Moxifloxacin Hydrochloride

Pronunciation: MOX-i-FLOX-a-sin HYE-droe-KLOR-ide
Class: Fluoroquinolone antibiotic

Trade Names

Avelox
- Tablets, oral 400 mg

Avelox IV
- Injection, solution 400 mg

Vigamox
- Solution, ophthalmic 0.5% (5 mg/mL)

Pharmacology

Interferes with microbial DNA synthesis.

Pharmacokinetics

Absorption

Bioavailability is approximately 90%; AUC is 36 to 39 mcg•h/mL; mean C _max is 3 to 4 mcg/mL. Steady state is achieved after at least 3 days with a 400 mg once-daily regimen. Coadministration of tablets with a high-fat meal or 1 cup of yogurt does not significantly affect absorption.

Distribution

Protein binding is approximately 30% to 50%; Vd is 1.7 to 2.7 L/kg.

Metabolism

Metabolized via glucuronide (approximately 14%) and sulfate (approximately 38%) conjugation in the liver.

Elimination

Moxifloxacin is eliminated in urine (approximately 20% unchanged) and feces (approximately 25%); sulfate conjugate is excreted in feces and glucuronide conjugate is excreted in urine. The half-life is approximately 12 h; mean apparent total Cl is approximately 12 L/h; renal Cl is approximately 2.6 L/h.

Special Populations

Renal Function Impairment

The pharmacokinetics are not significantly altered by mild, moderate, or severe impairment, or ESRD.

Hepatic Function Impairment

In moxifloxacin 400 mg single oral dose studies in 6 patients with mild (Child-Pugh class A) and 10 patients with moderate (Child-Pugh class B) hepatic insufficiency, AUC was 78% and 102%, respectively, of 18 healthy controls, and C _max was 79% and 84% of controls. The mean AUC of the sulfate conjugate of moxifloxacin (M1) increased 3.9- and 5.7-fold in the mild and moderate groups, respectively. The mean C _max of M1 increased approximately 3-fold in both groups. The mean AUC of the glucuronide conjugate of moxifloxacin (M2) increased 1.5-fold in both groups. The mean C _max of M2 increased 1.6- and 1.3-fold, respectively. The clinical significance of increased exposure to the sulfate and glucuronide conjugates has not been studied.

Elderly

No pharmacokinetics differences between younger and elderly patients have been observed.

Children

Pharmacokinetics have not been studied.

Gender

No differences in pharmacokinetics between men and women have been observed.

Race

Pharmacokinetics are similar between Japanese men and white men.

Indications and Usage

Treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, complicated and uncomplicated skin and skin structure infections, complicated intra-abdominal infections, and conjunctivitis caused by susceptible organisms (ophthalmic).

Unlabeled Uses

Hospital-acquired pneumonia, infective endocarditis, tuberculosis.

Contraindications

Hypersensitivity to moxifloxacin, any member of the quinolone class of antimicrobial agents, or any component of the product.

Dosage and Administration

Acute Bacterial Exacerbation of Chronic Bronchitis
Adults

IV / PO 400 mg/day for 5 days.

Acute Bacterial Sinusitis
Adults

IV / PO 400 mg/day for 10 days.

Community-Acquired Pneumonia
Adults

IV / PO 400 mg/day for 7 to 14 days.

Complicated Intra-Abdominal Infections
Adults

IV / PO 400 mg/day for 5 to 14 days. Therapy should be initiated with the IV formulation.

Complicated Skin and Skin Structure Infections
Adults

IV / PO 400 mg/day for 7 to 21 days.

Conjunctivitis
Adults and Children 1 y of age and older

Ophthalmic Instill 1 drop in affected eye(s) 3 times daily for 7 days.

Uncomplicated Skin and Skin Structure Infections
Adults

IV / PO 400 mg/day for 7 days.

General Advice

• Injection
• For IV infusion only. Not for intra-arterial, intradermal, intrathecal, intraperitoneal, subcutaneous, or IM administration.
• Infuse prescribed dose over 60 min by direct infusion or through a Y-type infusion set. Avoid rapid or bolus administration because of risk of prolonging QT interval.
• Do not add other medications or additives to the moxifloxacin injection bag.
• If other drugs are being administered through the same IV line, administer each medication separately and flush IV line with compatible solution before and after infusion of moxifloxacin.
• Moxifloxacin is compatible with the following IV solutions at ratios from 1:10 to 10:1: sodium chloride 0.9% injection, 1M sodium chloride injection, dextrose 5% injection, sterile water for injection, dextrose 10% for injection, Ringer's lactate for injection.

• Ophthalmic
• Ophthalmic solution is not for injection and should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.

• Oral
• May be taken with or without food.
• Administer at least 4 h before or 8 h after antacids containing magnesium or aluminum, sucralfate, metal cations (eg, iron), multivitamin preparations with zinc, and didanosine chewable/buffered tablets or pediatric powder for oral solution.

Storage/Stability

Store tablets between 59° and 86°F. Avoid high humidity. Store ophthalmic solution between 36° and 77°F. Store injection between 59° and 86°F. Do not refrigerate. Discard any unused solution.

Drug Interactions

Antacids containing aluminum, calcium, or magnesium; drug formulations containing divalent or trivalent cations (eg, some didanosine formulations, quinapril); metal cations (eg, iron); multivitamins containing iron or zinc; sucralfate

May decrease the absorption of moxifloxacin. Moxifloxacin should be taken at least 4 h before or 8 h after these agents.

Atenolol

The C _max of atenolol may be decreased. Monitor the patient. If an interaction is suspected, adjust the atenolol dose as needed.

Azole antifungal agents, cisapride, class IA antiarrhythmic agents (eg, procainamide, quinidine), class III antiarrhythmic agents (eg, amiodarone, sotalol), erythromycin, iloperidone, methadone, paliperidone, pentamidine, phenothiazines, tricyclic antidepressants (eg, amitriptyline), ziprasidone, any other drug known to prolong the QTc interval

Increased risk of torsades de pointes or other ventricular arrhythmias. If coadministration cannot be avoided, use with caution.

Corticosteroids (eg, prednisone)

Because of additive or synergistic effects, the risk of tendon rupture may be increased, especially in those 60 y of age and older. If tendon-related problems are suspected, moxifloxacin should be stopped and a nonquinolone antibiotic should be used if further antimicrobial treatment is necessary.

NSAIDs (eg, indomethacin)

Coadministration may increase the risk of CNS stimulation and convulsive seizures. Close clinical and laboratory monitoring is warranted.

Rifamycins (eg, rifampin)

Moxifloxacin plasma concentrations may be reduced, decreasing the efficacy. Monitor the patient's response. A larger dose of moxifloxacin may be needed during rifamycin administration.

Tramadol

The risk of seizures may be increased. Close clinical and laboratory monitoring is warranted.

Tretinoin

Additive effects of moxifloxacin and tretinoin may increase the risk of photosensitization. Concurrent use should be avoided.

Vaccines, live

Moxifloxacin may decrease the effectiveness of live vaccines. Concurrent use is not recommended.

Warfarin

Anticoagulant effect may be increased. Monitor coagulation parameters and adjust the warfarin dose as needed.

Adverse Reactions

Cardiovascular

Cardiac arrhythmia, palpitation, QT interval prolongation, tachycardia, vasodilatation (less than 2%); ventricular tachyarrhythmias (postmarketing).

CNS

Dizziness (2%); anxiety, asthenia, headache, insomnia, malaise, nervousness, somnolence, tremor, vertigo (less than 2%); altered coordination, exacerbation of myasthenia gravis, psychotic reaction (postmarketing).

Dermatologic

Rash (ophthalmic) (1% to 4%); pruritus, rash (maculopapular, purpuric, pustular), sweating, urticaria (less than 2%); photosensitivity/phototoxicity reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).

EENT

Conjunctivitis, decreased visual acuity, dry eye, keratitis, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage, tearing (ophthalmic) (1% to 6%); otitis media, pharyngitis, rhinitis (ophthalmic) (1% to 4%).

GI

Nausea (6%); diarrhea (5%); abdominal pain, anorexia, constipation, dry mouth, dyspepsia, flatulence, glossitis, increased GGT, oral moniliasis, stomatitis, vomiting (less than 2%).

Genitourinary

Vaginal moniliasis, vaginitis (less than 2%); renal dysfunction, renal failure (postmarketing).

Hematologic-Lymphatic

Eosinophilia, leukopenia, prothrombin decrease (PT/INR increased), thrombocythemia (less than 2%).

Hepatic

Abnormal LFT (less than 2%); hepatic failure, hepatitis (postmarketing).

Hypersensitivity

Anaphylactic reaction, anaphylactic shock, angioedema (including laryngeal edema) (postmarketing).

Lab Tests

Increases in albumin, bilirubin, chloride, globulin, ionized calcium, mean corpuscular hemoglobin, neutrophils, PT ratio, and WBCs; decreases in amylase, basophils, bilirubin, eosinophils, glucose, hemoglobin, neutrophils, pO ₂ , PT ratio, and RBCs (at least 2%).

Local

Injection-site reactions, including phlebitis (less than 2%).

Metabolic-Nutritional

Amylase increased, dehydration, LDH increased (less than 2%).

Musculoskeletal

Arthralgia, myalgia (less than 2%); tendon rupture (postmarketing).

Respiratory

Increased cough (ophthalmic) (1% to 4%).

Miscellaneous

Fever, infection (ophthalmic) (1% to 4%); allergic reaction, moniliasis, pain, taste perversion (less than 2%).

Precautions

Warnings Tendonitis Moxifloxacin has been associated with an increased risk of tendonitis and tendon rupture in patients of all ages. The risk is increased in patients older than 60 y of age, in patients taking corticosteroids, and in patients with kidney, heart, or lung transplants.

Pregnancy

Category C .

Lactation

Undetermined.

Children

PO/IV

Safety and efficacy not established.

Ophthalmic

Safety and efficacy in children younger than 1 y of age not established.

Elderly

Elderly patients may be more susceptible to drug-associated effects of QT interval and severe tendon disorders. Use with caution, especially in those on corticosteroids.

Hypersensitivity

Acute anaphylactic reactions and serious dermatological hypersensitivity reactions have been reported.

Hepatic Function

Use with caution in mild, moderate, or severe hepatic insufficiency (Child-Pugh class A, B, or C) because the metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation.

Superinfection

Use of antibiotics may result in bacterial or fungal overgrowth.

Clostridium difficile –associated diarrhea

Has been reported and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because C. difficile –associated diarrhea has been reported to occur more than 2 mo after the administration of antibacterial agents.

CNS effects

Convulsions have been reported in patients receiving quinolones. Quinolones also may cause CNS events, including the following: agitation, anxiety, confusion, depression, dizziness, hallucinations, insomnia, nervousness, nightmares, paranoia, tremors, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. Use with caution in patients with known or suspected CNS disorders (eg, epilepsy, severe cerebral arteriosclerosis) or in the presence of other risk factors that may predispose patients to seizures or lower the seizure threshold.

Peripheral neuropathy

Sensory or sensorimotor axonal polyneuropathy resulting in paresthesias, hypesthesia, dysesthesias, and weakness have been reported.

Phototoxicity

Because phototoxicity has been reported with other quinolones, avoid excessive exposure to sunlight or artificial UV light.

QT interval

QT interval may be prolonged in some patients; avoid use in patients with known prolongation of QT interval or uncorrected hypokalemia and in patients receiving class IA or III antiarrhythmics. Use moxifloxacin with caution in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia or acute myocardial ischemia.

Resistance

Prescribing antibacterial agents in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit and increases the risk of the development of drug-resistant bacteria.

Serious reactions

Clinical manifestations of serious and sometimes fatal reactions that have been reported with moxifloxacin include acute hepatic necrosis or failure, acute renal insufficiency or failure, agranulocytosis, allergic pneumonitis, anemia (including hemolytic and aplastic), arthralgia, fever, hepatitis, interstitial nephritis, jaundice, leukopenia, myalgia, pancytopenia, rash, serum sickness, Stevens-Johnson syndrome, thrombocytopenia (including thrombotic thrombocytopenic purpura), TEN, and vasculitis.

Overdosage

Symptoms

Possible QTc prolongation.

Patient Information

• Advise patients to read the Medication Guide and/or patient information leaflet before starting therapy and with each refill.
• Review dosing schedule and prescribed length of therapy with patient.

• Tablets
• Advise patients that medication can be taken with a full glass of water without regard to meals, but to take with food if GI upset occurs.
• Advise patients that if a dose is missed, to take it as soon as remembered. However, if it is nearing the time for the next dose, advise patients to skip the dose and take the next dose at the regularly scheduled time.
• Advise patients to take moxifloxacin 4 h before or 8 h after sucralfate, antacids containing magnesium or aluminum, didanosine-buffered tablets or pediatric powder, or other products containing iron or zinc.
• Remind patients to complete entire course of therapy even if symptoms of infection have disappeared.
• Advise patients to inform health care provider if infection does not improve or worsens.
• Advise patients to discontinue therapy and contact health care provider immediately if fainting, hives, itching, pain, palpitations, rupture of tendon, shortness of breath, skin rash, or tenderness occur.
• Advise patients to report the following signs of superinfection to health care provider: black, furry tongue; foul-smelling stools; vaginal itching or discharge; white patches in mouth.
• Warn patients that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted, and not to treat at home.
• Caution patients that drug may cause dizziness and light-headedness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise patients to avoid unnecessary exposure to direct and indirect sunlight or tanning lamps, and to use sunscreen and wear protective clothing to avoid photosensitivity reactions during therapy. Advise patients to discontinue therapy and notify health care provider if any of the following occur after exposure to sunlight or artificial UV light (eg, sunlamp): blistering, itching, rash, redness, sensation of skin burning, swelling.

• Ophthalmic Solution
• Review prescribed dosing schedule with patient.
• Teach patient proper technique for instilling eye drops: wash hands; do not allow dropper to touch eye. Tilt head back and look up; pull lower eyelid down and instill prescribed number of drops. Close eye for 1 to 2 min and apply gentle pressure to bridge of nose for 3 to 5 min. Do not rub eye.
• Advise patient that if more than 1 topical ophthalmic drug is being used, to administer the drugs at least 5 min apart.
• Inform patient that temporary blurred vision, eye itching, eye pain, or discomfort are the most common adverse reactions and to contact health care provider if they occur and are bothersome.
• Advise patient to contact eye doctor if eye or eyelid inflammation is noted, or if eye symptoms do not improve or worsen.
• Advise patient that the entire course of therapy must be completed to ensure max benefit and to complete full course of therapy even if symptoms have resolved.
• Instruct patient not to wear contact lenses during treatment.

• Injection
• Advise patient that medication will be prepared and administered by a health care provider in a health care setting when oral therapy is not feasible, but that the patient will be switched to oral therapy when the health care provider believes it is appropriate.

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