Delafloxacin

Indications

Delafloxacin is used for: Acute bacterial skin and skin structure infections

Adult Dose

Skin and Skin Structure Infections Parenteral 300 mg IV q12hr for 5-14 days, OR 300 mg IV q12hr, then switch to a 450-mg tablet PO q12hr for 5-14 days, OR Oral 450 mg PO q12hr for 5-14 days Hepatic impairment No dosage adjustment needed

Child Dose

Safety and efficacy not established

Renal Dose

Renal impairment IV CrCl 30-89 mL/min: No dosage adjustment needed CrCl 15-29 mL/min: 200 mg IV q12hr OR 200 mg IV q12hr, then switch to 450 mg PO q12hr CrCl <15 mL/min: Not recommended PO CrCl 15-89 mL/min: No dosage adjustment needed CrCl <15mL/min: Not recommended

Administration

IV Preparation Reconstitute 300-mg vial with10.5 mL D5W or 0.9% NaCl, resulting in 300 mg/12 mL (25 mg/mL) Shake vial vigorously until contents are completely dissolved; solution should appear clear yellow to amber colored Further dilute reconstituted solution to a total volume of 250 mL with D5W or 0.9% NaCl to achieve a final concentration of 1.2 mg/mL prior to administration IV Administration Infuse IV via volume control set or piggyback container Infuse IV over 60 minutes Oral Administration May take with or without food Missed dose: Take as soon as possible within 4 hr of missed dose; if >4 hr since missed dose, wait until next scheduled dose

Contra Indications

Documented hypersensitivity to delafloxacin or its components or other fluoroquinolones

Precautions

Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions from different body systems, including tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and CNS effects (eg, hallucinations, anxiety, depression, insomnia, severe headaches, confusion) Risk of tendinitis and tendon rupture in all ages; the Achilles tendon is most frequently involved, but rupture has also been reported with the rotator cuff, hand, biceps, thumb, and other tendons Fluoroquinolones are associated with increased risk of peripheral neuropathy; sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported (see Black Box Warnings) Increased risk of CNS reactions (eg, convulsions and increased intracranial pressure [including pseudotumor cerebri]; toxic psychosis); may also cause CNS reactions of nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or acts Fluoroquinolones elicit neuromuscular blocking activity and may exacerbate muscle weakness with myasthenia gravis Serious and occasional fatal hypersensitivity reactions (including after first dose) reported Clostridium difficile-associated diarrhea (CDAD) reported with use of nearly all systemic antibiotics Prescribing an antibiotic in the absence of proven or strongly suspected bacterial infection is unlikely to provide benefit and increases risk developing drug-resistant bacteria Lactation Unknown if distributed in human breast milk

Pregnancy-Lactation

Pregnancy Data are limited regarding use in pregnant women and are insufficient to inform a drug-associated risk of major birth defects and miscarriages Lactation Unknown if distributed in human breast milk Excreted in the breast milk of rats Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Fluoroquinolones form chelates with alkaline earth and transition metal cations Delafloxacin PO administration with antacids containing aluminum or magnesium, with sucralfate, with metal cations (eg, iron), or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations (eg, didanosine buffered tablets for oral suspension or the pediatric powder for oral solution), may substantially interfere with the absorption and decrease systemic exposure

Side Effects

Side effects of Delafloxacin : 1-10% Nausea (8%) Diarrhea (8%) Headache (3%) Transaminase elevations (3%) Vomiting (2%) Cardiac disorders: Sinus tachycardia, palpitations, bradycardia (<2%) Ear and labyrinth disorders: Tinnitus, vertigo (<2%) Eye disorders: Vision blurred (<2%) General disorders and administration site conditions: Infusion site extravasation, infusion site bruise, discomfort, edema, erythema, irritation, pain, phlebitis, swelling, thrombosis (<2%) Gastrointestinal disorders: Abdominal pain, dyspepsia (<2%) Immune system disorders: Hypersensitivity (<2%) Infections and infestations: Clostridium difficile infection, fungal infection, oral candidiasis, vulvovaginal candidiasis (<2%) Laboratory Investigations: Blood alkaline phosphatase increased, blood creatinine increased, blood creatine phosphokinase increased (<2%) Metabolism and nutrition disorders: Hyperglycemia, hypoglycemia (<2%) Musculoskeletal and connective tissue disorders: Myalgia (<2%) Nervous system disorders: Dizziness, hypoesthesia, paraesthesia, dysgeusia, presyncope, syncope (<2%) Psychiatric disorders: Anxiety, insomnia, abnormal dreams (<2%) Renal and urinary: Renal impairment, renal failure (<2%) Skin and subcutaneous tissue disorders: Pruritus, urticaria, dermatitis, rash (<2%) Vascular disorders: Flushing, hypotension, hypertension, phlebitis (<2%)

Mode of Action

Fluoroquinolone antibiotic; inhibits both bacterial topoisomerase IV and DNA gyrase (topoisomerase II) enzymes, which are required for bacterial DNA replication, transcription, repair, and recombination