Moxifloxacin

Usage

Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic prescribed for various bacterial infections. These include:

• Acute bacterial sinusitis
• Acute bacterial exacerbation of chronic bronchitis
• Community-acquired pneumonia
• Complicated skin and skin structure infections (including diabetic foot infections)
• Complicated intra-abdominal infections (including polymicrobial infections such as abscesses)
• Uncomplicated pelvic inflammatory disease (in combination with another appropriate antibacterial agent)
• Plague

Pharmacological Classification: Fluoroquinolone antibiotic.

Mechanism of Action: Moxifloxacin inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication and repair, leading to bacterial cell death.

Alternate Names

There are no widely recognized alternate names for Moxifloxacin itself. It is known internationally by this name.

Brand Names: Avelox, Moxifloxacin Kabi, Vigamox (ophthalmic solution)

How It Works

Pharmacodynamics: Moxifloxacin exerts its bactericidal effect by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. These enzymes are crucial for DNA replication, transcription, repair, and recombination in bacteria. By inhibiting these enzymes, moxifloxacin disrupts bacterial DNA function, leading to cell death.

Pharmacokinetics:

• Absorption: Well-absorbed orally, reaching peak plasma concentrations within 1-4 hours. Bioavailability is approximately 90%.
• Distribution: Widely distributed throughout the body, achieving therapeutic concentrations in various tissues and fluids, including lungs, skin, and intra-abdominal organs.
• Metabolism: Primarily metabolized in the liver through Phase II glucuronidation and sulfation pathways, with a small portion undergoing Phase I metabolism via CYP3A4.
• Elimination: Excreted primarily through the kidneys (approximately 40-50%) and in feces (approximately 20-25%). The elimination half-life is around 12 hours.

Mode of Action: Moxifloxacin binds to and inhibits bacterial DNA gyrase and topoisomerase IV. This inhibition prevents the supercoiling and relaxation of DNA, necessary for DNA replication and transcription, ultimately leading to bacterial cell death.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Moxifloxacin primarily acts through enzyme inhibition (DNA gyrase and topoisomerase IV).

Elimination Pathways: Moxifloxacin is primarily eliminated through renal excretion (as unchanged drug and metabolites) and to a lesser extent through hepatic metabolism and fecal excretion. Some metabolism occurs via CYP3A4, but it is not the major metabolic pathway.

Dosage

Standard Dosage

Adults:

• 400 mg once daily (orally or intravenously infused over 60 minutes).

Children:

Moxifloxacin is generally contraindicated in children and adolescents below 18 years of age due to the risk of musculoskeletal toxicity. However, in certain specific and exceptional circumstances, it might be used off-label under strict specialist supervision and after careful consideration of the benefit-risk profile. Dosing in such cases may be guided by pediatric protocols and specialist consultation.

Special Cases:

• Elderly Patients: No dose adjustment is typically required unless significant renal impairment is present.

• Patients with Renal Impairment: No dose adjustment is required for mild to severe renal dysfunction, including patients on dialysis.

• Patients with Hepatic Dysfunction: No dose adjustment is usually necessary for mild to moderate hepatic impairment. For severe hepatic impairment (Child-Pugh C), exercise caution, but no specific dosage recommendations are universally established.

• Patients with Comorbid Conditions: Close monitoring for drug interactions and adverse events is advised in patients with comorbidities such as diabetes (due to potential glucose fluctuations) and cardiovascular diseases (due to the potential for QT interval prolongation).

Clinical Use Cases

• The dosage remains consistent (400 mg once daily) across various clinical settings, including intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations. The duration of treatment, however, may vary according to the specific indication and clinical response.

Dosage Adjustments

Dose adjustments are usually not necessary based on patient-specific factors like renal/hepatic dysfunction or metabolic disorders. However, clinical judgment and careful monitoring are essential, especially in critically ill patients.

Side Effects

Common Side Effects

Nausea, vomiting, diarrhea, dizziness, headache.

Rare but Serious Side Effects

• QT interval prolongation (leading to potentially fatal arrhythmias)
• Tendinitis or tendon rupture
• Peripheral neuropathy
• Hepatotoxicity (rare)
• Clostridium difficile-associated diarrhea
• Hypersensitivity reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis - very rare).
• Seizures (rare)

Long-Term Effects

Peripheral neuropathy can persist even after discontinuation of moxifloxacin.

Adverse Drug Reactions (ADR)

Serious ADRs like QT prolongation, tendon rupture, and severe hypersensitivity reactions require immediate medical attention and discontinuation of the drug.

Contraindications

• Hypersensitivity to moxifloxacin or other fluoroquinolones.
• Pregnancy and breastfeeding.
• Children and adolescents below 18 years of age (except in specific, justifiable circumstances under specialist supervision).
• Patients with a history of QT interval prolongation, uncorrected hypokalemia, or those receiving Class IA or Class III antiarrhythmic drugs.
• Patients with myasthenia gravis.

Drug Interactions

• Antacids, Multivitamins, Iron, Zinc: May reduce moxifloxacin absorption. Administer moxifloxacin at least 2 hours before or 4 hours after these agents.
• Drugs that Prolong QT Interval: (e.g., antiarrhythmics, certain antidepressants, some antipsychotics): Avoid concomitant use due to increased risk of QT prolongation and arrhythmias.
• Warfarin: Moxifloxacin may enhance the anticoagulant effect of warfarin. Monitor INR closely.
• Theophylline: May increase theophylline concentrations. Monitor theophylline levels and adjust dose as necessary.
• Digoxin: Moxifloxacin may increase digoxin levels. Monitor digoxin levels.
• Corticosteroids: May increase the risk of tendinitis and tendon rupture, especially in elderly patients.

Pregnancy and Breastfeeding

Moxifloxacin is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus/infant.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV.
• Side Effects: Nausea, vomiting, diarrhea, dizziness, QT prolongation, tendon rupture, peripheral neuropathy.
• Contraindications: Hypersensitivity to fluoroquinolones, pregnancy, breastfeeding, children <18 years, QT prolongation risk factors, myasthenia gravis.
• Drug Interactions: Antacids, multivitamins, iron, zinc, QT-prolonging drugs, warfarin, theophylline, digoxin, corticosteroids.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 400 mg once daily (oral or IV).
• Monitoring Parameters: ECG (for QT interval), liver function tests, signs of tendinitis, blood glucose levels (in diabetics), theophylline/digoxin levels (if co-administered).

Popular Combinations

Moxifloxacin is typically used as monotherapy. However, for pelvic inflammatory disease, it is often combined with another antibiotic like ceftriaxone to cover potential Neisseria gonorrhoeae infections.

Precautions

• General Precautions: Assess for allergies, QT prolongation risk factors, renal/hepatic function, history of seizures, and myasthenia gravis before initiating treatment.
• Specific Populations: Avoid use in pregnancy and breastfeeding. Exercise caution in elderly patients and those with liver disease. Contraindicated in children <18 years (except in special circumstances).
• Lifestyle Considerations: Patients should avoid excessive sun exposure. Alcohol consumption should be moderate. Caution advised while driving or operating machinery due to potential dizziness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Moxifloxacin?

A: The standard adult dosage is 400 mg once daily, administered either orally or intravenously over 60 minutes.

Q2: Can Moxifloxacin be used in children?

A: Moxifloxacin is generally contraindicated in children and adolescents under 18 years due to the risk of musculoskeletal complications. Use is reserved for exceptional cases under specialist supervision.

Q3: What are the most serious side effects of Moxifloxacin?

A: QT interval prolongation, tendon rupture, peripheral neuropathy, and serious hypersensitivity reactions are among the most severe side effects.

Q4: Should Moxifloxacin dosage be adjusted in patients with renal impairment?

A: No dosage adjustment is necessary for patients with renal impairment, including those on dialysis.

Q5: What are the major drug interactions with Moxifloxacin?

A: Significant interactions can occur with antacids/multivitamins/iron/zinc (decreased absorption), QT-prolonging drugs (increased arrhythmia risk), warfarin (enhanced anticoagulation), theophylline and digoxin (increased serum levels), and corticosteroids (increased risk of tendinopathy).

Q6: Can Moxifloxacin be used during pregnancy or breastfeeding?

A: No, Moxifloxacin is contraindicated in both pregnancy and breastfeeding due to potential risks to the fetus/infant.

Q7: How is Moxifloxacin eliminated from the body?

A: Primarily through renal excretion (as unchanged drug and metabolites) and to a lesser extent via hepatic metabolism and fecal excretion.

Q8: What is the mechanism of action of Moxifloxacin?

A: Moxifloxacin inhibits bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, essential for bacterial DNA replication and repair.

Q9: What should be monitored in patients receiving Moxifloxacin?

A: Monitor ECG (for QT interval), liver function tests, signs of tendinitis, blood glucose (in diabetics), and serum levels of theophylline/digoxin if co-administered.

Q10: In what clinical settings is Moxifloxacin used?

A: Moxifloxacin is used to treat bacterial infections like pneumonia, bronchitis, sinusitis, skin and soft tissue infections, intra-abdominal infections, and pelvic inflammatory disease (in combination therapy).

Please note that this information is current as of February 16, 2025, and may be subject to change with updates in medical knowledge and guidelines.