Cefpodoxime (as cefpodoxime proxetil) ................. 100 mg
Excipients q.s …………………………………….. 1 tablet
Film coated tablet.
Product description
A capsule-shaped, brownish-red, film-coated tablet, scored on one side and imprinted with DHG on the other side with undamaged edges.
Box of 2 blisters x 10 film coated tablets.
Pharmacotherapeutic group: The third generation cephalosporins, ATC code: J01DD13.
Nifin 100 Tabs contains the active ingredient Cefpodoxime proxetil, which is a semi-synthetic beta-lactam antibiotic, belonging to the class of 3rd generation oral cephalosporins. It is the prodrug of cefpodoxime.
Orally-administered cefpodoxime proxetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases into cefpodoxime, a bactericidal antibiotic.
The mechanism of action of cefpodoxime is based on the inhibition of bacterial cell wall synthesis. Cefpodoxime is stable in the presence of beta-lactamase enzymes.
SPECTRUM OF ANTIBACTERIAL ACTIVITY
The breakpoints differentiating susceptible strains from intermediate strains, and the latter from resistant strains are as follows: S ≤ 1 mg/l and R > 2 mg/l.
The prevalence of acquired resistance in certain species can vary geographically and over time. It is therefore useful to have information on the prevalence of local resistance, especially when treating severe infections. These data are only guidelines indicating the probability of susceptibility of a bacterial strain to this antibiotic.
SUSCEPTIBLE SPECIES
Gram-positive aerobes: Corynebacterium diphtheriae, Streptococcus, Streptococcus pneumoniae.
Gram-negative aerobes: Branhamella catarrhalis, Citrobacter koseri, Escherichia coli, Haemophilus influenzae, Klebsiella, Neisseria gonorrhoeae, Pasteurella, Proteus mirabilis, Proteus vulgaris, Providencia.
Anaerobes: Fusobacterium, Prevotella, Propionibacterium acnes.
INTERMEDIATELY SUSCEPTIBLE SPECIES
(intermediate susceptibility in vitro)
Gram-positive aerobes: Methicillin-susceptible Staphylococcus.
RESISTANT SPECIES
Gram-positive aerobes: Enterococci, Listeria monocytogenes, methicillin-resistant Staphylococcus*
Gram-negative aerobes: Acinetobacter, Citrobacter freundii, Enterobacter, Morganella morganii, Pseudomonas, Serratia.
Anaerobes: Bacteroides fragilis, Clostridium, Peptostreptococcus.
* The prevalence of methicillin resistance is approximately 30% to 50% for all staphylococci and is mainly found in a hospital setting.
Absorption
In a tablet containing 100 mg of cefpodoxime proxetil, 40% to 50% of its active ingredient, cefpodoxime, is absorbed when administered orally to a fasting patient.
As absorption of the medicinal product is increased when taken with food, it should preferably be taken during meals.
Distribution
- Plasma concentrations:
+ Following oral administration of a single dose of 100 mg, peak plasma concentrations of cefpodoxime (Cmax) are 1 mg/l to 1.2 mg/l. After administration of a 200 mg dose, peak plasma concentrations are 2.2 - 2.5 mg/l. In both cases (100 mg or 200 mg), they are reached (Tmax) within 2 to 3 hours.
+ Residual concentrations after 12 hours are 0.08 mg/l after administration of 100 mg and 0.18 mg/l for 200 mg.
+ After administration of 100 mg to 200 mg, twice daily for 14.5 days, the plasma pharmacokinetic parameters of cefpodoxime remain unchanged, showing that there is no accumulation of the active substance.
- The volume of distribution of cefpodoxime is 30 - 35 l in young healthy patients (= 0.43 l/kg).
- Plasma protein binding: Cefpodoxime is approximately 40% bound to plasma proteins, primarily to albumin. This binding is non-saturable.
- Humoral and tissue distribution:
+ Cefpodoxime is well distributed in the lung parenchyma, bronchial mucosa, pleural fluid, tonsils, and interstitial fluid.
+ 4 to 7 hours after a single 100 mg dose, concentrations in the tonsils are 0.24 to 0.1 µg/g (20% to 25% of plasma concentrations).
+ After a single 200 mg dose, cefpodoxime concentrations in the interstitial fluid are 1.5 to 2.0 mg/l (80% of plasma concentrations).
+ 3 to 12 hours after a single 200 mg dose, cefpodoxime concentrations are 0.6 to 0.2 µg/g in the lung and 0.6 to 0.8 mg/l in the pleura.
+ In the bronchial mucosa, between 1 and 4 hours after administration of 200 mg, cefpodoxime concentrations are about 1 µg/g (40% to 45% of plasma concentrations).
+ The concentrations measured are higher than the MICs of susceptible microorganisms.
Metabolism and elimination
- Following absorption of the medicinal product, the main metabolite is cefpodoxime, resulting from hydrolysis of cefpodoxime proxetil.
- Cefpodoxime is very poorly metabolized.
- Following absorption of cefpodoxime proxetil, 80% of the cefpodoxime released is excreted unchanged in the urine.
- The mean elimination half-life of cefpodoxime is 2.4 hours.
At-risk patients
The pharmacokinetic parameters of cefpodoxime are very slightly changed in elderly patients with normal renal function.
However, the minor increase in peak plasma concentrations and elimination half-life does not warrant a dose reduction in this population, except in patients with a renal clearance of less than 40 ml/min.
In patients with renal failure in whom creatinine clearance is less than 40 ml/min, the increase in plasma elimination half-life and peak plasma concentrations makes it necessary to reduce the dose by half and administer it as a single daily dose.
In patients with liver failure, the minor pharmacokinetic changes observed do not warrant any specific dose adjustment.
If adverse effects occur, such as dizziness or encephalopathy (which can include seizure, confusion, consciousness disorders, or abnormal movements) (see sections Special warnings and precautions for use; Undesirable effects; Overdose), patients should not drive or use machines.
Pregnancy
Due to the expected benefit, the use of cefpodoxime may be considered during pregnancy if necessary, despite insufficient clinical and animal data.
Lactation
Excretion in breast milk is low and the amounts ingested by the infant are far lower than therapeutic doses. Consequently, breast-feeding is possible during the use of this antibiotic.
However, breast-feeding (or the medicinal product) should be discontinued if diarrhea, candidiasis, or skin eruption occurs in the infant.
INTERACTIONS
Food
A study has shown that whatever the nature of the meal, the bioavailability of cefpodoxime is increased when the product is administered during the meal.
Gastric pH changes
Increased gastric pH: H2 antagonists (ranitidine) and antacids (aluminum hydroxide, sodium bicarbonate) lead to reduced bioavailability.
Conversely, reduced gastric pH (pentagastrin) induces an increase in bioavailability.
The clinical implications of these effects have yet to be determined.
Specific problems of INR imbalance
Numerous cases of increased oral anticoagulant activity have been reported in patients receiving antibiotics. The severity of the infection or inflammation, age, and general health status of the patient appear to be risk factors. Under these circumstances, it seems difficult to determine to what extent the infection itself or its treatment play a role in the INR imbalance. However, certain classes of antibiotics are more involved, particularly fluoroquinolones, macrolides, cyclines, cotrimoxazole and certain cephalosporins.
INCOMPATIBILITIES: Not applicable.
Frequencies were defined using the following criteria: 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 (frequency cannot be estimated from the available data).
Blood and lymphatic system disorders
Uncommon: neutropenia.
Rare: thrombocytosis, leukopenia.
Not known: agranulocytosis, eosinophilia, thrombocytopenia, hemolytic anemia.
Ear and labyrinth disorders
Common: tinnitus.
Gastrointestinal disorders
Very common: abdominal pain, diarrhea.
Common: nausea, vomiting.
Uncommon: enterocolitis.
Not known: haematochezia, pseudomembranous colitis, Clostridium difficile colitis.
General disorders and administration site conditions
Not known: malaise, asthenia.
Hepatobiliary disorders
Common: elevation of AST (aspartate aminotransferase), elevation of ALT (alanine aminotransferase), elevation of alkaline phosphatase.
Not known: increased blood bilirubin, hepatic damage, hepatic cholestatic damage.
Immune system disorders
Uncommon: anaphylactic reactions, bronchospasm.
Not known: anaphylactic shock, angioedema.
Infections and infestations
Not known: superinfection.
Nervous system disorders
Very common: headache.
Common: dizziness.
Not known: paresthesia.
Beta-lactam antibiotics, including cefpodoxime, predispose patients to encephalopathy (which can include seizure, confusion, consciousness disorders, or abnormal movements), particularly if they have had an overdose or if they have renal failure.
Skin and subcutaneous tissue disorders
Common: rash, pruritus, urticaria.
Not known: purpura, dermatitis bullous, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).
Renal and urinary tract disorders
Rare: slight increase in blood urea and serum creatinine.
Not known: Renal impairment has been reported with antibiotics belonging to the same therapeutic class as cefpodoxime, especially when combined with strong aminoglycosides and/or diuretics.
Please inform your doctor of all undesirable effects upon drug administration.
Beta-lactam antibiotics, including cefpodoxime, predispose patients to encephalopathy, particularly if they have had an overdose or renal failure.
Store in dry places, not exceeding 30oC, protect from light.
24 months from the manufacturing date.
Special warnings
- Treatment must be discontinued if any signs of allergy occur.
- Before prescribing cephalosporins, patient history should be investigated, due to the 5 - 10% occurrence of cross-allergy between penicillins and cephalosporins:
+ Extreme caution should be exercised when administering cephalosporins in penicillin-sensitive patients: strict medical monitoring is necessary as of the first dose.
+ Use of cephalosporins is contraindicated in patients with a history of immediate allergy to cephalosporins. If in doubt, patients should consult a doctor for the first dose in order to avoid possible anaphylactic shock.
- Hypersensitivity reactions (anaphylaxis) observed with these two types of beta-lactam antibiotics can be serious and occasionally fatal.
+ The occurrence of an episode of diarrhea may, in exceptional cases, be symptomatic of pseudomembranous colitis, diagnosis of which is based on colonoscopy.
- Although rare with cephalosporins, if this event occurs, treatment must be immediately discontinued, and appropriate specific antibiotic therapy (vancomycin) instituted. In this case, administration of drugs promoting fecal stasis must be avoided.
Blood disorders
As with other beta-lactam antibiotics, neutropenia and more rarely agranulocytosis may develop during treatment with cefpodoxime, especially if the treatment is prolonged. In this case, haematological monitoring should be considered.
Bullous eruptions
As with other cephalosporins, cases of bullous eruptions (erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome) have been reported. If damage to the skin and/or mucous membranes occurs, patients should contact their doctor immediately before continuing treatment.
Superinfection
As with other antibiotics, administration of cefpodoxime, especially if treatment is prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during treatment, appropriate measures should be taken.
Encephalopathy
Beta-lactam antibiotics, including cefpodoxime, predispose patients to encephalopathy (which can include seizure, confusion, consciousness disorders, or abnormal movements), particularly if they have had an overdose or if they have impaired renal function.
Precautions for use
In patients who are allergic to other beta-lactam antibiotics, the possibility of cross-allergy should be taken into account.
In patients with severe renal failure, it may be necessary to adjust the daily dose based on creatinine clearance (see section “at-risk patients” and see section Posology and method of administration).
As with other broad-spectrum antibiotics, long-term use of cefpodoxime proxetil may result in overgrowth of non-susceptible organisms, which may require treatment discontinuation.
Interactions with laboratory tests
Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibiotics.
A false positive reaction for glucose in the urine may occur with reducing substances, but not when glucose oxidase methods are used.
Excipients
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, that is to say essentially "sodium-free".
The therapeutic indications of cefpodoxime are based on its antibacterial activity and pharmacokinetic properties.
In adults, they are limited to the treatment of infections due to susceptible bacteria, in particular:
- Documented group A beta-hemolytic streptococcal pharyngitis,
- Acute sinusitis,
- Acute bronchitis in at-risk patients (particularly alcoholics, smokers, patients over 65 years of age, etc.),
- Exacerbations of chronic obstructive pulmonary disease, particularly in repeated repeat episodes or in at-risk patients,
- Bacterial pneumonia, particularly in at-risk patients.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Hypersensitivity to the active substance or to any of the excipients.
Known allergy to cephalosporin antibiotics.
Previous severe hypersensitivity reaction to a penicillin or to any other type of beta-lactam drug.
METHOD OF ADMINISTRATION
For oral administration.
POSOLOGY
Adults
200 mg or 400 mg per day in 2 divided doses, every 12 hours during meals:
- 200 mg twice per day, i.e. 2 tablets to be taken in the morning and evening for:
+ acute sinusitis.
In acute maxillary sinusitis, a 5-day treatment has been shown to be effective.
+ acute bronchitis in at-risk patients.
+ exacerbations of chronic obstructive pulmonary disease, particularly in repeated episodes or in at-risk patients.
+ bacterial lung diseases, particularly in at-risk patients.
- 100 mg twice per day, i.e. 1 tablet to be taken in the morning and evening for tonsillitis.
The duration of treatment for tonsillitis is 5 days.
The elderly
No dose adjustment is required in the elderly with normal renal function.
Patients with kidney failure
No dose adjustment is required if creatinine clearance is over 40 ml/min.
If creatinine clearance is below 40 ml/min, the daily dose should be halved and limited to one single daily dose.
Patients with liver failure
No dose adjustment is required.
Or as directed by the physician.
Register an account - receive thousands of information
You will be one of the first to receive information, news, recruitment news... from Hau Giang Pharmaceutical as soon as possible. Register today to enjoy thousands of incentives from Hau Giang Pharmaceutical.
