delafloxacin

Inhibits bacterial DNA synthesis by inhibiting DNA gyrase (topoisomerase II) and topoisomerase IV enzymes.

Therapeutic effects:

Death of susceptible bacteria.

Spectrum:

Active against gram-positive pathogens, including:
- Enterococcus faecalis,
- Staphylococcus aureus(including methicillin-sensitive and methicillin-resistant strains [for skin and skin structure infections only]),
- Staphylococcus haemolyticus,
- Staphylococcus lugdunensis,
- Streptococcus agalactiae,
- Streptococcus anginosus,
- Streptococcus pneumoniae,
- Streptococcus pyogenes
Gram-negative spectrum notable for activity against:
- Enterobacter cloacae,
- Escherichia coli,
- Haemophilus influenzae,
- Haemophilus parainfluenzae,
- Klebsiella pneumoniae,
- Legionella pneumophila,
- Pseudomonas aeruginosa.
Also active against several other pathogens, including:
- Chlamydia pneumoniae,
- Mycoplasma pneumoniae,

Pharmacokinetics ⬆ ⬇

Absorption: 59% absorbed after oral administration; IV administration results in complete bioavailability.

Distribution: Widely distributed.

Metabolism/Excretion: Primarily undergoes glucuronidation. 50–65% excreted unchanged by the kidneys; 28–48% excreted unchanged in feces.

Half-Life: 3.7 hr (IV); 4.2–8.5 hr (PO).

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1 hr	12 hr
IV	rapid	end of infusion	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity (cross-sensitivity within class may exist);
History of myasthenia gravis (may worsen symptoms including muscle weakness and breathing problems);
End-stage renal disease (eGFR <15 mL/min);
Pedi: Use only if no alternatives in children 1–17 yr due to possible arthropathy.

Use Cautiously in:

Known or suspected CNS disorder;
Severe renal impairment (dose ↓ if eGFR 15–29 mL/min) (IV diluent may accumulate and ↑ SCr) (↑ risk of tendon rupture in renal failure);
Concurrent use of corticosteroids (↑ risk of tendinitis/tendon rupture);
Kidney, heart, or lung transplant patients (↑ risk of tendinitis/tendon rupture);
Patients with or at risk for aortic aneurysms;
Rheumatoid arthritis (↑ risk of tendon rupture);
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Geri: risk for tendon disorders/rupture and aortic aneurysm/dissection in older adults (within 2 mo following discontinuation).

Adv. Reactions/Side Effects ⬆ ⬇

CV: AORTIC ANEURYSM/DISSECTION

Endo: hyperglycemia, hypoglycemia

GI: ↑liver enzymes, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, nausea, vomiting

MS: arthralgia, myalgia, tendinitis, tendon rupture

Neuro: agitation, anxiety, attention disturbances, confusion, delirium, depression, disorientation, dizziness, ELEVATED INTRACRANIAL PRESSURE (INCLUDING PSEUDOTUMOR CEREBRI), hallucinations, headache, insomnia, memory impairment, nightmares, paranoia, peripheral neuropathy, SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, toxic psychosis, tremor

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, AND URTICARIA)

Interactions ⬆ ⬇

Drug-drug:

Administration with antacids, iron salts, bismuth subsalicylate, sucralfate, and zinc salts↓ absorption; take delafloxacin ≥2 hr before or ≥6 hr after these agents.
May ↑ risk of hypoglycemia when used with antidiabetic agents.

Route/Dosage ⬆ ⬇

Acute Bacterial Skin and Skin Structure Infections

Community-Acquired Bacterial Pneumonia

IV (Adults ): 300 mg every 12 hr for 5–14 days or 300 mg every 12 hr followed by switching to oral regimen (at dose stated below) for a total of 5–14 days.
PO (Adults ): 450 mg every 12 hr for 5–14 days.

Renal Impairment

IV (Adults ): eGFR 15–29 mL/min: 200 mg every 12 hr for 5–14 days or 200 mg every 12 hr followed by switching to oral regimen (450 mg every 12 hr) for a total of 5–14 days; eGFR <15 mL/min: Not recommended.
IV (Adults ): 300 mg every 12 hr for 5–10 days or 300 mg every 12 hr followed by switching to oral regimen (at dose stated below) for a total of 5–10 days.
PO (Adults ): 450 mg every 12 hr for 5–10 days.

Renal Impairment

IV (Adults ): eGFR 15–29 mL/min: 200 mg every 12 hr for 5–10 days or 200 mg every 12 hr followed by switching to oral regimen (450 mg every 12 hr) for a total of 5–10 days; eGFR <15 mL/min: Not recommended.

Availability ⬆ ⬇

Lyophilized powder for injection: 300 mg/vial
Tablets: 450 mg

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC; urinalysis; frequency and urgency of urination; cloudy or foul-smelling urine) at beginning of and throughout therapy.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify health care professional immediately if symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of
Clostridioides difficile
-associated diarrhea (CDAD). May begin up to several wk following cessation of therapy.

Lab Test Considerations:

Monitor blood glucose in patients with diabetes taking insulin or oral hypoglycemic agents. Delafloxacin may cause hyperglycemia or hypoglycemia.

Implementation ⬆ ⬇

PO: Administer without regard to food and with a full glass of water, at the same time each day. Products or foods containing calcium, magnesium, aluminum, iron, or zinc should not be ingested for 2 hr before and 6 hr after administration.

IV Administration:

Intermittent Infusion: Reconstitute with 10.5 mL D5W or 0.9% NaCl for each 300 mg vial. Shake vigorously to completely dissolve. Concentration: 25 mg/mL. Solution is clear yellow to amber; do not administer solutions that are discolored or contain particulate matter. Reconstituted solution is stable if refrigerated or at room temperature for 24 hrs. Diluent: Dilute to volume of 250 mL with 0.9% NaCl or D5W. 1.2 mg/mL. Diluted solution is stable if refrigerated or at room temperature for 24 hrs.
Rate: Infuse over 60 min.
Y-Site Incompatibility: Do not administer with other drugs; flush line before and after each dose.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed at evenly spaced times and to finish drug completely, even if feeling better. Take missed doses as soon as possible, up to 8 hr before next dose. Do not double doses. Advise patient that sharing of this medication may be dangerous. Advise patient to read Medication Guide before starting therapy.
Advise patient that antacids or medications containing calcium, magnesium, aluminum, iron, or zinc will decrease absorption and should not be taken within 2 hr before and 6 hr after taking this medication.
May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Caution patient to use sunscreen and protective clothing to prevent phototoxicity reactions during and for 5 days after therapy. Notify health care professional if a sunburn-like reaction or skin eruption occurs.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
Advise patient to report signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools).
Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Instruct patient to notify health care professional immediately if signs and symptoms of hepatotoxicity (anorexia, jaundice, dark urine, pruritus, or tender abdomen), rash, signs of hypersensitivity, serious CNS effects (seizures, increased intracranial pressure, and toxic psychosis including: nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, psychotic reactions, suicidal ideations/thoughts), peripheral neuropathy (pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations including light touch, pain, temperature, position sense and vibratory sensation, and/or motor strength) or tendon (shoulder, hand, Achilles, and other) pain, swelling, inflammation, or if symptoms of tendon rupture (patient hears or feels a snap or pop in a tendon area, bruising right after an injury in a tendon area, or is unable to move affected area or bear weight) occur. If tendon symptoms occur, avoid exercise and use of affected area. Increased risk in >65 yrs old, kidney, heart and lung transplant recipients, and patients taking corticosteroids concurrently. Therapy should be discontinued.
Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes ⬆ ⬇

Resolution of the signs and symptoms of bacterial infection. Time for complete resolution depends on organism and site of infection.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

70842- Melinta Therapeutics, Inc
- 70842-101- Baxdela
  - 70842-101-01- 1 BOTTLE in 1 CARTON (70842-101-01) > 20 TABLET in 1 BOTTLE

70842- Melinta Therapeutics, Inc
- 70842-101- Baxdela
  - 70842-101-02- 2 BLISTER PACK in 1 CARTON (70842-101-02) > 10 TABLET in 1 BLISTER PACK (70842-101-03)

70842- Melinta Therapeutics, Inc
- 70842-102- Baxdela
  - 70842-102-03- 10 VIAL, GLASS in 1 CARTON (70842-102-03) > 10.5 mL in 1 VIAL, GLASS (70842-102-01)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇