due to Staphylococcus aureus , Proteus mirabilis , and Pseudomonas aeruginosa {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Fluoroquinolone {01}.
Molecular weight—
    361.38 {01}


pH
    6.5 {01}.

Mechanism of action/Effect:

Bactericidal; ofloxacin acts intracellularly by inhibiting DNA gyrase. DNA gyrase is an essential bacterial enzyme that is a critical catalyst in the replication, transcription, deactivation, and repair of bacterial DNA. {01}

Absorption:

In two single-dose studies in adults with tympanostomy tubes, with and without otorrhea, mean serum ofloxacin concentrations were low after otic administration of a 0.3% ofloxacin solution (4.1 nanograms per mL [n=3] and 5.4 nanograms per mL [n=5], respectively). In a study in adults with perforated tympanic membranes, the maximum serum ofloxacin concentration after otic administration of a 0.3% solution was 10 nanograms per mL. Concentrations of ofloxacin in the middle ear mucosa of adult patients with perforated tympanic membranes (detectable in 11 of 16 subjects) varied widely, ranging from 1.2 to 602 micrograms per gram after otic administration of a 0.3% solution. Concentrations of ofloxacin in otorrhea were found to be high (389 to 2850 micrograms per gram) 30 minutes after otic administration of a 0.3% solution to 13 subjects with chronic suppurative otitis media and perforated tympanic membranes; however, this measurement does not necessarily reflect the exposure of the middle ear to ofloxacin. {01}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to systemic ofloxacin or to other quinolones or their derivatives may be sensitive to otic ofloxacin also {01}.

Carcinogenicity

Long-term studies have not been done {01}.

Mutagenicity

Ofloxacin was not found to be mutagenic in the Ames test, the sister chromatid exchange assay (Chinese hamster and human cell lines), the unscheduled DNA synthesis (UDS) assay using human fibroblasts, the dominant lethal assay, or the mouse micronucleus assay {01}. However, ofloxacin was positive in the rat hepatocyte UDS assay and in the mouse lymphoma assay {01}.

Pregnancy/Reproduction
Fertility—
Studies in male and female rats administered oral doses of ofloxacin of up to 360 mg per kg of body weight (mg/kg) per day (over 1000 times the maximum recommended clinical dose in humans, based on body surface area, assuming total absorption from the ear of a patient treated with ofloxacin otic solution twice a day) found no effect on reproductive performance {01}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done {01}.

Studies in rats and rabbits administered oral {03} doses of ofloxacin of 810 mg/kg per day and 160 mg/kg per day, respectively, found an embryocidal effect. These doses produced decreased fetal body weights and increased fetal mortality in rats and rabbits, respectively. Minor fetal skeletal variations were reported in rats administered oral {03} doses of ofloxacin of 810 mg/kg per day. No teratogenic effects have been shown in pregnant rats and rabbits administered oral {03} doses of ofloxacin as high as 810 mg/kg per day and 160 mg/kg per day, respectively. No adverse effects on the developing embryo or fetus have been found at doses relevant to the amount of ofloxacin that would be delivered topically to the ear at the recommended clinical doses. In addition, studies in rats administered oral {03} doses of ofloxacin of up to 360 mg/kg per day during late gestation found no adverse effects on late fetal development, labor, delivery, lactation, neonatal viability, or growth of the newborn. {01}

It is recommended that risk-benefit be considered before use of ofloxacin otic solution in pregnant women {01}.

FDA Pregnancy Category C {01}.

Breast-feeding

It is not known whether ofloxacin is distributed into human breast milk following topical otic administration. Administration of a single 200-mg oral dose in nursing women has been shown to produce an ofloxacin concentration in breast milk similar to that in plasma. Because of the potential for serious adverse reactions from ofloxacin in nursing infants, risk-benefit should be considered before making a decision about either continuing nursing or using the medication. {01}

Pediatrics

A study of audiometric parameters in 30 pediatric patients treated with otic ofloxacin found no changes in hearing function. Safety and efficacy in children 1 year of age and older have been demonstrated. However, safety and efficacy in children younger than 1 year of age have not been established. {01}

Although systemically administered quinolones, including ofloxacin, have been shown to cause arthropathy in immature animals, a study in which 0.3% ofloxacin otic solution was administered in the middle ear of young growing guinea pigs for 1 month found no systemic effects, quinolone-induced lesions, erosions of the cartilage in weight-bearing joints, or other signs of arthropathy {01}.


Geriatrics


No information is available on the relationship of age to the effects of otic ofloxacin in geriatric patients.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Sensitivity to ofloxacin or other quinolones or their derivatives{01}    (serious and occasionally fatal hypersensitivity [anaphylactic] reactions have been reported following systemic use of quinolones, including ofloxacin {01})



Side/Adverse Effects

Note: Systemic administration of quinolones, including ofloxacin, at doses much higher than those given or absorbed by the otic route, has resulted in lesions or erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species {01}. However, a study in which 0.3% ofloxacin otic solution was administered in the middle ear of young growing guinea pigs for 1 month found no systemic effects, quinolone-induced lesions, erosions of the cartilage in weight-bearing joints, or other signs of arthropathy {01}.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported with systemic administration of ofloxacin and other quinolones, some following the first dose. In some cases, the reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal, or facial edema), airway obstruction, dyspnea, urticaria, and itching {01}. If an allergic reaction to otic ofloxacin is suspected, it is recommended that the medication be stopped {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Application site reaction{01} (burning, itching, redness, skin rash, swelling, or other sign of irritation not present before use of this medicine)
    
dizziness or vertigo{01}

Incidence rare
    
Fever{01}
    
headache{01}
    
otorrhagia{01} (bleeding from the ear)
    
pharyngitis{01} (sore throat)
    
rhinitis or sinusitis{01} (runny or stuffy nose)
    
tachycardia{01} (fast heartbeat)
    
tinnitus{01} (ringing in the ear{01})



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Change in taste{01}
    
earache{01}
    
numbness or tingling{01}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ofloxacin (Otic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ofloxacin or other quinolones or their derivatives

Pregnancy—Studies with otic ofloxacin have not been done; because of the embryocidal and fetotoxic effects of large systemic doses in animals, risk-benefit should be considered before using during pregnancy; however, ofloxacin has not been shown to cause problems when given in doses comparable to doses administered by the otic route





Breast-feeding—It is not known whether otic ofloxacin is distributed into breast milk; however, oral ofloxacin is distributed into breast milk





Use in children—Safety and efficacy have not been established in children up to 1 year of age


Proper use of this medication
» Reading patient medication guide before using eardrops; checking with physician if patient has questions

» Proper administration technique; not touching applicator tip to any surface, including the ear, in order to avoid contamination

» Compliance with full course of therapy

» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose

» Proper storage

Precautions while using this medication
Checking with physician if no improvement within a few days

» Discontinuing medication and checking with physician immediately at the first sign of a rash or allergic reaction {01}


Side/adverse effects
Signs of potential side effects, especially application site reaction, dizziness or vertigo, fever, headache, otorrhagia, pharyngitis, rhinitis or sinusitis, tachycardia, and tinnitus


General Dosing Information
It is recommended that the bottle be held in the hand for 1 or 2 minutes before use to warm the solution; this will help prevent the dizziness that may occur following instillation of a cold solution into the ear {01}. The patient should lie with the affected ear up for instillation of the drops and hold this position for 5 minutes after instillation {01}. This procedure may then be repeated for the opposite ear, if necessary {01}.

As with other antiinfectives {03}, prolonged use may lead to overgrowth of nonsusceptible organisms, including fungi. It is recommended that cultures be obtained if the infection has not improved after 1 week, to aid in selection of further treatment. {01}

If otorrhea persists after a full course of therapy, or occurs two or more times during a period of 6 months, it is recommended that further evaluation be undertaken to exclude underlying conditions, such as cholesteatoma, foreign body, or tumor {01}.

Because of the serious anaphylactic reaction that has been reported with systemic ofloxacin, it is recommended that otic ofloxacin be discontinued at the first sign of an allergic reaction. Emergency medical treatment, including oxygen and airway management, including intubation, may be needed for serious acute hypersensitivity reactions. {01}

Ofloxacin otic solution is not for ophthalmic use or for injection. {01} {03}


Otic Dosage Forms

OFLOXACIN OTIC SOLUTION

Usual adult and adolescent dose
Otitis externa
Topical, to the ear canal, 10 drops in the affected ear two times a day for ten days {01}.

Otitis media, chronic suppurative (in patients with perforated tympanic membranes)
Topical, to the ear canal, 10 drops in the affected ear two times a day for fourteen days {01}. It is recommended that the tragus be pumped four times during instillation, by pushing inward, to facilitate penetration of the solution into the middle ear {01}.


Usual pediatric dose
Otitis externa
Children 12 years of age and older: See Usual adult and adolescent dose .

Children 1 to 12 years of age: Topical, to the ear canal, 5 drops in the affected ear two times a day for ten days {01}.

Children younger than 1 year of age: Safety and efficacy have not been established {01}.

Otitis media, acute (in pediatric patients with tympanostomy tubes)
Children 1 to 12 years of age: Topical, to the ear canal, 5 drops in the affected ear two times a day for ten days {01}. It is recommended that the tragus be pumped four times during instillation, by pushing inward, to facilitate penetration of the solution into the middle ear {01}.

Children younger than 1 year of age: Safety and efficacy have not been established {01}.


Strength(s) usually available
U.S.—


0.3% (Rx) [Floxin Otic (benzalkonium chloride 0.0025%) (sodium chloride 0.9%) (hydrochloric acid) (sodium hydroxide)]

Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F) {01}.

Auxiliary labeling:
   • For the ear.
   • Continue medicine for full time of treatment.



Revised: 08/27/1998



References
  1. Floxin Otic package insert (Daiichi Pharmaceutical Corporation—US), Issued 12/14/97, Rec 2/3/98; Rev 1/29/98, Rec 8/98.
  1. Floxin Otic Medication Guide—Important Patient Information and Instructions (Daiichi Pharmaceutical Corporation—US), Rev 12/15/97, Rec 8/26/98.
  1. Manufacturer comments 8/26/98.
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