Cephalosporins

Generation First Second Example Cephalexin Cephalothin Cefuroxime Cefaclor Cefotaxime* Ceftriaxone Cefpodoxime proxetil* Cefepime Cefpirome Spectrum Mostly gram positive Few gram negative Covers most gram negative Increased spectrum for gram negative Less active against gram positive Extended spectrum of activity

Third

Fourth

* Most active against gram positive organisms in the group

Cefpodoxime proxetil
3rd generation, extended spectrum, oral cephalosporins Prodrug- active metabolite is cefpodoxime Active against wide spectrum of gram positive & gram negative organisms Stable against many -lactamase producing organisms

Mechanism of Action
Inhibition of bacterial cell wall synthesis
Binds to PBPs & inhibits transpeptidation reaction involved in final step in synthesis of bacterial cell wall Also binds to the inhibitor of murein hydrolase which causes lysis of bacterial cell

Sales Training

Spectrum of Activity (1)

Aerobic Gram-Positive microorganisms: Staphylococcus aureus (including penicillinase producing & excluding MRSA)

Staphylococcus saphrophyticus
Streptococcus pneumoniae (excluding penicillinresistant) Streptococcus pyogenes
Sales Training

Spectrum of Activity (2)

Aerobic Gram-Negative microorganisms: Escherichia coli Klebsiella pneumoniae

Hemophilus influezae (including -lactamase producing)

Proteus mirabilis Moraxella (Branhamella) catarrhalis Neisseria gonorrhoeae ( including penicillinase producing)

Sales Training

Comparison of antibacterial activity of cefpodoxime

Organisms
Cefpodoxime
(MIC90 mcg/mL)

Cefixime
(MIC90 mcg/mL)

Cefaclor
(MIC90 mcg/mL)

Gram Positive Organisms Staph. aureus Strep. pyogenes 2 0.02 32 0.13 8 0.25

Strep. pneumoniae
Strep. agalactae H. influenzae

0.02
>0.12 0.25

0.13
0.28 0.25

0.25
32 16

Gram Negative Organisms

M. catarrhalis
K. pneumoniae

0.125
0.125
Sales Training

0.06
0.5

1
8

Pharmacokinetics
Rapidly absorbed from GIT & de-esterified to its active metabolite, cefpodoxime Bioavailability 50%

Food enhances absorption

Sales Training

Pharmacokinetics
Metabolism: Minimal metabolism of cefpodoxime Most drug excreted in urine as intact (29-33%) & metabolites Renal Failure: Elimination reduced in sever renal impairment
clearance <50 mL/min)

(Creatinine

Hepatic Failure: No dosage adjustment is recommended

Sales Training

Indications (1)
Treatment of infections caused by susceptible strains of microorganisms Acute otitis media Pharyngitis & Tonsillitis Community-acquired pneumonia Acute bacterial exacerbation of chronic bronchitis (AECB)
Sales Training

Indications (2)
Acute, uncomplicated ano-rectal infections in women
Uncomplicated skin & skin structure infections (SSTIs) Acute maxillary sinusitis

Uncomplicated urinary tract infections

Sales Training

Contraindications
Patients with known allergy to cefpodoxime or cephalosporin group Warnings: Allergy to penicillin group of antibiotics H/O severe antibacterial associated diarrhea
Sales Training

Precautions
Renal insufficiency Prolonged use Pregnancy & Lactation: Pregnancy category B Use only if clearly indicated Paediatric: Safety & efficacy not established in infants <2 months of age Elderly: No dose adjustment in patients with normal renal function
Sales Training

Drug Interactions
Antacids: High doses decreases absorption of cefpodoxime Probenecid: Decrease renal excretion of cefpodoxime

Nephrotoxic drugs: Close monitoring of renal function is advised

Sales Training

Adverse Reactions
Well tolerated in various clinical trials using recommended dosage range (100-400 mg BD)

Most were transient & mild to moderate in severity in clinical trials Diarrhea Nausea & Vomiting Abdominal pain
Sales Training

Dosage
Tablets administered with food to enhance absorption Suspension may be given without regard food

Adult & Adolescents (>12 yrs) 100-400 mg BD for 5-14 days Children (2 months to <12 yrs) 5 mg/kg BD (Max:200 mg/dose) for 5-10 days
Sales Training

Dosage Schedule
Children (2 months to <12 yrs)
Type of Infection Total daily dose (mg/kg/day) Frequency (mg/kg) Duration (Days)

Acute Otitis Media Pharyngitis &/or tonsilitis Acute maxillary sinusitis

10 (Max 400 mg/day) 10 (Max 200 mg/day) 10 (Max 400 mg/day)

Sales Training

5 BD (Max 200 mg/dose) 5 BD (Max 100 mg/dose) 5 BD (Max 200 mg/dose)

5-10

10

Adult & adolescents (>12 yrs)

Type of Infection Total daily dose Frequency Duration (Days)

Pharyngitis &/or tonsilitis

200 mg

100 mg BD

5-10

Acute CAP
AECB Uncomplicated gonorrhea SSTI Acute maxillary sinusitis Ucomplicated UTI

400 mg
400 mg

200 mg BD
200 mg BD

14
10

200 mg Single dose 800 mg 400 mg

Sales Training

400 mg BD 200 mg BD 100 mg BD

7-14 1 7

200 mg

Clinical Trials

Cefpodoxime Vs Cefixime in lower respiratory tract infections

Cefpodoxime
Clinical out come Cure Improvement Clinical success Failure 61.3% 35.7% 97.0% 3.0% Bacterial out come Eradication Failure 93.4% 6.6%
Sales Training

Cefixime
43% 43.8% 86.8% 13.2%

82.9% 17.1%

Cefpodoxime Vs Ceftriaxone in Communityacquired bronchopneumonia

Cefpodoxime

Ceftriaxone

Dose
Clinical cure

200 mg BD oral for 1 gm/day I.M. for 10 10 days days

98% 95%

Bacterial eradication

94.3%

97.4%

Sales Training

Zuck et al, 1990

Comparison of Cefpodoxime Vs Amoxicillin/Clavulanate

Parameters Cefpodoxime Amoxicillin/ clavulanate

Cured Improved Failed Recurrence rate

68% 24% 8% 24%

Sales Training

65% 23% 13% 25%

Clinical efficacy for Cefpodoxime proxetil b.i.d. is Equivalent to Amoxicillin/Clavulanate t.i.d. in AOM

Adverse events
40% 35% 30% 25% 20% 15% 10% 5% 0%

cefpodoxime Amoxycillin/cla vulanate

Pediatric pharmacology and therapeutics. J.Pediatr.1992

Sales Training

Conclusion
Cefpodoxime proxetil is well tolerated Superior alternative to other third generation cephalosporins Expanded spectrum of activity First line antimicrobial in pediatric patients of LRTIs
Sales Training