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MEDLIB-L  August 1997, Week 2

MEDLIB-L August 1997, Week 2

Subject:

maxipime

From:

"Martha M. Silveira" <[log in to unmask]>

Reply-To:

Medical Libraries Discussion List <[log in to unmask]>

Date:

Wed, 13 Aug 1997 11:01:27 -0300

Content-Type:

multipart/mixed

Parts/Attachments:

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text/plain (44 lines) , maxipime.txt (428 lines)

Did these MAXAPINE can to be Maxipime?
This informations are from MICROMEDEX HEALTHCARE SERIES
http://www.micromedex.com
[log in to unmask]
MAXIPIME
Drug Evaluations
Select a Reference:

CEFEPIME


MAXIPIME 0.5 G (SMITHKLINE BEECHAM PHARMA GMBH)

POWDER FOR INJECTION

AVAILABLE IN:
GERMANY

ACTIVE INGREDIENT(S):
CEFEPIME, 500 MG/VIAL

Available Container Sizes :
5 X 0.5 G VIALS

INACTIVE INGREDIENTS:
ARGININE

NOTE:
1.  CEFEPIME BASE 500 MG IS EQUIVALENT TO 601 MG CEFEPIME HYDROCHLORIDE-1-H2O

MANUFACTURER:
SMITHKLINE BEECHAM PHARMA GMBH
Leopoldstr. 175, 80804 Muenchen, Germany
(089) 36044-0 (Telefax:  (089) 36044-123)


Martha M. Silveira
Librarian
[log in to unmask]
Rede Sarah de Hospitais do Aparelho Locomotor
Salvador, Bahia  -  Brazil




To: [log in to unmask] Subject: RE: ? on antibiotic "maxapine" Did these MAXAPINE can to be Maxipime? This informations are from MICROMEDEX HEALTHCARE SERIES http://www.micromedex.com [log in to unmask] MAXIPIME Drug Evaluations Select a Reference: CEFEPIME MAXIPIME 0.5 G (SMITHKLINE BEECHAM PHARMA GMBH) POWDER FOR INJECTION AVAILABLE IN: GERMANY ACTIVE INGREDIENT(S): CEFEPIME, 500 MG/VIAL Available Container Sizes : 5 X 0.5 G VIALS INACTIVE INGREDIENTS: ARGININE NOTE: 1. CEFEPIME BASE 500 MG IS EQUIVALENT TO 601 MG CEFEPIME HYDROCHLORIDE-1-H2O MANUFACTURER: SMITHKLINE BEECHAM PHARMA GMBH Leopoldstr. 175, 80804 Muenchen, Germany (089) 36044-0 (Telefax: (089) 36044-123)   CEFEPIME 0.0 OVERVIEW A. CEFEPIME is considered to be a fourth generation cephalosporin antibiotic because it has good gram negative coverage similar to third generation cephalosporins but better gram positive coverage. B. DOSING INFORMATION: Most studies have used CEFEPIME in doses of 1 g IV every 12 hours; higher doses or more frequent administration may be required in pseudomonal infections. C. PHARMACOKINETICS: IM CEFEPIME is rapidly and completely absorbed. Peak serum occur in 0.5 to 1.5 hours. Therapeutic serum levels are maintained for at least 8 hours after a single 2 g dose. CEFEPIME penetrates into inflammatory fluid at concentrations approximately 80% of serum levels, and into bronchial mucosa at levels approximately 60% of those reached in the plasma. CEFEPIME is 16 to 19% bound to serum proteins; volume of distribution is 14 to 20 L. D. CAUTIONS: Phlebitis may occur with IV CEFEPIME; this usually resolves upon discontinuation of therapy. Headache, blurred vision, lightheadedness, dyspepsia, and antibiotic-associated diarrhea may also occur. Although transient elevations in serum transaminases may occur, no clinical hepatotoxicity has been reported. E. CLINICAL APPLICATIONS: Although more study is needed, CEFEPIME has been useful in the treatment of respiratory tract infections, skin and soft tissue infections, and urinary tract infections. It is particularly effective against infections involving gram-negative bacilli and Pseudomonas spp and may be beneficial in the treatment of respiratory infections in patients with cystic fibrosis. 1.0 DOSING INFORMATION 1.1 DOSAGE FORMS A. Information on specific dosage forms can be obtained by entering a brand name or trade name at the "Type In Topic" screen or by choosing "ProdIndx." B. SYNONYMS         1. BMY-28142 1.3 ADULT DOSAGE 1.3.1 NORMAL DOSE A. PARENTERAL 1. A dose of 0.5 to 1 gram every 12 hours for 7 to 10 days by the intramuscular or intravenous route is recommended for the treatment of mild to moderate URINARY TRACT INFECTIONS (including PYELONEPHRITIS) caused by E coli, K pneumoniae or P mirabilis (Prod Info Maxipime(R), 1996). 2. A dose of 1 to 2 grams intravenously every 12 hours for 10 days is recommended for the treatment of moderate to severe PNEUMONIA due to S pneumoniae, P aeruginosa, K pneumoniae, or Enterobacter species (Prod Info Maxipime(R), 1996). 3. A dose of 2 grams intravenously every 12 hours for 10 days is recommended for the treatment of severe URINARY TRACT INFECTIONS (including PYELONEPHRITIS) caused by E coli or K pneumoniae. This dose is also indicated for the treatment of moderate to severe SKIN AND SKIN STRUCTURE INFECTIONS caused by S aureus or S pyogenes (Prod Info Maxipime(R), 1996). 4. In the treatment of respiratory tract infections, including bronchitis and pneumonia, and for cellulitis, other skin and soft tissue infections, and urinary tract infections, 1 to 2 grams intravenously every 12 hours for 5 to 11 days has been effective (Clynes et al, 1989; Oster et al, 1990; Okamoto et al, 1993). 5. Some investigators have suggested that higher doses or more frequent administration (every 8 hours) may be necessary in infections caused by Pseudomonas (Chadha et al, 1990; Kovarik et al, 1991). 1.3.2 DOSAGE IN RENAL FAILURE A. The following dosing schedule has been recommended for patients with renal dysfunction (Prod Info Maxipime(R), 1996):         Cr Clearance Recommended Doses                       Mild Moderate Severe                       Infection Infection Infection         gt 60 mL/min 500mg q12h 1g q12h 2g q12h         30-60 mL/min 500mg q24h 1g q24h 2g q24h         11-29 mL/min 500mg q24h 500mg q24h 1g q24h         lt 10 mL/min 250mg q24h 250mg q24h 500mg q24h gt=greater than lt=less than B. CEFEPIME is primarily eliminated via the kidneys as unchanged drug, so dosing adjustments for renal dysfunction will be necessary. Cronovist et al (1992) suggest a dose of 1 gram every 12 hours for patients with a creatinine clearance greater than 30 milliliters/minute. For patients with a creatinine clearance of 10 to 30 milliliters/minute a dose of 500 milligrams every 24 hours was suggested, and a dose of 250 milligrams every 24 hours was suggested for patients with a creatinine clearance less than 10 milliliters/minute. C. From another study it was suggested the standard dose (0.5 to 2.0 grams)should be administered every 12 hours for patients with a creatinine clearance greater than 60 milliliters/minute; the standard dose every 18 hours for patients with a creatinine clearance of 60 to 31 milliliters/minute; the standard dose every 24 hours for patients with a creatinine clearance 30 to 10 milliliters/minute, and for patients with a creatinine clearance less than 10 milliliters/minute the standard dose should be given every 48 hours (Okamoto et al, 1993). 1.3.3 DOSAGE IN HEPATIC INSUFFICIENCY A. No dosage adjustments are necessary for patients with hepatic dysfunction (Prod Info Maxipime(R), 1996). 1.3.5 DOSAGE ADJUSTMENT DURING DIALYSIS A. HEMODIALYSIS 1. During a 3 hour hemodialysis session 68% of a dose of cefepime is removed. A supplemental dose, the same as the initial dose, is recommended after dialysis (Prod Info Maxipime(R), 1996). 2. CEFEPIME is removed by hemodialysis. Cronovist et al (1992) suggest administering a supplemental dose of 250 milligrams after each dialysis session. B. PERITONEAL DIALYSIS 1. For patients on continuous ambulatory peritoneal dialysis (CAPD) the normal recommended dose should be administered every 48 hours (Prod Info Maxipime(R), 1996). 2. CEFEPIME is removed by peritoneal dialysis but to a lesser extent than by hemodialysis. Barbhaiya et al (1992) recommend a dose of 1 or 2 grams every 48 hours. 1.4 PEDIATRIC DOSAGE 1.4.1 NORMAL DOSE A. INTRAVENOUS 1. A dose of CEFEPIME of 50 milligrams/kilogram (maximum dose 2 grams) every 8 hours was used to treat acute bronchopulmonary exacerbations of cystic fibrosis (Arguedas et al, 1992). 1.4.3 DOSAGE IN HEPATIC INSUFFICIENCY A. No dosage adjustments are necessary for patients with hepatic dysfunction (Prod Info Maxipime(R), 1996). 1.4.4 DOSAGE ADJUSTMENT DURING DIALYSIS A. HEMODIALYSIS 1. During a 3 hour hemodialysis session 68% of a dose of cefepime is removed. A supplemental dose, the same as the initial dose, is recommended after dialysis (Prod Info Maxipime(R), 1996). B. PERITONEAL DIALYSIS 1. For patients on continuous ambulatory peritoneal dialysis (CAPD) the normal recommended dose should be administered every 48 hours (Prod Info Maxipime(R), 1996). 2.0 PHARMACOKINETICS 2.1 ONSET AND DURATION 2.1.1 ONSET A. SERUM LEVEL 1. Thirty minutes following IV administration of a 500 milligram, 1 gram and 2 gram dose, serum concentrations of cefepime were 38.2, 78.7, and 163.1 mcg/mL, respectively (Prod Info Maxipime(R), 1996). 2. Thirty minutes following IM administration of a 500 milligram, 1 gram, and 2 gram dose, serum concentrations of cefepime were 8.2, 14.8, and 36.1 mcg/mL, respectively. The time to maximum concentration after IM administration was approximately 1.5 hours(Prod Info Maxipime(R), 1996). 2.1.2 DURATION A. SERUM LEVEL 1. Twelve hours following IV administration of a 500 milligram, 1 gram and 2 gram dose, serum concentrations of cefepime were 0.2, 0.6, and 1.1 mcg/mL, respectively (Prod Info Maxipime(R), 1996). Therapeutic serum concentrations of cefepime (greater than 2 mcg/mL) are maintained for at least 8 hours after a single 2 gram IV dose (Barbhaiya et al, 1990a). 2. Twelve hours following IM administration of a 500 milligram, 1 gram and 2 gram dose, serum concentrations of cefepime were 0.7, 1.4, 2.3 mcg/mL, respectively (Prod Info Maxipime(R), 1996). 2.2 DRUG CONCENTRATION LEVELS 2.2.1 THERAPEUTIC A. The maximum serum concentrations (Cmax) after IV administration of 500 milligrams, 1 gram, or 2 grams of cefepime were 39.1, 81.7 and 163.9 mcg/mL, respectively (Prod Info Maxipime(R), 1996). B. After a 1 g IM dose, the peak serum concentrations ranged from 63.5 to 73.9 mcg/mL (Barbhaiya et al, 1990). In another study, peak plasma concentrations were 7.8, 13.9, 29.6, and 57.5 mcg/mL after single IM doses of 250, 500, 1000, and 2000 mg, respectively (Barbhaiya et al, 1990a). C. After IV infusion of 250, 500, 1,000, and 2,000 mg of CEFEPIME the maximum serum concentrations were 17.5, 31.3, 66.9, and 137 mcg/mL (Barbhaiya et al, 1992). 2.3 ADME 2.3.1 ABSORPTION A. INTRAMUSCULAR 1. CEFEPIME is rapidly and completely absorbed after IM administration, with peak plasma levels occurring 0.5 to 1.5 hours post-administration (Prod Info Maxipime(R), 1996; Barbhaiya et al, 1990a). 2.3.2 DISTRIBUTION 2.3.2.1 DISTRIBUTION SITES A. PROTEIN BINDING 1. CEFEPIME is 16% to 20% bound to serum proteins (Prod Info Maxipime(R), 1996; Barbhaiya et al, 1990; Oster et al, 1990). B. APPENDIX TISSUE 1. After intravenous administration of CEFEPIME 2 g every 12 hours the average concentration of CEFEPIME in appendix tissue was 4.84 mcg/g in 33 patients undergoing appendectomy for perforated or gangrenous appendix. The level of CEFEPIME was obtained an average of 5.99 hours after the dose; plasma levels were 16.27 mcg/mL on the average (Okamoto et al, 1991). C. BLISTER FLUID 1. Blister fluid concentrations of cefepime 1.5 hours following administration of a 2 gram IV dose averaged 81.4 mcg/mL (Prod Info Maxipime (R), 1996). 2. Penetration of CEFEPIME into inflammatory fluid is rapid after a 2 g IV infusion, with a mean peak level of 91.5 mcg/mL achieved 0.9 hours after the end of the infusion, approximately 80% of serum levels. After this time, blister fluid concentrations exceed those in the plasma by approximately 40%, declining with a half-life of about 2.2 hours (Nye et al, 1989). D. PERITONEAL FLUID 1. After intravenous administration of CEFEPIME 2 g every 12 hours the average concentration of CEFEPIME in peritoneal fluid was 14.4 mcg/mL in 33 patients undergoing appendectomy for perforated or gangrenous appendix. The level of CEFEPIME was obtained an average of 5.99 hours after the dose; plasma levels were 16.27 mcg/mL on the average (Okamoto et al, 1991). E. TISSUES 1. After a single 2 g IV dose of CEFEPIME, concentrations approximately 60% of those reached in the plasma are achieved in bronchial mucosa (Chadha et al, 1990). F. PROSTATE TISSUE 1. Thirty patients undergoing elective prostate surgery were given a single 2 gram IV dose of CEFEPIME. The penetration into prostatic tissue from 1 to 12 hours after the dose ranged from 42.9% to 79.4% of serum concentrations. It was felt that concentrations would be adequate to treat bacterial prostatitis (Arkell et al, 1992). G. BRONCHIAL MUCOSA 1. Bronchial mucosa concentrations of cefepime 4.8 hours following administration of a 2 gram IV dose averaged 24.1 mcg/g (Prod Info Maxipime(R), 1996). H. SPUTUM 1. Sputum concentrations of cefepime 4 hours following administration of a 2 gram IV dose averaged 7.4 mcg/mL (Prod Info Maxipime(R), 1996). 2.3.2.2 DISTRIBUTION KINETICS A. DISTRIBUTION HALF-LIFE 1. The distribution half-life of CEFEPIME is approximately 0.3 to 0.5 hour (Nye et al, 1989). B. VOLUME OF DISTRIBUTION 1. The volume of distribution of CEFEPIME is approximately 14 to 20 L after a single IV dose of 1 to 2 g in healthy adults (Barbhaiya et al, 1990; Nye et al, 1989). 2.3.3 METABOLISM 2.3.3.1 METABOLISM SITES AND KINETICS A. Cefepime is excreted primarily as unchanged drug(85%); however, it is partial metabolized in the liver to N- methylpyrrolidine (NMP) which is then converted to the N-oxide metabolite, NMP-N-oxide. Less than 1% of a dose is excreted in the urine as NMP and 6.8% is excreted as NMP-N-oxide(Prod Info Maxipime(R), 1996). 2.3.3.2 METABOLITES A. Metabolites of cefepime are N-methylpyrrolidine(NMP), and N- oxide-NMP(Prod Info Maxipime(R), 1996). 2.3.4 EXCRETION 2.3.4.1 BREAST MILK A. Cefepime is excreted in breast milk in small amounts (0.5 mcg/mL) (Prod Info Maxipime(R), 1996). 2.3.4.2 KIDNEY A. CEFEPIME is cleared primarily via the kidneys. The majority of a dose (approximately 70%) is recovered unchanged in the urine within 4 hours, and 99% within 8 hours. Renal clearance is 110 mL/minute. Total clearance is approximately 130 to 140 mL/minute; nonrenal clearance is approximately 15 to 20 mL/minute (Barbhaiya et al, 1990; Nye et al, 1989; Barbhaiya et al, 1990a). 2.3.5 HALF-LIFE 2.3.5.1 PARENT COMPOUND A. The elimination half-life of CEFEPIME is approximately 2 hours (Prod Info Maxipime(R), 1996; Nye et al, 1989; Barbhaiya et al, 1990; Barbhaiya et al, 1990a). B. Barbhaiya et al (1990) found that the elimination half-life of CEFEPIME was 2.2 hours in normal volunteers, and increased to 13.5 hours in patients with renal failure (CrCl less than 10mL/min). C. The half-life was reported to be 13.5 hours for patients on hemodialysis and 19 hours for patients on continuous peritoneal dialysis (Prod Info Maxipime(R), 1996). 2.3.5.2 METABOLITES 2.3.6 EXTRACORPOREAL ELIMINATION 2.3.6.1 HEMODIALYSIS A. CEFEPIME is readily removed by dialysis and serum concentrations decrease rapidly during hemodialysis (Barbhaiya et al 1990). A 3-hour session should remove approximately 68% of a dose of the drug (Prod Info Maxipime(R), 1996). 3.0 CAUTIONS 3.1 CONTRAINDICATIONS A. CEFEPIME is contraindicated in patients with a history of hypersensitivity to it or other cephalosporin antibiotics. 3.2 PRECAUTIONS A. CEFEPIME should be used with caution in the presence of significant renal dysfunction; dosage adjustment may be required. B. CEFEPIME should be used with caution in patients with a history of hypersensitivity to penicillins. C. Cefepime should be used with caution in patients with a history of colitis. 3.3 ADVERSE REACTIONS 3.3.1 BLOOD A. HEMATOLOGIC EFFECTS 1. SUMMARY: EOSINOPHILIA occurs in 1.7% of patients; an abnormal PT(1.4%) or PTT(1.6%)has also been reported. Less than 1% of patients have had a decrease in hematocrit, neutrophils, platelets or white blood cells (Prod Info Maxipime(R), 1996). 2. In a study involving 74 patients treated with CEFEPIME LEUKOPENIA was reported in one patient. This resolved 4 days after discontinuing CEFEPIME. In the same study 43% of the patients developed a positive direct COOMBS' REACTION. The significance of this is unknown; however, because hemolytic anemia did NOT develop in any patient (Jauregui et al, 1993). 3.3.2 CARDIOVASCULAR A. CARDIOVASCULAR EFFECTS 1. SUMMARY: Local reactions including PHLEBITIS have occurred in 1.3% of patients receiving cefepime (Prod Info Maxipime(R), 1996). 2. Phlebitis occurred in 2 of 19 patients receiving CEFEPIME 1 g IV every 12 hours for a mean of 7.6 days; this complication resolved with local wound care and changing the venous catheter (Clynes et al, 1989). 3.3.3 CENTRAL NERVOUS SYSTEM A. CENTRAL NERVOUS SYSTEM EFFECTS 1. Headache has been reported in less than 1% of patients receiving cefepime (Prod Info Maxipime(R), 1996). 2. HEADACHE, BLURRED VISION, and light-headedness have occurred after both single and multiple IV and IM doses of CEFEPIME 1 and 2 g; one patient suffered moderate-to-severe headache which required ACETAMINOPHEN administration on 2 separate occasions (Barbhaiya et al, 1990a). 3. Transient light-headedness during the infusion of CEFEPIME was reported in 3 of 12 patients in one study (Arguedas et al, 1992). 4. SEIZURES, ENCEPHALOPATHY and NEUROMUSCULAR EXCITABILITY, were reported in a patient with renal dysfunction (creatinine clearance of 11 milliliters/minute) who received cefepime 2 grams q24h for 7 days (Prod Info Maxipime(R), 1996). 3.3.5 GASTROINTESTINAL A. GASTROINTESTINAL EFFECTS 1. The manufacturer reports the following adverse effects have occurred in less than 1% of patients receiving cefepime; colitis, including PSEUDOMEMBRANOUS COLITIS, diarrhea, nausea or vomiting (Prod Info Maxipime(R), 1996). 2. DYSPEPSIA and burning sensations in the stomach were reported in patients receiving single and multiple doses of CEFEPIME 1 to 2 g IV or IM; these effects resolved spontaneously without treatment (Barbhaiya et al, 1990a). 3. One patient receiving CEFEPIME for 6 days developed short-lived DIARRHEA lasting less than one day. Although Clostridium difficile toxin was detected in the stool, the patient was not treated because symptoms resolved so rapidly (Oster et al, 1990). 3.3.6 KIDNEY/GENITOURINARY A. RENAL EFFECTS 1. Increases in BUN and serum creatinine have been reported in less than 1% of patients (Prod Info Maxipime(R), 1996). B. GENITOURINARY EFFECTS 1. Vaginitis has been reported in less than 1% of patients receiving cefepime (Prod Info Maxipime(R), 1996). 3.3.7 LIVER A. HEPATOTOXICITY 1. The manufacturer reports INCREASES IN LIVER FUNCTION TESTS in 2.4% to 2.8% of patients (Prod Info Maxipime(R), 1996). 2. Mild elevations in ALT (SGPT) and AST (SGOT) occur infrequently with CEFEPIME; these increases are mild and values return to normal shortly after discontinuation of therapy (Barbhaiya et al, 1990a; Clynes et al, 1989; Oster et al, 1990). 3.3.10 SKIN A. DERMATOLOGIC EFFECTS 1. Skin RASH has been reported in 1.1% of patients receiving cefepime. Pruritus and urticaria have been reported in less than 1% of patients(Prod Info Maxipime(R), 1996). 3.3.12 OTHER A. CROSS-SENSITIVITY See Drug Consult reference: "CEPHALOSPORIN-PENICILLIN CROSS-SENSITIVITY" B. OVERDOSE See POISINDEX(R) Management "PENICILLIN/CEPHALOSPORINS" C. SERUM SICKNESS See Drug Consult reference: "CEPHALOSPORIN-INDUCED SERUM SICKNESS" 3.4 TERATOGENICITY/EFFECTS IN PREGNANCY A. TERATOGENICITY 1. Cefepime is classified as FDA Pregnancy Category B (Prod Info Maxipime(R), 1996). 2. For More Information: See Drug Consult reference: "PREGNANCY RISK CATEGORIES" See Drug Consult reference: "ANTIBIOTIC THERAPY DURING PREGNANCY" B. EFFECTS IN PREGNANCY 1. Cefepime is classified as FDA Pregnancy Category B (Prod Info Maxipime(R), 1996). 2. For More Information: See Drug Consult reference: "PREGNANCY RISK CATEGORIES" See Drug Consult reference: "ANTIBIOTIC THERAPY DURING PREGNANCY" 3.5 DRUG INTERACTIONS 3.5.1 DRUG-DRUG COMBINATIONS A. AMIKACIN 1. Summary: Coadministered cefepime and amikacin may result in an increased potential for nephrotoxicity and ototoxicity (Prod Info Maxipime(R), 1996). Caution should be used if aminoglycoside antibiotics are to be given concomitantly with cefepime, especially if high doses of the aminoglycoside are being administered. 2. Adverse Effect: nephrotoxicity 3. Clinical Management: Carefully monitor renal function in patients receiving cefepime in combination with high doses of an aminoglycoside. The risk of nephrotoxicity may be increased when this combination of agents is used. 4. Severity: moderate 5. Onset: delayed 6. Documentation: poor 7. Probable Mechanism: additive effect B. FUROSEMIDE 1. Summary: Although not reported with cefepime, nephrotoxicity has occurred when other cephalosporins have been coadministered with furosemide (Prod Info Maxipime, 1996). Caution is warranted when cefepime is to be given concomitantly with potent diuretics. 2. Adverse Effect: an increased risk of nephrotoxicity 3. Clinical Management: Carefully monitor renal function in patients receiving cefepime in combination with furosemide. The risk of nephrotoxicity may be increased when this combination of agents is used. 4. Severity: moderate 5. Onset: delayed 6. Documentation: poor 7. Probable Mechanism: additive effects C. STREPTOMYCIN 1. Summary: Coadministered cefepime and streptomycin may result in an increased potential for nephrotoxicity and ototoxicity (Prod Info Maxipime(R), 1996). Caution should be used if aminoglycoside antibiotics are to be given concomitantly with cefepime, especially if high doses of the aminoglycoside are being administered. 2. Adverse Effect: nephrotoxicity 3. Clinical Management: Carefully monitor renal function in patients receiving cefepime in combination with high doses of an aminoglycoside. The risk of nephrotoxicity may be increased when this combination of agents is used. 4. Severity: moderate 5. Onset: delayed 6. Documentation: poor 7. Probable Mechanism: additive effect D. NILVADIPINE 1. Summary: Structurally related drugs such as nifedipine may increase the bioavailability of cephalosporins by up to 70%; however, clinical data for nilvadipine are lacking (Fachinfo Escor(R)/Escor forte, 1996). 2. Severity: not specified 3. Onset: not specified 4. Documentation: not specified 3.5.3 DRUG-LAB MODIFICATIONS A. GLUCOSE ASSAY 1. Summary: False-positive urine glucose tests may occur in patients receiving cefepime therapy (Prod Info Maxipime(R), 1996). False results may occur if Clinitest(R) tablets are used in cefepime-treated patients. 2. Adverse Effect: false and spurious laboratory test results 3. Clinical Management: Instead of using Clinitest(R) tablets for urine glucose tests, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used in patients receiving cefepime therapy. Tests based on enzymatic glucose oxidase reactions include Clinistix(R) and Tes-Tape(R). 4. Severity: moderate 5. Onset: rapid 6. Documentation: fair 7. Probable Mechanism: unknown B. LIVER FUNCTION TESTS 1. Modest elevations in serum SGOT (ALT) and SGPT (AST) have been described in the literature (Barbhaiya et al, 1990a; Clynes et al, 1989; Oster et al, 1990). However, no hepatotoxicity has been reported, and the clinical significance of these findings is unknown. 4.0 CLINICAL APPLICATIONS 4.1 MONITORING PARAMETERS 4.1.1 THERAPEUTIC A. PHYSICAL EXAMINATION: Decrease in temperature; decrease in signs and symptoms of infection B. LABORATORY: Decrease in white blood cell count; repeat culture and sensitivities if necessary 4.1.2 TOXIC A. PHYSICAL EXAMINATION: signs of severe allergic reaction; signs of neurotoxicity such as delirium, seizures or coma with high doses, especially in patients with renal dysfunction B. LABORATORY: BUN, serum creatinine 4.2 PATIENT INSTRUCTIONS A. POSSIBLE SIDE EFFECTS FROM THIS MEDICATION 1. Diarrhea, dyspepsia, headache, blurred vision, and lightheadedness may occur with this drug. Report any side effects to your physician. 4.3 PLACE IN THERAPY A. CEFEPIME is a cephalosporin with an overall spectrum of activity similar to that of other third-generation agents. However, it has a degree of antipseudomonal activity similar to CEFTAZIDIME, and has good beta-lactamase stability and improved gram-positive activity over existing compounds in its class. In addition, the drug has been shown to inhibit various Enterobacteriaceae resistant to cefotaxime and CEFTAZIDIME. It has been shown to be more effective than other third-generation cephalosporins against several gram-negative isolates, and has been referred to as a "fourth-generation" cephalosporin. Early data indicate that CEFEPIME may be particularly useful in the treatment of serious gram-negative bacillary infections. However, further study is required to determine the ultimate place of CEFEPIME in contemporary therapeutics. B. CEFEPIME is a broad-spectrum cephalosporin that most closely resembles CEFTAZIDIME in its spectrum of activity, with possibly increased activity against many enterobacter species and gram-positive organisms. However, CEFEPIME, similar to other third generation cephalosporins, is not useful against methicillin-resistant ZONE, CEFOTAXIME, CEFPIMIZOLE, and MOXALACTAM against Enterobacteriaceae, and more active against Staphylococcus aureus than CEFTAZIDIME, CEFOTAXIME, and CEFOPERAZONE (Kessler et al, 1985; Tsuji et al, 1985; Norden & Neiderriter, 1987; Masuyoshi et al, 1989; Kovarik et al, 1991). Enterobacter strains are sensitive to cefipine, including some strains resistant to ceftazidine and its congers (Sanders et al, 1996). Emerging resistance patterns may after this profile and large numbers of patients should be followed to closely determine any changes in sensitivity to cefepime. CEFEPIME has poor activity against anaerobic organisms such as Clostridium and Bacteroides (Jones et al, 1985). Mycobacterium avium complex is moderately sensitive to CEFEPIME, with MIC-90 values ranging from 4 to 32 mcg/mL (Cynamon et al, 1987). D. MINIMUM INHIBITORY CONCENTRATIONS 1. The following IN VITRO minimum inhibitory concentrations (MIC-90) have been reported for CEFEPIME; the suggested sensitivity breakpoint is 8 mcg/mL (gt = greater than) (Bodey et al, 1985; Conrad et al, 1985; Fuchs et al, 1985; Jones et al, 1985; Kessler et al, 1985; Tsuji et al, 1985; Fuchs et al, 1986; Masuyoshi et al, 1989; Norden & Neiderriter, 1987; Van Landuyt et al, 1986; Cynamon et al, 1987):                                        MIC-90          ORGANISM (mcg/mL)          Acinetobacter anitratus 6.25-27          Acinetobacter calcoaceticus 4          Acinetobacter lwoffii 6.25          Acinetobacter spp 32          Aeromonas hydrophila 0.25          Bacteroides bivius 128          Bacteroides fragilis 128          Bacteroides melaninogenicus 16          Bacteroides thetaiotaomicron gt 256          Bacteroides spp gt 256          Branhamella catarrhalis 1          Capnocytophaga spp 0.03          Citrobacter diversus 0.03-0.1          Citrobacter freundii 4          Clostridium difficile 128          Enterobacter aerogenes 0.5          Enterobacter agglomerans 0.5          Enterobacter cloacae 4-32          Enterobacteriaceae spp 1          Enterococcus spp gt 100          Escherichia coli 0.06-50*          Haemophilus influenzae           (beta-lactamase negative) 0.06          Haemophilus influenzae           (beta-lactamase positive) 0.06          Hafnia alvei 0.03          Helicobacter spp 4          Klebsiella oxytoca 0.5          Klebsiella pneumoniae 0.06-12.5*          Listeria monocytogenes 51          Morganella morganii 0.5          Mycobacterium avium complex 4-32          Neisseria gonorrhoeae           (beta-lactamase-negative) 0.008          Neisseria gonorrhoeae           (beta-lactamase positive) 0.015          Neisseria meningitidis 0.008          Peptococcus-Peptostrepto-           coccus 8          Proteus inconstans 0.1          Proteus mirabilis 0.06-0.25          Proteus penneri 0.06          Proteus vulgaris 0.5          Providencia rettgeri 0.5          Providencia stuartii 0.06-0.1          Pseudomonas aeruginosa 6.25-50*          Pseudomonas aeruginosa           (tobramycin-resistant) 16          Pseudomonas fluorescens 32          Pseudomonas acidovorans 16          Pseudomonas cepacia 16-gt 64          Pseudomonas maltophilia 16          Pseudomonas putida 16          Pseudomonas stutzeri 16          Salmonella enteritidis 0.5          Salmonella spp 0.07          Serratia liquifaciens 0.5          Serratia marcescens 1-2          Shigella sonnei 0.06          Shigella spp 0.5          Staphylococci, coagulase-           negative           (beta-lactamase-negative) 1          Staphylococci, coagulase-           negative           (beta-lactamase-positive) 128          Staphylococcus aureus           (beta-lactamase-negative) 2          Staphylococcus aureus           (beta-lactamase-positive) 2          Staphylococcus aureus           (methicillin-resistant) 128          Staphylococcus epidermidis 3.12          Streptococcus agalactiae 0.06          Streptococcus faecalis 64          Streptococcus pneumoniae 0.5          Streptococcus pyogenes 0.01-0.1          Xanthomonas maltophilia 50          Yersinia enterocolitica 0.03          gt = greater than * = significant inoculum effect when inoculum density increased from 1 x 10(5) CFU/mL to 1 x 10(7) CFU/mL on Mueller-Hinton broth (Bodey et al, 1985) E. REVIEW ARTICLES 1. A review of the in vitro activity of CEFEPIME and how it compares to third generation cephalosporins and cefpirome has been provided (Sanders, 1993). 2. The mechanism, pharmacokinetics, and clinical efficacy of cefepime are reviewed (Heinzl, 1994). 3. A review article regarding the pharmacokinetics of cefepime has been authored (Van der Auwera and Santella, 1993). 4. Comprehensive reviews of cefepime summarizing the world literature have been published (Barradell and Bryson, 1994; Okamoto et al, 1994). 5. A review of the pharmacology is presented and therapeutic recommendations for parenteral cephalosporins are presented in the proceedings of the Paul-Ehrlich-Gesellschaft fuer Chemotherapie Consensus Conference (Anon, 1995). 4.5 THERAPEUTIC USES A. BONE AND JOINT INFECTIONS 1. The safety and efficacy of CEFEPIME (2 grams IV every 12 hours) was evaluated in an open, non-randomized trial for the treatment of 61 patients with OSTEOMYELITIS, SEPTIC ARTHRITIS, and other serious infections. The overall clinical cure rate was 85.3% of patients. Three of 23 patients treated for osteomyelitis failed therapy, and none of the 4 patients with septic arthritis failed treatment (Jauregui et Neisseria spp, P mirabilis, P aeruginosa, S marcescens, S aureus, S pneumoniae, and S viridans. The one treatment failure occurred in a patient harboring Enterobacter cloacae (Oster et al, 1990). D. SKIN AND SKIN STRUCTURE INFECTIONS FDA Labeled Indication 1. Cefepime has been approved for use in moderate to severe uncomplicated skin and skin structure infections caused by Staphylococcus aureus or Streptococcal pyogenes (Prod Info Maxipime(R), 1996). Two patients with CELLULITIS infected with, P mirabilis, S aureus, and S pyogenes were cured with cefepime therapy (Clyne et al. 1989). E. URINARY TRACT INFECTIONS FDA Labeled Indication 1. Cefepime is approved for the treatment of complicated and uncomplicated urinary tract infections including, PYELONEPHRITIS, caused by E coli, K pneumoniae or P mirabilis (Prod Info Maxipime(R), 1996). A total of 4 patients with urinary tract infections caused by E coli, P mirabilis and P aeruginosa were cured with cefepime therapy (Clyne et al, 1989; Oster et al, 1990). 4.6 COMPARATIVE EFFICACY AND EVALUATION WITH OTHER SIMILAR THERAPEUTIC AGENTS A. CEFOTAXIME 1. LOWER RESPIRATORY INFECTIONS a. Cefepime (41 patients) and cefotaxime (21 patients) showed no difference in clinical or bacteriologic cure rates in patients with lower respiratory tract infections. Cefotaxime was given in doses of 2 grams IV every 8 hours, and cefepime was given in doses of 2 grams IV every 12 hours. There was no difference between treatments in regard to clinical or bacteriological cure rates. Both antibiotics were very effective with few adverse effects (Brachow & Schwigon, 1993). 2. GYNECOLOGIC INFECTIONS a. Cetepime and cefotaxime demonstrated no statistically significant difference in the rate of overall response or safety, when given for acute pelvic infections. Cefepime dosed as 2 g every 12 hours and cefotaxime as 2 g every 8 hours. Both drugs were administered intravenously over 30 minutes (Newton et al, 1993). B. CEFTAZIDIME 1. SERIOUS INFECTIONS a. Ceftazidime (2 grams IV every 8 hours) was compared to cefepime (2 grams IV every 12 hours) for the treatment of serious infections in 114 patients. Patients were diagnosed with lower respiratory infections, urinary tract infections, or skin structure infections. Approximately 50% of patients also had the diagnosis of sepsis syndrome. Ceftazidime and cefepime were equally effective both clinically and by microbiological cure. Both drugs were safe and effective for the treatment of serious infections in non-neutropenic patients (Kieft et al, 1994). 2. COMMUNITY ACQUIRED PNEUMONIA a. Ceftazidime (1 gram intravenously (IV) every 8 hours) was equally effective at clinically curing community acquired pneumonia and erradicating the causative organism when compared to cefepime (1 gram IV every 12 hours) in 111 patients. Adverse effects to both drugs were minor. Although ceftazidime and cefepime were effective, other antibiotics including first or second generation cephalosporins are effective for treating community acquired pneumonias (Leophonte et al, 1993). C. FEBRILE NEUTROPENIA 1. The combination of cefepime and amikacin was as effective as ceftazidime and amikacin in the prophylaxis of febrile neutropenic patients (Cordonnier et al, 1997). Intravenous dosages given in this open, randomized, non-blinded study were cefepime 2 grams two time daily, ceftazidime 2 grams three times daily, and amikacin 7.5 milligrams/kilogram two times daily. Patients in the cefepime group (n=212) and the ceftazidime group (n=107) had similar outcomes to therapy when considering clinical response, need to add a glycopeptide antimicrobial agent, and the rate of new bacterial infections. Gram-positive organisms were the cause of 63 infections, gram-negative organisms caused 31 infections, and mixed organisms caused 5 infections. Drug-related toxicity was similar in both groups. The cefepime/amikacin combination may be reasonable first-line therapy in high-risk febrile neutropenic patients. 6.0 REFERENCES 1. Anon: Cephalosporine zur parenteralen Applikation. Consensuskonferenz der Paul-Ehrlich-Gesellschaft fuer Chemotherapie eV. Arzneimitteltherapie 1995; 13:131-145. 2. Arguedas AG, Stutman HR, Zaleska M et al: Cefepime: Pharmacokinetcs and clinical response in patients with cystic fibrosis. AJDC 1992; 146:797-802. 3. Arkell D, Ashrap M, Andrews JM et al: An evaluation of the penetration of cefepime into prostate tissue in patients undergoing elective prostatectomy (letter). J Antimicrob Chemother 1992; 29:473-474. 4. Barbhaiya RH, Forgue ST, Gleason CR: Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects. Antimicrob Agents Chemother 1992; 36:552-557. 5. Barbhaiya RH, Knupp CA, Forgue ST et al: Pharmacokinetics of cefepime in subjects with renal insufficiency. Clin Pharmacol Ther 1990; 48:268-276. 6. Barbhaiya RH, Knupp CA, Pfefer M et al: Pharmacokinetics of cefepime in patients undergoing continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother 1992; 36:1387-1391. 7. Barbhaiya RH, Knupp CA, Tenney J et al: Safety, tolerance, and pharmacokinetics of cefepime administered intramuscularly to healthy subjects. J Clin Pharmacol 1990a; 30:900-910. 8. Barckow D & Schwigon CD: Cefepime versus cefotzxime in the treatment of lower respiratory tract infections. J Antimicrob Chemother 1993; 32(Suppl B):187-193. 9. Barradell LB & Bryson HM: Cefepime: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1994; 47:471-505. 10. Bodey GP, Ho DH & LeBlanc B: In vitro studies of BMY-28142, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother 1985; 27:265-269. 11. Chadha D, Wise R, Baldwin DR et al: Cefepime concentrations in bronchial mucosa and serum following a single 2 gram intravenous dose. J Antimicrob Chemother 1990; 25:959-963. 12. Chin NX & Neu HC: Synergy of new C-3 substituted cephalosporins and tobramycin against Pseudomonas aeruginosa and Pseudomonas cepacia. Diagn Microbiol Infect Dis 1989; 12:343-349. 13. Clynes N, Scully BE & Neu HC: The use of cefepime (BMY 28142) to treat respiratory infections. Diagn Microbiol Infect Dis 1989; 12:257-260. 14. Conrad DA, Scribner RK, Weber AH et al: In vitro activity of BMY-28142 against pediatric pathogens, including isolates from cystic fibrosis sputum. Antimicrob Agents Chemother 1985; 28:58-63. 15. Cordonnier C, Herbrecht R, Pico JL et al: Cefepime/amikacin versus ceftazidime/amikacin as emperical therapy for febrile episodes in neutropenic patients: a comparative study. Clin Infect Dis 1997; 24:41-51. 16. Cronqvist J, Nilsson-Ehle I, Oqvist B et al: Pharmacokinetics of cefepime dihydrochloride arginine in subjects with renal impairment. Antimicrob Agents Chemother 1992; 36:2676-2680. 17. Cynamon MH, Palmer GS & Sorg TB: Comparative in vitro activities of ampicillin, BMY 28142, and imipenem against Mycobacterium avium complex. Diagn Microbiol Infect Dis 1987; 6:151-155. 18. Eggimann P, Glauser MP, Aoun M et al: Cefepime monotherapy for the empirical treatment of fever in granulocytopenic cancer patients. J Antimicrob Chemother 1993; 32(Suppl B):151-163. 19. Fachinformation: Escor(R)/Escor(R) forte, nilvadipine. Merck, Darmstadt, 1996. 20. Fuchs PC, Jones RN, Barry AL et al: Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother 1985; 27:679-682. 21. Fuchs PC, Jones RN, Barry AL et al: Tentative disk diffusion susceptibility interpretive criteria for BMY-28142, a new cephalosporin. J Clin Microbiol 1986; 23:634-636. 22. Hardman JG, Gilman AG & Limbird LE (Eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed. McGraw-Hill, New York, NY, 1996. 23. Heinzl S (ed): Cefepim - Profil eines neuen Cephalosporins. Arzneimitteltherapie extra 1994; 18:1-8. 24. Jauregui L, Matzke D, Scott M et al: Cefepime as treatment for osteomyelitis and other severe bacterial infections. J Antimicrob Chemother 1993; 32(Suppl B):141-149. 25. Jones RN, Barry AL & Packer RR: BMY28142, cefbuperazone (T-1982), and Sch 34343: antimicrobial activity against 94 anaerobes compared to seven other antimicrobial agents. Diagn Microbiol Infect Dis 1985; 3:263-268. 26. Kessler RE, Bies M, Buck RE et al: Comparison of a new cephalosporin, BMY 28142, with other broad-spectrum beta-lactam antibiotics. Antimicrob Agents Chemother 1985; 27:207-216. 27. Kieft H, Hoepelman AIM, Arska MR et al: Cefepime compared with ceftazidime as initial therapy for serious bacterial infections and sepsis syndrome. Antimicrob Agents Chemother 1994; 38:415-421. 28. Kovarik J, Rozenberg-Arska M, Visser M et al: Pharmacodynamics of cefepime. Scand J Infect Dis Suppl 1991; 74:270-273. 29. Leophonte P, Bertrand A, Nouver G et al: A comparative study of cefepime and ceftazidime in the treatment of community-acquired lower respiratory tract infections. J Antimcicrob Chemother 1993; 31(Suppl B):165-173. 30. Masuyoshi S, Hiraoka M, Inoue M et al: Comparison of the in vitro and in vivo antibacterial activities of cefepime, (BMY-28142) with ceftazidime, cefuzonam, cefotaxime and cefmenoxime. Drugs Exptl Clin Res 1989; 15:1-10. 31. Newton ER, Yeomans ER, Pastorek JG et al: Randomized comparative study of cefepime and cefotaxime in the treatment of acute obstetric and gynaecological infections. J Antimicrobial Chemother 1993; 32(suppl):195-204. 32. Norden CW & Neiderriter K: In vitro activity of BMY-28142, a new cephalosporin. Chemotherapy 1987; 33:15-17. 33. Nye KJ, Shi YG, Andrews JM et al: Pharmacokinetics and tissue penetration of cefepime. J Antimicrob Chemother 1989; 24:23-28. 34. Okamoto MP, Chin A, Gill MA et al: Analysis of cefepime tissue penetration into human appendix. Pharmacotherapy 1991; 11:353-358. 35. Okamoto MP, Nakahiro RK, Chin A: Cefepime clinical pharmacokinetics. Clin Pharmacokinet 1993; 25:88-102. 36. Okamoto MP, Nakahiro RK, Chin A et al: Cefepime: a new fourth-generation cephalosporin. Am J Hosp Pharm 1994; 51:463-477. 37. Oster S, Edelstein H, Cassano K et al: Open trial of cefepime (BMY 28142) for infections in hospitalized patients. Antimicrob Agents Chemother 1990; 34:954-957. 38. Product Information Maxipime(R), Cefepime. Bristol-Myers Squibb Company, Princeton, NJ, 1996. 39. Product Information: Maxipime(R), cefepime hydrochloride for injection. Bristol-Myers Squibb, Princeton, NJ, 1996. 40. Sanders CC: Cefepime: the next generation? Clin Infect Dis 1993; 17:369-379. 41. Sanders WE, Tenneg JH & Kessler RE: Efficacy of cefepime in the treatment of infections due to multiply resistant enterobacter species. Clin Infect Dis 1996; 23:454-461. 42. Tsuji A, Maniatis A, Bertram MA et al: In vitro activity of BMY-28142 in comparison with those of other beta-lactam antimicrobial agents. Antimicrob Agents Chemother 1985; 27:515-519. 43. Van der Auwera P & Santella PJ: Pharmacokinetics of cefepime: a review. J Antimicrob Chemother 1993; 32(Suppl B):103-115. 44. Van Landuyt HW, Lambert A, Boelaert J et al: In vitro activity of BRL 36650, a new penicillin. Antimicrob Agents Chemother 1986; 29:362-366. 7.0 AUTHOR INFORMATION     Original publication: 08/91     Most recent revision: 03/97     List of contributors:     Daniel M Colaluca, PharmD     Phillip J Wein, RPh     DRUGDEX(R) Editorial Staff     For further information on contributing authors,     see editorial board listings. (DE1381) ----------

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May 2010, Week 3
May 2010, Week 2
May 2010, Week 1
April 2010, Week 5
April 2010, Week 4
April 2010, Week 3
April 2010, Week 2
April 2010, Week 1
March 2010, Week 5
March 2010, Week 4
March 2010, Week 3
March 2010, Week 2
March 2010, Week 1
February 2010, Week 4
February 2010, Week 3
February 2010, Week 2
February 2010, Week 1
January 2010, Week 5
January 2010, Week 4
January 2010, Week 3
January 2010, Week 2
January 2010, Week 1
December 2009, Week 5
December 2009, Week 4
December 2009, Week 3
December 2009, Week 2
December 2009, Week 1
November 2009, Week 5
November 2009, Week 4
November 2009, Week 3
November 2009, Week 2
November 2009, Week 1
October 2009, Week 5
October 2009, Week 4
October 2009, Week 3
October 2009, Week 2
October 2009, Week 1
September 2009, Week 5
September 2009, Week 4
September 2009, Week 3
September 2009, Week 2
September 2009, Week 1
August 2009, Week 5
August 2009, Week 4
August 2009, Week 3
August 2009, Week 2
August 2009, Week 1
July 2009, Week 5
July 2009, Week 4
July 2009, Week 3
July 2009, Week 2
July 2009, Week 1
June 2009, Week 5
June 2009, Week 4
June 2009, Week 3
June 2009, Week 2
June 2009, Week 1
May 2009, Week 5
May 2009, Week 4
May 2009, Week 3
May 2009, Week 2
May 2009, Week 1
April 2009, Week 5
April 2009, Week 4
April 2009, Week 3
April 2009, Week 2
April 2009, Week 1
March 2009, Week 5
March 2009, Week 4
March 2009, Week 3
March 2009, Week 2
March 2009, Week 1
February 2009, Week 4
February 2009, Week 3
February 2009, Week 2
February 2009, Week 1
January 2009, Week 5
January 2009, Week 4
January 2009, Week 3
January 2009, Week 2
January 2009, Week 1
December 2008, Week 5
December 2008, Week 4
December 2008, Week 3
December 2008, Week 2
December 2008, Week 1
November 2008, Week 5
November 2008, Week 4
November 2008, Week 3
November 2008, Week 2
November 2008, Week 1
October 2008, Week 5
October 2008, Week 4
October 2008, Week 3
October 2008, Week 2
October 2008, Week 1
September 2008, Week 5
September 2008, Week 4
September 2008, Week 3
September 2008, Week 2
September 2008, Week 1
August 2008, Week 5
August 2008, Week 4
August 2008, Week 3
August 2008, Week 2
August 2008, Week 1
July 2008, Week 5
July 2008, Week 4
July 2008, Week 3
July 2008, Week 2
July 2008, Week 1
June 2008, Week 5
June 2008, Week 4
June 2008, Week 3
June 2008, Week 2
June 2008, Week 1
May 2008, Week 5
May 2008, Week 4
May 2008, Week 3
May 2008, Week 2
May 2008, Week 1
April 2008, Week 5
April 2008, Week 4
April 2008, Week 3
April 2008, Week 2
April 2008, Week 1
March 2008, Week 5
March 2008, Week 4
March 2008, Week 3
March 2008, Week 2
March 2008, Week 1
February 2008, Week 5
February 2008, Week 4
February 2008, Week 3
February 2008, Week 2
February 2008, Week 1
January 2008, Week 5
January 2008, Week 4
January 2008, Week 3
January 2008, Week 2
January 2008, Week 1
December 2007, Week 5
December 2007, Week 4
December 2007, Week 3
December 2007, Week 2
December 2007, Week 1
November 2007, Week 5
November 2007, Week 4
November 2007, Week 3
November 2007, Week 2
November 2007, Week 1
October 2007, Week 5
October 2007, Week 4
October 2007, Week 3
October 2007, Week 2
October 2007, Week 1
September 2007, Week 5
September 2007, Week 4
September 2007, Week 3
September 2007, Week 2
September 2007, Week 1
August 2007, Week 5
August 2007, Week 4
August 2007, Week 3
August 2007, Week 2
August 2007, Week 1
July 2007, Week 5
July 2007, Week 4
July 2007, Week 3
July 2007, Week 2
July 2007, Week 1
June 2007, Week 5
June 2007, Week 4
June 2007, Week 3
June 2007, Week 2
June 2007, Week 1
May 2007, Week 5
May 2007, Week 4
May 2007, Week 3
May 2007, Week 2
May 2007, Week 1
April 2007, Week 4
April 2007, Week 3
April 2007, Week 2
April 2007, Week 1
March 2007, Week 5
March 2007, Week 4
March 2007, Week 3
March 2007, Week 2
March 2007, Week 1
February 2007, Week 4
February 2007, Week 3
February 2007, Week 2
February 2007, Week 1
January 2007, Week 5
January 2007, Week 4
January 2007, Week 3
January 2007, Week 2
January 2007, Week 1
December 2006, Week 5
December 2006, Week 4
December 2006, Week 3
December 2006, Week 2
December 2006, Week 1
November 2006, Week 5
November 2006, Week 4
November 2006, Week 3
November 2006, Week 2
November 2006, Week 1
October 2006, Week 5
October 2006, Week 4
October 2006, Week 3
October 2006, Week 2
October 2006, Week 1
September 2006, Week 5
September 2006, Week 4
September 2006, Week 3
September 2006, Week 2
September 2006, Week 1
August 2006, Week 5
August 2006, Week 4
August 2006, Week 3
August 2006, Week 2
August 2006, Week 1
July 2006, Week 5
July 2006, Week 4
July 2006, Week 3
July 2006, Week 2
July 2006, Week 1
June 2006, Week 5
June 2006, Week 4
June 2006, Week 3
June 2006, Week 2
June 2006, Week 1
May 2006, Week 5
May 2006, Week 4
May 2006, Week 3
May 2006, Week 2
May 2006, Week 1
April 2006, Week 4
April 2006, Week 3
April 2006, Week 2
April 2006, Week 1
March 2006, Week 5
March 2006, Week 4
March 2006, Week 3
March 2006, Week 2
March 2006, Week 1
February 2006, Week 4
February 2006, Week 3
February 2006, Week 2
February 2006, Week 1
January 2006, Week 5
January 2006, Week 4
January 2006, Week 3
January 2006, Week 2
January 2006, Week 1
December 2005, Week 5
December 2005, Week 4
December 2005, Week 3
December 2005, Week 2
December 2005, Week 1
November 2005, Week 5
November 2005, Week 4
November 2005, Week 3
November 2005, Week 2
November 2005, Week 1
October 2005, Week 5
October 2005, Week 4
October 2005, Week 3
October 2005, Week 2
October 2005, Week 1
September 2005, Week 5
September 2005, Week 4
September 2005, Week 3
September 2005, Week 2
September 2005, Week 1
August 2005, Week 5
August 2005, Week 4
August 2005, Week 3
August 2005, Week 2
August 2005, Week 1
July 2005, Week 5
July 2005, Week 4
July 2005, Week 3
July 2005, Week 2
July 2005, Week 1
June 2005, Week 5
June 2005, Week 4
June 2005, Week 3
June 2005, Week 2
June 2005, Week 1
May 2005, Week 5
May 2005, Week 4
May 2005, Week 3
May 2005, Week 2
May 2005, Week 1
April 2005, Week 5
April 2005, Week 4
April 2005, Week 3
April 2005, Week 2
April 2005, Week 1
March 2005, Week 5
March 2005, Week 4
March 2005, Week 3
March 2005, Week 2
March 2005, Week 1
February 2005, Week 4
February 2005, Week 3
February 2005, Week 2
February 2005, Week 1
January 2005, Week 5
January 2005, Week 4
January 2005, Week 3
January 2005, Week 2
January 2005, Week 1
December 2004, Week 5
December 2004, Week 4
December 2004, Week 3
December 2004, Week 2
December 2004, Week 1
November 2004, Week 5
November 2004, Week 4
November 2004, Week 3
November 2004, Week 2
November 2004, Week 1
October 2004, Week 5
October 2004, Week 4
October 2004, Week 3
October 2004, Week 2
October 2004, Week 1
September 2004, Week 5
September 2004, Week 4
September 2004, Week 3
September 2004, Week 2
September 2004, Week 1
August 2004, Week 5
August 2004, Week 4
August 2004, Week 3
August 2004, Week 2
August 2004, Week 1
July 2004, Week 5
July 2004, Week 4
July 2004, Week 3
July 2004, Week 2
July 2004, Week 1
June 2004, Week 5
June 2004, Week 4
June 2004, Week 3
June 2004, Week 2
June 2004, Week 1
May 2004, Week 4
May 2004, Week 3
May 2004, Week 2
May 2004, Week 1
April 2004, Week 5
April 2004, Week 4
April 2004, Week 3
April 2004, Week 2
April 2004, Week 1
March 2004, Week 5
March 2004, Week 4
March 2004, Week 3
March 2004, Week 2
March 2004, Week 1
February 2004, Week 5
February 2004, Week 4
February 2004, Week 3
February 2004, Week 2
February 2004, Week 1
January 2004, Week 5
January 2004, Week 4
January 2004, Week 3
January 2004, Week 2
January 2004, Week 1
December 2003, Week 5
December 2003, Week 4
December 2003, Week 3
December 2003, Week 2
December 2003, Week 1
November 2003, Week 5
November 2003, Week 4
November 2003, Week 3
November 2003, Week 2
November 2003, Week 1
October 2003, Week 5
October 2003, Week 4
October 2003, Week 3
October 2003, Week 2
October 2003, Week 1
September 2003, Week 5
September 2003, Week 4
September 2003, Week 3
September 2003, Week 2
September 2003, Week 1
August 2003, Week 5
August 2003, Week 4
August 2003, Week 3
August 2003, Week 2
August 2003, Week 1
July 2003, Week 5
July 2003, Week 4
July 2003, Week 3
July 2003, Week 2
July 2003, Week 1
June 2003, Week 5
June 2003, Week 4
June 2003, Week 3
June 2003, Week 2
June 2003, Week 1
May 2003, Week 5
May 2003, Week 4
May 2003, Week 3
May 2003, Week 2
May 2003, Week 1
April 2003, Week 5
April 2003, Week 4
April 2003, Week 3
April 2003, Week 2
April 2003, Week 1
March 2003, Week 5
March 2003, Week 4
March 2003, Week 3
March 2003, Week 2
March 2003, Week 1
February 2003, Week 4
February 2003, Week 3
February 2003, Week 2
February 2003, Week 1
January 2003, Week 5
January 2003, Week 4
January 2003, Week 3
January 2003, Week 2
January 2003, Week 1
December 2002, Week 5
December 2002, Week 4
December 2002, Week 3
December 2002, Week 2
December 2002, Week 1
November 2002, Week 5
November 2002, Week 4
November 2002, Week 3
November 2002, Week 2
November 2002, Week 1
October 2002, Week 5
October 2002, Week 4
October 2002, Week 3
October 2002, Week 2
October 2002, Week 1
September 2002, Week 5
September 2002, Week 4
September 2002, Week 3
September 2002, Week 2
September 2002, Week 1
August 2002, Week 5
August 2002, Week 4
August 2002, Week 3
August 2002, Week 2
August 2002, Week 1
July 2002, Week 5
July 2002, Week 4
July 2002, Week 3
July 2002, Week 2
July 2002, Week 1
June 2002, Week 5
June 2002, Week 4
June 2002, Week 3
June 2002, Week 2
June 2002, Week 1
May 2002, Week 5
May 2002, Week 4
May 2002, Week 3
May 2002, Week 2
May 2002, Week 1
April 2002, Week 5
April 2002, Week 4
April 2002, Week 3
April 2002, Week 2
April 2002, Week 1
March 2002, Week 5
March 2002, Week 4
March 2002, Week 3
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February 2002, Week 4
February 2002, Week 3
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February 2002, Week 1
January 2002, Week 5
January 2002, Week 4
January 2002, Week 3
January 2002, Week 2
January 2002, Week 1
December 2001, Week 5
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December 2001, Week 3
December 2001, Week 2
December 2001, Week 1
November 2001, Week 5
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November 2001, Week 3
November 2001, Week 2
November 2001, Week 1
October 2001, Week 5
October 2001, Week 4
October 2001, Week 3
October 2001, Week 2
October 2001, Week 1
September 2001, Week 5
September 2001, Week 4
September 2001, Week 3
September 2001, Week 2
September 2001, Week 1
August 2001, Week 5
August 2001, Week 4
August 2001, Week 3
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August 2001, Week 1
July 2001, Week 5
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July 2001, Week 1
June 2001, Week 5
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June 2001, Week 2
June 2001, Week 1
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May 2001, Week 2
May 2001, Week 1
April 2001, Week 5
April 2001, Week 4
April 2001, Week 3
April 2001, Week 2
April 2001, Week 1
March 2001, Week 5
March 2001, Week 4
March 2001, Week 3
March 2001, Week 2
March 2001, Week 1
February 2001, Week 4
February 2001, Week 3
February 2001, Week 2
February 2001, Week 1
January 2001, Week 5
January 2001, Week 4
January 2001, Week 3
January 2001, Week 2
January 2001, Week 1
December 2000, Week 5
December 2000, Week 4
December 2000, Week 3
December 2000, Week 2
December 2000, Week 1
November 2000, Week 5
November 2000, Week 4
November 2000, Week 3
November 2000, Week 2
November 2000, Week 1
October 2000, Week 5
October 2000, Week 4
October 2000, Week 3
October 2000, Week 2
October 2000, Week 1
September 2000, Week 5
September 2000, Week 4
September 2000, Week 3
September 2000, Week 2
September 2000, Week 1
August 2000, Week 5
August 2000, Week 4
August 2000, Week 3
August 2000, Week 2
August 2000, Week 1
July 2000, Week 5
July 2000, Week 4
July 2000, Week 3
July 2000, Week 2
July 2000, Week 1
June 2000, Week 5
June 2000, Week 4
June 2000, Week 3
June 2000, Week 2
June 2000, Week 1
May 2000, Week 5
May 2000, Week 4
May 2000, Week 3
May 2000, Week 2
May 2000, Week 1
April 2000, Week 5
April 2000, Week 4
April 2000, Week 3
April 2000, Week 2
April 2000, Week 1
March 2000, Week 5
March 2000, Week 4
March 2000, Week 3
March 2000, Week 2
March 2000, Week 1
February 2000, Week 5
February 2000, Week 4
February 2000, Week 3
February 2000, Week 2
February 2000, Week 1
January 2000, Week 5
January 2000, Week 4
January 2000, Week 3
January 2000, Week 2
January 2000, Week 1
December 1999, Week 5
December 1999, Week 4
December 1999, Week 3
December 1999, Week 2
December 1999, Week 1
November 1999, Week 5
November 1999, Week 4
November 1999, Week 3
November 1999, Week 2
November 1999, Week 1
October 1999, Week 5
October 1999, Week 4
October 1999, Week 3
October 1999, Week 2
October 1999, Week 1
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May 1999, Week 2
May 1999, Week 1
April 1999, Week 5
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April 1999, Week 3
April 1999, Week 2
April 1999, Week 1
March 1999, Week 5
March 1999, Week 4
March 1999, Week 3
March 1999, Week 2
March 1999, Week 1
February 1999, Week 4
February 1999, Week 3
February 1999, Week 2
February 1999, Week 1
January 1999, Week 5
January 1999, Week 4
January 1999, Week 3
January 1999, Week 2
January 1999, Week 1
December 1998, Week 5
December 1998, Week 4
December 1998, Week 3
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December 1998, Week 1
November 1998, Week 5
November 1998, Week 4
November 1998, Week 3
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November 1998, Week 1
October 1998, Week 5
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October 1998, Week 1
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May 1998, Week 1
April 1998, Week 5
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April 1998, Week 3
April 1998, Week 2
April 1998, Week 1
March 1998, Week 5
March 1998, Week 4
March 1998, Week 3
March 1998, Week 2
March 1998, Week 1
February 1998, Week 4
February 1998, Week 3
February 1998, Week 2
February 1998, Week 1
January 1998, Week 5
January 1998, Week 4
January 1998, Week 3
January 1998, Week 2
January 1998, Week 1
December 1997, Week 5
December 1997, Week 4
December 1997, Week 3
December 1997, Week 2
December 1997, Week 1
November 1997, Week 5
November 1997, Week 4
November 1997, Week 3
November 1997, Week 2
November 1997, Week 1
October 1997, Week 5
October 1997, Week 4
October 1997, Week 3
October 1997, Week 2
October 1997, Week 1
September 1997, Week 5
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September 1997, Week 3
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September 1997, Week 1
August 1997, Week 5
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August 1997, Week 1
July 1997, Week 5
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July 1997, Week 3
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May 1997, Week 5
May 1997, Week 4
May 1997, Week 3
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May 1997, Week 1
April 1997, Week 5
April 1997, Week 4
April 1997, Week 3
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April 1997, Week 1
March 1997, Week 5
March 1997, Week 4
March 1997, Week 3
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March 1997, Week 1
February 1997, Week 4
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February 1997, Week 1
January 1997, Week 5
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January 1997, Week 3
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January 1997, Week 1
December 1996, Week 5
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December 1996, Week 3
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April 1996, Week 1
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February 1996, Week 5
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February 1996, Week 1
January 1996, Week 5
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January 1996, Week 3
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January 1996, Week 1
December 1995, Week 5
December 1995, Week 4
December 1995, Week 3
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December 1994, Week 5
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