Meiact

100 mg tablet: Each tablet of MEIACT Tablets 100 contains the following active ingredient: Cefditoren pivoxil 100 mg (potency).
200 mg tablet: Elliptical white tablet printed on one side with the "TMF" logo in blue ink.
Each film-coated tablet contains 200 mg of cefditoren equivalent to 245.1 mg of cefditoren pivoxil.
Fine granules for oral suspension: One gram of MEIACT Fine Granules contains the following active ingredient: Cefditoren pivoxil 100 mg (potency).
Excipients/Inactive Ingredients: 200 mg tablet: 26.2 mg sodium of per 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 suspension: 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., Propionibacterium 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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Fine granules for oral suspension: Clinical Studies: Clinical results of MEIACT granules: 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: 100 mg tablet: Absorption and distribution: Blood concentration: 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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Body fluid and tissue concentrations: 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.
Metabolism and excretion: 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. 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 suspension: Pharmacokinetic parameters of MEIACT Granules, that has been confirmed to be bioequivalent to this product, were as follows.
Absorption and distribution: Blood concentration: 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: The drug transferred to the sputum, tonsillar tissue, mucous membrane of maxillary sinus and skin tissue of patients.
Metabolism and excretion: Cefditoren pivoxil is metabolized upon absorption and becomes cefditoren which has antibacterial activity, and pivalic acid. The latter is conjugated with carnitine and excreted into urine as pivaloyl carnitine. Cefditoren is hardly metabolized and is excreted mainly into urine and bile. 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.
100 mg tablet and Fine granules for oral suspension: Absorption and distribution: Protein binding: In vitro, binding rate to human serum protein determined by ultrafiltration method was 91.5% at concentration of 25 μg/mL.
Serum concentration and urinary excretion in patients with renal function disorder: 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: 100 mg tablet and 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.
200 mg tablet: Studies to evaluate the carcinogenic potential of cefditoren pivoxil have not been performed.

Folliculitis, pyelonephritis, cystitis.
100 mg tablet and Fine granules for oral suspension: 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 suspension only): Pharyngolaryngitis (throat abscess), acute bronchitis, tonsillitis (peritonsillitis, peritonsillar abscess), pneumonia; Otitis media, sinusitis; Superficial secondary infection in trauma, surgical wound, etc; Furuncle, furunculosis, carbuncle, impetigo, contagiosa, erysipelas, phlegmon, lymphangitis (lymphadenitis), suppurative perionychia (paronychia), subcutaneous abscess, infectious atheroma.
100 mg tablet: Chronic bronchitis, bronchiectasis with infection, secondary infection in chronic respiratory disease, pulmonary suppuration.
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, impetigo and boils.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Fine granules for oral suspension: Urinary tract infections; Scarlet fever; Pertussis.

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 daily after meal.
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 for oral suspension: 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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Poisoning symptoms: In general, the following symptoms of poisoning are known with cephem antibiotics: Nausea, vomiting, epigastric pain, black hairy tongue, faeces soft; Diarrhea: Occasionally causes severe pseudomembranous colitis with fever, abdominal pain, leukocytosis, and fulminant diarrhea with mucus and bloody stools as the main symptoms; Granulocytopenia, eosinophilia, hemolytic anemia; Thrombocytopenia; Liver damage (jaundice, increased AST/ALT/Al-P); Rash, urticaria, erythema, itching; Bleeding tendency, decreased blood pressure, arrhythmia, cardiac arrest, shock, anaphylactic shock; Convulsions, renal damage, tubular necrosis.
Treatment method: Since the cephem preparation for internal use is highly safe due to its excellent selective toxicity, the following treatments (2) and (3) may be performed except when a very large amount is taken: 1. Gastric lavage (take a large amount and do it within 1 hour after taking)
2. Adsorbent Activated carbon (40-60 g adjust to 200 mL with water).
3. Laxative Magnesium sulfate (30 g adjust to 200 mL with water) or Magcorol P (1 packet adjust to 200 mL with water).
4. Infusion (Liver protective agent, B vitamins, vitamin K2 injection added).

Patients with a history of hypersensitivity to any of the ingredients of this product.

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.

Important Precautions: 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.
Since shock may occur, patients should be carefully interviewed.
Since abnormal laboratory test values (AST increased, ALT increased, eosinophilia, etc.) tend to appear more frequently in patients under long-term treatment with this product, these patients should be monitored by performing periodic laboratory tests.
Patients with severe renal function disorder (Previous formulation ^Note)): The dosing interval should be prolonged. Serum concentration persists. (See Pharmacology: Pharmacokinetics under Actions.)
Note): This product has been confirmed to be bioequivalent to the previous formulation (100 mg and 200 mg tablet).
Bioequivalence between this product and the previous fine granule formulation, the previous fine granule formulation and the granule formulation, and MEIACT MS tablets and the previous tablets has been verified (fine granules for oral suspension).
Patients with Complication or History of Diseases, etc.: Cefditoren should be administered with care in the following patients: Patients with a history of hypersensitivity to cephem or penicillin antibiotics. However, do not administer to patients with a history of hypersensitivity to this product.
Patients with a personal or familial predisposition to allergic symptoms such as bronchial asthma, rash or urticaria.
Patients with poor oral food intake or who are receiving parenteral alimentation, and patients in poor general health. Patients should be observed carefully. Vitamin K deficiency symptoms may develop.
Effects on ability to drive and use machines: 100 mg tablet and fine granules for oral suspension: Not available.
200 mg tablet: MEIACT has minor or moderate influence on the ability to drive and use machines. Cefditoren pivoxil may cause dizziness and somnolence (see Adverse Reactions).
100 mg and 200 mg tablet: Important Precautions: Since hepatic function disorder may occur, periodic laboratory tests should be performed.
Since serious renal disorder such as acute renal failure may occur, periodic laboratory tests should be performed.
Since agranulocytosis or hemolytic anemia may occur, periodic laboratory tests should be performed.
Other precautions: It has been reported that administration of antibiotics which have a pivoxil group including this product (cefditoren pivoxil, cefcapene pivoxil hydrochloride hydrate, cefteram pivoxil and tebipenem pivoxil) cause serum carnitine decrease resulting from the metabolism/excretion of pivalic acid (a metabolite of antibiotics with a pivoxil group).
200 mg tablet: Hypersensitive to casein: For patients who are hypersensitive to casein, it should be noted that the medicinal product contains sodium caseinate.
Use in Children: No clinical studies have been conducted in pediatric patients (100 mg tablet and 200 mg tablet) and low birth weight infants and newborns (fine granules for oral suspension) to assess efficacy and safety.
Attention should be paid to decreased carnitine.
Do not administer this product if patients are found to have inborn errors of metabolism which may cause serum carnitine to decrease. Administration of antibiotics with a pivoxil group (pediatric formulations) may cause hypoglycemia accompanying hypocarnitinemia in children (in particular, infants and small children).
Fine granules for oral suspension: When this product is administered to children younger than 3 years in a single dose of 6 mg (potency)/kg 3 times a day, diarrhea/faeces soft may occur with high frequency. If these symptoms are observed, appropriate measures such as symptomatic treatment should be taken according to the symptoms. In a clinical study in which this product was administered to children with pneumonia, otitis media or sinusitis in a single dose of 6 mg (potency)/kg 3 times a day, the incidence of the adverse reaction of diarrhea/faeces soft was 36.2% (17/47) in children younger than 3 years and 16.2% (11/68) in children 3 years or older.
Use in the Elderly: The product should be carefully administered, paying attention to the following points, and dosage and dosing interval should be adjusted. The incidence of adverse reactions in the elderly does not differ from that in non-elderly adult patients, however in general, elderly patients often have reduced physiological function.
Since delay in excretion of this product has been observed in patients with renal hypofunction, blood concentrations may increase.
Bleeding tendency due to vitamin K deficiency has been reported after the use of other similar drugs.

Pregnancy: This product should be used in pregnant women or women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment. Hypocarnitinemia has been reported in women who have taken antibiotics containing a pivoxil group during the last trimester of pregnancy, as well as in the neonates born to them.
Lactation: 200 mg tablet: There is insufficient evidence available on whether cefditoren is present in human milk. Therefore, the administration of MEIACT is not recommended during lactation.

Adverse Reactions [Common (for fine granules in oral suspension)]: Clinically significant adverse reactions: Shock or anaphylaxis (all incidence unknown): If any abnormalities such as feeling unwell, oral cavity discomfort, stridor, vertigo, defecation desire, tinnitus or diaphoresis are observed, administration should be discontinued and appropriate measures should be taken.
Serious colitis with bloody stool such as pseudomembranous colitis (incidence unknown): If abdominal pain or frequent diarrhea occurs, administration should be discontinued immediately and appropriate measures should be taken.
Toxic Epidermal Necrolysis (TEN), oculomucocutaneous syndrome (Stevens-Johnson syndrome) or erythema multiforme (all incidence unknown).
Interstitial pneumonia or PIE syndrome (all incidence unknown): Interstitial pneumonia or PIE syndrome, etc., with fever, cough, dyspnea, abnormal chest X-ray, eosinophilia, etc., may occur. Patients should be carefully monitored and if these symptoms occur, administration should be discontinued and appropriate measures such as administration of adrenocortical hormones should be taken.
Hepatic function disorder (incidence unknown): Hepatic function disorder with jaundice or markedly increased AST, ALT or Al-P may occur.
Serious renal disorder such as acute kidney injury (incidence unknown).
Agranulocytosis or hemolytic anemia (all incidence unknown).
Adverse Reactions (Children) (for fine granules in oral suspension): Clinically significant adverse reactions: Hypoglycemia accompanying hypocarnitinemia (incidence unknown): It has been reported that administration of antibiotics which have a pivoxil group (including this product, cefcapene pivoxil hydrochloride hydrate, cefteram pivoxil and tebipenem pivoxil) cause serum carnitine decrease resulting from the metabolism/excretion of pivalic acid (a metabolite of antibiotics with a pivoxil group). Administration of antibiotics with a pivoxil group may cause hypoglycemia accompanying hypocarnitinemia in children (in particular, infants and small children). Therefore when symptoms of hypoglycemia such as convulsions or consciousness disorder are observed, administration should be discontinued and appropriate measures should be taken.
Other adverse reactions: See Table 6.

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Clinical Studies: 100 mg and 200 mg tablet: Dose-ranging study in Japan ^(Note): Chronic bronchitis: Adverse reaction reported was 1 case (2.6%) of nausea/upper abdominal pain in the 300 mg group.
Complicated urinary tract infection: Adverse reactions reported were 1 case each (1.5%) of dizziness/coldness, stomach feeling heavy, stomach pain, and dizziness in the 300 mg group, and diarrhea in the 600 mg group.
Double-blind study in Japan ^(Note): Complicated urinary tract infection: Adverse reactions reported were 2 cases (1.5%) of diarrhea and 1 case each (0.7%) of stomach pain and faeces soft.
Bacterial pneumonia: Adverse reactions reported were 3 cases (3.4%) of diarrhea, 2 cases each (2.3%) of rash and queasy (nausea) and 1 case (1.1%) of stomach discomfort/diarrhea.
Chronic respiratory tract infection: Adverse reactions reported were 3 cases (3.4%) of diarrhea and 1 case each (1.0%) of rash/pruritus, fever, queasy, stomach discomfort, faeces soft and constipation.
Superficial suppurative disease: Adverse reactions reported were 2 cases (2.6%) of faeces soft and 1 case each (1.3%) of stomach feeling heavy, stomach discomfort/faeces soft, queasy/faeces soft, bloating, stomach discomfort, queasy and watery stool.
General clinical studies in Japan ^(Note): Adverse reactions occurred in 91 (3.95%) of 2,301 patients evaluated for the safety of the product. The main adverse reactions were digestive symptoms (87 cases; 3.78%) such as diarrhea, faeces soft, queasy and stomach discomfort and allergic symptoms (11 cases; 0.48%) such as rash. Changes in laboratory test values were observed in 6.80% (119/1,749). They included abnormal hepatic function such as LDH increased in 5.45% (3/55), ALT increased in 4.21% (69/1,638), AST increased in 3.11% (51/1,641), and abnormal hematology such as eosinophilia in 1.77% (25/1,412).
Note): This product has been confirmed to be bioequivalent to the previous formulation.
Fine granules for oral suspension: Clinical studies in Japan (granules ^Note) at the time of approval): Adverse reactions were reported in 19 (4.17%) of 456 cases evaluated for the safety of the product. The main adverse reactions were gastrointestinal symptoms (diarrhea only) in 17 (3.73%) and allergic symptoms (rash and redness in 1 case each) in 2 (0.44%). Changes in laboratory test values were observed in 3.60% (10/278). The main adverse reactions were abnormal hematology such as eosinophilia 1.97% (5/254), and abnormal hepatic function such as ALT increase 0.90% (2/222) and AST increase 0.45% (1/222).
Clinical studies in Japan (previous fine granules ^Note1) at the time of approval of additional indications): Of the total 72 patients treated, 1 (1.4%) of watery stools was reported as an adverse reaction. Abnormal changes in laboratory test values were observed with an eosinophil count increased of 6.9% (4/58).
Clinical studies in Japan (at the time of approval for a partial change in dosage and administration): Adverse reactions were reported in 36 (31.3%) of 115 cases evaluated for the safety of the product. The main adverse reactions were diarrhea/faeces soft in 28 cases (24.3%). Abnormal changes laboratory test values were observed in 7 (6.2%) of 113 cases evaluated for the safety of the product who underwent testing. The main adverse reactions were increased platelet count, etc.
Note): Bioequivalence between this product and the previous fine granule formulation, and the previous fine granule formulation and the granule formulation has been verified.

Effects of antacids: It is reported that the combined use of antacids reduces the absorption rate, and the combined use of probenecid reduces the urinary excretion rate.
Effects/Influence on laboratory tests: Since false-positive results may occur in urine sugar/glucose tests with Benedict's solution, Fehling's solution (and Clinitest for Fine granules for oral suspension) except Tes-Tape, caution should be taken.
Since this product may cause a positive response in the direct Coombs' test, caution should be taken.
100 mg and 200 mg tablet: Effect of H₂-receptor antagonists: It is reported that concomitant administration of intravenous famotidine and oral cefditoren pivoxil produced a decrease in C_max and AUC cefditoren.
Effect of oral contraceptives: It is reported that administration of cefditoren pivoxil did not alter the pharmacokinetic properties of the oral contraceptive ethinyl estradiol.

100 mg and 200 mg tablet: Precautions concerning use: In the case of press-through packages (PTPs), 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.
Fine granules for oral suspension: Precautions for Handling: 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.

100 mg tablet: Storage Condition: Store in a tight container at below 30°C.
Avoid moisture after opening.
200 mg tablet: Special precautions for storage: Do not store above 30°C. Store in the original package.
Shelf life: 3 years.

Cephalosporins

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

D