grepafloxacin

Action and Spectrum

Drug Interaction

Adverse Reaction

Frequency not defined 

Irregular heart rate 

Burning/stinging sensation in the skin 

Joint pain 

Swelling of your face, tongue/throat, 

Difficulty breathing 

Clicking/grinding sensation in the joints 

Liver enzyme abnormalities 

Hives 

Rash 

Stiffness and swelling in the joints 

Dizziness 

Black Box Warning

Black Box Warning: 

• Cardiac Arrhythmias: grepafloxacin was associated with a significant risk of causing QT interval prolongation, which can lead to serious cardiac arrhythmias such as torsades de pointes. This type of arrhythmia can be life-threatening. 
• Tendon Rupture: Like other fluoroquinolone antibiotics, grepafloxacin may have carried a warning about the risk of tendonitis and tendon rupture, particularly in older adults and those taking corticosteroids.  
• Neurological and Psychiatric Effects: Some fluoroquinolones have been associated with neurological and psychiatric effects, including seizures, dizziness, confusion, and hallucinations.

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity or Allergy: grepafloxacin should not be used in individuals with known hypersensitivity or allergy to the drug or other fluoroquinolone antibiotics. 
• QT Prolongation and Arrhythmias: grepafloxacin is associated with a risk of QT interval prolongation and serious cardiac arrhythmias, including torsades de pointes. It is typically contraindicated in individuals with a history of QT interval prolongation, certain pre-existing cardiac conditions, electrolyte imbalances, and those taking medications that can affect the QT interval. 
• Pregnancy and Lactation: Fluoroquinolone antibiotics, including grepafloxacin, are generally not recommended during pregnancy condition and lactation because of its potential risks to the developing fetus or nursing infant. 
• Children and Adolescents: grepafloxacin is typically not recommended for use in children and adolescents due to concerns about its effects on growing bodies and developing cartilage. 
• Elderly: Elderly individuals may be more susceptible to the adverse effects of grepafloxacin, including QT prolongation and tendon issues, so caution should be exercised. 
• Tendon Rupture: Fluoroquinolones, including grepafloxacin, have been associated with an enhanced risk of tendonitis and tendon rupture, particularly in older adults and those taking corticosteroids. Individuals with a history of tendon disorders or those taking corticosteroids may be at higher risk. 
• Neurological and Psychiatric Effects: grepafloxacin use has been associated with neurological and psychiatric effects, including seizures, dizziness, confusion, and hallucinations. It may be contraindicated in individuals with a history of seizures or certain psychiatric disorders. 
• Myasthenia Gravis: grepafloxacin use may exacerbate the symptoms of myasthenia gravis, a neuromuscular disorder. 
• Renal Impairment: Dose adjustments may be necessary for individuals with impaired renal function to avoid the accumulation of the drug. 
• Diabetes: grepafloxacin may affect blood sugar levels, so caution is needed in individuals with diabetes. 
• Liver Impairment: Caution is advised in individuals with liver impairment, as grepafloxacin is metabolized in the liver. 

Caution 

• Cardiac Issues: grepafloxacin can prolong the QT interval, which may lead to serious cardiac arrhythmias. It should be used cautiously in individuals with a history of QT interval prolongation, heart rhythm disorders, heart disease, electrolyte imbalances, and those taking medications that affect the QT interval. 
• Tendon Rupture: Like other fluoroquinolone antibiotics, grepafloxacin has been associated with an enhanced risk of tendonitis and tendon rupture, especially in older adults and those taking corticosteroids. Caution is advised in individuals with a history of tendon disorders or those taking corticosteroids. 
• Central Nervous System Effects: grepafloxacin can cause neurological and psychiatric effects such as seizures, dizziness, confusion, and hallucinations. Caution is needed in individuals with a history of seizures or certain psychiatric disorders. 
• Myasthenia Gravis: Fluoroquinolone antibiotics like grepafloxacin may exacerbate the symptoms of myasthenia gravis. 
• Renal Impairment: Dose adjustments may be necessary for individuals with impaired renal (kidney) function to avoid the accumulation of the drug. 
• Liver Impairment: grepafloxacin is metabolized in the liver, so caution is advised in individuals with liver impairment. 
• Diabetes: grepafloxacin may affect blood sugar levels, so individuals with diabetes should exercise caution and monitor their blood sugar closely. 
• Elderly: Elderly individuals may be more susceptible to the adverse effects of grepafloxacin, including QT prolongation, neurological effects, and tendon issues. 
• Hypersensitivity: Individuals with a history of hypersensitivity or allergic reactions to fluoroquinolones should use grepafloxacin cautiously. 
• Pregnancy and Lactation: Fluoroquinolone antibiotics are generally not recommended during pregnancy condition and lactation because of its potential risks to the developing fetus or nursing infant. 
• Drug Interactions: grepafloxacin may interact with other drugs, potentially affecting their efficacy or enhancing the risk of adverse effects. Caution is advised when using grepafloxacin alongside other medications. 
• Phototoxicity: Fluoroquinolones, including grepafloxacin, can increase sensitivity to sunlight (phototoxicity). Patients should be cautious about sun exposure and use sun protection. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: C 

Lactation:   

Excreted into human milk: Yes. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

grepafloxacin is a fluoroquinolone antibiotic with a mechanism of action involving the inhibition of the bacterial DNA gyrase and topoisomerase IV enzymes, essential for DNA replication and transcription. This interference disrupts bacterial cell division and growth, leading to eventual cell death. grepafloxacin exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria, making it effective against respiratory, urinary, skin, and soft tissue infections. 

Pharmacodynamics: 

Mechanism of action: The action of grepafloxacin involves targeting enzymes called DNA gyrase and topoisomerase IV, which are essential for DNA replication, transcription, and repair in bacteria. 

• DNA Gyrase Inhibition: DNA gyrase is an enzyme that introduces negative supercoils into the bacterial DNA molecule. This process is crucial for relieving the torsional strain that builds up as DNA strands unwind during replication and transcription. grepafloxacin binds to the DNA gyrase enzyme and prevents it from effectively introducing negative supercoils. As a result, bacterial DNA replication and transcription are disrupted, inhibiting bacterial growth and division. 
• Topoisomerase IV Inhibition: Topoisomerase IV is another enzyme that separates daughter DNA strands during cell division. It is involved in unlinking intertwined DNA strands that occur during replication and transcription. grepafloxacin also inhibits topoisomerase IV, further contributing to the disruption of DNA replication and the cell division in bacteria. 

By targeting these essential enzymes, grepafloxacin interferes with the processes necessary for bacterial survival and propagation. This disruption ultimately leads to the accumulation of DNA damage and the inability of bacteria to reproduce and proliferate, resulting in bacterial cell death. 

Pharmacokinetics: 

Absorption 

grepafloxacin is well absorbed after oral administration. Peak plasma concentrations are typically reached within a few hours after dosing. However, food intake can affect its absorption, and it was often recommended to take grepafloxacin on an empty stomach for optimal absorption. 

Distribution 

grepafloxacin has a relatively large volume of distribution, indicating that it can distribute into various tissues throughout the body. It is found in therapeutic concentrations in tissues such as the lungs, urinary tract, skin, and soft tissues, which makes it practical for treating various infections. 

Metabolism 

grepafloxacin undergoes hepatic (liver) metabolism primarily through the cytochrome P450 enzyme system, specifically the CYP1A2 isoenzyme. It is metabolized into several metabolites, including desmethylgrepafloxacin, which is pharmacologically active. The metabolites are eventually eliminated from the body. 

Elimination and Excretion 

Most of the administered dose of grepafloxacin and its metabolites is excreted in the urine. Renal excretion is a significant pathway for eliminating grepafloxacin from the body. A smaller portion of the drug and its metabolites is excreted in the feces. 

Adminstartion

Administration: 

The general administration of fluoroquinolone antibiotics (grepafloxacin). 

Dosage: The dosage of a fluoroquinolone antibiotic, including grepafloxacin, depends on factors such as the type of infection, severity, patient age, weight, and renal function. Dosages are typically expressed in milligrams (mg) and may vary for different infections. Dosage adjustments may be necessary for patients with impaired renal function. 

Route of Administration: Fluoroquinolones are usually available in oral tablets or suspension forms. Sometimes, they may also be available as intravenous (IV) formulations for more severe infections. 

Timing: Fluoroquinolones are often taken once or twice daily, depending on the specific antibiotic and the treated infection. They are usually taken with a full glass of water and can be taken with or without food. However, some fluoroquinolones may be less effective with certain minerals, vitamins, or dairy products. Always follow your healthcare provider’s instructions regarding timing and food interactions. 

Duration: The duration of treatment with fluoroquinolones varies depending on the type and severity of the infection. It is essential to complete the entire course of treatment as prescribed, even if symptoms improve before the medication is finished. This helps prevent the development of antibiotic resistance. 

Interactions: Fluoroquinolones can interact with other medications, so you must inform the healthcare provider about all the drugs, supplements, and herbal product. 

Adverse Effects: Like all medications, fluoroquinolones can have potential side effects. Common side effects may include gastrointestinal symptoms (nausea, vomiting, diarrhea), dizziness, headache, and skin sensitivity to sunlight. Serious side effects like tendon rupture and cardiac arrhythmias have also been associated with some fluoroquinolones, emphasizing caution and careful monitoring. 

Special Populations: Caution is advised when prescribing fluoroquinolones to pregnant or breastfeeding individuals, children, elderly individuals, and those with certain medical conditions (e.g., history of seizures, heart conditions). 

Patient Information Leaflet

Patient information leaflet 

Generic Name: grepafloxacin 

Why do we use grepafloxacin? 

grepafloxacin, a fluoroquinolone antibiotic, was used to treat various bacterial infections. 

grepafloxacin was primarily indicated for the treatment of the following bacterial infections: 

• Community-Acquired Pneumonia (CAP): grepafloxacin was used to treat mild to moderate cases of pneumonia acquired outside of a hospital or healthcare setting. 
• Acute Bacterial Exacerbations of the Chronic Bronchitis: It was used to treat acute worsening of chronic bronchitis caused by susceptible bacteria. 
• Uncomplicated Urinary Tract Infections (UTIs): grepafloxacin was indicated for treating uncomplicated urinary tract infections (UTI) caused by susceptible bacteria. 
• Skin and Soft Tissue Infections: It treated specific skin and soft tissue infections which are caused by susceptible bacteria. 
• Sexually Transmitted Infections (STIs): grepafloxacin was occasionally used to treat certain sexually transmitted infections like gonorrhea, when appropriate and based on susceptibility testing.