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Cephalosporin (1)
-lactum antibiotics containing 7aminocephalosporanic acid nucleus Classification: Based on antibacterial activity 1st generation- good activity against gram positive & relatively modest activity against gram negative
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Cephalosporin (2)
2nd generation- increased activity against gram negative 3rd generation- increased spectrum of activity against gram negative, but less active against gram positive than 1st generation 4th generation- extended spectrum of activity against gram positive & negative

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Cephalosporin (3)
Generation Example Cephalexin Cephalothin Cefuroxime Cefaclor Cefotaxime* Ceftriaxone Cefpodoxime proxetil* Cefepime Cefpirome
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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

First

Second

Third

Fourth

* Most active against gram positive organisms in the group

Cefpodoxime proxetil

CH3 COOCHOCOOCH(CH 3)2 O N

S H2N C CONH N OCH 3

CH2OCH 3

Methoxymethyl group improves the antibacterials activity against gram+ve bacteria and increases the GI stability.

Methoxymino group protects against hydrolysis by beta lactamases

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

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Spectrum of Activity (1)

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

Staphylococcus saphrophyticus
Streptococcus pneumoniae (excluding penicillinresistant) Streptococcus pyogenes
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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)

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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 Strep. pneumoniae Strep. agalactae H. influenzae 2 0.02 0.02 >0.12 0.25 32 0.13 0.13 0.28 0.25 8 0.25 0.25 32 16

Gram Negative Organisms

M. catarrhalis
K. pneumoniae

0.125
0.125
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0.06
0.5

1
8

Pharmacokinetics
Rapidly absorbed from GIT & de-esterified to its active metabolite, cefpodoxime Bioavailability 50% Cmax = 1.4 mcg/mL (100 mg) 2.3 mcg/mL (200 mg) 3.9 mcg/mL (400 mg) T1/2 = 2.09 to 2.84 Plasma Protein Binding = 21-29% Food enhances absorption
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Pharmacokinetics
Distribution: Skin-blister fluid: 200 mg BD for 5 days-mean maximum concentration 1.6 mcg/mL Tonsil tissue: 100 mg single dose-0.24 mcg/mL at 4 hrs & 0.09 mcg/mL at 7 hrs (exceed MIC90 for S. pyogenes) Lung tissue: 200 mg single oral dose- 0.63 mcg/mL at 3 hrs; 0.52 mcg/mL at 6 hrs & 0.19 at 12 hrs (exceed MIC90 for S. pneumoniae & H. influenzae)

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

Hepatic Failure: No dosage adjustment is recommended Elderly Patients: Do not require dosage adjustment if normal renal function

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

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Contraindications
Patients with known allergy to cefpodoxime or cephalosporin group Warnings: Allergy to penicillin group of antibiotics H/O severe antibacterial associated diarrhea
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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
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Drug Interactions
Antacids: High doses decreases absorption of cefpodoxime Probenecid: Decrease renal excretion of cefpodoxime

Nephrotoxic drugs: Close monitoring of renal function is advised

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Adverse Reactions
Well tolerated in various clinical trials using recommended dosage range (100400 mg BD)

Most were transient & mild to moderate in severity in clinical trials Diarrhea Nausea & Vomiting Abdominal pain
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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 / dose BD (Max:200 mg/dose) for 5-10 days
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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)

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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 Acute CAP AECB

200 mg 400 mg 400 mg

100 mg BD 200 mg BD 200 mg BD

5-10 14 10

Uncomplicated gonorrhea
SSTI Acute maxillary sinusitis Ucomplicated UTI
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200 mg Single dose

800 mg 400 mg 200 mg 400 mg BD 200 mg BD 100 mg BD 7-14 5 7

Application of Switch Therapy

Structural similarity to parenteral antibiotic, Ceftriaxone

Hospital-acquired pneumonia
Pneumonia caused by Gram-negative bacilli Sepsis of unknown origin Sepsis caused by Gram-negative bacilli Pyelonephritis Arthritis caused by Gram-negative bacilli

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J of Antimicrobial Chemotherapy1994;33:169-171

Step-Down therapy for Ceftriaxone

Similar spectrum of activity (Gram positive as well as gram negative) Reduces need for IV administration Early hospital discharge Reduces cost of therapy
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Clinical Trial

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Cefpodoxime Vs Cefixime in lower respiratory tract infections

Study design :
Prospective, open label, comparative, multicentric study

Mean age of recruitment :

6 months12 years, (10 years) with LRTIs

Drug intervention :
Cefpodoxime in 396 patients-5mg/kg Cefixime in 380 patients,-4 mg/kg
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Comparison of MIC of Cefpodoxime and Cefixime

MIC (mcg/mL )
H. influenza M. catarrhalis S. pneumoniae

Cefpodoxime
0.06-0.12 0.12-0.25 0.03
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Cefixime
0.06 0.12 0.25

Comparison of clinical out come

Cefpodoxime
Clinical out come

Cefixime

Cure
Improvement

61.3%
35.7%

43%
43.8%

Clinical success
Failure

97.0%
3.0% Bacterial out come

86.8%
13.2%

Eradication Failure

93.4% 6.6%
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82.9% 17.1%

Comparison of clinical out come

60% 50% 40% 30% 20% 10% 0% Excellent V.Good
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Physicians global assessment

Cefpodoxime cefixime

Good

Fair

Poor

Indian Journal of Pediatrics; Volume 71;2004

Comparison of clinical out come

60% 50% 40% 30% 20% 10% 0% Excellent V.Good
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Patients global assessment

Cefpodoxime cefixime

Good

Fair

Poor

Indian Journal of Pediatrics; Volume 71;2004

Cefpodoxime Vs Ceftriaxone in Community-acquired bronchopneumonia

Cefpodoxime Dose
Clinical cure Bacterial eradication

Ceftriaxone

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

98% 94.3% 95% 97.4%

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Zuck et al, 1990

Comparison of Cefpodoxime Vs Amoxicillin/Clavulanate

Study design :
Multicentric, randomized, double blind, clinical study

Recruitment for study :

229 children with acute Otitis media

Drug intervention:
Cefpodoxime proxetil -10mg/kg BD for 10 days Amoxicillin/clavulanate -40mg/10mg per kg TID for 10 days
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Bacteriological cure rate

Parameters Cefpodoxime Amoxicillin/ clavulanate

Cured Improved Failed Recurrence rate

68% 24% 8% 24%

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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

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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
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