Cefodox® is a bactericidal cephalosporin antibiotic active against a wide range of Gram-negative and Gram-positive organisms. It is indicated for the treatment of the following infections either before the infecting organism has been identified or when caused by bacteria of established sensitivity.

Indications include:
Upper respiratory tract infections caused by organisms sensitive to cefpodoxime, including acute otitis media, sinusitis, tonsillitis and pharyngitis.

Cefodox® should be reserved for recurrent or chronic infections, or for infections where the causative organism is known or suspected to be resistant to commonly used antibiotics.

Lower respiratory tract infections caused by organisms sensitive to cefpodoxime. Including pneumonia, acute bronchitis and when bacterial super-infection complicates bronchiolitis.

Cefodox® for oral suspension may be given without regard to food. The recommended dosages, durations of treatment, and applicable patient populations are as described in the following chart:

Adults and Adolescents (age 12 years and older):

Infants and Pediatric Patients (age 2 months through 12 years):

Patients with Renal Dysfunction:

For patients with severe renal impairment (<30 mL/min creatinine clearance), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.
When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to estimate creatinine clearance (mL/min). For this estimate to be valid, the serum creatinine level should represent a steady state of renal function.

   Males:                                           Weight (kg) x (140 - age) 
   (mL/min)                                  72 x serum creatinine (mg/100 mL)

   Females:                                   0.85 x above value
   (mL/min)

Patients with Cirrhosis: Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population.

Instructions for Reconstitution:
Invert the bottle and shake powder loose. Add boiled and cooled water in two portions up to the mark indicated on the bottle; shake after each addition until a homogeneous suspension is achieved.

Preliminary enquiry about allergy to penicillin is necessary before prescribing cephalosporins since cross allergy to penicillins occurs in 5-10% of cases.

Particular care will be needed in patients sensitive to penicillin: strict medical surveillance is necessary from the very first administration. Where there is doubt, medical assistance should be available at the initial administration, in order to treat any anaphylactic episode.

In patients who are allergic to other cephalosporins, the possibility of cross allergy to Cefodox® should be borne in mind. Cefodox® should not be given to those patients with a previous history of immediate type hypersensitivity to cephalosporins.
Hypersensitivity reactions (anaphylaxis) observed with beta-lactam antibiotics can be serious and occasionally fatal.
The onset of any manifestation of hypersensitivity indicates that treatment should be stopped.
Cefodox® is not the preferred antibiotic for the treatment of staphylococcal pneumonia and should not be used in the treatment of atypical pneumonia caused by organisms such as Legionella, Mycoplasma and Chlamydia.
In cases of severe renal insufficiency it may be necessary to reduce the dosage regimen dependent on the creatinine clearance.
Antibiotics should always be prescribed with caution in patients with a history of gastrointestinal disease, particularly colitis. Cefodox® may induce diarrhea, antibiotic associated colitis and pseudomembranous colitis. These side-effects, which may occur more frequently in patients receiving higher doses for prolonged periods, should be considered as potentially serious. The presence of C. difficile should be investigated. In all potential cases of colitis, the treatment should be stopped immediately. The diagnosis should be confirmed by sigmoidoscopy and specific antibiotic therapy (vancomycin) substituted if considered clinically necessary. The administration of products which cause faecal stasis must be avoided. Although any antibiotic may cause pseudomembranous colitis, the risk may be higher with broad-spectrum drugs, such as the cephalosporins.

As with all beta-lactam antibiotics, neutropenia, and more rarely agranulocytosis may develop, particularly during extended treatment. For cases of treatment lasting longer than 10 days, blood count should therefore be monitored, and treatment discontinued if neutropenia is found.
Cephalosporins may be absorbed onto the surface of red cell membranes and react with antibiotics directed against the drug. This can produce a positive Coombs' test and very rarely, haemolytic anaemia. Cross-reactivity may occur with penicillin for this reaction.

The product should not be used in infants less than 15 days old as no clinical trial data in this age group yet exists.
Changes in renal function have been observed with antibiotics of the same class, particularly when given concurrently with potentially nephrotoxic drugs such as aminoglycosides and/or potent diuretics. In such cases, renal function should be monitored.
As with other antibiotics, the prolonged use of cefpodoxime proxetil may result in the overgrowth of non-susceptible organisms. With oral antibiotics the
normal colonic flora may be altered, allowing overgrowth by clostridia with consequent pseudomembranous colitis. Repeated evaluation of the patient is essential and if superinfection occurs during therapy, appropriate measures should be taken.
Patients with rare hereditary problems of galactose intolerance, fructose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

No clinically significant drug interactions have been reported during the course of clinical studies.
Histamine H2-antagonists and antacids reduce the bioavailibility of cefpodoxime. Probenecid reduces the excretion of cephalosporins. Cephlasporins potentially enhance the anticoagulant effect of coumarins and reduce the contraceptive effect of oestrogens.
As with other cephalosporins, isolated cases showing development of a positive Coombs' test have been reported (see Precautions).
Studies have shown that bioavailability is decreased by approximately 30% when Cefodox® is administered with drugs which neutralize gastric pH or inhibit acid secretions. Therefore, such drugs as antacids of the mineral type and H2 blockers such as ranitidine, which cause an increase in gastric pH, should be taken 2 or 3 hours after Cefodox® administration.
In contrast, drugs which decrease gastric pH such as pentagastrine will increase bioavailability. The clinical consequences remain to be established.
The bioavailability increases if the product is administered during meals.
A false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.

Not applicable since this Dosage form indicated for pediatric patients

Dizziness has been reported during treatment with cefpodoxime and may affect the ability to drive and use machines.

Adverse drug reactions are listed below by system organ class and frequency. Frequencies are defined as:
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000),
Not known (cannot be estimated from the available data)

In the event of overdosage with Cefodox®, supportive and symptomatic therapy is indicated.
In cases of overdosage, particularly in patients with renal insufficiency, encephalopathy may occur. The encephalopathy is usually reversible once cefpodoxime plasma levels have fallen.

Pharmacotherapeutic group: Other beta-lactam antibacterials, 3rd generation cephalosporins.

ATC Code: J01DD13

Mode of Action: Cefpodoxime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.

PK/PD relationship For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefpodoxime for individual target species (i.e. %T>MIC).

Mechanism(s) of resistance: Resistance to cephalosporins results from a variety of mechanisms:

1) alteration of the cell-wall permeability of gram-negative bacteria

2) alteration of the penicillin binding proteins (PBPs)

3) β-lactamase production

4) bacterial efflux pumps

Breakpoints: European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints for MIC testing are presented below. EUCAST clinical MIC breakpoints for cefpodoxime (2011-01-05, v 1.3)

1 Susceptibility of staphylococci to cephalosporins is inferred from the cefoxitin susceptibility.

2 The beta-lactam susceptibility of beta-haemolytic streptococcus groups A, B, C and G is inferred from the penicillin susceptibility.

3 Strains with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate must be sent to a reference laboratory.

*Insufficient evidence

Susceptibility: The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

$natural intermediate susceptibility

+Resistance rates >50% in at least 1 region

% ESBL producing species are always resistant

Cefodox® is taken up in the intestine and is hydrolysed to the active metabolite cefpodoxime. When cefpodoxime proxetil is administered orally to fasting subjects as a tablet corresponding to 100mg of cefpodoxime, 51.5% is absorbed and absorption is increased by food intake. The volume of distribution is 32.3 l and peak levels of cefpodoxime occur 2 to 3 hrs after dosing. The maximum plasma concentration is 1.2mg/l and 2.5mg/l after doses of 100mg and 200mg respectively. Following administration of 100mg and 200mg twice daily over 14.5 days, the plasma pharmacokinetic parameters of cefpodoxime remain unchanged.
Serum protein binding of cefpodoxime, 40% principally to albumin. This binding is non saturable in type.
Concentrations of cefpodoxime in excess of the minimum inhibitory levels (MIC) for common pathogens can be achieved in lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid and prostate tissue.
As the majority of cefpodoxime is eliminated in the urine, the concentration is high. (Concentrations in 0-4, 4-8, 8-12 hr fractions after a single dose exceed MIC90 of common urinary pathogens). Good diffusion of cefpodoxime is also seen into renal tissue, with concentrations above MIC90 of the common urinary pathogens, 3-12hrs after an administration of a single 200mg dose (1.6-3.1μG/G). Concentrations of cefpodoxime in the medullary and cortical tissues is similar.
Studies in healthy volunteers show median concentrations of cefpodoxime in the total ejaculate 6-12hrs following administration of a single 200mg dose to be above the MIC90 of N. gonorrhoeae.
The main route of excretion is renal, 80% is excreted unchanged in the urine, with an elimination half life of approx 2.4 hours.
CHILDREN
In children, studies have shown the maximum plasma concentration occurs approximately 2-4 hours after dosing. A single 5mg/kg dose in 4-12 year olds produced a maximum concentration similar to that in adults given a 200mg dose.
In patients below 2 years receiving repeated doses of 5mg/kg 12 hourly, the average plasma concentrations, 2hrs post dose, are between 2.7mg/l (1-6 months) and 2.0mg/l (7 months-2 years).
In patients between 1 month and 12 years receiving repeated doses of 5mg/kg 12 hourly, the residual plasma concentrations at steady state are between 0.2-0.3mg/l (1 month-2 years) and 0.1mg/l (2-12 years).

There are no findings from chronic toxicity investigations suggesting that any side effects unknown to date could occur in humans.
Furthermore, in vivo and in vitro studies did not yield any indication of a potential to cause reproductive toxicity or mutagenicity. Studies on carcinogenicity have not been conducted.

The product contains Hydroxy propyl cellulose, Microcrystalline cellulose, Maize starch, Sucrose, Citric acid, Colloidal silicon dioxide, Simethicone oil, Microcrystalline cellulose and Carboxymethyl cellulose, Sodium saccharin, Xanthan gum, Lemon powder flavor, artificial vanilla powder flavor.

None reported during clinical studies.

Store dry powder below 30°C.
The reconstituted suspension should be used within 14 days, and to be stored in the refrigerator (2-8°C).

Cefodox® Suspension 100mg/5ml Powder for Oral Suspensions are available in 100ml Amber glass bottles and come with a measuring spoon (10ml) & a Child resistant cap. The bottle contains powder to be mixed with water, to form a Lemon flavoured medicine ready for use.

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