Levofloxacin
1. Drug Name
Generic Name: Levofloxacin
Brand Names: Levaquin, Quixin, Iquix, and others.
2. Drug Classification
Class: Antibiotic, Fluoroquinolone
Subclass: None (Fluoroquinolone class)
3. Mechanism of Action
Primary Action: Levofloxacin is a broad-spectrum antibiotic that works by inhibiting bacterial DNA synthesis. It binds to two critical bacterial enzymes—DNA gyrase and topoisomerase IV. These enzymes are responsible for supercoiling and untangling bacterial DNA during replication. Inhibition of these enzymes prevents DNA replication, leading to bacterial cell death.
Spectrum of Activity: Levofloxacin has a broad spectrum of activity against both gram-positive and gram-negative bacteria, including:
Gram-positive organisms: Streptococcus pneumoniae, Staphylococcus aureus (including MRSA), Enterococcus species.
Gram-negative organisms: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae.
Atypical organisms: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila.
Resistance Mechanisms: Bacterial resistance to levofloxacin can arise through mutations in the target enzymes (DNA gyrase and topoisomerase IV), or through efflux pumps that expel the drug from the bacterial cell. Additionally, plasmid-mediated resistance has been noted, particularly in gram-negative organisms.
4. Pharmacokinetics
Absorption: Levofloxacin is well absorbed after oral administration, with bioavailability of approximately 99%, meaning the oral dose is nearly as effective as the intravenous formulation.
Distribution: Levofloxacin is widely distributed throughout the body, including the lungs, urine, and tissues. It has good penetration into various tissues, making it effective in treating respiratory and urinary tract infections.
Metabolism: Levofloxacin is minimally metabolized in the liver. Only about 5-10% of the drug is metabolized, with the rest excreted unchanged in the urine.
Excretion: The half-life of levofloxacin is approximately 6 to 8 hours. It is primarily excreted unchanged via the kidneys (approximately 87% of the dose) and to a lesser extent in the feces.
Special Considerations: Levofloxacin dose adjustments are recommended for patients with renal impairment (e.g., creatinine clearance <50 mL/min). Elderly patients and those with impaired renal function may require adjusted dosing to prevent drug accumulation.
5. Indications
Primary Indications:
Respiratory Tract Infections: Including community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, and sinusitis.
Urinary Tract Infections: Acute cystitis, pyelonephritis, and complicated UTIs.
Skin and Soft Tissue Infections: Treatment of infections caused by both gram-positive and gram-negative organisms.
Chronic Prostatitis: Caused by susceptible organisms.
Plague: Levofloxacin is one of the treatment options for plague caused by Yersinia pestis.
Anthrax: Levofloxacin is used in post-exposure prophylaxis and treatment of inhalational anthrax.
Off-label Uses:
Bone and Joint Infections: Levofloxacin can be used for osteomyelitis and joint infections caused by susceptible organisms.
Gastrointestinal Infections: For intra-abdominal infections, especially in combination with other agents.
Specific Populations: Levofloxacin is effective in both adult and pediatric populations. Special considerations should be given when treating children, pregnant women, and elderly patients due to potential adverse effects.
6. Dosage and Administration
Adult Dosing:
Respiratory Tract Infections: 500 mg once daily for 7 to 14 days for conditions like community-acquired pneumonia or bronchitis.
Urinary Tract Infections: 250 mg to 500 mg once daily for 3 to 10 days, depending on infection severity.
Skin Infections: 500 mg once daily for 7 to 14 days.
Plague and Anthrax (Post-exposure Prophylaxis): 500 mg twice daily for 14 days (plague), 60 days for anthrax exposure.
Pediatric Dosing:
Pediatric doses depend on the severity and type of infection but generally range from 10-20 mg/kg once daily for infections such as pneumonia or UTI.
Renal Adjustments: Dose adjustments are necessary for patients with impaired renal function. In severe renal impairment (creatinine clearance <30 mL/min), the dose should be reduced or the dosing interval extended.
Route of Administration: Oral (tablet, oral solution) and intravenous formulations are available.
7. Contraindications
Absolute Contraindications:
Known hypersensitivity to levofloxacin, other quinolones, or any components of the formulation.
Relative Contraindications:
Tendon Disorders: Levofloxacin has been associated with tendonitis and tendon rupture, especially in elderly patients and those on corticosteroid therapy.
QT Prolongation: Should be used with caution in patients with a history of QT prolongation or arrhythmias.
Pregnancy and Lactation: Levofloxacin should be used during pregnancy only if the potential benefits outweigh the risks (Category C). It is excreted in breast milk, so caution is advised in breastfeeding mothers.
8. Warnings and Precautions
Tendonitis and Tendon Rupture: Levofloxacin has been associated with an increased risk of tendonitis and tendon rupture, particularly in older adults and those taking corticosteroids.
QT Prolongation: Fluoroquinolones, including levofloxacin, may prolong the QT interval and increase the risk of torsades de pointes. Use cautiously in patients with a history of arrhythmias or those taking other QT-prolonging drugs.
C. difficile-Associated Diarrhea: As with other broad-spectrum antibiotics, levofloxacin can lead to overgrowth of Clostridium difficile, resulting in diarrhea that can range from mild to severe.
CNS Effects: Levofloxacin can cause CNS effects, including dizziness, confusion, and seizures, especially in elderly patients.
9. Adverse Effects
Common Adverse Effects (≥10%):
Gastrointestinal upset: nausea, diarrhea, vomiting, and abdominal pain.
Less Common but Clinically Significant:
Cardiovascular: QT prolongation, arrhythmias, hypotension, and tachycardia.
Musculoskeletal: Tendonitis, tendon rupture, and joint pain.
Hematologic: Leukopenia, thrombocytopenia, and eosinophilia.
Serious Adverse Reactions:
Tendon rupture (particularly Achilles tendon).
Seizures, peripheral neuropathy.
Anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Severe hypoglycemia or hyperglycemia (especially in diabetic patients).
10. Drug Interactions
Major Drug Interactions:
Antacids and Cationic Compounds: Drugs like aluminum, magnesium, or calcium-containing antacids can reduce the absorption of levofloxacin. It should be taken at least 2 hours before or 2 hours after these drugs.
CYP450 Inhibitors (e.g., amiodarone, ciprofloxacin): Levofloxacin is metabolized through CYP enzymes and may have interactions with other drugs that inhibit this pathway, leading to elevated drug levels.
Warfarin: Levofloxacin may potentiate the effects of warfarin, increasing the risk of bleeding. Monitoring of INR is recommended.
QT Prolonging Drugs: Co-administration with drugs that prolong the QT interval (e.g., antiarrhythmics, antipsychotics) may increase the risk of torsades de pointes.
Food-Drug Interactions: Levofloxacin can be taken with or without food. However, food can delay the absorption slightly, but this does not significantly affect its therapeutic effect.
Lab Test Interference: Levofloxacin may cause transient increases in liver enzymes (ALT, AST) and may interfere with certain laboratory tests, including urine glucose testing.
11. Clinical Pharmacology
Pharmacodynamics: Levofloxacin inhibits bacterial DNA synthesis, primarily by targeting DNA gyrase and topoisomerase IV, which are crucial for DNA replication and cell division. This action is bactericidal and occurs primarily during the logarithmic phase of bacterial growth.
Additional Effects: Levofloxacin has been shown to have anti-inflammatory properties, which may contribute to its effectiveness in certain infections, such as chronic obstructive pulmonary disease (COPD) exacerbations.
12. Special Populations
Pregnancy: Levofloxacin is classified as a Category C drug, meaning that it should only be used during pregnancy if the potential benefits justify the risks. Animal studies have shown evidence of fetal harm.
Lactation: Levofloxacin is excreted in breast milk in small amounts, and caution should be exercised when prescribing it to breastfeeding mothers. Monitor the infant for possible side effects.
Pediatrics: Levofloxacin can be used in pediatric patients, though it is generally reserved for serious infections due to concerns about joint and tendon problems.
Geriatrics: Elderly patients are more likely to experience side effects such as tendonitis, tendon rupture, and CNS effects. Renal dose adjustments are also often required in this population.
13. Therapeutic Uses
First-Line Therapy: Community-acquired pneumonia, acute bacterial sinusitis, acute exacerbations of chronic bronchitis, and uncomplicated UTIs.
Second-Line Therapy: For resistant strains of pathogens or when first-line therapies fail.
Combination Therapy: Levofloxacin can be used in combination with other antibiotics for certain resistant infections (e.g., tuberculosis, H. pylori eradication).
14. Monitoring and Follow-Up
Lab Tests: Liver function tests, renal function tests, and complete blood counts should be monitored during prolonged therapy.
Monitoring for Adverse Effects: Regular monitoring for tendonitis or tendon rupture, especially in older adults, is recommended.
Electrolyte and Cardiac Monitoring: For patients with QT prolongation or on medications affecting the heart rhythm, regular electrocardiogram (ECG) monitoring may be required.
15. Overdose Management
Symptoms of Overdose: Overdose symptoms include nausea, dizziness, tremors, and confusion.
Treatment Protocols: There is no specific antidote for levofloxacin overdose. Symptomatic treatment with supportive care is recommended.
Supportive Measures: Monitoring of vital signs, hydration, and administration of activated charcoal if the overdose is recent.
16. Patient Counseling Information
Key Points to Discuss with Patients:
Complete the full course of treatment, even if you feel better before finishing.
Avoid taking antacids, dairy products, or iron supplements within 2 hours of taking levofloxacin.
Drink plenty of fluids to stay hydrated.
Signs/Symptoms to Watch For:
Pain, swelling, or tenderness in the joints (signs of tendonitis).
Severe diarrhea or gastrointestinal upset.
Unusual bruising or bleeding.