delafloxacin

Action and Spectrum

Actions and spectrum: 

Actions and spectrum: 

• Mechanism of action: delafloxacin inhibits bacterial DNA synthesis by targeting DNA gyrase and topoisomerase IV, which are enzymes required for bacterial DNA replication. 
• Spectrum of activity: delafloxacin has a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including many strains that are resistant to other antibiotics. It is particularly effective against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. 
• Clinical uses: delafloxacin is used to treat a variety of bacterial infections, including skin and soft tissue infections, acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD), and community-acquired pneumonia (CAP). 
• Pharmacokinetics: delafloxacin is available in both oral and intravenous formulations. It is well absorbed from the gastrointestinal tract and has good tissue penetration, allowing it to effectively target infections in various parts of the body. 
• Adverse effects: Common adverse effects of delafloxacin include nausea, diarrhoea, headache, and dizziness. It can also cause phototoxicity, which is an abnormal skin reaction to sunlight. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Vomiting (2%) 

Transaminase elevations (3%) 

Headache (3%) 

Diarrhea (8%) 

Nausea (8%)  

<2% 

• Ear and labyrinth disorders: vertigo, Tinnitus 
• administration site conditions and General disorders: Infusion site extravasation, discomfort, infusion site bruise, edema, erythema, pain, irritation, phlebitis, thrombosis, swelling 
• Immune disorders: Hypersensitivity 
• Laboratory Investigations: increased Blood alkaline phosphatase, increased blood creatinine, increased blood creatine phosphokinase 
• connective tissue and Musculoskeletal disorders: Myalgia 
• Psychiatric disorders: insomnia, Anxiety, abnormal dreams 
• Skin disorders: urticaria, Pruritus, dermatitis, rash 
• Cardiac disorders: palpitations, Sinus tachycardia, bradycardia 
• Eye disorders: Vision blurred 
• Gastrointestinal disorders: dyspepsia, Abdominal pain 
• Infections and infestations: fungal infection, Clostridium difficile infection, vulvovaginal candidiasis, oral candidiasis 
• nutrition and metabolism disorders: Hypoglycemia, Hyperglycemia, 
• Nervous system disorders: hypoesthesia, Dizziness, paraesthesia, presyncope, dysgeusia, syncope 
• Renal and urinary: renal failure, renal impairment 
• Vascular disorders: hypotension, Flushing, phlebitis, hypertension 

Black Box Warning

Black Box Warning: 

The black box warning for delafloxacin relates to the risk of tendonitis and tendon rupture, which is a rare but serious side effect associated with fluoroquinolone antibiotics. Tendons are the fibrous tissues that connect muscles to bones, and tendonitis is an inflammation of these tissues. Tendon rupture is a complete tear of the tendon. 

The warning advises that fluoroquinolone antibiotics, including delafloxacin, should be reserved for patients with no alternative treatment options of chronic bronchitis, acute bacterial sinusitis (ABS), and uncomplicated urinary tract infections (UTI) who have no other treatment options. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: delafloxacin is contraindicated in patients who have a history of hypersensitivity or allergic reaction to delafloxacin or any other fluoroquinolone antibiotics. 
• Tendonitis and tendon rupture: As mentioned in the previous answer, delafloxacin is contraindicated in patients with a history of tendonitis or tendon rupture associated with fluoroquinolone antibiotics. 
• Myasthenia gravis: delafloxacin is contraindicated in patients with a history of myasthenia gravis, a neuromuscular disorder that causes muscle weakness and fatigue. 
• Pregnancy and breastfeeding: delafloxacin are classified as Pregnancy Category C, which means that it may be harmful to a developing fetus. It is also not recommended for use during breastfeeding, as it may be excreted in breast milk and could harm a nursing infant. 
• Children and adolescents: delafloxacin are not recommended to use in adolescents and children below the age of 18, as it may affect bone development.

Caution: 

• Renal impairment: delafloxacin is primarily eliminated by the kidneys, so patients with renal impairment may require dosage adjustments to avoid accumulation of the medication in the body. 
• Hepatic impairment: delafloxacin is primarily metabolized in the liver, so patients with hepatic impairment may require dosage adjustments to avoid accumulation of the medication in the body. 
• CNS disorders: delafloxacin can cause CNS side effects, such as dizziness and headache, which may be exacerbated in patients with CNS disorders. 
• Electrolyte disturbances: delafloxacin may cause electrolyte disturbances, such as hypokalemia and hypomagnesemia, which may require monitoring and correction. 
• QT prolongation: delafloxacin can prolong the QT interval, which measures the time it takes for the heart to recharge between beats.  
• Diabetes: delafloxacin may cause hypoglycemia or hyperglycemia in patients with diabetes, which may require monitoring and adjustment of blood glucose levels. 
• Gastrointestinal disorders: delafloxacin may cause gastrointestinal side effects, such as nausea, vomiting, and diarrhea, which may be exacerbated in patients with gastrointestinal disorders.

Comorbidities: 

• Cardiovascular disease: delafloxacin can prolong the QT interval, which may increase the risk of life-threatening cardiac arrhythmias, especially in patients with underlying cardiovascular disease. 
• Diabetes: delafloxacin may cause hypoglycemia or hyperglycemia in patients with diabetes, which may require monitoring and adjustment of blood glucose levels. 
• Renal impairment: delafloxacin is primarily eliminated by the kidneys, so patients with renal impairment may require dosage adjustments to avoid accumulation of the medication in the body. 
• Hepatic impairment: delafloxacin is primarily metabolized in the liver, so patients with hepatic impairment may require dosage adjustments to avoid accumulation of the medication in the body. 
• Immunosuppression: delafloxacin may be less effective in patients with immunosuppression, such as those with HIV/AIDS or receiving immunosuppressive therapy. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: It is not known whether delafloxacin is excreted in human milk  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

delafloxacin is a fluoroquinolone antibiotic that exerts its pharmacological effects by inhibiting the activity of bacterial DNA gyrase and topoisomerase IV, two enzymes that are essential for bacterial DNA replication, recombination, and repair. This inhibition leads to the disruption of DNA synthesis and bacterial growth and results in bacterial cell death. 

delafloxacin has a broad-spectrum of activity against both Gram-positive and Gram-negative bacteria, including those that are resistant to other antibiotics. 

In addition to its antibacterial properties, delafloxacin has been shown to have immunomodulatory effects, including the suppression of pro-inflammatory cytokine production and the modulation of T-cell proliferation and activation.  

Pharmacodynamics: 

delafloxacin is a fluoroquinolone antibiotic that exerts its pharmacodynamic effects by inhibiting the bacterial enzymes DNA gyrase and topoisomerase IV. These enzymes are essential for bacterial DNA replication and repair, and inhibition of these enzymes leads to bacterial cell death. 

delafloxacin has broad-spectrum activity against Gram-positive and Gram-negative bacteria, including those that are resistant to other antibiotics. It has a higher affinity for bacterial DNA gyrase and topoisomerase IV than for human topoisomerases, which reduces the risk of adverse effects on human cells. 

The pharmacodynamics of delafloxacin are dose-dependent, with higher doses leading to greater bacterial killing. It has a short half-life of 4-6 hours, which allows for once-daily dosing.  

Pharmacokinetics: 

Absorption 

delafloxacin is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours. Food does not significantly affect its absorption. 

Distribution 

delafloxacin has a moderate volume of distribution, indicating that it is distributed widely throughout the body. It is approximately 85% protein-bound, primarily to albumin, and crosses the blood-brain barrier (BBB), allowing it to treat infections in the central nervous system. 

Metabolism 

delafloxacin is primarily metabolized by the liver through glucuronidation and oxidation, with the cytochrome P450 (CYP) enzyme system playing a minor role in its metabolism. The primary metabolite, M1, is inactive. 

Elimination and excretion 

delafloxacin is primarily eliminated by the kidneys, with approximately 60% of the dose excreted unchanged in the urine and 20% excreted as M1. The elimination half-life is 4-6 hours, which allows for once-daily dosing. delafloxacin is not significantly removed by hemodialysis or peritoneal dialysis. 

Adminstartion

Administration: 

delafloxacin is available in tablet and intravenous (IV) formulations. The specific administration of delafloxacin will depend on the indication being treated and the severity of the infection. 

Oral administration: delafloxacin tablets can be taken with or without food. The tablets should be administered whole and not crushed, chewed, or broken. The usual dose for adults is 450 mg once daily for 5-14 days depending on the severity of the infection. The duration of therapy may vary depending on the type of infection and the patient’s response to treatment. 

Intravenous administration: delafloxacin is also available as an IV formulation. It is administered as an intravenous infusion over 60 minutes. The usual dose for adults is 300 mg every 12 hours for 5-14 days depending on the severity of the infection. The duration of therapy may vary depending on the type of infection and the patient’s response to treatment. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: delafloxacin 

Pronounced: [ DEL-a-FLOX-a-sin]  

Why do we use delafloxacin? 

• Acute bacterial skin and its structure infections (ABSSSI): delafloxacin is approved for the treatment of ABSSSI caused by susceptible Gram-positive and Gram-negative bacteria. 
• Community-acquired bacterial pneumonia (CABP): delafloxacin is approved for the treatment of CABP caused by susceptible Gram-positive and Gram-negative bacteria. 
• ventilator-associated bacterial pneumonia (VABP) and Hospital-acquired bacterial pneumonia (HABP): delafloxacin is approved for the treatment of HABP and VABP caused by susceptible Gram-negative bacteria. 
• Urinary tract infections (UTIs): delafloxacin is approved for the treatment of uncomplicated UTIs caused by susceptible Gram-negative bacteria.