Delafloxacin

Dosage Forms

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 disodium]

Tablet, Oral:

Baxdela: 450 mg

Pharmacology

Mechanism of Action

Delafloxacin inhibits DNA gyrase (topoisomerase II) and topoisomerase IV enzymes, which are required for bacterial DNA replication, transcription, repair, and recombination.

Pharmacokinetics/Pharmacodynamics

Distribution

30 to 48 L

Metabolism

Glucuronidation by UGT1A1, UGT1A3, and UGT2B15.

Excretion

IV: Urine (65% as unchanged drug); Feces (28% as unchanged drug); Oral: Urine (50% as unchanged drug); Feces (48% as unchanged drug)

Time to Peak

~1 hour

Half-Life Elimination

IV: 3.7 hours (single dose); Oral: 4.2 to 8.5 hours (multiple dose)

Protein Binding

~84%, primarily albumin

Use in Specific Populations

Special Populations: Renal Function Impairment

Mean total exposure (AUC_t) 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 ESRD on hemodialysis, respectively, compared to normal subjects following a single IV dose. Mean AUC_t 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.

Use: Labeled Indications

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.

Contraindications

Hypersensitivity to delafloxacin, other fluoroquinolones, or any component of the formulation

Dosage and Administration

Dosing: Adult

Pneumonia, community-acquired:

Oral: 450 mg every 12 hours.

IV: 300 mg every 12 hours.

Duration of therapy: Duration is for a minimum of 5 days; patients should be clinically stable, including normal vital signs, before therapy is discontinued (ATS/IDSA [Metlay 2019]).

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.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Reconstitute 300 mg vials with 10.5 mL of D5W or NS (resulting concentration: 25 mg/mL). Shake vigorously until completely dissolved. Dilute to a total volume of 250 mL with NS or D5W to achieve a final concentration of 1.2 mg/mL.

Administration

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.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

The reconstituted powder may be stored under refrigeration (2°C to 8°C [36°F to 46°F]) or at 20°C to 25°C (68°F to 77°F) for up to 24 hours and then further diluted for IV infusion. The reconstituted solution in the infusion bag may be stored under refrigeration (2°C to 8°C [36°F to 46°F]) or at 20°C to 25°C (68°F to 77°F) for up to 24 hours. Do not freeze.

Drug Interactions

Amphetamines: May enhance the cardiotoxic effect of Quinolones. 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. Exceptions: Sodium Bicarbonate. Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Blood Glucose Lowering Agents: Quinolones may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Calcium Salts: May decrease the absorption of Quinolones. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. 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. Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. 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. Exceptions are discussed in separate monographs. 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. Consider therapy modification

Heroin: Quinolones may enhance the adverse/toxic effect of Heroin. 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 levo-, nor-, oflox-, pefloxacin, or nalidixic acid) oral iron. Exceptions: Ferric Carboxymaltose; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. 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. 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-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Consider therapy modification

Methylphenidate: May enhance the cardiotoxic effect of Quinolones. 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: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). 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: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification

Mycophenolate: Quinolones may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy

Nadifloxacin: May enhance the adverse/toxic effect of Quinolones. 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. Monitor therapy

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. Monitor therapy

Quinapril: May decrease the serum concentration of Quinolones. Management: Separate doses of quinapril and oral quinolones by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the quinolone if these products are used concomitantly. Consider therapy modification

Sevelamer: May decrease the absorption of Quinolones. Management: Administer oral quinolones at least 2 hours before or 6 hours after sevelamer. Consider therapy modification

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. 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. 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. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Varenicline: Quinolones may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concurrent use of levofloxacin or other quinolone antibiotics, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Quinolones may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Zinc Salts: 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 levo-, nor-, pe- or ofloxacin or nalidixic acid) oral zinc salts. Exceptions: Zinc Chloride. Consider therapy modification

Adverse Reactions

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%)

Central nervous system: Headache (3%), abnormal dreams (<2%), agitation (<2%), anxiety (<2%), confusion (<2%), dizziness (<2%), hypoesthesia (<2%), insomnia (<2%), paresthesia (<2%), vertigo (<2%)

Dermatologic: Dermatitis (<2%), pruritus (<2%), skin rash (<2%), urticaria (<2%)

Endocrine & metabolic: Hyperglycemia (<2%), hypoglycemia (<2%)

Gastrointestinal: Nausea (8%), diarrhea (5% to 8%), vomiting (2%), abdominal pain (<2%), Clostridioides difficile associated diarrhea (<2%), dysgeusia (<2%), dyspepsia (<2%), oral candidiasis (<2%)

Genitourinary: Vulvovaginal candidiasis (<2%)

Hematologic & oncologic: Agranulocytosis (<2%), anemia (<2%), leukopenia (<2%), neutropenia (<2%), pancytopenia (<2%)

Hepatic: Increased serum transaminases (3% to 5%), increased serum alkaline phosphatase (<2%)

Hypersensitivity: Hypersensitivity reaction (<2%)

Infection: Fungal infection (<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:

Central nervous system: Central nervous system disease, exacerbation of myasthenia gravis, peripheral neuropathy

Neuromuscular & skeletal: Rupture of tendon, tendonitis

Warnings/Precautions

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 tendinitis 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.

- Tendinitis/Tendon rupture: Fluoroquinolones have been associated with an increased risk of tendonitis 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 tendinitis 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”.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Adverse effects (eg, tendon rupture) may be increased in elderly patients.

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.

Monitoring Parameters

WBC, signs of infection, serum creatinine; signs and symptoms of disordered glucose regulation

Pregnancy

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Nausea
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Nerve problems like sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet
• Tendon inflammation or rupture like pain, bruising, or swelling in the back of the ankle, shoulder, hand, or other joints
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
• Depression like thoughts of suicide, anxiety, emotional instability, or confusion
• Anxiety
• Nightmares
• Trouble sleeping
• Vision changes
• Sensing things that seem real but are not
• Agitation
• Restlessness
• Behavioral changes
• Mood changes
• Seizures
• Severe headache
• Fast heartbeat
• Dizziness
• Confusion
• Passing out
• Tremors
• Trouble focusing
• Trouble with memory
• Severe or persistent abdominal pain
• Severe or persistent chest pain
• Severe or persistent back pain
• Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.