Asilee-TS

Approved Indications (Systemic Use - Oral and IV):

• Community-Acquired Pneumonia (CAP), including cases caused by multidrug-resistant Streptococcus pneumoniae
• Hospital-Acquired Pneumonia (HAP)
• Acute Bacterial Sinusitis
• Acute Exacerbation of Chronic Bronchitis (AECB)
• Uncomplicated and Complicated Urinary Tract Infections (UTIs)
• Acute Pyelonephritis
• Chronic Bacterial Prostatitis
• Complicated and Uncomplicated Skin and Skin Structure Infections
• Post-Exposure Prophylaxis of Inhalational Anthrax
• Treatment of Plague (including pneumonic and septicemic forms)

Ophthalmic Indications:

• Bacterial Conjunctivitis

Otic Indications:

• Acute Otitis Externa

Clinically Accepted Off-Label Uses:

• Traveler’s Diarrhea (when alternative treatments are not suitable)
• Multidrug-Resistant Tuberculosis (as part of combination therapy)

Route: Oral, Intravenous, Ophthalmic, Otic
Note: Oral and IV doses are bioequivalent; switching between routes does not require dose adjustment.

Adults (Oral/IV):

Pediatrics (Plague or Anthrax Only):

• 6 months to <50 kg: 8 mg/kg orally or IV every 12 hours (max 250 mg/dose)
• ≥50 kg: 250 mg every 12 hours
• Duration: 10–14 days

Note: Use in children is limited due to the risk of musculoskeletal toxicity.

Renal Impairment:

Hepatic Impairment:

• No dose adjustment required.

Ophthalmic Use (Bacterial Conjunctivitis):

• Days 1–2: 1–2 drops in the affected eye(s) every 2 hours while awake (up to 8 times/day)
• Days 3–7: 1–2 drops every 4 hours (up to 4 times/day)

Otic Use (Acute Otitis Externa):

• 4 drops into the affected ear once daily for 7 days.

Levofloxacin is a broad-spectrum bactericidal antibiotic that inhibits bacterial DNA replication. It targets two essential bacterial enzymes: DNA gyrase (topoisomerase II) and topoisomerase IV. These enzymes are responsible for supercoiling and uncoiling of bacterial DNA, processes essential for replication, repair, and transcription. Inhibition leads to the disruption of bacterial cell division and ultimately cell death. Levofloxacin is active against a broad range of Gram-positive and Gram-negative organisms, atypical bacteria, and some anaerobes.

• Absorption:
  Rapid and nearly complete after oral administration; bioavailability ~99%.
• Peak Plasma Time:
  1–2 hours (oral); immediate (IV)
• Distribution:
• Widely distributed in body tissues (lungs, sinuses, urinary tract, skin)
• Volume of distribution: ~89–112 L
• Plasma protein binding: ~24–38%
• Metabolism:
  Minimally metabolized in the liver.
• Half-life:
  Approximately 6–8 hours.
• Elimination:
  Primarily excreted via the kidneys (≥85% unchanged). Minor fecal elimination.

• Pregnancy:
  FDA Category C
  Animal studies indicate possible cartilage toxicity. There are no adequate and well-controlled studies in pregnant women. Use only when clearly needed and if potential benefits justify potential risks.
• Lactation:
  Levofloxacin is excreted in breast milk. Due to potential toxicity (e.g., cartilage damage), breastfeeding should be avoided during therapy or the drug should be used only if essential.

• Primary Class: Antibiotic
• Subclass: Fluoroquinolone (third generation)

• Known hypersensitivity to Levofloxacin or other fluoroquinolones
• History of tendon disorders related to fluoroquinolone use
• Patients with myasthenia gravis (may worsen muscle weakness)
• Concurrent use with tizanidine is contraindicated

• Tendonitis and Tendon Rupture: Especially in elderly, transplant patients, or those on corticosteroids
• Peripheral Neuropathy: May be irreversible; discontinue if symptoms occur
• CNS Effects: Seizures, tremors, confusion, and psychosis may occur
• QT Prolongation: Risk increased in patients with cardiac conditions or on QT-prolonging drugs
• Hypoglycemia and Hyperglycemia: Monitor glucose closely in diabetics
• Phototoxicity: Advise patients to avoid sunlight or UV exposure
• Aortic Aneurysm/Dissection Risk: Caution in patients with vascular disorders
• C. difficile-Associated Diarrhea: May range from mild to fatal colitis

Common (≥1%):

• Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain
• Neurological: Headache, dizziness, insomnia
• Musculoskeletal: Arthralgia, tendonitis
• Dermatological: Rash, pruritus, photosensitivity

Serious and Rare:

• Tendon rupture
• Peripheral neuropathy
• QT prolongation and arrhythmias (e.g., torsades de pointes)
• Hypersensitivity reactions (e.g., Stevens-Johnson syndrome, anaphylaxis)
• CNS effects (e.g., seizures, hallucinations)
• Severe dysglycemia
• Hepatotoxicity
• Clostridioides difficile infection

• Antacids, Iron, Zinc, Sucralfate: Reduce absorption—separate doses by ≥2 hours
• Warfarin: Increased anticoagulant effect—monitor INR
• NSAIDs: May increase CNS stimulation or seizure risk
• Antidiabetic Drugs: Risk of blood sugar disturbances
• QT-Prolonging Agents (e.g., amiodarone, sotalol): Additive risk of arrhythmias
• CYP450 Interactions: Levofloxacin does not significantly inhibit or induce CYP450 enzymes

• FDA Black Box Warning (Updated 2018):
  Reinforced risk of disabling and potentially permanent adverse effects involving tendons, muscles, joints, nerves, and the central nervous system. Reserved for use when no alternatives exist.
• Clinical Guideline Adjustments:
  Levofloxacin is now considered a second-line or restricted-use agent for respiratory and urinary infections due to safety concerns.
• WHO Classification:
  Listed in the WHO Model List of Essential Medicines as a critical fluoroquinolone.

• Tablets:
  Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C. Protect from light and moisture.
• IV Solution:
  Store between 15°C and 30°C. Do not freeze. Use diluted solution within recommended timeframe.
• Ophthalmic/Otic Drops:
  Store at 2°C to 25°C (36°F to 77°F). Do not freeze. Discard 28 days after opening.
• Handling Instructions:
  Do not crush tablets. Follow aseptic technique for IV preparation. Shake ophthalmic/otic solutions before use if suspension-based.