AVELOX (moxifloxacin)

AVELOX (moxifloxacin)

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AVELOX (moxifloxacin)

AVELOX (moxifloxacin) is a synthetic antibacterial agent for oral and intravenous administration. Moxifloxacin, a fluoroquinolone, is available as the monohydrochloride salt of 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3 quinoline carboxylic acid. It is a slightly yellow to yellow crystalline substance with a molecular weight of 437.9. Its empirical formula is C21H24FN3O4HCl

AVELOX Tablets

  • AVELOX Tablets are available as film-coated tablets containing 400 mg moxifloxacin (equivalent to 436.33 mg moxifloxacin hydrochloride).
  • The inactive ingredients are croscarmellose sodium, ferric oxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol and titanium dioxide.

AVELOX Injection

  • AVELOX Injection for intravenous use is available in ready-to-use single-dose 250 mL flexible bags as a sterile, preservative free, 0.8% sodium chloride aqueous solution of 400 mg moxifloxacin (equivalent to 436.33 mg moxifloxacin hydrochloride) with pH ranging from 4.1 to 4.6. The flexible bag is not made with natural rubber latex.
  • The appearance of the intravenous solution is yellow. The color does not affect, nor is it indicative of, product stability.
  • The inactive ingredients are sodium chloride, USP, Water for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment.
  • AVELOX Injection contains approximately 34.2 mEq (787 mg) of sodium in 250 mL.

Indications and usage

AVELOX is a fluoroquinolone antibacterial indicated for treating infections in adults 18 years of age and older caused by designated susceptible bacteria, in the conditions listed below:

  • Community Acquired Pneumonia
  • Skin and Skin Structure Infections: Uncomplicated and Complicated
  • Complicated Intra-Abdominal Infections
  • Plague
  • Acute Bacterial Sinusitis
  • Acute Bacterial Exacerbation of Chronic Bronchitis

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVELOX and other antibacterial drugs. AVELOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Mechanism of Action

The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination.

Resistance

The mechanism of action for fluoroquinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin. Resistance to fluoroquinolones occurs primarily by a mutation in topoisomerase II (DNA gyrase) or topoisomerase IV genes, decreased outer membrane permeability or drug efflux. In vitro resistance to moxifloxacin develops slowly via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8 x 10–9 to < 1 x 10–11 for Gram-positive bacteria.

Cross Resistance

Cross-resistance has been observed between moxifloxacin and other fluoroquinolones against Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may, however, still be susceptible to moxifloxacin. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.

Antimicrobial Activity

Moxifloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections.

Gram-positive bacteria:

  • Enterococcus faecalis
  • Staphylococcus aureus
  • Streptococcus anginosus
  • Streptococcus constellatus
  • Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP] **)
  • Streptococcus pyogenes

**MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillinresistant S. pneumoniae), and are isolates resistant to two or more of the following antibiotics: penicillin (MIC) ≥2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.

Gram-negative bacteria:

  • Enterobacter cloacae
  • Escherichia coli
  • Haemophilus influenzae
  • Haemophilus parainfluenzae
  • Klebsiella pneumoniae
  • Moraxella catarrhalis
  • Proteus mirabilis
  • Yersinia pestis

Anaerobic bacteria:

  • Bacteroides fragilis
  • Bacteroides thetaiotaomicron
  • Clostridium perfringens
  • Peptostreptococcus species

Other microorganisms

  • Chlamydophila pneumoniae
  • Mycoplasma pneumoniae

Dosage and administration

Type of InfectionDose Every 24 hoursDuration (days)
Community Acquired Pneumonia400 mg7–14
Uncomplicated Skin and Skin Structure Infections (SSSI)400 mg7
Complicated SSSI400 mg7–21
Complicated Intra-Abdominal Infections400 mg5–14
Plague400 mg10–14
Acute Bacterial Sinusitis400 mg10
Acute Bacterial Exacerbation of Chronic Bronchitis400 mg5
  • No dosage adjustment in patients with renal or hepatic impairment.
  • AVELOX Injection: Slow intravenous infusion over 60 minutes. Avoid rapid or bolus intravenous injection.
  • Do not mix with other medications in intravenous bag or in an intravenous line

Contraindications

  • Known hypersensitivity to AVELOX or other quinolones

Warnings and precautions

  • Prolongation of the QT interval and isolated cases of torsade de pointes has been reported. Avoid use in patients with known prolongation, proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia, hypokalemia, hypomagnesemia, and with drugs that prolong the QT interval.
  • Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions, including anaphylactic reactions, may occur after first or subsequent doses of AVELOX. Discontinue AVELOX at first sign of skin rash, jaundice or any other sign of hypersensitivity.
  • Clostridioides difficile-Associated Diarrhea: Evaluate if diarrhea occurs
  • Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects:
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    Fluoroquinolones, including AVELOX, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion).
  • Exacerbation of Myasthenia Gravis: Fluoroquinolones, including AVELOX, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis.
  • Risk of Aortic Aneurysm and Dissection: Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified.
  • Blood Glucose Disturbances: As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with AVELOX. In AVELOX-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin.
  • Photosensitivity/Phototoxicity: Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones, including AVELOX, after sun or UV light exposure

Drug interactions

Antacids, Sucralfate, Multivitamins and other Products Containing Multivalent Cations: Fluoroquinolones, including AVELOX, form chelates with alkaline earth and transition metal cations. Oral administration of AVELOX with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine buffered tablets for oral suspension or the pediatric powder for oral solution, may substantially interfere with the absorption of AVELOX, resulting in systemic concentrations considerably lower than desired.

Warfarin: Fluoroquinolones, including AVELOX, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population.

Antidiabetic Agents: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones, including AVELOX, and an antidiabetic agent.

Nonsteroidal Anti-Inflammatory Drugs: The concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with a fluoroquinolone, including AVELOX, may increase the risks of CNS stimulation and convulsions.

Use in specific populations

Pregnancy: There are no available human data establishing a drug associated risk with the use of moxifloxacin.

Lactation: It is not known if moxifloxacin is present in human milk. Based on animal studies in rats, moxifloxacin may be excreted in human milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AVELOX and any potential adverse effects on the breastfed child from AVELOX or from the underlying maternal condition.

Pediatric Use: Effectiveness in pediatric patients and adolescents less than 18 years of age has not been established. AVELOX causes arthropathy in juvenile animals. Limited information on the safety of AVELOX in 301 pediatric patients is available from the cIAI trial. Active Controlled Trial in Complicated Intra-Abdominal Infection (cIAI)

Geriatric Use: Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as AVELOX. This risk is further increased in patients receiving concomitant corticosteroid therapy.

Overdosage

Single oral overdoses up to 2.8 g were not associated with any serious adverse events. In the event of acute overdose, empty the stomach and maintain adequate hydration. Monitor ECG due to the possibility of QT interval prolongation. Carefully observe the patient and give supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.

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