Leo0.5%

Leo is a fluoroquinolone antibiotic indicated for the treatment of infections caused by susceptible strains of bacteria. Because of the risk of serious adverse effects associated with fluoroquinolones, Leo should be reserved for patients who have no alternative treatment options for certain indications.

Established/FDA-approved uses

• Community-acquired pneumonia and nosocomial (hospital-acquired) pneumonia
• Acute bacterial sinusitis
• Acute bacterial exacerbation of chronic bronchitis
• Uncomplicated and complicated urinary tract infections, including acute pyelonephritis
• Uncomplicated and complicated skin and skin structure infections
• Chronic bacterial prostatitis

Guideline-supported / special-situation uses

• Post-exposure prophylaxis and treatment of inhalational anthrax (with other measures as advised by health authorities)
• Treatment of plague (Yersinia pestis infection)

Off-label uses (used in some settings, not FDA-approved indications)

• As part of combination regimens for multidrug-resistant tuberculosis, under specialist supervision
• Certain intra-abdominal infections in combination with an agent active against anaerobes

Leo should only be used for infections confirmed or strongly suspected to be caused by susceptible bacteria; it is not effective against viral infections such as the common cold or flu.

Each tablet/vial of Levofloxacin preparations contains Levofloxacin (as levofloxacin hemihydrate) as the active pharmaceutical ingredient. Levofloxacin is available in Bangladesh as oral tablets (commonly 250 mg, 500 mg, and 750 mg), oral solution, and injectable (intravenous infusion) formulations, along with an ophthalmic solution for eye infections. Excipients vary by manufacturer and formulation.

Leo is a broad-spectrum, third-generation fluoroquinolone antibacterial agent. It is the pure (S)-enantiomer of the racemic drug ofloxacin and is active against a wide range of Gram-positive and Gram-negative bacteria, as well as some atypical pathogens (e.g., Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila).

Leo is administered orally or intravenously and is well absorbed with high oral bioavailability, allowing switch from IV to oral therapy in appropriate patients.

Leo belongs to the fluoroquinolone class of antibacterial agents.

Mechanism of action

Levofloxacin exerts its bactericidal effect by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes required for bacterial DNA replication, transcription, repair, and recombination. Inhibition of these enzymes prevents bacterial DNA from unwinding and duplicating, leading to bacterial cell death.

Pharmacokinetics

• Absorption: Rapidly and almost completely absorbed after oral administration; oral bioavailability is approximately 99%.
• Distribution: Widely distributed into body tissues and fluids, including lung tissue, with moderate plasma protein binding (~24-38%).
• Metabolism: Undergoes minimal hepatic metabolism.
• Excretion: Primarily eliminated unchanged in the urine via renal excretion; elimination half-life is approximately 6-8 hours in patients with normal renal function.

Leo tablets should be swallowed whole with water. Oral doses can be taken with or without food, but should be separated by at least 2 hours from antacids, iron, zinc, calcium, or dairy products. The injectable form is given only by slow intravenous infusion (over 60-90 minutes) by a healthcare professional; it should not be mixed with other medicines in the same infusion unless compatibility has been confirmed.

Leo has several clinically significant drug interactions:

• Antacids, sucralfate, multivitamins/minerals (iron, zinc), and calcium/dairy products: These form chelation complexes with Leo, substantially reducing its absorption and effectiveness. Administer Leo at least 2 hours before or after these products.
• Warfarin and other oral anticoagulants: Leo may enhance anticoagulant effects; monitor prothrombin time/INR closely and watch for bleeding.
• NSAIDs (e.g., ibuprofen): Concurrent use with Leo may increase the risk of central nervous system stimulation and seizures.
• Corticosteroids: Concurrent use increases the risk of tendinitis and tendon rupture, especially in older adults.
• Theophylline: Leo may increase theophylline plasma concentrations, raising the risk of theophylline toxicity; monitor levels.
• Antidiabetic agents (insulin, oral hypoglycemics): Concurrent use may cause significant blood glucose disturbances (both hypoglycemia and hyperglycemia); monitor blood glucose closely, particularly in diabetic patients.
• Drugs that prolong the QT interval (e.g., certain antiarrhythmics, antipsychotics): Concurrent use with Leo may increase the risk of QT prolongation and arrhythmia.
• Tizanidine: Concurrent use is contraindicated due to markedly increased tizanidine levels (see Contraindications).

Most patients tolerate Leo well, but side effects can occur.

Common side effects

• Nausea, vomiting, diarrhea, abdominal pain
• Headache, dizziness, insomnia
• Flatulence, constipation

Less common but serious side effects

• Tendinitis and tendon rupture (especially Achilles tendon), which can occur during or after treatment (see Precautions and Warnings)
• Peripheral neuropathy (numbness, tingling, weakness) that may be irreversible
• Central nervous system effects: seizures, confusion, tremors, hallucinations, anxiety, depression, and rarely suicidal thoughts
• Photosensitivity (increased sensitivity to sunlight, causing exaggerated sunburn)
• QT interval prolongation and, rarely, serious arrhythmias
• Clostridioides difficile-associated diarrhea, ranging from mild to life-threatening colitis
• Hypersensitivity reactions, including rash, and rarely severe skin reactions or anaphylaxis
• Blood glucose disturbances (hypoglycemia or hyperglycemia), particularly in diabetic patients
• Aortic aneurysm and aortic dissection (rare but serious risk signal, especially in older adults with risk factors)

Patients should seek prompt medical attention if they experience tendon pain/swelling, unusual numbness or tingling, severe diarrhea, sudden severe chest/back/abdominal pain, fainting, or signs of an allergic reaction while taking Leo.

Pregnancy: Leo is generally not recommended during pregnancy. Animal studies have shown Leo and other fluoroquinolones can cause cartilage and joint damage in immature animals, raising theoretical concern for the developing fetus. Leo should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus and no safer alternative antibiotic is suitable; consult a physician before use.

Lactation: Leo is excreted into human breast milk. Because of the potential risk of joint/cartilage effects and other adverse effects in the nursing infant, a decision should be made whether to discontinue breastfeeding or discontinue Leo, taking into account the importance of the drug to the mother; consult a physician.

Take Leo exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice.

• Tendinitis and tendon rupture: Fluoroquinolones, including Leo, are associated with an increased risk of tendinitis and tendon rupture, most commonly involving the Achilles tendon, across all ages. Risk is higher in patients over 60 years, those taking corticosteroids concurrently, and organ transplant recipients. Stop Leo and seek medical attention immediately if pain, swelling, or inflammation of a tendon occurs.
• Peripheral neuropathy: Leo may cause peripheral neuropathy that can occur soon after starting treatment and may be irreversible. Discontinue immediately if symptoms of neuropathy (pain, burning, tingling, numbness, weakness) occur.
• Central nervous system effects: May cause seizures, increased intracranial pressure, confusion, and rarely psychiatric reactions including suicidal thoughts. Use with caution in patients with known or suspected CNS disorders (e.g., epilepsy).
• Myasthenia gravis: Avoid use, as fluoroquinolones can worsen muscle weakness (see Contraindications).
• QT prolongation: Use with caution in patients with known QT prolongation, uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia), or concurrent use of other QT-prolonging drugs.
• Aortic aneurysm/dissection: Fluoroquinolones are associated with an increased risk of aortic aneurysm and dissection, particularly in older adults; avoid use in patients with a history of aneurysm or at increased risk unless no other treatment options are available.
• C. difficile-associated diarrhea: May occur during or up to several months after treatment; evaluate if diarrhea occurs and manage appropriately.
• Photosensitivity: Avoid excessive sun/UV exposure and use sun protection during treatment.
• Blood glucose disturbances: Monitor blood glucose closely in diabetic patients, especially those on insulin or oral hypoglycemic agents.
• Hepatic effects: Rare cases of severe hepatotoxicity have been reported; discontinue if signs of liver dysfunction occur.
• Use only for confirmed or strongly suspected bacterial infections to help prevent the development of drug-resistant bacteria.

In case of a suspected Leo overdose, seek immediate medical attention or contact a poison control center/emergency services right away. Specific antidote is not available. Management is supportive and symptomatic, and may include gastric emptying/decontamination if performed promptly by medical professionals, close monitoring of ECG (for QT prolongation) and hydration status, and general supportive care. Hemodialysis and peritoneal dialysis are not effective at removing Leo from the body. Do not attempt to manage an overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

Dose adjustment of Leo is required in patients with reduced renal function. As creatinine clearance decreases, either the dose or the dosing interval (or both) must be reduced according to the specific indication and creatinine clearance; consult full prescribing information or a physician for exact renal dosing adjustments. Leo is not effectively removed by hemodialysis or peritoneal dialysis.

Hepatic impairment

No dosage adjustment is generally required in hepatic impairment, as Leo undergoes minimal hepatic metabolism; however, caution is advised, and rare cases of severe liver injury have been reported.

Elderly patients

Elderly patients, particularly those on concurrent corticosteroids or with renal impairment, are at increased risk of tendon disorders, aortic aneurysm/dissection, and QT prolongation with Leo; use with caution and appropriate dose adjustment for renal function.

Pediatric use

See Pediatric Uses section below.

Duration of Leo therapy depends on the indication and typically ranges from 3 days (uncomplicated UTI) to 28 days (chronic bacterial prostatitis), as outlined in the Dosage and Administration section. Patients must complete the full course prescribed by their physician even if symptoms resolve earlier, to ensure eradication of infection and reduce the risk of antibiotic resistance.

Levofloxacin is classified as a fluoroquinolone antibacterial (a subclass of quinolone antibiotics).

Levofloxacin inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication and repair, resulting in bactericidal activity against susceptible organisms.

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Leo is generally not recommended for use in children and adolescents under 18 years of age for most infections, because fluoroquinolones have been associated with an increased incidence of musculoskeletal adverse events (e.g., arthralgia, tendon disorders) in pediatric patients compared with controls in clinical trials.

Exceptions where Leo may be used in children (age 6 months and older), under specialist guidance, include:

• Post-exposure prophylaxis and treatment of inhalational anthrax
• Treatment of plague

In these specific situations, pediatric dosing is weight-based (e.g., approximately 8 mg/kg per dose, not to exceed 250 mg per dose, given twice daily for children under 50 kg) and must be determined and supervised by a physician. For all other indications in children, safety and efficacy of Leo have not been established, and alternative antibiotics are generally preferred.