Baxdela (delafloxacin meglumine)

Dosage of delafloxacin meglumine is expressed in terms of delafloxacin.

Delafloxacin meglumine is administered orally or by IV infusion.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

Oral Quinolones/Strontium Gluconate And Ranelate

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Strontium may form a complex with oral quinolones, preventing their absorption.(1,2)

CLINICAL EFFECTS: Simultaneous administration of strontium with oral quinolones may result in decreased levels and effectiveness of the oral quinolone.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The UK(1) and US(2) manufacturers of strontium states that strontium therapy should be suspended during treatment with an oral quinolone.

DISCUSSION: Divalent cations such as strontium can form complexes with oral quinolones.(1,2)

Selected Antibiotics/Cholera Vaccine Live

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Antibiotics with activity against Vibrio cholerae may attenuate the immunization response to the live cholera vaccine.(1)

CLINICAL EFFECTS: Concurrent or recent antibiotic use may make the cholera vaccine ineffective.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of live cholera vaccine states that it should not be administered to patients who have received antibiotics within 14 days prior to vaccination.(1) If antimalarial prophylaxis with chloroquine is required, administer the live cholera vaccine at least 10 days before beginning chloroquine.(1) Antibiotics linked to this monograph are: macrolides, quinolones, tetracyclines, ampicillin, cefprozil, chloramphenicol, furazolidone, sulfamethoxazole-trimethoprim, and sulfametrole-trimethoprim.(2,3)

DISCUSSION: Antibiotics with activity against Vibrio cholerae may attenuate the immunization response to the live cholera vaccine, rendering the vaccine ineffective.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Selected Antimycobacterials/Live Bcg

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Bacillus Calmette-Guerin (BCG) is a live, attenuated strain of Mycobacterium bovis (M.bovis) used to induce a granulomatous response in the treatment of localized bladder cancer and as a vaccine to prevent tuberculosis.(1-2) Co-treatment with antibacterial agents active against M.bovis may lead to an attenuation of the immune response associated with BCG administration.(1-2)

CLINICAL EFFECTS: The effectiveness of chemotherapy may be impaired, or the vaccine may be ineffective. Agents linked to this monograph may have activity against M.bovis: amikacin, capreomycin, ciprofloxacin, clofazimine, cycloserine, ethambutol, ethionamide, gatifloxacin, isoniazid, kanamycin, levofloxacin, moxifloxacin, ofloxacin, rifabutin, rifampin, rifapentine, and streptomycin.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Intravesical instillation of BCG should be postponed during treatment with antibacterials which may decrease effectiveness.(2) Administration of BCG vaccine to patients receiving antibiotic therapy should only be done under close medical supervision.(1) If a patient develops a systemic BCG infection due to intravesicular or vaccine administration, treatment with multiple antimycobacterial agents may be required.

DISCUSSION: Because antibiotic therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of BCG vaccine states that administration of BCG vaccine to patients receiving antibiotic therapy should only be done under close medical supervision.(1) Pyrazinamide is not included in this interaction as BCG is not sensitive to pyrazinamide.(2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Oral Fluoroquinolones/Sevelamer

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Sevelamer may bind to oral fluoroquinolones, preventing its absorption.(1)

CLINICAL EFFECTS: Simultaneous administration of sevelamer may result in decreased levels and clinical effectiveness of oral fluoroquinolones.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If concurrent therapy is warranted, the oral fluoroquinolone should be administered at least two hours before or six hours after sevelamer.(2)

DISCUSSION: In a study in 15 subjects, simultaneous administration of ciprofloxacin (750 mg) and sevelamer (seven 403 mg capsules) decreased the bioavailability of ciprofloxacin by 48%.(1,2)

Oral Quinolones/Strontium

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Strontium may form a complex with oral quinolones, preventing their absorption.(1,2)

CLINICAL EFFECTS: Simultaneous administration of strontium with oral quinolones may result in decreased levels and effectiveness of the oral quinolone.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Separate the administration times of oral quinolones and dietary supplements containing strontium by as much time as possible.

DISCUSSION: Divalent cations such as strontium can form complexes with oral quinolones.(1,2)

Quinolones, Oral/Didanosine Pediatric Suspension+Antacids

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum and magnesium may form chelation compounds with the quinolones.(1-15)

CLINICAL EFFECTS: Simultaneous administration or administration of aluminum or magnesium products close to the administration time of an oral quinolone may result in decreased absorption and clinical effectiveness of the quinolone.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid concomitant use of an oral quinolone antibiotic and Videx (didanosine) pediatric oral solution, which is mixed with Maximum Strength Mylanta Liquid, which contains aluminum and magnesium hydroxide. If it necessary to administer these agents concurrently, follow the manufacturers' recommendations regarding the timing of administration of the quinolone with Videx pediatric suspension or aluminum- or magnesium containing compounds. Manufacturer recommendations regarding the separation of administration times of quinolones and products containing aluminum and magnesium vary: ---Do not give ciprofloxacin for at least 2 hours before or 6 hours after oral cations.(1) ---Do not give delafloxacin for at least 2 hours before or 6 hours after oral cations.(2) ---Do not give enoxacin for at least 2 hours before or 8 hours after oral cations.(3) ---Do not give gatifloxacin for at least 4 hours before oral cations.(4) ---Do not give gemifloxacin for at least 2 hours before or 3 hours after oral cations.(5) ---Do not give levofloxacin for at least 2 hours before or 2 hours after oral cations.(6) ---Do not give lomefloxacin for at least 2 hours before or 4 hours after oral cations.(7) ---Do not give moxifloxacin for at least 4 hours before or 8 hours after oral cations.(8) ---Do not give nalidixic acid for at least 2 hours before or 2 hours after oral cations.(9) ---Do not give norfloxacin for at least 2 hours before or 2 hours after oral cations.(10) ---Do not give ofloxacin for at least 2 hours before or 2 hours after oral cations.(11) ---Do not give prulifloxacin for at least 2 hours before or 4 hours after oral cations.(12) ---Do not give sparfloxacin for at least 4 hours before oral cations.(13) ---Do not give trovafloxacin for at least 2 hours before or after oral cations.(14) ---Do not give sitafloxacin for at least 2 hours before or after oral cations.(15)

DISCUSSION: Magnesium and aluminum compounds have been shown to form chelation compounds with quinolone antibiotics, resulting in decreased absorption of the quinolone.(1-28) Concurrent administration of an antacid with ciprofloxacin has been shown to reduce the bioavailability of ciprofloxacin by as much as 90% and administration of an antacid 2 hours prior to ciprofloxacin has been shown to decrease ciprofloxacin concentrations by 20-50%. Magnesium- and aluminum-containing antacids have been shown to decrease the bioavailability of lomefloxacin by 48%. The chewable/dispersible formulation of Videx (didanosine) contains magnesium hydroxide and magnesium stearate. The administration of ciprofloxacin 2 hours prior to Videx chewable/dispersible tablets decreased ciprofloxacin concentrations by 26%.(31) Manufacturer recommendations regarding the separation of aluminum and/or magnesium compounds and quinolone antibiotic vary. The manufacturers' recommendations for the separating of Videx pediatric suspension are the same as for aluminum- or magnesium-containing antacids.

Quinolones, Oral/Sucralfate

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Sucralfate decreases the absorption of certain quinolones. The probable mechanism is quinolone chelation with the aluminum contained in sucralfate.

CLINICAL EFFECTS: The pharmacologic effects of certain quinolones may be decreased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid the concomitant administration of sucralfate and an oral quinolone. If an oral quinolone is administered during sucralfate therapy, the antibiotic should be administered at least two hours before sucralfate. Differences in gastric emptying time may impact the the effectiveness of spacing the administration times in some patients.

DISCUSSION: Sucralfate has been shown to extensively decrease the bioavailability of ciprofloxacin (87.5-95.7% decrease in area-under-curve, AUC), lomefloxacin (51% decrease in AUC), norfloxacin (91% decrease in AUC), and ofloxacin (61% decrease in AUC), as well as the urinary concentration of norfloxacin when the agents were administered at the same time.

Quinolones/Corticosteroids

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Quinolone-induced arthropathy is a class effect of the quinolones.(1) Exactly how corticosteroid use increases the risk of tendon rupture is unknown.

CLINICAL EFFECTS: Concurrent use of quinolones and corticosteroids may increase the risk of tendonitis and/or tendon rupture. This affect is most common in the Achilles tendon, but has been reported in the rotator cuff (shoulder), hand, biceps, thumb, and other tendons.(2-9)

PREDISPOSING FACTORS: Risk factors for tendinitis and tendon rupture include age greater than 60; a history of kidney, heart, or lung transplantation, strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.

PATIENT MANAGEMENT: Quinolone use should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients experiencing discomfort or pain should be instructed to rest and refrain from exercise until the diagnosis of tendonitis tendon rupture has been excluded.(2-9)

DISCUSSION: Ruptures of the shoulder, hand, Achilles tendon, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving ciprofloxacin,(2) gatifloxacin,(3) levofloxacin,(4) lomefloxacin,(5) moxifloxacin,(6) nalidixic acid,(7) norfloxacin,(8) and ofloxacin.(9) A retrospective review of the IMS Health database examined quinolone use use from July 1, 1992 to June 30, 1998. The adjusted relative risk of tendon disorder with concurrent quinolone use was 1.9. Relative risk increased to 3.2 in patients aged 60 or older compared to 0.9 in patients aged less than 60. In patients aged 60 or older who used corticosteroids and quinolones concurrently, relative risk increased to 6.2.(10) In contrast, another retrospective review examined patients from a health insurance claims database and found no apparent effect from concurrent quinolone and corticosteroid use.(11) In a review of the follow-up to 42 spontaneously reported case of quinolone-associated tendon disorders in the Netherlands between January, 1988 and January, 1998, risk factors for tendon disorders included age older than 60, oral corticosteroid use, and existing joint problems.(12) In a review of the Swiss Drug Monitoring system, four of seven cases of levofloxacin-associated tendon problems also involved concurrent oral or inhaled corticosteroids.(13) In a review of the Medline database from 1966-2001, 98 case reports of tendinopathy associated with quinolones were located. Thirty-two (32.7%) of the patients had received systemic or inhaled corticosteroids before and during quinolone therapy. Of the 40 patients who suffered a tendon rupture, 21 (52.5%) were receiving corticosteroids.(14) Other authors have reported cases of tendon disorders in patients receiving concurrent corticosteroids and ciprofloxacin,(15) levofloxacin, (16-20) and ofloxacin.(21)

Selected Oral Quinolones/Selected Oral Cations

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, and zinc may form chelation compounds with the quinolones.(1-40)

CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or zinc close to the administration time of an oral quinolone may result in decreased absorption and clinical effectiveness of the quinolone.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid concurrent therapy with quinolones and cation-containing products. If it is necessary to administer these agents concurrently, follow the manufacturers' recommendations regarding timing of administration of the quinolone and cation-containing products. Manufacturer recommendations regarding the separation of administration times of quinolones and products containing aluminum, calcium, iron, lanthanum, magnesium, and/or zinc vary: ---Do not give ciprofloxacin for at least 2 hours before or 6 hours after oral cations.(1) ---Do not give delafloxacin for at least 2 hours before or 6 hours after oral cations.(2) ---Do not give enoxacin for at least 2 hours before or 8 hours after oral cations.(3) ---Do not give levofloxacin for at least 2 hours before or 2 hours after oral cations.(4) ---Do not give nalidixic acid for at least 2 hours before or 2 hours after oral cations.(5) ---Do not give norfloxacin for at least 2 hours before or 2 hours after oral cations.(6) ---Do not give ofloxacin for at least 2 hours before or 2 hours after oral cations.(7) ---Do not give sparfloxacin for at least 4 hours before oral cations.(8) ---Do not give sitafloxacin for at least 2 hours before or 2 hours after oral cations.(9) The US manufacturer of lanthanum recommends that quinolones be taken at least 1 hour before or 4 hours after lanthanum;(10) however, it would be prudent to follow the specific quinolone manufacturers' recommendations regarding concurrent administration of cations. The US manufacturer of ferric maltose recommends separation of ferric maltose by at least 4 hours. For quinolones not listed above, separate their administration from oral cations by as much time as feasible.

DISCUSSION: Aluminum, calcium, iron, magnesium, and zinc products have been shown to form chelation compounds with quinolone antibiotics, resulting in decreased absorption of the quinolone.(1-40) Treatment failures have been reported.(11-12) In a study in 12 healthy subjects, simultaneous administration of didanosine chewable tablets, which contain aluminum and magnesium, decreased ciprofloxacin area-under-curve (AUC) and maximum concentration (Cmax) by 92% and 98%, respectively.(14) The administration of ciprofloxacin 2 hours prior to Videx chewable/dispersible tablets decreased ciprofloxacin concentrations by 26%.(15,16) In a study in healthy subjects, pretreatment with an antacid containing aluminum-magnesium hydroxide at 5-10 minutes, 2 hours, and 4 hours before a single dose of ciprofloxacin decreased ciprofloxacin AUC by 84.9%, 76.8%, and 30%, respectively. There was no effect when the antacid was administered 6 hours before or 2 hours after.(17) In a study in 12 healthy subjects, aluminum hydroxide decreased ciprofloxacin AUC by 85%.(18) In a study in patients on continuous ambulatory peritoneal dialysis, peak levels of ciprofloxacin were decreased by 67% to 92% in patients receiving aluminum-containing antacids.(19) In a study in 15 healthy subjects, simultaneous administration of calcium acetate decreased the bioavailability of ciprofloxacin by 51%.(20) In a study in 6 healthy males, simultaneous administration of calcium carbonate decreased ciprofloxacin Cmax and AUC by 40% and 43%, respectively.(21) In a study in 12 healthy subjects, calcium carbonate decreased ciprofloxacin AUC by 40%.(18) In a study in 13 healthy males, calcium carbonate had no effect on ciprofloxacin bioavailability when administered 2 hours prior to the antibiotic.(22,23) In a study in healthy males, simultaneous administration of calcium polycarbophil decreased ciprofloxacin AUC by 50%.(24) In a study in 8 healthy males, simultaneous administration of ferrous fumarate (200 mg) decreased ciprofloxacin AUC by 70%.(25) In a study in healthy subjects, ferrous gluconate decreased ciprofloxacin bioavailability by 50%; however, no significant effects were seen with iron-ovotransferrin.(26) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered ciprofloxacin by 54% and 57%, respectively.(27) In a study in 8 healthy subjects, administration of ferrous sulfate decreased the Cmax and AUC of ciprofloxacin by 33% and 46%, respectively. Administration of ferrous gluconate decreased the Cmax and AUC of ciprofloxacin by 57% and 67%, respectively. Administration of a multivitamin product containing calcium, copper, iron, magnesium, manganese, and zinc decreased the Cmax and AUC of ciprofloxacin by 53% and 56%, respectively.(28) In a study in 12 healthy males, ferrous sulfate decreased ciprofloxacin AUC by 63%.(29) In a study in 12 healthy subjects, lanthanum carbonate decreased the area-under-curve (AUC) and maximum concentration (Cmax) of concurrently administered ciprofloxacin by 54% and 56%, respectively.(30) In a study in 12 healthy males, a multivitamin containing zinc decreased ciprofloxacin AUC by 22%.(29) In a study in 12 healthy subjects, an antacid containing aluminum-magnesium hydroxide had no effect on the pharmacokinetics of intravenous enoxacin.(31) In a study in 10 healthy subjects, administration of an aluminum-magnesium hydroxide antacid 0.5 hours or 2 hours before oral enoxacin (400 mg single dose) decreased the AUC of enoxacin by 73% and 43%, respectively. There were no significant effects on enoxacin AUC when the antacid was administered 8 hours before or 2 hours after enoxacin.(32) In a study in 9 healthy subjects, colloidal aluminum phosphate had no effect on the amount of enoxacin absorbed; however, ferrous sulfate (1050 mg) decreased the amount of enoxacin absorption by 10%.(33) In a study in 5 healthy subjects and 5 patients with cystic fibrosis, separation of levofloxacin (750 mg) and calcium carbonate (500 mg 3 times daily with meals) by 2 hours resulted in no interaction in healthy subjects; however, levofloxacin levels were not bioequivalent in patients with cystic fibrosis.(34) Concurrent magnesium-aluminum hydroxide or calcium have been shown to decrease the bioavailability of norfloxacin by 91.0% and 63.5%, respectively.(35) Concurrent zinc has been shown to decrease the bioavailability of norfloxacin.(36) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 75% and 73%, respectively.(27) Simultaneous aluminum phosphate was found to decrease the rate, but not the extent, of absorption of ofloxacin.(37) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 36% and 25%, respectively.(27) In an in vitro study, ferrous sulfate, aluminum hydroxide, and calcium carbonate decreased ofloxacin availability by 32.6%, 30.7%, and 26.2%, respectively. However, in vivo tests showed a significant effect with only aluminum hydroxide.(38) In a study in 9 healthy subjects, simultaneous administration colloidal aluminum phosphate had no effect on ofloxacin (200 mg) absorption; however, ferrous sulfate (1050 mg) decreased the ofloxacin fraction of dose absorbed by 10.85%.(33) In a study in 16 subjects, administration of either aluminum-magnesium hydroxide or calcium carbonate at least 2 hours before or after ofloxacin administration had no significant effects on ofloxacin levels.(39) The administration of an antacid containing aluminum hydroxide and magnesium hydroxide 2 hours before, 2 hours after, and 4 hours after sparfloxacin decreased sparfloxacin levels by 23%, 17%, and 5%, respectively.(40) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

Selected Quinolones/Enteral Nutrition

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Absorption of orally administered quinolones may be decreased with concurrent enteral nutrition administration.

CLINICAL EFFECTS: Administration of a quinolone during enteral nutritional therapy may result in a decrease in clinical effect of the quinolone as a result of lower serum and urine levels.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Quinolone blood levels should be carefully monitored if the patient is receiving concurrent enteral nutrition. An alternate antibiotic agent may need to be considered.

DISCUSSION: In a study, concurrent administration of ciprofloxacin, levofloxacin, and ofloxacin with Ensure resulted in average decreases in quinolone serum levels of 82.5%, 61.3% and 45.7% respectively.(1) In another study, concurrent Ensure reduced the percent of relative bioavailability of ciprofloxacin significantly more than ofloxacin.(2) In a study in 26 hospitalized patients, administration of ciprofloxacin via jejunostomy tube with an enteral formula decreased ciprofloxacin mean bioavailability by 67%.(3) Conversely, a study showed that ciprofloxacin is well absorbed after administration via a nasogastric tube in the presence of enteral feeding compared with an orally administered tablet.(4) Gatifloxacin administration with concomitant gastric tube feeding did not affect gatifloxacin bioavailability, but critical illness resulted in significant variability in bioavailability.(5) Conversely, administration with Ensure significantly decreased gatifloxacin maximum concentration (Cmax) by 44.6%, time to reach Cmax (Tmax) by 60%, area-under-curve (AUC) by 26.2%, and relative oral bioavailability by 26%.(6) In a study, the oral bioavailability of moxifloxacin administered as a crushed tablet was not affected by concomitant enteral feeding through a nasogastric tube.(7) The relative bioavailability of temafloxacin was not affected by enteral nutrition.(8)

Selected Quinolones/Selected Antidiabetic Agents

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of quinolones and antidiabetic agents may result in severe hypoglycemia.(1-7) Hypoglycemia can lead to coma.

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.(5)

PATIENT MANAGEMENT: Patients maintained on antidiabetic agents who require concurrent therapy with a quinolone should be closely monitored for hypoglycemia.(1-4) Patients should be instructed to discontinue quinolone use and contact their doctor if hypoglycemia occurs.(2,4) Signs of hypoglycemia may include confusion, dizziness, feeling shaky, unusual hunger, headaches, irritability, pounding heart or very fast pulse, pale skin, sweating, trembling, weakness, or unusual anxiety.

DISCUSSION: Hypoglycemia has been reported with concurrent ciprofloxacin and glyburide,(1,8,9) levofloxacin and glyburide,(2,10,11) norfloxacin and glyburide,(3) levofloxacin and glipizide (12) as well as levofloxacin and metformin-glibenclamide.(14) There has been one report of fatal hypoglycemia with concurrent levofloxacin and glyburide(9) and one of the above reports of hypoglycemia with concurrent levofloxacin and glyburide resulted in hypoxic brain injury.(11) A review of postmarketing adverse event data for the fluoroquinolones and hypoglycemic coma identified 56 reports in FAERS search from October 1987- April 2017 and 11 additional cases in the medical literature. Most patients had risk factors for hypoglycemia. 41 patients were taking one or more hypoglycemic drugs. 13 deaths occurred (some of these patients had renal insufficiency). 9 patients did not fully recover and had resultant disability.(13)

Delafloxacin meglumine is contraindicated in patients with known hypersensitivity to delafloxacin, any component of the preparation, or other fluoroquinolones.

• Aortic aneurysm
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Dissection of aorta
• Ehlers-danlos syndrome
• History of aortic aneurysm
• Loeys-dietz syndrome
• Marfan syndrome
• Myasthenia gravis

• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Clostridioides difficile infection
• Depression
• Idiopathic intracranial hypertension
• Intracranial hypertension
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Peripheral neuropathy
• Suicidal ideation
• Tendon rupture

• Diabetes mellitus
• Hypoglycemic disorder
• Lower seizure threshold
• Seizure disorder

Adverse effects occurring in 2% or more of patients receiving delafloxacin include GI effects (nausea, diarrhea, vomiting), headache, and elevated aminotransferase concentrations.

More Frequent

• Abnormal hepatic function tests

Rare or Very Rare

• Anaphylaxis
• Aortic aneurysm
• Arterial dissection
• Bradycardia
• Clostridioides difficile infection
• Delirium
• Dissection of aorta
• Drug-induced psychosis
• Extravasation injury
• Hallucinations
• Hypertension
• Hypoglycemic disorder
• Hypotension
• Idiopathic intracranial hypertension
• Injection site sequelae
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Muscle weakness
• Neuromuscular blockade
• Peripheral neuropathy
• Renal failure
• Rhabdomyolysis
• Seizure disorder
• Sinus tachycardia
• Suicidal
• Suicidal ideation
• Tendon rupture
• Tendonitis
• Valvular regurgitation

More Frequent

• Diarrhea
• Headache disorder
• Nausea
• Vomiting

Less Frequent

• Dizziness

Rare or Very Rare

• Acute abdominal pain
• Acute cognitive impairment
• Agitation
• Arthralgia
• Arthritis
• Blurred vision
• Depression
• Disturbance of attention
• Dream disorder
• Dysesthesia
• Dysgeusia
• Dyspepsia
• Facial edema
• Flushing
• Fungal infection
• Hyperglycemia
• Insomnia
• Memory impairment
• Myalgia
• Nervousness
• Nightmares
• Oral candidiasis
• Palpitations
• Paranoid disorder
• Paresthesia
• Phlebitis after infusion
• Pruritus of skin
• Skin rash
• Symptoms of anxiety
• Tinnitus
• Tremor
• Urticaria
• Vertigo
• Vulvovaginal candidiasis

No enhanced messaging available.

Safety and efficacy of delafloxacin have not been established in pediatric patients younger than 18 years of age, and use of the drug in pediatric patients is not recommended.

Fluoroquinolones cause arthropathy in juvenile animals.

The manufacturer states that clinical trials evaluating delafloxacin for the treatment of bacterial skin and skin structure infections did not include patients younger than 18 years of age because the risks versus benefits of the drug do not support use for the treatment of such infections in this age group.

The American Academy of Pediatrics (AAP) states that use of a systemic fluoroquinolone may be justified in children younger than 18 years of age in certain specific circumstances when there are no safe and effective alternatives and the drug is known to be effective. For information regarding when fluoroquinolones may be a preferred option in children, see Cautions: Pediatric Precautions in Ciprofloxacin 8:12.18.

Available data regarding use of delafloxacin in pregnant women are insufficient to inform any drug-associated risk for miscarriages or major birth defects.

When delafloxacin (as the N-methyl glucamine salt) was administered orally to pregnant rats during organogenesis, no malformations or fetal deaths were observed at delafloxacin concentrations up to 7 times the estimated clinical exposure. Maternal toxicity and reduced fetal body weight were observed at the highest dosage (1.6 g/kg daily); fetal ossification delays were observed at all doses. When IV delafloxacin was administered to rats in late pregnancy through lactation, no adverse effects on offspring were observed at clinically relevant concentrations.

It is not known whether delafloxacin is distributed into human milk, affects the breast-fed infant, or affects milk production. Delafloxacin is distributed into milk in lactating rats.

The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for delafloxacin and potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Approximately 15% of patients receiving delafloxacin in clinical studies were 65 years of age or older. The clinical response rate at 48-72 hours after initiation of delafloxacin was 75.7% in patients 65 years of age or older compared with 82.3% in those younger than 65 years of age. In the comparator group, the clinical response rate in patients 65 years of age or older was 71.3% compared with 82.1% in those younger than 65 years of age.

The risk of developing severe tendon disorders, including tendon rupture, is increased in older adults (usually those older than 60 years of age). This risk is further increased in those receiving concomitant corticosteroids. (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.) Caution is advised if delafloxacin is used in geriatric adults, especially those receiving concomitant corticosteroids.

The risk of aortic aneurysm and dissection may be increased in geriatric patients. (See Risk of Aortic Aneurysm and Dissection under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Pharmacokinetic data indicate that mean peak plasma concentration and area under the plasma concentration-time curve (AUC) of delafloxacin reported in geriatric individuals 65 years of age or older are about 35% higher than those reported in younger adults (18-40 years of age); this difference is not considered clinically important.