Levofloxacin

Oral:
Acute bacterial sinusitis; Acute bacterial exacerbation of chronic bronchitis; Acute pyelonephritis; Community-acquired pneumonia; Complicated urinary tract infections; Uncomplicated urinary tract infections; Chronic bacterial prostatitis; Inhalational anthrax:
Patients on haemodialysis or CAPD: For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 48 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 125 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 125 mg 24 hourly.

CrCl (mL/min)	Dosage
<10	For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 48 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 125 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 125 mg 24 hourly.
10-19	For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 48 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 125 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 125 mg 12 hourly.
20-50	For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 24 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 250 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 250 mg 12 hourly.

Dosage and treatment recommendations may vary among countries and between individual products (refer to local or specific product guidelines).

Complicated skin and skin structure infections; Nosocomial pneumonia:
Patients on haemodialysis or CAPD: Initially, 750 mg followed by 500 mg 48 hourly.

CrCl (mL/min)	Dosage
10-19	Initially, 750 mg followed by 500 mg 48 hourly.
20-49	750 mg 48 hourly.

Intravenous:
Community-acquired pneumonia; Complicated skin and soft tissue infections; Complicated urinary tract infections; Chronic bacterial prostatitis; Inhalational anthrax:
Patients on haemodialysis or CAPD: For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 48 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 125 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 125 mg 24 hourly.

CrCl (mL/min)	Dosage
<10	For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 48 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 125 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 125 mg 24 hourly.
10-19	For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 48 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 125 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 125 mg 12 hourly.
20-50	For dosing of 250 mg 24 hourly: Initially, 250 mg followed by 125 mg 24 hourly. For dosing of 500 mg 24 hourly: Initially, 500 mg followed by 250 mg 24 hourly. For dosing of 500 mg 12 hourly: Initially, 500 mg followed by 250 mg 12 hourly.

Dosage and treatment recommendations may vary among countries and between individual products (refer to local or specific product guidelines).

Nosocomial pneumonia:
Patients on haemodialysis or CAPD: Initially, 750 mg followed by 500 mg 48 hourly.

CrCl (mL/min)	Dosage
10-19	Initially, 750 mg followed by 500 mg 48 hourly.
20-49	750 mg 48 hourly.

Inhalation:

CrCl (mL/min)	Dosage
<20	Not recommended.

Levofloxacin oral soln: Should be taken on an empty stomach.
Levofloxacin tab: May be taken with or without food.
Levofloxacin hemihydrate May be taken with or without food.

Concentrated IV solution for infusion: Further dilute vials containing levofloxacin 25 mg/mL with compatible IV solution (e.g. dextrose 5%, NaCl 0.9%) to a final concentration of 5 mg/mL before infusion. Refer to specific product guidelines for detailed preparation instructions.

Do not mix with heparin or alkaline solutions (e.g. Na bicarbonate).

Hypersensitivity to levofloxacin or other quinolones. Epilepsy, history of tendon disorders related to fluoroquinolone use.

Patient with risk factors for QT interval prolongation (e.g. congenital long QT syndrome, uncorrected electrolyte imbalance [e.g. hypomagnesaemia, hypokalaemia], heart failure, MI, bradycardia, concomitant use of agents known to prolong QT interval); conditions predisposing to seizures or lower seizure threshold; positive family history of aneurysm, congenital heart valve disease, pre-existing aortic aneurysm and/or dissection or heart valve disease, conditions predisposing to aortic aneurysm and dissection and/or heart valve regurgitation (e.g. Marfan syndrome, Ehlers-Danlos syndrome, Behcet disease, hypertension, atherosclerosis, Turner syndrome, Takayasu arteritis, giant cell arteritis, infective endocarditis); latent or actual defects in G6PD activity, diabetes mellitus, psychosis or history of psychiatric disorder, rheumatoid arthritis, solid organ transplant; haemoptysis (inhalation). Levofloxacin may only be used in situations where other usual recommended antibiotics are considered inappropriate: There is resistance to other 1st-line antibiotics, other 1st-line antibiotics are contraindicated or have caused adverse effects requiring treatment discontinuation, and 1st-line treatment has failed; refer to official local guidelines for latest recommendations. Discontinue treatment immediately and avoid use in patients who have experienced tendinitis, tendon rupture, peripheral neuropathy, and CNS effects. Avoid use in patients with history of myasthenia gravis. Avoid rapid or bolus IV infusion. Renal impairment. Children and elderly. Pregnancy and lactation.

Significant: Blood glucose disturbances, including symptomatic hyperglycaemia and hypoglycaemia (particularly in diabetic patients receiving antidiabetic agents); peripheral neuropathy, tendinopathy or tendon rupture, arthropathy, arthralgia, psychiatric and neurologic effects (e.g. confusion, agitation, insomnia, drowsiness, anxiety, depression, hallucinations, suicidal ideation or tendencies, delusions, toxic psychosis, seizures); fungal or bacterial superinfection (prolonged use), photosensitivity or phototoxicity; prolonged QT interval, ventricular arrhythmias (e.g. torsades de pointes); crystalluria, cylindruria; increased risk of aortic aneurysm and dissection (particularly in elderly), aortic and mitral valve regurgitation; bronchospasm, cough, haemoptysis (inhalation).
Eye disorders: Burning sensation of the eye, blurred or decreased vision, eye irritation or discomfort (ophthalmic).
Gastrointestinal disorders: Nausea, vomiting, diarrhoea; dysgeusia (ophthalmic, inhalation).
General disorders and administration site conditions: Infusion site pain or reddening (IV); fatigue, decreased exercise tolerance, fever (inhalation).
Investigations: Increased hepatic enzymes (e.g. AST, ALT, alkaline phosphatase, GGT); decreased FEV (inhalation).
Metabolism and nutrition disorders: Anorexia.
Nervous system disorders: Dizziness, headache.
Reproductive system and breast disorders: Vaginitis; vulvovaginal candidiasis (inhalation).
Respiratory, thoracic and mediastinal disorders: Dyspnoea; changes in bronchial secretions, dysphonia (inhalation).
Vascular disorders: Phlebitis (IV).
Potentially Fatal: Clostridioides difficile-associated diarrhoea or pseudomembranous colitis; hypersensitivity reactions (e.g. angioedema, anaphylactic shock), severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms); severe hypoglycaemia, severe hepatotoxicity; may exacerbate muscle weakness (in patients with myasthenia gravis). Rarely, haemolytic reactions (in patients with G6PD deficiency).

Ophth/Parenteral/PO: C

This drug may cause dizziness, drowsiness, fatigue, or visual disturbances, if affected, do not drive or operate machinery. Avoid excessive exposure to sunlight or artificial UV rays (e.g. sunray lamp, solarium) during treatment and for 48 hours after stopping the treatment. Ensure adequate hydration during treatment. Ophthalmic: Avoid wearing contact lenses during treatment.

Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor hepatic, renal and haematopoietic functions (periodically) and WBC count. Assess for altered mental status and signs or symptoms of infection, tendinopathy, peripheral neuropathy, disturbances in glucose regulation (particularly in diabetic patients), hypersensitivity reaction; bronchospasm or haemoptysis (following inhalation use).

Decreased oral absorption with Fe salts, Zn-containing multivitamins, Mg- or Al-containing antacids, sucralfate, and didanosine. May increase the risk of seizures with agents that lower seizure threshold (e.g. NSAIDs, theophylline). Decreased renal clearance with cimetidine and probenecid. Increased prothrombin time or INR with vitamin K antagonists (e.g. warfarin). Increased risk of tendinitis and tendon rupture with corticosteroids. Increased risk of QT interval prolongation with class IA and class III antiarrhythmics, TCAs, macrolides, and antipsychotic agents. May cause disturbances in blood glucose levels of patients receiving oral hypoglycaemic agents (e.g. glibenclamide) or insulin.

May give false-positive results for determination of opioids in urine using immunoassay. May give false-negative results for bacteriological diagnosis of TB.

Description:
Mechanism of Action: Levofloxacin, a fluoroquinolone anti-infective agent, acts by inhibiting bacterial topoisomerase IV and DNA-gyrase, the enzymes required for DNA replication, transcription, repair, recombination, and transposition. This inhibition prevents the relaxation of supercoiled DNA and promotes the breakage of bacterial DNA strands.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed (oral). Bioavailability: Approx 99%. Time to peak plasma concentration: 1-2 hours (oral); approx 0.5-1 hour (inhalation).
Distribution: Widely distributed into body tissues, including lungs, blister fluid, skin, and prostate; poor penetration into CSF. Enters breast milk. Volume of distribution: 74-112 L (oral, IV); approx 250 L (inhalation). Plasma protein binding: Approx 24-38%, mainly to albumin.
Metabolism: Metabolised to a very small extent in the liver into inactive metabolites.
Excretion: Mainly via urine (approx 87% as unchanged drug, <5% as metabolites); faeces (<4%). Elimination half-life: 6-8 hours (oral, IV); approx 5-7 hours (inhalation).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 149096, Levofloxacin. https://pubchem.ncbi.nlm.nih.gov/compound/Levofloxacin. Accessed Oct. 28, 2024.

Tab/IV inj: Store below 30°C. Protect from light. Oral solution: Store between 15-30°C. 0.5% ophthalmic solution: Store below 30°C. Protect from light. 1.5% ophthalmic solution: Store between 15-25°C. Nebuliser solution: Store between 15-30°C. Protect from light. Storage recommendations may vary between individual products (refer to specific product guidelines).

Eye Anti-Infectives & Antiseptics / Quinolones

J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
S01AE05 - levofloxacin ; Belongs to the class of quinolone antiinfectives. Used in the treatment of eye infections.

Anon. Levofloxacin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/07/2024.

Brayfield A, Cadart C (eds). Levofloxacin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2024.

Cravit Ophthalmic Solution (Santen Pharma Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/07/2024.

Joint Formulary Committee. Levofloxacin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2024.

Levin 250/500 Tablet (Hetero Labs). MIMS Singapore. http://www.mims.com/singapore. Accessed 04/07/2024.

Levofloxacin (Ophthalmic). UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 01/07/2024.

Levofloxacin (Oral Inhalation). UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 01/07/2024.

Levofloxacin (Systemic). UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 01/07/2024.

Levofloxacin 250 mg Film-coated Tablets (Bristol Laboratories Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2024.

Levofloxacin 5 mg/mL Eye Drops Solution (Accord-UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2024.

Levofloxacin 5 mg/mL Solution for Infusion (Mercury Pharmaceuticals Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2024.

Levofloxacin Injection, Solution, Concentrate (Eugia US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 03/07/2024.

Levofloxacin Kabi 5 mg/mL Solution for Infusion (Fresenius Kabi Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/07/2024.

Levofloxacin Solution (Lannett Company, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/07/2024.

Levofloxacin Solution/Drops (BPI Labs LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/07/2024.

Levofloxacin Tablet, Film Coated (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 03/07/2024.

Levoquin 250/500 Film Coated Caplet (DKSH Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/07/2024.

Quinsair 240 mg Nebuliser Solution (Chiesi Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2024.