Meiact

Cefditoren pivoxil.

100 mg tablet: Each tablet of MEIACT Tablets 100 contains the following active ingredient: Cefditoren pivoxil 100 mg (potency).
200 mg tablet: Each film-coated tablet contains 200 mg of cefditoren equivalent to 245.1 mg of cefditoren pivoxil.
Fine granules for oral susp: One gram of MEIACT Fine Granules contains the following active ingredient: Cefditoren pivoxil 100 mg (potency).
Excipients/Inactive Ingredients: 200 mg tablet: Core: Sodium caseinate, Sodium croscarmellose, Mannitol E421, Sodium tripolyphosphate, Magnesium stearate.
Tablet coating: Opadry Y-1-7000 containing: Hypromellose, Titanium dioxide E171, Macrogol 400; Carnauba wax.
Printing Ink: OPACODE S-1-205000 blue including: Shellac glaze, Brilliant blue lacquer, Titanium dioxide E171, Propylene glycol, Concentrated ammonia solution.

Pharmacotherapeutic group: Cephalosporins and related substances. ATC code: J01DA.
Pharmacology: 100 mg tablet and Fine granules for oral susp: Antibacterial activity: Cefditoren pivoxil is metabolized into cefditoren upon absorption from the intestinal wall and shows its antibacterial activity.
Cefditoren exerts antibacterial activity in vitro against a wide spectrum of gram-positive and gram-negative bacteria. Its activity against gram-positive bacteria including Staphylococcus sp. and Streptococcus sp. such as Streptococcus pneumoniae as well as against gram-negative bacteria including E. coli, B. catarrhalis, Klebsiella sp., Proteus sp. and H. influenzae and anaerobic bacteria including Peptostreptococcus sp., P. acnes and Bacteroides sp., is particularly noteworthy.
In vitro, cefditoren was stable to β-lactamase produced by various bacteria. It also shows strong antibacterial activity against strains that produce β-lactamase.
Mechanism of action: Cefditoren inhibits the synthesis of bacterial cell wall. It has high affinity to penicillin binding proteins (PBPs) in various bacteria, showing a bactericidal effect.
Therapeutic efficacy on experimental infections: Cefditoren pivoxil demonstrated excellent therapeutic efficacy on experimental infections by Staphylococcus aureus, S. pneumoniae, E. coli, Klebsiella pneumoniae and Proteus sp., in mice. Its therapeutic efficacy on the infections by β-lactamase - producing strains was equivalent or superior to similar drugs.
Pharmacodynamics: 200 mg tablet: Mode of action: Cefditoren exerts its antibacterial action by inhibiting bacterial cell wall synthesis due to its affinity for penicillin-binding proteins (PBPs).
Pharmacokinetic/Pharmacodynamic relationship: With a dosage of 200 mg twice daily, plasma concentrations exceed the minimum inhibitory concentrations (MIC₉₀) for Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pyogenes and penicillin-susceptible Streptococcus pneumoniae strains for at least 50% of the dose interval. The dosage of 400 mg twice daily, also provides a time above the minimum inhibitory concentrations which is enough to exceed the MIC₉₀ of Streptococcus pneumoniae resistant to penicillin.
Mechanisms of resistance: Bacterial resistance to cefditoren may be due to one or more of the following mechanisms: Hydrolysis by beta-lactamases. Cefditoren may be efficiently hydrolysed by certain of the extended-spectrum beta-lactamases (ESBLs) and by the chromosomally encoded (AmpC) beta-lactamases that may be induced or stably derepressed in certain aerobic gram-negative bacterial species.
Reduced affinity of penicillin-binding proteins for cefditoren.
Outer membrane impermeability, which restricts access of cefditoren to penicillin-binding proteins in gram-negative organisms.
Active substance efflux pumps.
More than one of these mechanisms of resistance may co-exist in a single bacterial cell. Depending on the mechanism(s) present, bacteria may express cross-resistance to several or all other beta-lactams and/or antibacterial active substances of other families.
Gram-negative micro-organisms containing inducible chromosomally encoded beta-lactamases, like Enterobacter spp., Serratia spp., Citrobacter spp., and Providencia spp., should be regarded as resistant for cefditoren pivoxil in spite of apparent in vitro susceptibility.
Breakpoints: The recommended MIC breakpoints for cefditoren, which allow susceptible micro-organisms to be distinguished from intermediately susceptible micro-organisms, and intermediately susceptible organisms from resistant micro-organisms are: Susceptible ≤ 0.5 µg/ml, Resistant ≥ 2 µg/ml (or > 1 µg/ml according to recent criteria).
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. (See Table 1.)

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Clinical Studies: Fine granules for oral susp: Clinical results of MEIACT granules, that has been confirmed to be bioequivalent to this product, were as follows. Clinical trials were conducted in medical institutions nationwide to investigate the efficacy of MEIACT granules. The results obtained in 443 patients treated with this product are summarized as follows: Superficial suppurative diseases: The efficacy rate was 93.1% (54/58) in patients with impetigo contagiosa, phlegmon, lymphadenitis (lymphangitis), suppurative perionychia (paronychia) and subcutaneous abscess.
Infections in surgical fields: The efficacy rate was 100% (1/1) in a patient with perianal abscess.
Respiratory tract infections: The efficacy rate was 97.9% (277/283) in patients with pharyngolaryngitis (throat abscess), acute bronchitis, tonsillitis (peritonsillitis, peritonsillar abscess) and pneumonia.
Urinary tract infections: The efficacy rate was 94.6% (35/37) in patients with urinary tract infections (pyelonephritis and cystitis).
Scarlet fever: The efficacy rate was 100% (36/36) in patients with scarlet fever.
Pertussis: The efficacy rate was 100% (11/11) in patients with pertussis.
Otorhinologic infections: The efficacy rate was 100% (18/18) in patients with otitis media and sinusitis.
Pharmacokinetics: Absorption and Distribution: Blood concentration: 100 mg tablet: The serum concentrations (Figure 1) and pharmacokinetic parameters (Table 2) of Cefditoren after oral administration of 100 or 200 mg to healthy adults after meals demonstrated dose dependency. Absorption was better when administered after meals than when given at fasting. (See Figure 1 and Table 2.)

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Fine granules: When cefditoren was orally administered to pediatric patients with normal renal function at doses of 3 mg/kg or 6 mg/kg after meals, the serum concentrations (Figure 2) and pharmacokinetic parameters (Table 3) of cefditoren demonstrated dose dependency. (See Figure 2 and Table 3.)

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Body fluid and tissue concentrations: 100 mg tablet: The drug transferred to the sputum, tonsillar tissue, mucous membrane of maxillary sinus, skin tissue, mammary gland tissue, gallbladder tissue, vagina, uterine neck, tarsal gland tissue and wound after tooth extraction. No transfer to the milk was noted.
Fine granules: The drug transferred to the sputum, tonsillar tissue, mucous membrane of maxillary sinus and skin tissue of patients.
Protein binding: 100 mg tablet and Fine granules for oral susp: In vitro, binding rate to human serum protein determined by ultrafiltration method was 91.5% at concentration of 25 μg/mL.
Metabolism and excretion: 100 mg tablet: Cefditoren pivoxil is metabolized upon absorption and becomes cefditoren which has antibacterial activity, and pivalic acid. Pivalic acid is conjugated with carnitine and excreted into urine as pivaloyl carnitine. Cefditoren is hardly metabolized and is excreted mainly into urine and bile.
100 mg tablet: The urinary excretion rate (0-24 hours) of cefditoren upon oral administration after meals at doses of 100 mg and 200 mg to healthy adults was about 20%. No accumulation of the drug was observed after continuous administration (200 mg x 3 times/day, for 8 days).
Fine granules for oral susp: The urinary excretion rate (0-8 hours) of cefditoren upon oral administration after meals at doses of 3 and 6 mg/kg to pediatric patients with normal renal function were about 20 and 17%, respectively.
Serum concentration and urinary excretion in patients with renal function disorder: 100 mg tablet and Fine granules for oral susp: The serum concentrations (Figure 3) and pharmacokinetic parameters (Table 4) of cefditoren are as follows. Oral administration of 200 mg to adult patients with renal function disorder or to those receiving artificial dialysis after meals demonstrated higher levels in all the cases, showing delay in T_½ in parallel with degree of renal function disorder. (See Figure 3 and Table 4.)

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Urinary excretion rate lowered in parallel with degree of renal function disorder, showing delay in excretion.
200 mg tablet: Absorption: Following oral administration, cefditoren pivoxil is absorbed in the gastrointestinal tract and is hydrolysed to cefditoren by the action of esterases. The absolute bioavailability of orally administered cefditoren is approximately 15-20%.
The presence of food in the gastrointestinal tract increases the absorption of cefditoren pivoxil, with the C_max and the AUC approximately 50% and 70% higher compared to fasting values.
A 200 mg dose administered with food gives a mean C_max of 2.6 µg/ml after approximately 2.5 hours, while a 400 mg dose gives a mean C_max value of 4.1 µg/ml in approximately the same time period.
Distribution: Plasma protein binding to cefditoren is 88%.
The volume of distribution at steady state is not significantly different from that calculated after a single dose administration and is relatively independent of the administered dose (40-65 litres).
After a single dose administration of 400 mg, penetration in bronchial mucosa and in bronchial secretion was 60% and 20% respectively of the plasma concentration. After the same dose, cefditoren concentrations in skin blister fluid reached 40% and 56% of plasma AUC after 8 and 12 hours, respectively.
Metabolism/Elimination: Following multiple dose administration, pharmacokinetic parameters were similar to those obtained after single dose administration, with no accumulation detected.
Up to 18% of the administered dose of cefditoren is recovered by excretion in urine without being metabolised.
The plasma elimination half-life of cefditoren is between 1 and 1.5 hours. Total clearance adjusted for bioavailability is from 25-30 l/h, while renal clearance is approximately 80-90 ml/min. Studies with labelled cefditoren in healthy volunteers suggest that the non-absorbed fraction is eliminated in faeces, where the majority of the administered cefditoren appears as inactive metabolites.
Cefditoren pivoxil is not detected in faecal extracts or in urine. The pivalate portion is eliminated through renal excretion as the conjugated pivaloylcarnitine.
Special populations: Gender: Pharmacokinetics of cefditoren pivoxil do not show clinically relevant differences between males and females.
Elderly: Plasma levels of cefditoren in elderly subjects (over 65 years) show C_max and AUC that are approximately 26% and 33% higher than in younger adults. However, no dose adjustment is required except in cases of advanced hepatic and/or renal insufficiency.
Renal insufficiency: After multiple doses of cefditoren pivoxil 400 mg to patients with moderate to severe renal impairment, C_max was 2-fold and AUC between 2.5 and 3-fold than those observed in normal healthy volunteers (see Dosage & Administration). There are no data available for patients undergoing dialysis.
Hepatic insufficiency: In mild hepatic insufficiency (Child-Pugh A) to moderate hepatic insufficiency (Child-Pugh B), multiple doses of 400 mg cefditoren pivoxil gave a slight increase in pharmacokinetic parameters compared to normal subjects. No data are available in patients with severe insufficiency (Child-Pugh C) (See Dosage & Administration).
Toxicology: Preclinical safety data: 200 mg tablet: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction.
Studies to evaluate the carcinogenic potential of cefditoren pivoxil have not been performed.

100 mg tablet and Fine granules for oral susp: The following infections caused by cefditoren-susceptible strains of Staphylococcus sp., Streptococcus sp., Peptostreptococcus sp., Branhamella catarrhalis, Propionibacterium acnes, Escherichia coli, Citrobacter sp., Klebsiella sp., Enterobacter sp., Serratia sp., Proteus sp. (Proteus mirabilis, Proteus vulgaris), Morganella sp., Providencia sp., Haemophilus influenzae, Bacteroides sp., and Bordetella pertussis (for Fine granules for oral susp only): Otitis media, sinusitis.
Superficial secondary infection in trauma, surgical wound, etc.
Folliculitis, furuncle, furunculosis, carbuncle, impetigo, contagiosa, erysipelas, phlegmon, lymphangitis (lymphadenitis), suppurative perionychia (paronychia), subcutaneous abscess, infectious atheroma.
100 mg tablet and 200 mg tablet: Pyelonephritis, cystitis.
100 mg tablet: Pharyngolaryngitis (throat abscess), acute bronchitis, tonsillitis (peritonsillitis, peritonsillar abscess), chronic bronchitis, bronchiectasis with infection, secondary infection in chronic respiratory disease, pneumonia, pulmonary suppuration.
Urinary tract infections (pyelonephritis, cystitis).
Fine granules for oral susp: Pharyngolaryngitis (throat abscess), acute bronchitis, tonsillitis (peritonsillitis, peritonsillar abscess), pneumonia.
Scarlet fever.
Pertussis.
200 mg tablet: MEIACT is indicated for the treatment of the following infections caused by susceptible microorganisms (see Pharmacology: Pharmacodynamics under Actions): Acute pharyngo-tonsillitis; Acute maxillary sinusitis; Acute exacerbations of chronic bronchitis; Community-acquired pneumonia, mild to moderate; Uncomplicated skin and skin structure infections, such as cellulitis, infected wounds, abscesses, folliculitis, impetigo and boils.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

100 mg tablet: In case of adults, cefditoren pivoxil is usually orally administered at a dose of 100 mg (potency) 3 times a day, after meals. The daily dose may be adjusted according to the patient's age and symptoms. A dose of 200 mg (potency) is orally administered 3 times a day after meals to patients with severe infections or to those for whom the usual dosage may be insufficient.
The dosage in the treatment of lower urinary tract infection or for switch therapy of urinary tract infection following clinical response with intravenous cephalosporins is 400 mg once.
200 mg tablet: The recommended dosage depends on the severity of the infection, the basal condition of the patient and the potential micro-organisms involved.
Method of Administration: Tablets should be swallowed whole with a sufficient quantity of water. Tablets should be taken with meals.
Posology: Adults and adolescents (over 12 years): Acute pharyngo-tonsillitis: 200 mg cefditoren every 12 hours for 10 days.
Acute maxillary sinusitis: 200 mg cefditoren every 12 hours for 10 days.
Acute exacerbations of chronic bronchitis: 200 mg cefditoren every 12 hours for 5 days.
Community-acquired pneumonia: In mild cases: 200 mg cefditoren every 12 hours for 14 days; In moderate cases: 400 mg cefditoren every 12 hours for 14 days.
Uncomplicated skin and skin structure infections: 200 mg cefditoren every 12 hours for 10 days.
Pyelonephritis, cystitis: The dosage in the treatment of lower urinary tract infection or for switch therapy of urinary tract infection following clinical response with intravenous cephalosporins is 400 mg once daily after meal.
Children under 12 years: MEIACT is not recommended for use in children under 12 years. The experience in children is limited.
Elderly: No dose adjustments are necessary for elderly patients, except in the case of severe renal and/or hepatic function impairment.
Renal insufficiency: No dose adjustment is necessary for patients with mild renal impairment. In patients with moderate renal insufficiency (creatinine clearance 30-50 ml/min), the total daily dose should not exceed 200 mg cefditoren every 12 hours. In patients with severe renal insufficiency (creatinine clearance < 30 ml/min), it is recommended a single dose of 200 mg cefditoren once a day. The recommended dose has not been determined in patients undergoing dialysis (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Hepatic insufficiency: No dose adjustments are necessary for patients with mild hepatic insufficiency (Child-Pugh A) to moderate hepatic insufficiency (Child-Pugh B). In the case of severe hepatic insufficiency (Child-Pugh C), there are no data available that would allow a recommended dose to be established (see Pharmacology: Pharmacokinetics under Actions).
Fine granules: In case of children, cefditoren pivoxil is usually administered at a single oral dose of 9-18 mg (potency)/kg, divided to 2-3 times a day, after meals. The daily dose should be adjusted according to the age of patients and severity of symptoms. (See Table 5.)

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200 mg tablet: No case of overdose has been reported.
Symptoms of overdose reported for other cephalosporin antibiotics are cerebral irritancy leading to convulsions. In case of overdose, gastric lavage should be performed. The patient should be closely monitored and given the proper symptomatic and support treatment.
Cefditoren pivoxil can be partially eliminated through hemodialysis.

100 mg tablet: Patients with a history of anaphylactic shock due to any of the ingredients of the product.
Relative Contraindications: Patients with a history of hypersensitivity to any of the ingredients of the product or other cephem antibiotics. If the use of MEIACT Tablets 100 is considered essential, it should be administered with care.
200 mg tablet: Patients with a history of hypersensitivity to any of the ingredients contained in this product.
Hypersensitivity to the active substance cefditoren, to any other cephalosporin or to any of the excipients. For patients who are hypersensitive to casein, it should be noted that the medicinal product contains sodium caseinate.
Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other type of beta-lactam active substance.
As with other pivalate-producing compounds, cefditoren pivoxil is contraindicated in cases of primary carnitine deficiency.

200 mg tablet: Contraindicated in patients hypersensitive to this drug.
Using this drug in penicillin-allergic patients may cause a severe allergic reaction possibly leading to death.
If any of the following symptoms occurs after using this drug, e.g. fever, rashes, blisters, skin peeling, stomatitis, pharyngitis, rhinitis, conjunctivitis, genital inflammation, stop using and consult the physician or pharmacist.

100 mg tablet and Fine granules for oral susp: Careful administration (MEIACT should be administered with care in the following patients): Patients with a history of hypersensitivity to penicillins.
Patients with a personal or familial predisposition to allergic symptoms such as bronchial asthma, exanthema or urticaria.
Patients with severely impaired renal function [Serum concentration persists. (See Pharmacology: Pharmacokinetics under Actions.)]
Patients with poor oral food intake or who are receiving parenteral alimentation, and patients in poor general health (Patients should be observed carefully because vitamin K deficiency may develop).
100 mg tablet: As a general rule, the duration of administration of this drug should be limited to the minimum period required for the treatment of the patient's condition, after susceptibility of the microorganism to the drug has been confirmed, in order to prevent the emergence of drug-resistant microorganisms.
In patients with severely impaired renal function, the administration interval should be prolonged (see "careful administration" as previously mentioned and Pharmacology: Pharmacokinetics under Actions).
100 mg tablet and Fine granules for oral susp: Important Precautions: The patient should be carefully interviewed to assess the risk of shock.
Effects on Laboratory Tests: False-positive results may occur in urine glucose tests with Benedict's solution, Fehling's solution and Clinitest, but not with Tes-Tape.
Positive results may occur in the direct Coombs' test. Caution is required.
Other Precautions: 100 mg tablet: It has been reported that this product decreases serum carnitine.
Fine granules for oral susp: Since this product has been reported to reduce serum carnitine level, it is recommended to use the product in children for not more than 2 weeks.
200 mg tablet: Before therapy with cefditoren is instituted, careful inquiry should be made to determine whether the patient has had any previous hypersensitivity reactions to cefditoren, cephalosporins, penicillins, or other beta-lactam active substances.
Cefditoren should be given with caution to patients who have had any other type of hypersensitivity reaction to a penicillin or any other beta-lactam active substance.
Antibiotic-associated diarrhoea, colitis and pseudomembranous colitis have all been reported with the use of cefditoren. These diagnoses should be considered in any patient who develops diarrhoea during or shortly after treatment.
Cefditoren should be discontinued if severe, and/or bloody diarrhoea occurs during treatment and appropriate therapy instituted.
Cefditoren should be used with caution in individuals with a previous history of gastrointestinal disease, particularly colitis.
In patients with moderate to severe renal impairment the rate and extent of exposure to cefditoren is increased (see Pharmacology: Pharmacokinetics under Actions). For this reason, the total daily dosage should be reduced when cefditoren is administered to patients with acute or chronic moderate to severe renal insufficiency in order to avoid potential clinical consequences, such as seizures (see Dosage & Administration).
Cephalosporin antibiotics should be given with caution to patients receiving concurrent treatment with nephrotoxic active substances such as aminoglycoside antibiotics or potent diuretics (such as furosemide) as these combinations may have undesirable effects on renal function and have been associated with ototoxicity.
Prolonged use of cefditoren may result in the overgrowth of non-susceptible organisms, such as Enterococci and Candida spp.
During treatment with cephalosporins, a decrease in prothrombin activity may occur. Therefore, the prothrombin time should be monitored in patients at risk, such as patients with renal or hepatic insufficiency or patients being treated with anticoagulant therapy.
Administration of pivalate prodrugs has been associated with decreases in plasma carnitine concentrations. However, clinical studies concluded that no clinical effects of carnitine decrease were associated with the administration of cefditoren pivoxil.
Effects on ability to drive and use machines: 200 mg tablet only: MEIACT has minor or moderate influence on the ability to drive and use machines. Cefditoren pivoxil may cause dizziness and somnolence (see Adverse Reactions).
Use in Children: 100 mg tablet: The safety of this product in low birth-weight infants, newborns, suckling infants, infants and children has not been established (few clinical experience).
Fine granules for oral susp: The safety of this product in low birth-weight infants and newborns has not been established.
Use in the Elderly: 100 mg tablet: The incidence of adverse reactions in the elderly does not differ from that in non-elderly adult patients. However, since the physiological functions are generally reduced in the elderly, the product should be administered carefully, paying attention to the following two points: dose and dose intervals should be adjusted according to the patient's condition.
Delay in excretion has been observed in patients with renal hypofunction. Therefore, high serum levels of the product may persist for a longer period of time in the elderly.
As for other analogous drugs, bleeding tendency due to vitamin K deficiency has been reported to occur in the elderly.

100 mg tablet: This product should be administered to pregnant women or women who may possibly be pregnant, only if the expected therapeutic benefits outweigh the possible risks associated with treatment. [The safety of this product during pregnancy has not been established.]
200 mg tablet: Pregnancy: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see Pharmacology: Toxicology: Preclinical safety data under Actions). There are no adequate data from the use of cefditoren pivoxil in pregnant women.
Lactation: There is insufficient evidence available on whether cefditoren is present in human milk. Therefore, the administration of MEIACT is not recommended during lactation.

100 mg tablet: Adverse reactions occurred in 127 (4.37%) of the 2,909 patients evaluated for the safety of the product. Digestive symptoms including diarrhea, loose stools, nausea and stomach discomfort accounted for 121 patients (4.16%), followed by 16 patients (0.55%) with allergic symptoms such as exanthema. Changes in laboratory test values were observed in 8.17% (187/2,289). These included abnormal hepatic function such as increased AST (GOT) in 3.37% (73/2,167) and increased ALT (GPT) in 4.21% (91/2,164); and abnormal hematology, such as eosinophilia, in 2.63% (47/1,790) (at the time of approval).
Fine granules: Incidences of adverse reactions by MEIACT Granules, that have been confirmed to be bioequivalent to MEIACT fine granules, were as follows.
Adverse reactions occurred in 19 (4.17%) of the 456 patients evaluated for the safety of the product. Principal symptoms observed were diarrhea in 17 (3.73%) patients and allergic symptoms (1 patient each with exanthema and redness) in 2 (0.44%) patients. Changes in laboratory test values were observed in 3.60% (10/278). They included abnormal hepatic function such as increased AST (GOT) in 0.45% (1/222) and increased ALT (GPT) in 0.90% (2/222), and abnormal hematology, such as eosinophilia, in 1.97% (5/254) (at the time of approval of MEIACT granules).
100 mg tablet and Fine granules for oral susp: Clinically significant adverse reactions: Shock, anaphylactoid reaction (<0.1%) may occur. Therefore, patients should be monitored thoroughly and if any anaphylactic shock-related signs or symptoms such as discomfort, oral cavity discomfort, stridor, vertigo, defecation desire, tinnitus or diaphoresis develop, the administration should be discontinued and suitable measures should be taken.
Serious colitis with bloody stool such as pseudomembranous colitis (<0.1%) may occur. Therefore, the patient should be monitored thoroughly and if abdominal pain or frequent diarrhea occurs, the administration should be discontinued immediately and suitable measures should be taken.
Muco-cutaneo-ocular syndrome (Stevens Johnson syndrome) or toxic epidermal necrolysis (Lyell syndrome) (<0.1%) may occur. Therefore, the patients should be thoroughly monitored and if any abnormality occurs, the administration should be discontinued and suitable measures should be taken.
Interstitial pneumonia, PIE syndromes (<0.1%) etc., accompanied with fever, coughing, dyspnea, abnormal chest X-ray images, eosinophilia, etc., may occur. Therefore, the patients should be monitored thoroughly and if these symptoms occur, the administration should be discontinued and suitable measures such as the administration of corticosteroid should be taken.
Hepatic function disorders (<0.1%) associated with jaundice and markedly increased AST (GOT), ALT (GPT) and Al-P may occur. Therefore, periodical clinical examinations should be carried out to thoroughly monitor patients and if any abnormality occurs, the administration should be discontinued and suitable measures should be taken.
Serious renal dysfunction (<0.1%) such as acute renal failure may occur. Therefore, periodical clinical examinations should be carried out to thoroughly monitor patients and if any abnormality occurs, the administration should be discontinued and suitable measures should be taken.
Agranulocytosis (<0.1%) and hemolytic anemia (<0.1%) may occur. Therefore, periodical clinical examinations should be carried out to thoroughly monitor patients and if any abnormality occurs, the administration should be discontinued and suitable measures should be taken.
Other adverse reactions: (See Table 6.)

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200 mg tablet: Approximately 6000 patients received cefditoren at either 200 mg or 400 mg twice daily for up to 14 days in clinical trials. About 24% of patients reported at least one adverse reaction. Treatment discontinuation as a consequence of adverse reactions occurred in 2.6% of the patients.
The most commonly occurring adverse reactions were gastrointestinal events. In most studies, diarrhoea occurred in more than 10% of all patients and was more common with 400 mg than with 200 mg twice daily. The observed adverse reactions, reported either during clinical trials or post-marketing experience, are described as follows: Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 7.)

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The following adverse reactions could appear as they have been observed with other cephalosporins: cholestasis and aplastic anemia.

200 mg tablet: Antacids: Co-administration of antacids containing magnesium and aluminium hydroxide and cefditoren pivoxil together with food produced a decrease in C_max and AUC cefditoren of 14% and 11% respectively. It is recommended that a period of 2 hours should lapse between the administration of antacids and cefditoren pivoxil.
H₂-receptor antagonists: Concomitant administration of intravenous famotidine and oral cefditoren pivoxil produced a decrease in C_max and AUC cefditoren of 27% and 22% respectively. Therefore, the concomitant use of cefditoren pivoxil with H₂-receptor antagonists is not recommended.
Probenecid: Co-administration of probenecid with cefditoren pivoxil reduces the renal excretion of cefditoren, resulting in a 49% increase in C_max, a 122% increase in AUC, and a 53% increase in the elimination half-life.
Oral contraceptives: Administration of cefditoren pivoxil did not alter the pharmacokinetic properties of the oral contraceptive ethinyl estradiol. Cefditoren pivoxil may be taken concomitantly with combination oral contraceptives containing ethinyl estradiol.
Medicinal Products/Laboratory Test Interactions: Cephalosporins can induce a false positive in the direct Coombs test, which may interfere with cross matching of blood.
False positive results for glucose in urine may occur with copper reduction tests but not with enzyme-based tests.
As a false-negative result may occur in the ferricyanide test for glucose determination in plasma or blood, it is recommended that either the glucose oxidase or hexokinase methods be used to determine blood/plasma glucose levels in patients receiving cefditoren pivoxil.

100 mg tablet: Precautions concerning Use: Precautions regarding dispensing: In the case of press-through packages, instruct the patient to remove the drug from the package prior to use. [If the PTP sheet is swallowed, its sharp corners may penetrate the esophageal mucosa, leading to serious complications such as mediastinitis.]
200 mg tablet: Incompatibilities: Not applicable.
Special precautions for disposal and other handling: No special requirements.

100 mg tablet: Store in a tight container at below 25°C. Avoid moisture after opening.
200 mg tablet: Do not store above 30°C. Store in the original package.
Fine granules for oral susp: To protect from moisture, stopper the bottle tightly after dispensing. Direct patients to store sachets avoiding moisture and light and to open sachets just before taking the product.
Shelf life: 200 mg tablet: 3 years.

Cephalosporins

J01DD16 - cefditoren ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

D