Delameg

Approved Indications:

• Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Treatment of ABSSSI caused by susceptible Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).
• Community-Acquired Bacterial Pneumonia (CABP): For treatment of CABP caused by susceptible pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae.

Clinically Accepted Off-label Uses:

• Treatment of complicated urinary tract infections (cUTIs) (off-label in some regions).
• Other infections caused by susceptible bacteria based on clinical judgment.

• Adults:
• ABSSSI:
• Oral or intravenous (IV) route: 450 mg IV every 12 hours, or 450 mg orally every 12 hours.
• Duration: Typically 5 to 14 days depending on infection severity.
• CABP:
• 450 mg IV every 12 hours, transitioning to oral 450 mg every 12 hours as clinically appropriate.
• Duration: Generally 5 to 10 days.
• Pediatrics:
• Safety and efficacy not established; not recommended.
• Elderly:
• No dose adjustment needed solely based on age.
• Renal Impairment:
• Mild to moderate impairment (CrCl ≥30 mL/min): No adjustment necessary.
• Severe impairment (CrCl <30 mL/min): Use with caution; insufficient data; not recommended.
• Hepatic Impairment:
• No dose adjustment required for mild to moderate impairment.
• Severe hepatic impairment: Use with caution; data limited.
• Administration:
• IV infusion over 60 minutes.
• Oral tablets to be taken without regard to food.

Delafloxacin is a fluoroquinolone antibiotic that exerts bactericidal activity by inhibiting bacterial DNA gyrase and topoisomerase IV, essential enzymes involved in bacterial DNA replication, transcription, repair, and recombination. By stabilizing the DNA-enzyme complex, delafloxacin prevents DNA strand break re-ligation, resulting in double-stranded DNA breaks and rapid bacterial cell death. Its unique chemical structure enhances activity in acidic environments and against Gram-positive pathogens including MRSA.

• Absorption:
• Oral bioavailability approximately 58.8%.
• Peak plasma concentration (Cmax) reached in 1 to 2 hours after oral dosing.
• Distribution:
• Volume of distribution approximately 30–35 L.
• Penetrates well into skin tissues and lungs.
• Metabolism:
• Minimal hepatic metabolism; primarily unchanged drug.
• Half-life:
• Approximately 8 to 12 hours, supporting twice-daily dosing.
• Elimination:
• Excreted mainly via urine (~65%) and feces (~28%) as unchanged drug.
• Renal clearance plays a significant role.

• Pregnancy:
• Classified as FDA Pregnancy Category C. Animal studies show adverse effects on fetal development; no adequate human studies. Use only if benefits justify potential risks.
• Lactation:
• Excreted in breast milk in limited amounts; effects on nursing infants unknown. Caution advised; breastfeeding is generally not recommended during treatment.

• Primary Therapeutic Class: Fluoroquinolone antibiotic
• Subclass: Respiratory fluoroquinolone with expanded Gram-positive coverage

• Known hypersensitivity to delafloxacin, other fluoroquinolones, or formulation components.
• History of tendinitis or tendon rupture related to fluoroquinolone use.
• Concomitant use with tizanidine (due to increased risk of hypotension and CNS effects).

• Tendinitis and Tendon Rupture: Increased risk, especially in elderly, renal impairment, or corticosteroid use.
• Peripheral Neuropathy: May cause irreversible nerve damage; discontinue if symptoms develop.
• Central Nervous System Effects: Including seizures, tremors, and psychiatric effects; use cautiously in patients with CNS disorders.
• QT Prolongation: Avoid use in patients with known QT prolongation or on QT-prolonging drugs.
• Hypersensitivity Reactions: Serious allergic reactions possible; discontinue immediately if they occur.
• Clostridioides difficile-associated diarrhea: Consider if diarrhea develops.
• Photosensitivity: Advise patients to avoid excessive sunlight.
• Clinical Monitoring: Liver function, renal function, and blood glucose monitoring recommended in high-risk patients.

Common:

• Gastrointestinal: Nausea, diarrhea, vomiting
• Central Nervous System: Headache, dizziness
• Skin: Rash, pruritus, photosensitivity reactions

Serious and Rare:

• Tendon rupture or tendinitis
• Peripheral neuropathy
• Seizures
• Hypersensitivity/anaphylaxis
• Hepatotoxicity
• QT prolongation and arrhythmias

Onset varies; some serious effects may appear early or delayed. Dose-dependence observed primarily for GI symptoms.

• Drug-Drug:
• Antacids, sucralfate, iron, zinc, magnesium supplements reduce absorption; administer delafloxacin 2 hours before or 6 hours after these agents.
• Inhibitors/inducers of CYP3A4 have minimal impact due to limited metabolism.
• Avoid concomitant use with tizanidine.
• May increase effects of warfarin; monitor INR.
• Drug-Food:
• Food does not significantly affect oral bioavailability; can be taken with or without food.
• Drug-Alcohol:
• No direct interaction, but alcohol may exacerbate CNS side effects.

• Recent guidelines support delafloxacin as an effective option for ABSSSI with MRSA coverage and CABP due to broad-spectrum activity and favorable safety profile.
• FDA and EMA continue to monitor safety signals regarding tendinopathy and neuropathy; label updates emphasize warnings.
• Ongoing trials are evaluating expanded indications and dosing regimens.
• No major changes in dosing recommendations in recent years.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in original packaging until use.
• Do not freeze.
• Keep out of reach of children.