Moxifloxacin

Moxifloxacin is an Antibiotic agent belonging to Fluoroquinolones and second line TB drug

Moxifloxacin is used in the Treatment of mild to moderate community-acquired pneumonia, including multidrug-resistant Streptococcus pneumoniae (MDRSP); acute bacterial exacerbation of chronic bronchitis; acute bacterial rhinosinusitis; complicated and uncomplicated skin and skin structure infections; complicated intra-abdominal infections; prophylaxis and treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis. It is also used to treat Anthrax; Bite wound infection, prophylaxis of high-risk bite or treatment (animal or human bite); Diabetic foot infection; Endophthalmitis, severe, acute bacterial postcataract; Meningitis, bacterial; Mycoplasma genitalium; Neutropenic fever, empiric therapy for low-risk patients with cancer; Pelvic inflammatory disease; Surgical prophylaxis; Tuberculosis, drug resistant; Tuberculosis, drug susceptible.

The Tmax of Moxifloxacin was achieved within 1-2 hours .Cmax was about 24 – 6 ug/mL

Moxifloxacin shows common side effects like Headache, dizziness, Diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Moxifloxacin is available in the form of Tablets, and Injection Solution.

Moxifloxacin is available in India, Germany, Canada, Italy, USA

Moxifloxacin is a bactericidal, concentration dependent, anti-infective. It interferes with bacterial survival by binding to DNA gyrase (topoisomerase II) and topoisomerase IV, essential bacterial enzymes involved in the replication, translation, repair and recombination of deoxyribonucleic acid.

Moxifloxacin is available in the form of Tablets and Injection.

Oral: Administer without regard to meals. Administer at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron, or zinc, including antacids, sucralfate, multivitamins, and didanosine (buffered tablets for oral suspension or the pediatric powder for oral solution).

IV: Infuse over 60 minutes; do not infuse by rapid or bolus intravenous infusion.

Moxifloxacin is used in the Treatment of mild to moderate community-acquired pneumonia, including multidrug-resistant Streptococcus pneumoniae (MDRSP); acute bacterial exacerbation of chronic bronchitis; acute bacterial rhinosinusitis; complicated and uncomplicated skin and skin structure infections; complicated intra-abdominal infections; prophylaxis and treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis. It is also used to treat Anthrax; Bite wound infection, prophylaxis of high-risk bite or treatment (animal or human bite); Diabetic foot infection; Endophthalmitis, severe, acute bacterial postcataract; Meningitis, bacterial; Mycoplasma genitalium; Neutropenic fever, empiric therapy for low-risk patients with cancer; Pelvic inflammatory disease; Surgical prophylaxis; Tuberculosis, drug resistant; Tuberculosis, drug susceptible.

Moxifloxacin is a fluoroquinolone anti-infective agent, which inhibits bacterial topoisomerase IV and DNA gyrase (topoisomerase II) enzymes which are essential for bacterial DNA replication, transcription, repair and recombination thereby impeding bacterial growth.

Moxifloxacin is approved for use in the following clinical indications

Treatment of mild to moderate community-acquired pneumonia, including multidrug-resistant Streptococcus pneumoniae (MDRSP); acute bacterial exacerbation of chronic bronchitis; acute bacterial rhinosinusitis; complicated and uncomplicated skin and skin structure infections; complicated intra-abdominal infections; prophylaxis and treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis.

Limitations of use: Because fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions (eg, tendinopathy and tendon rupture, peripheral neuropathy, CNS effects), reserve use of moxifloxacin for acute exacerbation of chronic bronchitis or acute sinusitis for patients who have no alternative treatment options.

• Although not approved there have been certain off label use documented for Moxifloxacin which includes:

Anthrax; Bite wound infection, prophylaxis of high-risk bite or treatment (animal or human bite); Diabetic foot infection; Endophthalmitis, severe, acute bacterial postcataract; Meningitis, bacterial; Mycoplasma genitalium; Neutropenic fever, empiric therapy for low-risk patients with cancer; Pelvic inflammatory disease; Surgical prophylaxis; Tuberculosis, drug resistant; Tuberculosis, drug susceptible

Moxifloxacin is available in various strengths as 250 mg/50 mL (50 mL); 500 mg/100 mL (100 mL); 750 mg/150 mL (150 mL); 25 mg/mL (20 mL, 30 mL); 25 mg/mL (10 mL, 100 mL, 200 mL, 480 mL), 250 mg, 500 mg, 750 mg.

• Dosage Adjustment in Kidney Patient

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction.

Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary .

Peritoneal dialysis: Poorly dialyzed: No dosage adjustment necessary.

CRRT: No dosage adjustment necessary .

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary

• Dosage Adjustment in Hepatic impairment Patient
• Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
• Severe impairment (eg, cirrhosis with or without ascites): Maximum dose: 400 mg/day

· Dosage Adjustment for Pediatric Patients

General dosing:

· Infants ≥3 months and Children <2 years: Oral, IV: 6 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose .

· Children 2 to <6 years: Oral, IV: 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose .

· Children 6 to <12 years: Oral, IV: 4 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.

· Children ≥12 years and Adolescents <18 years :

· <45 kg: Oral, IV: 4 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.

· ≥45 kg: Oral, IV: 400 mg every 24 hours.

Adolescents ≥18 years: Oral, IV: 400 mg every 24 hours

Anthrax; meningitis or disseminated infection when meningitis cannot be ruled out; treatment: Note: Consult public health officials for event-specific recommendations. Administer as part of an appropriate combination regimen for at least 2 to 3 weeks and until patient is clinically stable; treatment must be followed by prophylaxis, for a total antibiotic course of 60 days.

Infants ≥3 months, Children, and Adolescents <18 years (AAP [Bradley 2014]): Limited data available:

• Infants ≥3 months and Children <2 years: IV: 6 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.

• Children 2 to <6 years: IV: 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.

• Children 6 to <12 years: IV: 4 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.

• Children ≥12 years and Adolescents <18 years:

• <45 kg: IV: 4 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.

• ≥45 kg: IV: 400 mg every 24 hours.

• Adolescents ≥18 years: IV: 400 mg every 24 hours

Intra-abdominal infection, complicated (alternative agent): Note: Beta-lactam-based regimens are preferred; moxifloxacin may be less effective as compared to beta-lactam comparators. In clinical trials, patients ≥20 kg received ≥3 days of IV therapy prior to transitioning to oral therapy; patients <20 kg completed course using IV therapy. Total duration of therapy was 5 to 14 days, though a small number of patients received treatment for >14 days (maximum: 24 days).

Infants ≥3 months, Children, and Adolescents <18 years :

• Infants ≥3 months and Children <2 years: IV, Oral: 6 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose (Bradley 2021; Wirth 2018).
• Children 2 to <6 years: IV, Oral: 5 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.
• Children 6 to <12 years: IV, Oral: 4 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.
• Children ≥12 years and Adolescents <18 years:
• <45 kg: IV, Oral: 4 mg/kg/dose every 12 hours; maximum dose: 200 mg/dose.
• ≥45 kg: IV, Oral: 400 mg every 24 hours.
• Adolescents ≥18 years: IV, Oral: 400 mg every 24 hours

Nontuberculous mycobacterial infection, pulmonary:

• Infants, Children, and Adolescents: Oral: 7.5 to 10 mg/kg/dose once daily; maximum dose: 400 mg/dose. Use as part of an appropriate combination regimen until patient is culture negative on therapy for ≥1 year

Pneumonia, community-acquired ( M. pneumoniae, C. pneumoniae, C. trachomatis), mild infection/step-down therapy:

• Adolescents with skeletal maturity: Oral: 400 mg once daily
• Surgical (perioperative) prophylaxis (alternative agent):
• Children and Adolescents: IV: 10 mg/kg within 120 minutes prior to surgical incision; maximum dose: 400 mg/dose

Tuberculosis, treatment:

• Drug-susceptible tuberculosis, pulmonary: Note: Use in combination with rifapentine, isoniazid, and pyrazinamide; see guidelines for regimen details

• Children ≥12 years and Adolescents, weighing ≥40 kg: Oral: 400 mg once daily for 17 weeks (119 total doses)

• Drug-resistant tuberculosis : Note: Use as part of an appropriate combination regimen; consult current guidelines for detailed information ; . Pharmacokinetic studies suggest that higher doses may be necessary in pediatric patients to achieve target concentrations, but doses higher than 15 mg/kg/dose every 24 hours require further evaluation.

• Infants, Children, and Adolescents: Oral, IV: 10 to 15 mg/kg/dose every 24 hours; usual maximum dose: 400 mg/dose; higher maximum doses (600 or 800 mg) may be used with higher minimum inhibitory concentrations (MICs) or in cases of malabsorption . Duration of therapy should be individualized based on patient-specific factors (eg, extent of disease, rapidity of culture conversion, clinical response, and toxicity)

Increased risk of bradycardia with potassium-reducing agents (e.g. loop diuretics). Increased risk of tendon disorder with corticosteroids. Decreased absorption by forming chelates with antacids containing Al, Mg, Fe, sucralfate and multivalent cations. May enhance anticoagulant effects of warfarin. Potentially Fatal: Increased risk of QT prolongation with class IA (e.g. quinidine) and class III (e.g. amiodarone) antiarryhthmics, terfenadine, cisapride, erythromycin, antipsychotics (e.g. haloperidol), and TCA (e.g. amitriptyline).

Hypersensitivity to moxifloxacin or other quinolone antibiotics. Patient with history of tendon disorders, myasthenia gravis, QT interval prolongation, ventricular arrhythmias, proarrhythmic conditions (e.g. bradycardia, acute MI), peripheral neuropathy, uncorrected electrolyte disorders (e.g. hypokalaemia, hypomagnesemia). Concomitant use with Class 1A and Class III antiarrhythmics, antihistamines, and other drugs that prolong QT interval (e.g. cisapride, erythromycin, antipsychotics, and TCA).

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.

Special populations:

• Older adult: Adverse effects (eg, hepatotoxicity, tendon rupture, QT changes, aortic dissection) may be increased in the elderly.

• G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency .

• Pediatric: Safety of use in pediatric patients for >14 days of therapy has not been studied; increased incidence of musculoskeletal disorders (eg, arthralgia, tendon rupture) has been observed in children.

Moxifloxacin may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Teratogenic Effects - Pregnancy Category C

Moxifloxacin has not been shown to have any teratogenic effects at oral doses as high as 810 mg/kg/day (11 times the recommended maximum human dose based on mg/m² or 50 times based on mg/kg) and 160 mg/kg/day (4 times the recommended maximum human dose based on mg/m² or 10 times based on mg/kg) when administered to pregnant rats and rabbits, respectively. Additional studies in rats with oral doses up to 360 mg/kg/day (5 times the recommended maximum human dose based on mg/m² or 23 times based on mg/kg) demonstrated no adverse effect on late fetal development, labor, delivery, lactation, neonatal viability, or growth of the newborn. Doses equivalent to 50 and 10 times the recommended maximum human dose of Moxifloxacin (based on mg/kg) were fetotoxic (i.e., decreased fetal body weight and increased fetal mortality) in rats and rabbits, respectively. Minor skeletal variations were reported in rats receiving doses of 810 mg/kg/day, which is more than 10 times higher than the recommended maximum human dose based on mg/m².

Absorption is not affected by administration with a high-fat meal or yogurt.

• Common Adverse effects

CNS effects including seizures, increased intracranial pressure, lightheadedness, dizziness, tremor; psychotic reactions (e.g. hallucinations, nervousness, delirium), sensory or sensorimotor peripheral neuropathy, prolonged QT interval, blood glucose disturbances (hypo-/hyperglycaemia), phototoxicity, superinfection (prolonged use), bronchospasm.

• Less Common Adverse effects:

CNS effects including seizures, increased intracranial pressure, lightheadedness, dizziness, tremor; psychotic reactions (e.g. hallucinations, nervousness, delirium), sensory or sensorimotor peripheral neuropathy, prolonged QT interval, blood glucose disturbances (hypo-/hyperglycaemia), phototoxicity, superinfection (prolonged use), bronchospasm

• Rare Adverse effects

Hepatitis, jaundice. Injury, poisoning and procedural complications: Infusion site reaction (e.g. pain, reddening), phlebitis. Investigations: Increased hepatic enzymes (ALT/AST, alkaline phosphatase, GGT), decreased forced expiratory volume.

Decreased absorption with Fe salts, Zn-containing multivitamins, Mg- or Al-containing antacids, didanosine. Decreased bioavailability with sucralfate. Increased risk of CNS stimulation and seizures with drugs which may affect seizure threshold (e.g. theophylline, NSAIDs). Decreased renal clearance with cimetidine and probenecid due to blockage of renal tubular secretion of levMoxifloxacin . May increase the half-life of ciclosporin. Increased INR and/or bleeding with vitamin K antagonists (e.g. warfarin). Increased risk of severe tendon disorders with corticosteroids. Increased risk for QT interval prolongation with class IA and III antiarrhythmics, TCA, macrolides and antipsychotic agents. May result to altered blood glucose levels with antidiabetic agents (e.g. insulin, glibenclamide).

The common side effects of Moxifloxacin include the following nausea; diarrhea; headache; vomiting; dizziness; nervousness; agitation; nightmares

Symptoms: QT prolongation.

Management: Administer activated charcoal immediately after absorption. Perform ECG monitoring.

Pharmacodynamic

Moxifloxacin is a DNA gyrase inhibitor, and also inhibits topoisomerase IV. DNA gyrase (topoisomerase II) is an essential bacterial enzyme that maintains the superhelical structure of DNA. DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; inhibition is bactericidal.

Pharmacokinetics

• Absorption: Readily absorbed from the gastrointestinal tract. Absolute bioavailability: Approx 90%.
• Distribution: Rapidly distributed to extravascular spaces. Volume of distribution: 1.7-2.7 L/kg. Plasma protein binding: Approx. 30-50%.
  • Metabolism: Metabolized in the liver via glucuronide and sulfate conjugation.
  • Excretion: Via urine (20% as unchanged drug, glucuronide conjugate); faeces (25% as unchanged drug, sulfate conjugate). Elimination half-life: Approx 12 hours.

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
• https://reference.medscape.com/drug/colestid-Moxifloxacin -342452
• https://go.drugbank.com/drugs/DB00375
• https://www.sciencedirect.com/topics/medicine-and-dentistry/Moxifloxacin
• https://europepmc.org/article/med/6988203