Levaquin Information
Levaquin (Levofloxacin)
Levaquin (Levofloxacin) Indications And Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Levaquin (Levofloxacin) and other antibacterial drugs, Levaquin (Levofloxacin) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Levaquin (Levofloxacin) Tablets/Injection and Oral Solution are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed in this section. Levaquin (Levofloxacin) Injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form).
Levaquin (Levofloxacin) Dosage And Administration
The usual dose of Levaquin (Levofloxacin) Tablets or Oral Solution is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1. The usual dose of Levaquin (Levofloxacin) Injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in Table 1.
These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required .
Administer Levaquin (Levofloxacin) with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.
No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.
In patients with impaired renal function (creatinine clearance <50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance .
Table 3 shows how to adjust dose based on creatinine clearance.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Because only limited data are available on the compatibility of Levaquin (Levofloxacin) Injection with other intravenous substances, additives or other medications should not be added to Levaquin (Levofloxacin) Injection Premix in Single-Use Flexible Containers and Levaquin (Levofloxacin) Injection in Single-Use Vials, or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of Levaquin (Levofloxacin) Injection with an infusion solution compatible with Levaquin (Levofloxacin) Injection and with any other drug(s) administered via this common line
Levaquin (Levofloxacin) Dosage Forms And Strengths
TABLETS, Film-coated, capsule-shaped
ORAL SOLUTION, 25mg/mL, clear yellow to clear greenish-yellow color
INJECTION, Single-Use Vials of concentrated solution for dilution for intravenous infusion, clear yellow to clear greenish-yellow in appearance
INJECTION (5 mg/mL in 5% Dextrose) Premix in Single-Use Flexible Containers, for intravenous infusion
Levaquin (Levofloxacin) Contraindications
Levaquin (Levofloxacin) is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials
Levaquin (Levofloxacin) Warnings And Precautions
Fluoroquinolones, including Levaquin (Levofloxacin) , are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Levaquin (Levofloxacin) should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug. .
Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with fluoroquinolones, including Levaquin (Levofloxacin) . These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:
The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted
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If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of and surgical evaluation should be instituted as clinically indicated
Levaquin (Levofloxacin) is indicated in pediatric patients (≥6 months of age) only for the prevention of inhalational anthrax (post-exposure) . An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendonopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving Levaquin (Levofloxacin)
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In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species
Levaquin (Levofloxacin) Adverse Reactions
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
Hypotension has been associated with rapid or bolus intravenous infusion of Levaquin (Levofloxacin) . Levaquin (Levofloxacin) should be infused slowly over 60 to 90 minutes, depending on dosage
Crystalluria and cylindruria have been reported with quinolones, including Levaquin (Levofloxacin) . Therefore, adequate hydration of patients receiving Levaquin (Levofloxacin) should be maintained to prevent the formation of a highly concentrated urine
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to Levaquin (Levofloxacin) in 7537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with Levaquin (Levofloxacin) for a wide variety of infectious diseases . Patients received Levaquin (Levofloxacin) doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3–14 days, and the mean number of days on therapy was 10 days.
The overall incidence, type and distribution of adverse reactions was similar in patients receiving Levaquin (Levofloxacin) doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of Levaquin (Levofloxacin) due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%).
Adverse reactions occurring in ≥1% of Levaquin (Levofloxacin) -treated patients and less common adverse reactions, occurring in 0.1 to <1% of Levaquin (Levofloxacin) -treated patients, are shown in Table 6 and Table 7, respectively. The most common adverse drug reactions (≥3%) are nausea, headache, diarrhea, insomnia, constipation, and dizziness.
In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with quinolones, including Levaquin (Levofloxacin) . The relationship of the drugs to these events is not presently established.
Levaquin (Levofloxacin) Use In Specific Populations
In phase 3 clinical trials, 1,945 Levaquin (Levofloxacin) -treated patients (26%) were ≥ 65 years of age. Of these, 1,081 patients (14%) were between the ages of 65 and 74 and 864 patients (12%) were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.
Severe, and sometimes fatal, cases of hepatotoxicity have been reported post-marketing in association with Levaquin (Levofloxacin) . The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levaquin (Levofloxacin) should be discontinued immediately if the patient develops signs and symptoms of hepatitis .
Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using Levaquin (Levofloxacin) with concomitant drugs that can result in prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known QT prolongation, uncorrected hypokalemia) .
The pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. However, since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function .
Levaquin (Levofloxacin) Overdosage
In the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.
Levaquin (Levofloxacin) exhibits a low potential for acute toxicity. Mice, rats, dogs and monkeys exhibited the following clinical signs after receiving a single high dose of Levaquin (Levofloxacin) : ataxia, ptosis, decreased locomotor activity, dyspnea, prostration, tremors, and convulsions. Doses in excess of 1500 mg/kg orally and 250 mg/kg IV produced significant mortality in rodents.
Levaquin (Levofloxacin) Description
Levaquin (Levofloxacin) is a synthetic broad-spectrum antibacterial agent for oral and intravenous administration. Chemically, levofloxacin, a chiral fluorinated carboxyquinolone, is the pure (-)-(S)-enantiomer of the racemic drug substance ofloxacin. The chemical name is (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate.
The empirical formula is CHFNO • ½ HO and the molecular weight is 370.38. Levofloxacin is a light yellowish-white to yellow-white crystal or crystalline powder. The molecule exists as a zwitterion at the pH conditions in the small intestine.
The data demonstrate that from pH 0.6 to 5.8, the solubility of levofloxacin is essentially constant (approximately 100 mg/mL). Levofloxacin is considered in this pH range, as defined by USP nomenclature. Above pH 5.8, the solubility increases rapidly to its maximum at pH 6.7 (272 mg/mL) and is considered in this range. Above pH 6.7, the solubility decreases and reaches a minimum value (about 50 mg/mL) at a pH of approximately 6.9.
Levofloxacin has the potential to form stable coordination compounds with many metal ions. This in vitro chelation potential has the following formation order: Al>Cu>Zn>Mg>Ca.
Levaquin (Levofloxacin) Nonclinical Toxicology
In a lifetime bioassay in rats, levofloxacin exhibited no carcinogenic potential following daily dietary administration for 2 years; the highest dose (100 mg/kg/daywas 1.4 times the highest recommended human dose (750 mg) based upon relative body surface area. Levofloxacin did not shorten the time to tumor development of UV-induced skin tumors in hairless albino (Skh-1) mice at any levofloxacin dose level and was therefore not photo-carcinogenic under conditions of this study. Dermal levofloxacin concentrations in the hairless mice ranged from 25 to 42 mcg/g at the highest levofloxacin dose level (300 mg/kg/day) used in the photo-carcinogenicity study. By comparison, dermal levofloxacin concentrations in human subjects receiving 750 mg of Levaquin (Levofloxacin) averaged approximately 11.8 mcg/g at C.
Levofloxacin was not mutagenic in the following assays: Ames bacterial mutation assay ( and , CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and sister chromatid exchange (CHL/IU cell line) assays.
Levofloxacin caused no impairment of fertility or reproductive performance in rats at oral doses as high as 360 mg/kg/day, corresponding to 4.2 times the highest recommended human dose based upon relative body surface area and intravenous doses as high as 100 mg/kg/day, corresponding to 1.2 times the highest recommended human dose based upon relative body surface area.
Levofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested In immature dogs (4–5 months old), oral doses of 10 mg/kg/day for 7 days and intravenous doses of 4 mg/kg/day for 14 days of levofloxacin resulted in arthropathic lesions. Administration at oral doses of 300 mg/kg/day for 7 days and intravenous doses of 60 mg/kg/day for 4 weeks produced arthropathy in juvenile rats. Three-month old beagle dogs dosed orally with levofloxacin at 40 mg/kg/day exhibited clinically severe arthrotoxicity resulting in the termination of dosing at Day 8 of a 14-day dosing routine. Slight musculoskeletal clinical effects, in the absence of gross pathological or histopathological effects, resulted from the lowest dose level of 2.5 mg/kg/day (approximately 0.2-fold the pediatric dose based upon AUC comparisons). Synovitis and articular cartilage lesions were observed at the 10 and 40 mg/kg dose levels (approximately 0.7-fold and 2.4-fold the pediatric dose, respectively, based on AUC comparisons). Articular cartilage gross pathology and histopathology persisted to the end of the 18-week recovery period for those dogs from the 10 and 40 mg/kg/day dose levels.
When tested in a mouse ear swelling bioassay, levofloxacin exhibited phototoxicity similar in magnitude to ofloxacin, but less phototoxicity than other quinolones.
While crystalluria has been observed in some intravenous rat studies, urinary crystals are not formed in the bladder, being present only after micturition and are not associated with nephrotoxicity.
In mice, the CNS stimulatory effect of quinolones is enhanced by concomitant administration of non-steroidal anti-inflammatory drugs.
In dogs, levofloxacin administered at 6 mg/kg or higher by rapid intravenous injection produced hypotensive effects. These effects were considered to be related to histamine release.
Levaquin (Levofloxacin) Clinical Studies
Adult patients with clinically and radiologically documented nosocomial pneumonia were enrolled in a multicenter, randomized, open-label study comparing intravenous Levaquin (Levofloxacin) (750 mg once daily) followed by oral Levaquin (Levofloxacin) (750 mg once daily) for a total of 7–15 days to intravenous imipenem/cilastatin (500–1000 mg every 6–8 hours daily) followed by oral ciprofloxacin (750 mg every 12 hours daily) for a total of 7–15 days. Levaquin (Levofloxacin) -treated patients received an average of 7 days of intravenous therapy (range: 1–16 days); comparator-treated patients received an average of 8 days of intravenous therapy (range: 1–19 days).
Overall, in the clinically and microbiologically evaluable population, adjunctive therapy was empirically initiated at study entry in 56 of 93 (60.2%) patients in the Levaquin (Levofloxacin) arm and 53 of 94 (56.4%) patients in the comparator arm. The average duration of adjunctive therapy was 7 days in the Levaquin (Levofloxacin) arm and 7 days in the comparator. In clinically and microbiologically evaluable patients with documented infection, 15 of 17 (88.2%) received ceftazidime (N=11) or piperacillin/tazobactam (N=4) in the Levaquin (Levofloxacin) arm and 16 of 17 (94.1%) received an aminoglycoside in the comparator arm. Overall, in clinically and microbiologically evaluable patients, vancomycin was added to the treatment regimen of 37 of 93 (39.8%) patients in the Levaquin (Levofloxacin) arm and 28 of 94 (29.8%) patients in the comparator arm for suspected methicillin-resistant infection.
Clinical success rates in clinically and microbiologically evaluable patients at the posttherapy visit (primary study endpoint assessed on day 3–15 after completing therapy) were 58.1% for Levaquin (Levofloxacin) and 60.6% for comparator. The 95% CI for the difference of response rates (Levaquin (Levofloxacin) minus comparator) was [-17.2, 12.0]. The microbiological eradication rates at the posttherapy visit were 66.7% for Levaquin (Levofloxacin) and 60.6% for comparator. The 95% CI for the difference of eradication rates (Levaquin (Levofloxacin) minus comparator) was [-8.3, 20.3]. Clinical success and microbiological eradication rates by pathogen are detailed in Table 13.
To evaluate the safety and efficacy of higher dose and shorter course of Levaquin (Levofloxacin) , 528 outpatient and hospitalized adults with clinically and radiologically determined mild to severe community-acquired pneumonia were evaluated in a double-blind, randomized, prospective, multicenter study comparing Levaquin (Levofloxacin) 750 mg, IV or orally, every day for five days or Levaquin (Levofloxacin) 500 mg IV or orally, every day for 10 days.
Clinical success rates (cure plus improvement) in the clinically evaluable population were 90.9% in the Levaquin (Levofloxacin) 750 mg group and 91.1% in the Levaquin (Levofloxacin) 500 mg group. The 95% CI for the difference of response rates (Levaquin (Levofloxacin) 750 minus Levaquin (Levofloxacin) 500) was [-5.9, 5.4]. In the clinically evaluable population (31–38 days after enrollment) pneumonia was observed in 7 out of 151 patients in the Levaquin (Levofloxacin) 750 mg group and 2 out of 147 patients in the Levaquin (Levofloxacin) 500 mg group. Given the small numbers observed, the significance of this finding cannot be determined statistically. The microbiological efficacy of the 5-day regimen was documented for infections listed in Table 17.
Levaquin (Levofloxacin) is approved for the treatment of acute bacterial sinusitis (ABS) using either 750 mg by mouth × 5 days or 500 mg by mouth once daily × 10–14 days. To evaluate the safety and efficacy of a high dose short course of Levaquin (Levofloxacin) , 780 outpatient adults with clinically and radiologically determined acute bacterial sinusitis were evaluated in a double-blind, randomized, prospective, multicenter study comparing Levaquin (Levofloxacin) 750 mg by mouth once daily for five days to Levaquin (Levofloxacin) 500 mg by mouth once daily for 10 days.
Clinical success rates (defined as complete or partial resolution of the pre-treatment signs and symptoms of ABS to such an extent that no further antibiotic treatment was deemed necessary) in the microbiologically evaluable population were 91.4% (139/152) in the Levaquin (Levofloxacin) 750 mg group and 88.6% (132/149) in the Levaquin (Levofloxacin) 500 mg group at the test-of-cure (TOC) visit (95% CI [-4.2, 10.0] for Levaquin (Levofloxacin) 750 mg minus Levaquin (Levofloxacin) 500 mg).
Rates of clinical success by pathogen in the microbiologically evaluable population who had specimens obtained by antral tap at study entry showed comparable results for the five- and ten-day regimens at the test-of-cure visit 22 days post treatment.
Three hundred ninety-nine patients were enrolled in an open-label, randomized, comparative study for complicated skin and skin structure infections. The patients were randomized to receive either Levaquin (Levofloxacin) 750 mg once daily (IV followed by oral), or an approved comparator for a median of 10 ± 4.7 days. As is expected in complicated skin and skin structure infections, surgical procedures were performed in the Levaquin (Levofloxacin) and comparator groups. Surgery (incision and drainage or debridement) was performed on 45% of the Levaquin (Levofloxacin) -treated patients and 44% of the comparator treated patients, either shortly before or during antibiotic treatment and formed an integral part of therapy for this indication.
Among those who could be evaluated clinically 2–5 days after completion of study drug, overall success rates (improved or cured) were 116/138 (84.1%) for patients treated with Levaquin (Levofloxacin) and 106/132 (80.3%) for patients treated with the comparator.
Success rates varied with the type of diagnosis ranging from 68% in patients with infected ulcers to 90% in patients with infected wounds and abscesses. These rates were equivalent to those seen with comparator drugs.
Adult patients with a clinical diagnosis of prostatitis and microbiological culture results from urine sample collected after prostatic massage (VB) or expressed prostatic secretion (EPS) specimens obtained via the Meares-Stamey procedure were enrolled in a multicenter, randomized, double-blind study comparing oral Levaquin (Levofloxacin) 500 mg, once daily for a total of 28 days to oral ciprofloxacin 500 mg, twice daily for a total of 28 days. The primary efficacy endpoint was microbiologic efficacy in microbiologically evaluable patients. A total of 136 and 125 microbiologically evaluable patients were enrolled in the Levaquin (Levofloxacin) and ciprofloxacin groups, respectively. The microbiologic eradication rate by patient infection at 5–18 days after completion of therapy was 75.0% in the Levaquin (Levofloxacin) group and 76.8% in the ciprofloxacin group (95% CI [-12.58, 8.98] for Levaquin (Levofloxacin) minus ciprofloxacin). The overall eradication rates for pathogens of interest are presented in Table 19.
Eradication rates for when found with other co-pathogens are consistent with rates seen in pure isolates.
Clinical success (cure + improvement with no need for further antibiotic therapy) rates in microbiologically evaluable population 5–18 days after completion of therapy were 75.0% for Levaquin (Levofloxacin) -treated patients and 72.8% for ciprofloxacin-treated patients (95% CI [-8.87, 13.27] for Levaquin (Levofloxacin) minus ciprofloxacin). Clinical long-term success (24–45 days after completion of therapy) rates were 66.7% for the Levaquin (Levofloxacin) -treated patients and 76.9% for the ciprofloxacin-treated patients (95% CI [-23.40, 2.89] for Levaquin (Levofloxacin) minus ciprofloxacin).
To evaluate the safety and efficacy of the higher dose and shorter course of Levaquin (Levofloxacin) , 1109 patients with cUTI and AP were enrolled in a randomized, double-blind, multicenter clinical trial conducted in the US from November 2004 to April 2006 comparing Levaquin (Levofloxacin) 750 mg IV or orally once daily for 5 days (546 patients) with ciprofloxacin 400 mg IV or 500 mg orally twice daily for 10 days (563 patients). Patients with AP complicated by underlying renal diseases or conditions such as complete obstruction, surgery, transplantation, concurrent infection or congenital malformation were excluded. Efficacy was measured by bacteriologic eradication of the baseline organism(s) at the post-therapy visit in patients with a pathogen identified at baseline. The post-therapy (test-of-cure) visit occurred 10 to 14 days after the last active dose of Levaquin (Levofloxacin) and 5 to 9 days after the last dose of active ciprofloxacin.
The bacteriologic cure rates overall for Levaquin (Levofloxacin) and control at the test-of-cure (TOC) visit for the group of all patients with a documented pathogen at baseline (modified intent to treat or mITT) and the group of patients in the mITT population who closely followed the protocol (Microbiologically Evaluable) are summarized in Table 20.
Microbiologic eradication rates in the Microbiologically Evaluable population at TOC for individual pathogens recovered from patients randomized to Levaquin (Levofloxacin) treatment are presented in Table 21.
To evaluate the safety and efficacy of the 250 mg dose, 10 day regimen of Levaquin (Levofloxacin) , 567 patients with uncomplicated UTI, mild-to-moderate cUTI, and mild-to-moderate AP were enrolled in a randomized, double-blind, multicenter clinical trial conducted in the US from June 1993 to January 1995 comparing Levaquin (Levofloxacin) 250 orally once daily for 10 days (285 patients) with ciprofloxacin 500 mg orally twice daily for 10 days (282 patients). Patients with a resistant pathogen, recurrent UTI, women over age 55 years, and with an indwelling catheter were initially excluded, prior to protocol amendment which took place after 30% of enrollment. Microbiological efficacy was measured by bacteriologic eradication of the baseline organism(s) at 1–12 days post-therapy in patients with a pathogen identified at baseline.
The bacteriologic cure rates overall for Levaquin (Levofloxacin) and control at the test-of-cure (TOC) visit for the group of all patients with a documented pathogen at baseline (modified intent to treat or mITT) and the group of patients in the mITT population who closely followed the protocol (Microbiologically Evaluable) are summarized in Table 22.
The effectiveness of Levaquin (Levofloxacin) for this indication is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levaquin (Levofloxacin) has not been tested in humans for the post-exposure prevention of inhalation anthrax. The mean plasma concentrations of Levaquin (Levofloxacin) associated with a statistically significant improvement in survival over placebo in the rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving the recommended oral and intravenous dosage regimens
Levofloxacin pharmacokinetics have been evaluated in adult and pediatric patients. The mean (± SD) steady state peak plasma concentration in human adults receiving 500 mg orally or intravenously once daily is 5.7 ± 1.4 and 6.4 ± 0.8 mcg/mL, respectively; and the corresponding total plasma exposure (AUC) is 47.5 ± 6.7 and 54.6 ± 11.1 mcg.h/mL, respectively. The predicted steady-state pharmacokinetic parameters in pediatric patients ranging in age from 6 months to 17 years receiving 8 mg/kg orally every 12 hours (not to exceed 250 mg per dose) were calculated to be comparable to those observed in adults receiving 500 mg orally once daily
In adults, the safety of Levaquin (Levofloxacin) for treatment durations of up to 28 days is well characterized. However, information pertaining to extended use at 500 mg daily up to 60 days is limited. Prolonged Levaquin (Levofloxacin) therapy in adults should only be used when the benefit outweighs the risk.
In pediatric patients, the safety of levofloxacin for treatment durations of more than 14 days has not been studied. An increased incidence of musculoskeletal adverse events (arthralgia, arthritis, tendonopathy, gait abnormality) compared to controls has been observed in clinical studies with treatment duration of up to 14 days. Long-term safety data, including effects on cartilage, following the administration of levofloxacin to pediatric patients is limited .
A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 49 LD (~2.7 × 10) spores (range 17 – 118 LD) of (Ames strain) was conducted. The minimal inhibitory concentration (MIC) of levofloxacin for the anthrax strain used in this study was 0.125 mcg/mL. In the animals studied, mean plasma concentrations of levofloxacin achieved at expected T (1 hour post-dose) following oral dosing to steady state ranged from 2.79 to 4.87 mcg/mL. Steady state trough concentrations at 24 hours post-dose ranged from 0.107 to 0.164 mcg/mL. Mean (SD) steady state AUC was 33.4 ± 3.2 mcg.h/mL (range 30.4 to 36.0 mcg.h/mL). Mortality due to anthrax for animals that received a 30 day regimen of oral Levaquin (Levofloxacin) beginning 24 hrs post exposure was significantly lower (1/10), compared to the placebo group (9/10) [P=0.0011, 2-sided Fisher's Exact Test]. The one levofloxacin treated animal that died of anthrax did so following the 30-day drug administration period.
Levaquin (Levofloxacin) How Supplied/storage And Handling
Levaquin (Levofloxacin) Tablets are supplied as 250, 500, and 750 mg capsule-shaped, coated tablets. Levaquin (Levofloxacin) Tablets are packaged in bottles and in unit-dose blister strips in the following configurations:
Levaquin (Levofloxacin) Tablets should be stored at 15° to 30°C (59° to 86°F) in well-closed containers.
Levaquin (Levofloxacin) Tablets are manufactured for PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ 08869 by Janssen Ortho LLC, Gurabo, Puerto Rico 00778.
Levaquin (Levofloxacin) Oral Solution is supplied in a 16 oz. multi-use bottle (NDC 0045-1515-01). Each bottle contains 480 mL of the 25 mg/mL levofloxacin oral solution
Levaquin (Levofloxacin) Oral Solution should be stored at 25°C (77°F); excursions permitted to 15° – 30°C (59° to 86°F) [refer to USP controlled room temperature].
Levaquin (Levofloxacin) Oral Solution is manufactured for PriCara, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ 08869 by Janssen Pharmaceutica N.V, Beerse, Belgium.
Levaquin (Levofloxacin) Injection is supplied in single-use vials. Each vial contains a concentrated solution with the equivalent of 500 mg of levofloxacin in 20 mL vials and 750 mg of levofloxacin in 30 mL vials.
Levaquin (Levofloxacin) Injection in Single-Use Vials should be stored at controlled room temperature and protected from light.
Levaquin (Levofloxacin) Injection in Single-Use Vials is manufactured for Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ 08869 by Janssen Pharmaceutica N.V., Beerse, Belgium.
Levaquin (Levofloxacin) (levofloxacin in 5% dextrose) Injection is supplied as a single-use, premixed solution in flexible containers. Each bag contains a dilute solution with the equivalent of 250, 500, or 750 mg of levofloxacin, respectively, in 5% Dextrose (D5W).
Levaquin (Levofloxacin) Injection Premix in Flexible Containers should be stored at or below 25°C (77°F); however, brief exposure up to 40°C (104°F) does not adversely affect the product. Avoid excessive heat and protect from freezing and light. Levaquin (Levofloxacin) Injection Premix in Flexible Containers is manufactured for Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ 08869 by Hospira, Inc., Lake Forest, IL 60045.
Levaquin (Levofloxacin) Patient Counseling Information
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Patients should be informed that Levaquin (Levofloxacin) Tablets may be taken with or without food. Levaquin (Levofloxacin) Oral Solution should be taken 1 hour before or 2 hours after eating. The tablet and oral solution should be taken at the same time each day.
Patients should drink fluids liberally while taking Levaquin (Levofloxacin) to avoid formation of a highly concentrated urine and crystal formation in the urine.
Antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine should be taken at least two hours before or two hours after oral Levaquin (Levofloxacin) administration.
Patients should be informed that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue Levaquin (Levofloxacin) and consult a physician.
Patients should be informed that concurrent administration of warfarin and Levaquin (Levofloxacin) has been associated with increases of the International Normalized Ratio (INR) or prothrombin time and clinical episodes of bleeding. Patients should notify their physician if they are taking warfarin, be monitored for evidence of bleeding, and also have their anticoagulation tests closely monitored while taking warfarin concomitantly.
Manufactured by:
Manufactured for:
©Ortho-McNeil-Janssen Pharmaceuticals, Inc
U.S. Patent No. 5,053,407.
Issued July 2009
Levaquin (Levofloxacin)
Levaquin (Levofloxacin)
