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To reduce the development of drug-resistant bacteria and maintain the effec-tiveness of Cefpodoxime Proxetil Tablets, USP and other antibacterial drugs,Cefpodoxime Proxetil Tablets, USP should be used only to treat or prevent infec-tions that are proven or strongly suspected to be caused by bacteria.For Oral Use OnlyDESCRIPTIONCefpodoxime proxetil is an orally administered, extended spectrum, semi-synthetic antibiotic of the cephalosporin class. The chemical name is (RS)-1(iso-propoxycarbonyloxy) ethyl (+)-(6R,7R)-7-[2-(2-amino-4-thiazolyl)-2-{(Z)methoxyimino} acetamido]-3-methoxymethyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate.Its empirical formula is C

21H27N5O9S2and its structural formula is repre-sented below:

The molecular weight of cefpodoxime proxetil is 557.6.Cefpodoxime proxetil is a prodrug; its active metabolite is cefpodoxime. All dosesof cefpodoxime proxetil in this insert are expressed in terms of the active cef-podoxime moiety. The drug is supplied as film-coated tablets.Cefpodoxime Proxetil Tablets, USP contain cefpodoxime proxetil equivalent to100 mg or 200 mg of cefpodoxime activity. Each film-coated tablet contains thefollowing inactive ingredients: carboxymethylcellulose calcium, crospovidone,FD&C Yellow No. 6, hydroxypropyl cellulose, hypromellose, lactose monohydrate,magnesium stearate, sodium lauryl sulfate, talc and titanium dioxide.CLINICAL PHARMACOLOGYAbsorption and ExcretionCefpodoxime proxetil is a prodrug that is absorbed from the gastrointestinaltract and de-esterified to its active metabolite, cefpodoxime. Following oraladministration of 100 mg of cefpodoxime proxetil to fasting subjects, approxi-mately 50% of the administered cefpodoxime dose was absorbed systemically.Over the recommended dosing range (100 to 400 mg), approximately 29 to 33%of the administered cefpodoxime dose was excreted unchanged in the urine in12 hours. There is minimal metabolism of cefpodoxime in vivo.Effects of FoodThe extent of absorption (mean AUC) and the mean peak plasma concentra-tion increased when film-coated tablets were administered with food. Followinga 200 mg tablet dose taken with food, the AUC was 21 to 33% higher than underfasting conditions, and the peak plasma concentration averaged 3.1 mcg/mL infed subjects versus 2.6 mcg/mL in fasted subjects. Time to peak concentrationwas not significantly different between fed and fasted subjects.When a 200 mg dose of the suspension was taken with food, the extent ofabsorption (mean AUC) and mean peak plasma concentration in fed subjects werenot significantly different from fasted subjects, but the rate of absorption was slowerwith food (48% increase in T

max).Pharmacokinetics of Cefpodoxime Proxetil Film-coated TabletsOver the recommended dosing range (100 to 400 mg), the rate and extent ofcefpodoxime absorption exhibited dose-dependency; dose-normalized C

maxandAUC decreased by up to 32% with increasing dose. Over the recommendeddosing range, the T maxwas approximately 2 to 3 hours and the T1/2ranged from2.09 to 2.84 hours. Mean C

maxwas 1.4 mcg/mL for the 100 mg dose, 2.3mcg/mL for the 200 mg dose, and 3.9 mcg/mL for the 400 mg dose. In patientswith normal renal function, neither accumulation nor significant changes inother pharmacokinetic parameters were noted following multiple oral doses ofup to 400 mg Q 12 hours.

Cefpodoxime Plasma Levels (mcg/mL) in Fasted Adults AfterFilm-coated Tablet Administration (Single Dose)

DistributionProtein binding of cefpodoxime ranges from 22 to 33% in serum and from 21

to 29% in plasma.Skin BlisterFollowing multiple-dose administration every 12 hours for 5 days of 200 mgor 400 mg cefpodoxime proxetil, the mean maximum cefpodoxime concentra-tion in skin blister fluid averaged 1.6 and 2.8 mcg/mL, respectively. Skin blisterfluid cefpodoxime levels at 12 hours after dosing averaged 0.2 and 0.4 mcg/mLfor the 200 mg and 400 mg multiple-dose regimens, respectively.Tonsil TissueFollowing a single, oral 100 mg cefpodoxime proxetil film-coated tablet, themean maximum cefpodoxime concentration in tonsil tissue averaged 0.24 mcg/gat 4 hours post-dosing and 0.09 mcg/g at 7 hours post-dosing. Equilibrium wasachieved between plasma and tonsil tissue within 4 hours of dosing. No detec-tion of cefpodoxime in tonsillar tissue was reported 12 hours after dosing. Theseresults demonstrated that concentrations of cefpodoxime exceeded the MIC90ofS. pyogenesfor at least 7 hours after dosing of 100 mg of cefpodoxime proxetil.Lung TissueFollowing a single, oral 200 mg cefpodoxime proxetil film-coated tablet, themean maximum cefpodoxime concentration in lung tissue averaged 0.63 mcg/gat 3 hours post-dosing, 0.52 mcg/g at 6 hours postdosing, and 0.19 mcg/g at12 hours post-dosing. The results of this study indicated that cefpodoxime pen-etrated into lung tissue and produced sustained drug concentrations for at least12 hours after dosing at levels that exceeded the MIC

90for S. pneumoniae andH. influenzae.CSFAdequate data on CSF levels of cefpodoxime are not available.Effects of Decreased Renal FunctionElimination of cefpodoxime is reduced in patients with moderate to severe renalimpairment (<50 mL/min creatinine clearance). (See PRECAUTIONSand DOSAGEAND ADMINISTRATION.) In subjects with mild impairment of renal function (50to 80 mL/min creatinine clearance), the average plasma half-life of cefpodoximewas 3.5 hours. In subjects with moderate (30 to 49 mL/min creatinine clearance)or severe renal impairment (5 to 29 mL/min creatinine clearance), the half-lifeincreased to 5.9 and 9.8 hours, respectively. Approximately 23% of the admin-istered dose was cleared from the body during a standard 3-hour hemodialysisprocedure.Effect of Hepatic Impairment (cirrhosis)Absorption was somewhat diminished and elimination unchanged in patientswith cirrhosis. The mean cefpodoxime T

1/2and renal clearance in cirrhoticpatients were similar to those derived in studies of healthy subjects. Ascites didnot appear to affect values in cirrhotic subjects. No dosage adjustment is rec-ommended in this patient population.Pharmacokinetics in Elderly SubjectsElderly subjects do not require dosage adjustments unless they have dimin-ished renal function. (See PRECAUTIONS.) In healthy geriatric subjects, cefpo-doxime half-life in plasma averaged 4.2 hours (vs 3.3 in younger subjects) andurinary recovery averaged 21% after a 400 mg dose was administered every 12hours. Other pharmacokinetic parameters (C

max, AUC, and Tmax) were unchangedrelative to those observed in healthy young subjects.MicrobiologyMechanism of ActionCefpodoxime is a bactericidal agent that acts by inhibition of bacterial cell wallsynthesis. Cefpodoxime has activity in the presence of some beta-lactamases,both penicillinases and cephalosporinases, of Gram-negative and Gram-positivebacteria.Mechanism of ResistanceResistance to Cefpodoxime is primarily through hydrolysis by beta-lactamase,alteration of penicillin-binding proteins (PBPs), and decreased permeability.Cefpodoxime has been shown to be active against most isolates of the followingbacteria, both in vitroand in clinical infections as described in the Indications and

Usage (1) section:Gram-positive bacteriaStaphylococcus aureus(methicillin-susceptible strains, including those pro-ducing penicillinases)Staphylococcus saprophyticusStreptococcus pneumoniae(excluding penicillin-resistant isolates)Streptococcus pyogenesGram-negative bacteriaEscherichia coliKlebsiella pneumoniaeDoseTime after Oral Ingestion

(CefpodoximeEquivalents)

1hr2hr3hr4hr6hr8hr12hr

100 mg0.981.41.310.590.290.08

200 mg1.52.22.21.81.20.620.18

400 mg2.23.73.83.32.31.30.38

Proteus mirabilisHaemophilus influenzae(including beta-lactamase producing isolates)Moraxella catarrhalisNeisseria gonorrhoeae(including penicillinase-producing isolates)The following in vitro data are available, but their clinical significance isunknown. At least 90 percent of the following microorganisms exhibit an invitro minimum inhibitory concentration (MIC) less than or equal to the suscep-tible breakpoint for Cefpodoxime. However, the efficacy of Cefpodoxime in treat-ing clinical infections due to these microorganisms has not been established inadequate and well-controlled clinical trials.Gram-positive bacteriaStreptococcus agalactiaeStreptococcus spp. (Groups C, F, G)Gram-negative bacteriaCitrobacter diversusKlebsiella oxytocaProteus vulgarisProvidencia rettgeriHaemophilus parainfluenzaeAnaerobic Gram-positive bacteriaPeptostreptococcus magnusSusceptibility Test MethodsWhen available, the clinical microbiology laboratory should provide the resultsof in vitrosusceptibility test results for antimicrobial drug products used in res-

ident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should

aid the physician in selecting an antibacterial drug product for treatment.Dilution techniquesQuantitative methods are used to determine antimicrobial minimal inhibitoryconcentrations (MICs). These MICs provide estimates of the susceptibility of bac-teria to antimicrobial compounds. The MICs should be determined using astandardized test method.1,3The MIC values should be interpreted accordingto criteria provided in Table 1.Diffusion techniquesQuantitative methods that require measurement of zone diameters also pro-

v ide reproducible estimates of the susceptibility of bacteria to antimicrobial c ompounds. The zone size provides an estimate of the susceptibility of bacteria t o antimicrobial compounds. The zone size should be determined using a stan- d ardized test method.

2,3This procedure uses paper disks impregnated with 10

m cg Cefpodoxime to test the susceptibility of microorganisms to Cefpodoxime. T he disk diffusion interpretive criteria are provided in Table 1. T able 1. Susceptibility Test Interpretive Criteria for Cefpodoxime 2 * The current absence of resistant isolates precludes defining any results other t han "Susceptible." Isolates yielding MIC results other than "Susceptible" s hould be submitted to a reference laboratory for further testing. S usceptibility of staphylococci to Cefpodoxime may be deduced from testing o nly penicillin and either cefoxitin or oxacillin. A report of Susceptibleindicates that the antimicrobial is likely to inhibit g rowth of the pathogen if the antimicrobial compound reaches the concentration a t the infection site necessary to inhibit growth of the pathogen. A report of I ntermediateindicates that the result should be considered equivocal, and if the m icroorganism is not fully susceptible to alternative, clinically feasible drugs, the t est should be repeated. This category implies possible clinical applicability in body s ites where the drug is physiologically concentrated or in situations where a high d osage of drug can be used. This category also provides a buffer zone that pre- v ents small uncontrolled technical factors from causing major discrepancies in i nterpretation. A report of Resistantindicates that the antimicrobial is not likely t o inhibit growth of the pathogen if the antimicrobial compound reaches the con- c entrations usually achievable at the infection site; other therapy should be s elected. Q uality Control S tandardized susceptibility test procedures require the use of laboratory con- t rols to monitor and ensure the accuracy and precision of supplies and reagents u sed in the assay, and the techniques of the individual performing the test. 1,2,3 Standard Cefpodoxime powder should provide the following range of MIC val- u es noted in Table 2. For the diffusion technique using the 10 mcg disk, the cri- t eria in Table 2 should be achieved. T able 2. AcceptableQuality Control Ranges for Cefpodoxime ATCC¨ is a registered trademark of the American Type Culture Collection.

INDICATIONS AND USAGECefpodoxime proxetil is indicated for the treatment of patients with mild to mod-erate infections caused by susceptible strains of the designated microorganismsin the conditions listed below.Recommended dosages, durations of therapy, and applicable patient pop-ulations vary among these infections. Please see DOSAGE AND ADMINIS-TRATION for specific recommendations.

Acute otitis mediacaused by Streptococcus pneumoniae(excluding penicillin-resistant strains), Streptococcus pyogenes, Haemophilus influenzae(includingbeta-lactamase-producing strains), or Moraxella (Branhamella) catarrhalis(includ-ing beta-lactamase-producing strains).Pharyngitis and/or tonsillitiscaused by Streptococcus pyogenes.NOTE:Only penicillin by the intramuscular route of administration has beenshown to be effective in the prophylaxis of rheumatic fever. Cefpodoxime prox-etil is generally effective in the eradication of streptococci from the oropharynx.However, data establishing the efficacy of cefpodoxime proxetil for the prophy-laxis of subsequent rheumatic fever are not available.Community-acquired pneumoniacaused by S. pneumoniaeor H. Influenzae(including beta-lactamase-producing strains).Acute bacterial exacerbation of chronic bronchitiscaused by S. pneumoniae,H. influenzae(non-beta-lactamase-producing strains only), or M. catarrhalis. Dataare insufficient at this time to establish efficacy in patients with acute bacterialexacerbations of chronic bronchitis caused by beta-lactamase-producing strainsof H. influenzae.Acute, uncomplicated urethral and cervical gonorrheacaused by Neisseriagonorrhoeae(including penicillinase-producing strains).Acute, uncomplicated ano-rectal infections in womendue to Neisseria gon-orrhoeae(including penicillinase-producing strains).NOTE:The efficacy of cefpodoxime in treating male patients with rectal infec-tions caused by N. gonorrhoeaehas not been established. Data do not supportthe use of cefpodoxime proxetil in the treatment of pharyngeal infections due toN. gonorrhoeaein men or women.Uncomplicated skin and skin structure infectionscaused by Staphylococcusaureus(including penicillinase-producing strains) or Streptococcus pyogenes.Abscesses should be surgically drained as clinically indicated.NOTE:In clinical trials, successful treatment of uncomplicated skin and skinstructure infections was dose-related. The effective therapeutic dose for skin infec-tions was higher than those used in other recommended indications. (SeeDOSAGE AND ADMINISTRATION.)Acute maxillary sinusitiscaused by Haemophilus influenzae(including beta-lactamase-producing strains), Streptococcus pneumoniae,and Moraxellacatarrhalis.Uncomplicated urinary tract infections (cystitis)caused by Escherichia coli,Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus.NOTE:In considering the use of cefpodoxime proxetil in the treatment of cys-titis, cefpodoxime proxetil"s lower bacterial eradication rates should be weighedagainst the increased eradication rates and different safety profiles of someother classes of approved agents. (See CLINICAL STUDIESsection.)Appropriate specimens for bacteriological examination should be obtained inorder to isolate and identify causative organisms and to determine their sus-ceptibility to cefpodoxime. Therapy may be instituted while awaiting the resultsof these studies. Once these results become available, antimicrobial therapyshould be adjusted accordingly.Pathogen

Minimum Inhibitory

C oncentrations (mcg/mL)Disk Diffusion D iameters (mm)

SIRSIR

Enterobacteriaceae< 24≥ 8≥2118-20< 17

Haemophilus

i nfluenzae*< 2--≥21--

Streptococcus

p

Neisseria

g

QC Strains

Mi nimum I nhibitory C oncentrations mcg/mL)Disk Diffusion Z one diameters mm)

Escherichia coli ATCC 259220.25 - 123 - 28

Haemophilus influenzaeATCC 492470.25 - 125 - 31

Streptococcus pneumoniaeATCC 496190.03 - 0.1228 - 34 Neisseria gonorrhoeae ATCC 492260.03 - 0.1235 - 43

Staphylococcus aureus ATCC 25923-19 - 25

Staphylococcus aureus ATCC 292131 - 8-

To reduce the development of drug-resistant bacteria and maintain the effec-tiveness of Cefpodoxime Proxetil Tablets, USP and other antibacterial drugs,Cefpodoxime Proxetil Tablets, USP should be used only to treat or preventinfections that are proven or strongly suspected to be caused by susceptible bac-teria. When culture and susceptibility information are available, they should beconsidered in selecting or modifying antibacterial therapy. In the absence of suchdata, local epidemiology and susceptibility patterns may contribute to theempiric selection of therapy.CONTRAINDICATIONSCefpodoxime proxetil is contraindicated in patients with a known allergy to cef-podoxime or to the cephalosporin group of antibiotics.WARNINGSBEFORE THERAPY WITH CEFPODOXIME PROXETIL IS INSTITUTED, CARE-FUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HASHAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFPODOXIME, OTHERCEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF CEFPODOXIME IS TOBE ADMINISTERED TO PENICILLIN SENSITIVE PATIENTS, CAUTION SHOULDBE EXERCISED BECAUSE CROSS HYPERSENSITIVITY AMONG BETA-LACTAMANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLER-GIC REACTION TO CEFPODOXIME PROXETIL OCCURS, DISCONTINUE THEDRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREAT-MENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDINGOXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINE, AND AIR-WAY MANAGEMENT, AS CLINICALLY INDICATED.Clostridium difficileassociated diarrhea (CDAD) has been reported with useof nearly all antibacterial agents, including cefpodoxime proxetil tablets, USP, andmay range in severity from mild diarrhea to fatal colitis. Treatment with anti-bacterial agents alters the normal flora of the colon leading to overgrowth of C.difficile.C. difficileproduces toxins A and B which contribute to the development ofCDAD. Hypertoxin producing strains of C. difficilecause increased morbidity andmortality, as these infections can be refractory to antimicrobial therapy and mayrequire colectomy. CDAD must be considered in all patients who present with diar-rhea following antibiotic use. Careful medical history is necessary since CDAD

h as been reported to occur over two months after the administration of antibacterial a gents. I f CDAD is suspected or confirmed, ongoing antibiotic use not directed against C . difficilemay need to be discontinued. Appropriate fluid and electrolyte man- a gement, protein supplementation, antibiotic treatment of C. difficile, and surgi- c al evaluation should be instituted as clinically indicated. A concerted effort to monitor for C. difficilein cefpodoxime-treated patients w ith diarrhea was undertaken because of an increased incidence of diarrhea asso- c iated with C. difficilein early trials in normal subjects. C. difficileorganisms or t oxin was reported in 10% of the cefpodoxime-treated adult patients with diar- r hea; however, no specific diagnosis of pseudomembranous colitis was made in t hese patients. I n post-marketing experience outside the United States, reports of pseudomem- b ranous colitis associated with the use of cefpodoxime proxetil have been r eceived. P

RECAUTIONS

G eneral I n patients with transient or persistent reduction in urinary output due to r enal insufficiency, the total daily dose of cefpodoxime proxetil should be reduced b ecause high and prolonged serum antibiotic concentrations can occur in such i ndividuals following usual doses. Cefpodoxime, like other cephalosporins, s hould be administered with caution to patients receiving concurrent treatment w ith potent diuretics. (See DOSAGE AND ADMINISTRATION.) A s with other antibiotics, prolonged use of cefpodoxime proxetil may result in o vergrowth of non-susceptible organisms. Repeated evaluation of the patient"s c ondition is essential. If superinfection occurs during therapy, appropriate meas- u res should be taken. P rescribing Cefpodoxime Proxetil Tablets, USP in the absence of a proven or s trongly suspected bacterial infection or a prophylactic indication is unlikely to p rovide benefit to the patient and increases the risk of the development of drug- r esistant bacteria. I nformation for Patients P atients should be counseled that antibacterial drugs including Cefpodoxime P roxetil Tablets, USP should only be used to treat bacterial infections. They do n ot treat viral infections (e.g., the common cold). When Cefpodoxime Proxetil T ablets, USP is prescribed to treat a bacterial infection, patients should be told t hat although it is common to feel better early in the course of therapy, the med- i cation should be taken exactly as directed. Skipping doses or not completing the f ull course of therapy may (1) decrease the effectiveness of the immediate treat-

ment and (2) increase the likelihood that bacteria will develop resistance and willnot be treatable by Cefpodoxime Proxetil Tablets, USP or other antibacterialdrugs in the future.

Diarrhea is a common problem caused by antibiotics which usually endswhen the antibiotic is discontinued. Sometimes after starting treatment withantibiotics, patients can develop watery and bloody stools (with or without stom-ach cramps and fever) even as late as two or more months after having taken thelast dose of the antibiotic. If this occurs, patients should contact their physicianas soon as possible.Drug InteractionsAntacidsConcomitant administration of high doses of antacids (sodium bicarbonate andaluminum hydroxide) or H2blockers reduces peak plasma levels by 24% to 42%and the extent of absorption by 27% to 32%, respectively. The rate of absorp-tion is not altered by these concomitant medications. Oral anti-cholinergics (e.g.,propantheline) delay peak plasma levels (47% increase in T

max), but do not affectthe extent of absorption (AUC).ProbenecidAs with other beta-lactam antibiotics, renal excretion of cefpodoxime wasinhibited by probenecid and resulted in an approximately 31% increase in AUCand 20% increase in peak cefpodoxime plasma levels.Nephrotoxic drugsAlthough nephrotoxicity has not been noted when cefpodoxime proxetil was givenalone, close monitoring of renal function is advised when cefpodoxime proxetil isadministered concomitantly with compounds of known nephrotoxic potential.Drug/Laboratory Test InteractionsCephalosporins, including cefpodoxime proxetil, are known to occasionallyinduce a positive direct Coombs" test.Carcinog

enesis, Mutagenesis, Impairment of FertilityLong-term animal carcinogenesis studies of cefpodoxime proxetil have not beenperformed. Mutagenesis studies of cefpodoxime, including the Ames test bothwith and without metabolic activation, the chromosome aberration test, theunscheduled DNA synthesis assay, mitotic recombination and gene conversion,the forward gene mutation assay and the in vivomicronucleus test, were all neg-ative. No untoward effects on fertility or reproduction were noted when 100mg/kg/day or less (2 times the human dose based on mg/m2) was administeredorally to rats.PregnancyTeratogenic EffectsPregnancy Category BCefpodoxime proxetil was neither teratogenic nor embryocidal when admin-istered to rats during organogenesis at doses up to 100 mg/kg/day (2 times thehuman dose based on mg/m

2) or to rabbits at doses up to 30 mg/kg/day (1 to2 times the human dose based on mg/m

2).There are, however, no adequate and well-controlled studies of cefpodoximeproxetil use in pregnant women. Because animal reproduction studies are notalways predictive of human response, this drug should be used during pregnancyonly if clearly needed.Labor and DeliveryCefpodoxime proxetil has not been studied for use during labor and delivery.Treatment should only be given if clearly needed.Nursing MothersCefpodoxime is excreted in human milk. In a study of 3 lactating women, lev-els of cefpodoxime in human milk were 0%, 2% and 6% of concomitant serumlevels at 4 hours following a 200 mg oral dose of cefpodoxime proxetil. At 6 hourspost-dosing, levels were 0%, 9% and 16% of concomitant serum levels. Becauseof the potential for serious reactions in nursing infants, a decision should be madewhether to discontinue nursing or to discontinue the drug, taking into accountthe importance of the drug to the mother.Pediatric UseSafety and efficacy in infants less than 2 months of age have not been established.Geriatric UseOf the 3338 patients in multiple-dose clinical studies of cefpodoxime proxetilfilm-coated tablets, 521 (16%) were 65 and over, while 214 (6%) were 75 andover. No overall differences in effectiveness or safety were observed between theelderly and younger patients. In healthy geriatric subjects with normal renalfunction, cefpodoxime half-life in plasma averaged 4.2 hours and urinary recov-ery averaged 21% after a 400 mg dose was given every 12 hours for 15 days.Other pharmacokinetic parameters were unchanged relative to those observedin healthy younger subjects.Dose adjustment in elderly patients with normal renal function is not necessary.ADVERSE REACTIONSClinical TrialsFilm-coated Tablets (Multiple dose)In clinical trials using multiple dosesof cefpodoxime proxetil filmcoated tablets,4696 patients were treated with the recommended dosages of cefpodoxime (100

1.2.3.(See Reverse)

Cefpodoxime Proxetil

Tablets, USP

46116116

46116116 280x330 PM1288 Cefpodoxime Tabs FP 07-2013_Layout 1 10/16/13 3:52 PM Page 1

Reference ID: 3446338

to 400 mg Q 12 hours). There were no deaths or permanent disabilities thoughtrelated to drug toxicity. One-hundred twenty-nine (2.7%) patients discontinuedmedication due to adverse events thought possibly or probably related to drugtoxicity. Ninety-three (52%) of the 178 patients who discontinued therapy(whether thought related to drug therapy or not) did so because of gastrointestinaldisturbances, nausea, vomiting, or diarrhea. The percentage of cefpodoxime prox-etil-treated patients who discontinued study drug because of adverse events wassignificantly greater at a dose of 800 mg daily than at a dose of 400 mg dailyor at a dose of 200 mg daily. Adverse events thought possibly or probably relatedto cefpodoxime in multiple-dose clinical trials (N=4696 cefpodoxime-treatedpatients) were:

Incidence Greater Than 1%

Diarrhea or loose stools were dose-related: decreasing from 10.4% of patientsreceiving 800 mg per day to 5.7% for those receiving 200 mg per day. Ofpatients with diarrhea, 10% had C. difficileorganism or toxin in the stool. (SeeWARNINGS.)

Incidence Less Than 1%: By body system in decreasing orderClinical Studies Adverse events thought possibly or probably related to cefpodoxime proxetil that occurred in less than 1% of patients (N=4696)

Body- fungal infections, abdominal distention, malaise, fatigue, asthenia,fever, chest pain, back pain, chills, generalized pain, abnormal microbiological tests,moniliasis, abscess, allergic reaction, facial edema, bacterial infections, parasiticinfections, localized edema, localized pain.Cardiovascular

- congestive heart failure, migraine, palpitations, vasodila-tion, hematoma, hypertension, hypotension.Digestive

- vomiting, dyspepsia, dry mouth, flatulence, decreased appetite, con-stipation, oral moniliasis, anorexia, eructation, gastritis, mouth ulcers, gastroin-testinal disorders, rectal disorders, tongue disorders, tooth disorders, increasedthirst, oral lesions, tenesmus, dry throat, toothache.Hemic and Lymphatic

- anemia.Metabolic and Nutritional - dehydration, gout, peripheral edema, weightincrease.Musculo-skeletal - myalgia.Nervous

- dizziness, insomnia, somnolence, anxiety, shakiness, nervous-ness, cerebral infarction, change in dreams, impaired concentration, confusion,nightmares, paresthesia, vertigo.Respiratory

- asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dysp-nea, pleural effusion, pneumonia, sinusitis.Skin

- urticaria, rash, pruritus non-application site, diaphoresis, maculopapularrash, fungal dermatitis, desquamation, dry skin non-application site, hair loss,vesiculobullous rash, sunburn.Special Senses

- taste alterations, eye irritation, taste loss, tinnitus.Urogenital

- hematuria, urinary tract infections, metrorrhagia, dysuria, urinaryfrequency, nocturia, penile infection, proteinuria, vaginal pain.Film-coated Tablets (Single dose)In clinical trials using a single doseof cefpodoxime proxetil film-coatedtablets, 509 patients were treated with the recommended dosage of cefpodoxime(200 mg). There were no deaths or permanent disabilities thought related to drugtoxicity in these studies.Adverse events thought possibly or probably related to cefpodoxime in single-dose clinical trials conducted in the United States were:

Incidence Greater Than 1%

I ncidence Less Than 1% C entral Nervous System:Dizziness, headache, syncope. D ermatologic:Rash. G enital:Vaginitis. Gquotesdbs_dbs43.pdfusesText_43

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