Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including tendinopathy and tendon rupture, peripheral neuropathy, and CNS effects.
Discontinue delafloxacin immediately and avoid the use of fluoroquinolones in patients who experience any of these serious adverse reactions.
Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid delafloxacin in patients with known history of myasthenia gravis.
Pneumonia, community-acquired, outpatients with comorbidities or inpatients (alternative agent):
Note: Clinical experience is limited; some experts reserve for patients who cannot take other agents (Ref).
Oral: 450 mg every 12 hours.
IV: 300 mg every 12 hours.
Duration of therapy: Duration is a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (Ref).
Skin and skin structure infection:
Oral: 450 mg every 12 hours for 5 to 14 days.
IV: 300 mg every 12 hours for 5 to 14 days.
Missed dose: If ≥8 hours prior to next dose, missed dose should be taken as soon as possible. If <8 hours before next dose, wait until next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral, IV:
Estimated glomerular filtration rate (eGFR) 30 to 89 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to 29 mL/minute/1.73 m2:
Oral: No dosage adjustment necessary.
IV: 200 mg every 12 hours
eGFR <15 mL/minute/1.73 m2: Use is not recommended.
ESRD on hemodialysis: Use is not recommended.
No dosage adjustment necessary.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Bradycardia (<2%), flushing (<2%), hypertension (<2%), hypotension (<2%), palpitations (<2%), presyncope (<2%), sinus tachycardia (<2%), syncope (<2%), ventricular premature contractions (<2%)
Dermatologic: Dermatitis (<2%), pruritus (<2%), skin rash (<2%), urticaria (<2%)
Endocrine & metabolic: Hyperglycemia (<2%), hypoglycemia (<2%)
Gastrointestinal: Abdominal pain (<2%), Clostridioides difficile associated diarrhea (<2%), diarrhea (5% to 8%), dysgeusia (<2%), dyspepsia (<2%), nausea (8%), oral candidiasis (<2%), vomiting (2%)
Genitourinary: Vulvovaginal candidiasis (<2%)
Hematologic & oncologic: Agranulocytosis (<2%), anemia (<2%), leukopenia (<2%), neutropenia (<2%), pancytopenia (<2%)
Hepatic: Increased serum alkaline phosphatase (<2%), increased serum transaminases (3% to 5%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Infection: Fungal infection (<2%)
Nervous system: Abnormal dreams (<2%), agitation (<2%), anxiety (<2%), confusion (<2%), dizziness (<2%), headache (3%), hypoesthesia (<2%), insomnia (<2%), paresthesia (<2%), vertigo (<2%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (<2%), myalgia (<2%)
Ophthalmic: Blurred vision (<2%)
Otic: Tinnitus (<2%), vestibular disturbance (<2%)
Renal: Increased serum creatinine (<2%), renal failure syndrome (<2%), renal insufficiency (<2%)
Miscellaneous: Infusion related reaction (<2%)
Frequency not defined:
Nervous system: Central nervous system disease, exacerbation of myasthenia gravis, peripheral neuropathy
Neuromuscular & skeletal: Rupture of tendon, tendinopathy
Postmarketing: Hepatic: Hepatotoxicity (Chalasani 2021)
Hypersensitivity to delafloxacin, other fluoroquinolones, or any component of the formulation
Concerns related to adverse effects:
• Aortic aneurysm and dissection: Fluoroquinolones have been associated with aortic aneurysm ruptures or dissection within 2 months following use, particularly in elderly patients. Fluoroquinolones should not be used in patients with a known history of aortic aneurysm or those at increased risk, including patients with peripheral atherosclerotic vascular diseases, hypertension, genetic disorders involving blood vessel changes (eg, Marfan syndrome, Ehlers-Danlos syndrome), and elderly patients, unless no other treatment options are available. Longer treatment duration (eg, >14 days) may increase risk (Lee 2018).
• Glucose regulation: Fluoroquinolones have been associated with disturbances in glucose regulation, including hyperglycemia and hypoglycemia. These events have occurred most often in patients receiving concomitant oral hypoglycemic agents or insulin. Severe cases of hypoglycemia, including coma and death, have been reported. Diabetic patients should be monitored closely for signs/symptoms of disordered glucose regulation. Discontinue if a hypoglycemic reaction occurs and immediately initiate appropriate therapy.
• Hypersensitivity reactions: Severe and sometimes fatal hypersensitivity reactions, including anaphylaxis, have occurred with fluoroquinolone therapy. May occur after first or subsequent doses, and may be accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Discontinue therapy at the first sign of skin rash or any other sign of a hypersensitivity reaction.
• Serious adverse reactions: [US Boxed Warning]: Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that may occur together, including tendinopathy and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue delafloxacin immediately and avoid use of fluoroquinolones in patients who experience any of these serious adverse reactions. Patients of any age or without preexisting risk factors have experienced these reactions; may occur within hours to weeks after initiation.
- CNS effects: Fluoroquinolones have been associated with an increased risk of CNS effects including seizures, increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. May occur following the first dose; discontinue immediately and avoid further use of fluoroquinolones in patients who experience these reactions. Use with caution in patients with known or suspected CNS disorder, or risk factors that may predispose to seizures or lower the seizure threshold.
- Peripheral neuropathy: Fluoroquinolones have been associated with an increased risk of peripheral neuropathy; may occur soon after initiation of therapy and may be irreversible; discontinue if symptoms of sensory or sensorimotor neuropathy occur. Avoid use in patients who have previously experienced peripheral neuropathy.
- Psychiatric reactions: Fluoroquinolones have been associated with an increased risk of psychiatric reactions, including toxic psychosis, hallucinations, or paranoia; may also cause nervousness, agitation, delirium, attention disturbances, insomnia, anxiety, nightmares, memory impairment, confusion, depression, and suicidal thoughts or actions. Use with caution in patients with a history of or risk factor for depression. Reactions may occur following the first dose; discontinue if reaction occurs and institute appropriate therapy.
- Tendinopathy/Tendon rupture: Fluoroquinolones have been associated with an increased risk of tendinopathy and tendon rupture in all ages; risk may be increased with concurrent corticosteroids, solid organ transplant recipients, and in patients >60 years of age, but has also occurred in patients without these risk factors. Rupture of the Achilles tendon has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps, hand) have also been reported. Inflammation and rupture may occur bilaterally. Cases have been reported within hours or days of initiation, and up to several months after discontinuation of therapy. Strenuous physical activity, renal failure, and previous tendon disorders may be independent risk factor for tendon rupture. Discontinue at first sign of tendon pain, swelling, inflammation, or rupture. Avoid use in patients with a history of tendon disorders or who have experienced tendinopathy or tendon rupture.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Myasthenia gravis: [US Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis; avoid use in patients with known history of myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support, and deaths have been reported.
• Renal impairment: Use with caution and reduce dose in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/minute/1.73 m2). Use is not recommended in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2). See also “Dosage form specific issues: Injection”.
Special populations:
• Older adult: Adverse effects (eg, tendon rupture) may be increased in elderly patients.
• G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency (Luzzatto 2020).
Dosage form specific issues:
• Injection: Avoid use of IV formulation in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2); injection contains excipient cyclodextrin (sulfobutylether-beta-cyclodextrin [SBECD]), which may accumulate. Closely monitor serum creatinine levels in patients with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2) and consider using oral delafloxacin in these patients if serum creatinine levels increase; discontinue use if eGFR decreases to <15 mL/minute/1.73 m2.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Baxdela: 300 mg (1 ea) [contains edetate (edta) disodium]
Tablet, Oral:
Baxdela: 450 mg
No
Solution (reconstituted) (Baxdela Intravenous)
300 mg (per each): $170.28
Tablets (Baxdela Oral)
450 mg (per each): $85.05
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Oral: Administer with or without food. Administer at least 2 hours before or 6 hours after antacids containing magnesium or aluminum, sucralfate, metal cations (eg, iron), multivitamins containing zinc or iron, or with didanosine buffered tablets for oral suspension or pediatric powder for oral solution.
IV: Administer by IV infusion over 60 minutes. Do not administer with any solution containing multivalent cations (eg, calcium and magnesium) through the same IV line. Do not co-infuse with other medications.
If a common IV line is being used to administer other drugs in addition to delafloxacin, the line should be flushed before and after each infusion with NS or D5W.
An FDA-approved patient medication guide, which is available with the product and as follows, must be dispensed with this medication:
Baxdela: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208611s007lbl.pdf#page=28
Pneumonia, community-acquired: Treatment of adults with community-acquired bacterial pneumonia caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Skin and skin structure infection: Treatment of acute bacterial skin and skin structure infection caused by susceptible isolates of S. aureus (including methicillin-resistant and methicillin-susceptible isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, Enterococcus faecalis, E. coli, Enterobacter cloacae, K. pneumoniae, and P. aeruginosa.
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (minor), UGT1A1, UGT1A3, UGT2B15; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Blood Glucose Lowering Effects: Quinolones may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Amphetamines: May enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
Antacids: May decrease the absorption of Quinolones. Of concern only with oral administration of quinolones. Management: Avoid concurrent administration of quinolones and antacids to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone; see full monograph for details. Risk D: Consider therapy modification
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Calcium Salts: May decrease the absorption of Quinolones. Of concern only with oral administration of both agents. Management: Consider administering an oral quinolone at least 2 hours before or 6 hours after the dose of oral calcium to minimize this interaction. Monitor for decreased therapeutic effects of quinolones during coadministration. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Risk C: Monitor therapy
Delamanid: Quinolones may enhance the QTc-prolonging effect of Delamanid. Management: Avoid concomitant use if possible. If coadministration is unavoidable, frequent monitoring of electrocardiograms (ECGs) throughout the full delamanid treatment period should occur. Risk D: Consider therapy modification
Didanosine: Quinolones may decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolones. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Risk D: Consider therapy modification
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Iron Preparations: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for enox-, levo-, nor-, oflox-, peflox, or nalidixic acid) oral iron. Risk D: Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Quinolones. Management: Administer oral quinolone antibiotics at least one hour before or four hours after lanthanum. Risk D: Consider therapy modification
Magnesium Salts: May decrease the serum concentration of Quinolones. Management: Administer oral quinolones several hours before (4 h for moxi/pe/spar/enox-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe/enox-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Risk D: Consider therapy modification
Methylphenidate: May enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Quinolones. Specifically, polyvalent cations in multivitamin products may decrease the absorption of orally administered quinolone antibiotics. Management: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased quinolone efficacy. Risk D: Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Quinolones. Specifically, minerals in the multivitamin/mineral product may impair absorption of quinolone antibiotics. Management: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased therapeutic effects of quinolones. Risk D: Consider therapy modification
Mycophenolate: Quinolones may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Nadifloxacin: May enhance the adverse/toxic effect of Quinolones. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: May decrease the absorption of Quinolones. Management: Give oral quinolones at least 2 hours before or at least 6 hours after polyethylene glycol-electrolyte solutions that contain magnesium sulfate (Suflave brand). Other products without magnesium do not require dose separation. Risk D: Consider therapy modification
Probenecid: May decrease the excretion of Quinolones. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolones. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Strontium Ranelate: May decrease the serum concentration of Quinolones. Management: In order to minimize any potential impact of strontium ranelate on quinolone antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during quinolone therapy. Risk X: Avoid combination
Sucralfate: May decrease the serum concentration of Quinolones. Management: Avoid concurrent administration of quinolones and sucralfate to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Quinolones may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for enox-, levo-, nor-, pe- or ofloxacin or nalidixic acid) oral zinc salts. Risk D: Consider therapy modification
Adverse events were observed in some animal reproduction studies.
It is not known if delafloxacin is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
WBC, signs of infection, serum creatinine; signs and symptoms of disordered glucose regulation
Delafloxacin inhibits DNA gyrase (topoisomerase II) and topoisomerase IV enzymes, which are required for bacterial DNA replication, transcription, repair, and recombination.
Distribution: 30 to 48 L
Protein binding: ~84%, primarily albumin
Metabolism: Glucuronidation by UGT1A1, UGT1A3, and UGT2B15.
Bioavailability: Oral: 58.8%
Half-life elimination: IV: 3.7 hours (single dose); Oral: 4.2 to 8.5 hours (multiple dose)
Time to peak: ~1 hour
Excretion: IV: Urine (65% as unchanged drug); Feces (28% as unchanged drug); Oral: Urine (50% as unchanged drug); Feces (48% as unchanged drug)
Altered kidney function: Mean total exposure (AUCt) was 1.3, 1.6, 1.8, 2.1, and 2.6-fold higher in subjects with mild impairment (eGFR 51 to 80 mL/minute/1.73 m2), moderate impairment (eGFR 31 to 50 mL/minute/1.73 m2), severe impairment (eGFR 15 to 29 mL/minute/1.73 m2), or end-stage renal disease on hemodialysis, respectively, compared to normal subjects following a single IV dose. Mean AUCt was 1.5-fold higher in subjects with moderate (eGFR 31 to 50 mL/minute/1.73 m2) or severe (eGFR 15 to 29 mL/minute/1.73 m2) impairment compared to normal subjects following a single oral dose.
Anti-infective considerations:
Parameters associated with efficacy:
Concentration dependent, associated with free drug area under the curve (fAUC24)/minimum inhibitory concentration (MIC) (Thabit 2016). Note: Based on other fluoroquinolones, in critically ill patients, some experts recommend AUC24/MIC goal >125 to 250 and Cmax/MIC goal ≥12 (Abdul-Aziz 2020).
Pathogen specific:
E. coli: fAUC24/MIC: 14.5 (bacteriostatic); 26.2 (1-log10 kill) (Cho 2018).
K. pneumoniae: fAUC24/MIC: 1.4 to 155 (bacteriostatic); 5.47 to 321 (1-log10 kill) (Lepak 2016; Thabit 2016; Zhao 2019).
P. aeruginosa: fAUC24/MIC: 3.41 to 24.8 (bacteriostatic); 9.82 to 51.6 (1-log10 kill) (Zhao 2019).
S. aureus (methicillin-sensitive S. aureus): fAUC24/MIC 0.4 to 3.12 (bacteriostatic); 0.4 to 10.8 (1-log10 kill) (Lepak 2016; Thabit 2016).
S. aureus (methicillin-resistant S. aureus): fAUC24/MIC: <1.05 to 8.1 (bacteriostatic); 6.61 to 24.7 (1-log10 kill) (Lepak 2016; Thabit 2016).
S. pneumoniae: fAUC24/MIC: <0.26 to 7.1 (bacteriostatic); 0.39 to 31.8 (1-log10 kill) (Lepak 2016; Thabit 2016).
Expected drug exposure in adults with normal renal function:
AUC24:
300 mg every 12 hours (steady state): IV: 46.8 mg•hour/L.
450 mg twice daily (steady state): Oral: 61.6 mg•hour/L.
Cmax (peak):
300 mg every 12 hours (steady state): IV: 9.29 mg/L.
450 mg twice daily (steady state): Oral: 7.45 mg/L.
Postantibiotic effect: Bacterial killing continues after drug concentration falls below the MIC of targeted pathogen and varies based on the organism. No data are available for delafloxacin specifically; however, for other fluoroquinolones, the postantibiotic effect is generally 1 to 3 hours (Boswell 1999; Craig 1991; Fu 1992; Fuursted 1987; Houston 1994; Kumar 1992; Licata 1997; Spangler 1998).
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