DESCRIPTION
White film coated tablet.
MEIACT 100 TABLET:
Cefditoren pivoxil 100 mg (potency)
MEIACT 200 TABLET:
Cefditoren pivoxil 200 mg (potency)
MEIACT 400 TABLET:
Cefditoren pivoxil 400 mg (potency)
INDICATIONS
Cefditoren pivoxil is indicated for the treatment of following infections which are caused by susceptible strains.
- Community acquired pneumoniae
- Acute exacerbation of chronic bronchitis
- Pharyngotonsilitis
- Acute sinusitis
- Uncomplicated skin and soft structure infections
DOSAGE AND ADMINISTRATION
- Community acquired pneumoniae 400 mg BID for 14 days
- Acute exacerbation of chronic bronchitis 400 mg BID for 10 days
- Pharyngotonsilitis 200 mg BID for 10 days
- Acute sinusitis 200 mg BID for 10 days
- Uncomplicated skin and soft structure infections 200 mg BID for 10 days Should be taken after meals
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.
- In patients with severely impaired renal function, the administration interval should be prolonged. (See "Careful Administration" section and "PHARMACOKINETICS" section).
CONTRAINDICATIONS (MEIACT Tablets is contraindicated in the following patients)
- Patients with a history of anaphylactic shock due to any of the ingredients of the product.
- Patients with cow's milk allergy (This product contains sodium caseinate as an inactive ingredient)
RELATIVE CONTRAINDICATIONS (As a general rule, MEIACT Tablets is contraindicated in the following patients. If the use of MEIACT Tablets is considered essential, it should be administered with care).
Patients with a history of hypersensitivity to any of the ingredients of the product or other cephem antibiotics.
PRECAUTIONS
| 1 | Careful Administration (MEIACT Tablets should be administered with care in the following patients) | |||||||||||||||||||||||||||||||||||||||
| (1) | Patients with a history of hypersensitivity to penicillins. | |||||||||||||||||||||||||||||||||||||||
| (2) | Patients with a personal or familial predisposition to allergic symptoms such as bronchial asthma, exanthema or urticaria. | |||||||||||||||||||||||||||||||||||||||
| (3) | Patients with severely impaired renal function [Serum concentration persists. (See "PHARMACOKINETICS" section). | |||||||||||||||||||||||||||||||||||||||
| (4) | Elderly patients (See "Use in the Elderly" section). | |||||||||||||||||||||||||||||||||||||||
| (5) | 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). | |||||||||||||||||||||||||||||||||||||||
| 2 | Important Precautions; The patients should be carefully interviewed to asses .the risk of shock. | |||||||||||||||||||||||||||||||||||||||
| 3 | Adverse Reaction; 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 (0.55%) patients with allergic symptoms such as exanthema. Changes in laboratory test values were observed in 8.17% (187/2,289). They 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). | |||||||||||||||||||||||||||||||||||||||
| (1) | Clinically significant adverse reactions | |||||||||||||||||||||||||||||||||||||||
| 1) | Shock, anaphylactoid symptoms (‹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 and sweating develop, the administration should be discontinued and suitable measures should be taken. | |||||||||||||||||||||||||||||||||||||||
| 2) | Serious colitis with bloody stool such as pseudomembranous colitis (‹ 0.1%) may occur. Therefore, the patients should be monitored thoroughly and if abdominal pain or frequent diarrhea occurs, the administrations should be discontinued immediately and suitable measures should be taken. | |||||||||||||||||||||||||||||||||||||||
| 3) | Muco-cutaneo-ocular syndrome (Stevens-Johnson syndrome) and 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. | |||||||||||||||||||||||||||||||||||||||
| 4) | Interstitial pneumonia, PIE syndrome (‹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. | |||||||||||||||||||||||||||||||||||||||
| 5) | 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. | |||||||||||||||||||||||||||||||||||||||
| 6) | 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. | |||||||||||||||||||||||||||||||||||||||
| 7) | 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. | |||||||||||||||||||||||||||||||||||||||
| (2) | Other adverse reactions
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| 4 | Use in the Elderly 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. | |||||||||||||||||||||||||||||||||||||||
| (1) | Delay in excretion has been observed in patients with impaired renal function. Therefore, high serum levels of the product may persist for a longer period of time in the elderly. | |||||||||||||||||||||||||||||||||||||||
| (2) | As for other analogous drugs, bleeding tendency due to vitamin K deficiency has been reported to occur in the elderly. | |||||||||||||||||||||||||||||||||||||||
| 5 | Use during Pregnancy, Delivery or Lactation 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]. | |||||||||||||||||||||||||||||||||||||||
| 6 | Pediatric Use The safety of this product in low birth-weight infants, new borns, suckling infants, infants and children has not been established (few clinical experience). | |||||||||||||||||||||||||||||||||||||||
| 7 | Effects on Laboratory Test | |||||||||||||||||||||||||||||||||||||||
| (1) | False-positive results may occur in urine glucose tests with Benedict's solution. Fehling's solution, and Clinitests, but not with Tes-Tape. | |||||||||||||||||||||||||||||||||||||||
| (2) | Positive results may occur in the direct Coombs test. Caution is required. | |||||||||||||||||||||||||||||||||||||||
| 8 | 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 severe complications such as mediastinitis.] | |||||||||||||||||||||||||||||||||||||||
| 9 | Other Precautions It has been reported that this product reduces serum carnitine. | |||||||||||||||||||||||||||||||||||||||
PHARMACOKINETICS
| 1 | Absorption and distribution | ||||||||||||||||||||||||||||||||||||||
| (1) | Blood concentration 1,2) The serum concentrations (Fig.l) and pharmacokinetics (Table 1) 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. 
Fig. I Serum concentrations of Cefditoren after oral administration in healthy adults
Table I. Pharmacokinetic parameter in healthy adults
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| (2) | Body fluid and tissue concentrations 3-11) 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. | ||||||||||||||||||||||||||||||||||||||
| (3) | Protein binding 12) In vitro binding rate to human serum protein determined by ultra filtration method was 91.5% at concentration of 25 μ.g/mL. | ||||||||||||||||||||||||||||||||||||||
| 2 | Metabolism and excretion 1, 9, 13-16 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 pivaloil 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). | ||||||||||||||||||||||||||||||||||||||
| 3 | Serum concentration and urinary excretion in patients with renal function disorder 17) The serum concentrations (Fig. 2) and pharmacokinetics parameters (Table 2) 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 T½ in parallel with degree of renal function disorder. 
Fig. 2 Serum concentrations of cefditoren in patients with renal function disorder
Table 2 Pharmacokinetic parameter in patients with renal function disorder
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PHARMACOLOGY
| 1 | Antibacterial activity 29-34) | ||
| (1) | Cefditoren pivoxil is metabolized into cefditoren upon absorption from the intestinal wall and shows its antibacterial activity. | ||
| (2) | 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. | ||
| (3) | In vitro, cefditoren demonstrated stability against β-lactamase produced by various bacteria. It also shows strong antibacterial activity against strains that produce β-lactamase. | ||
| 2 | Mechanism of action 29, 31, 33) Cefditoren inhibits the synthesis of bacterial cell wall. It has high affinity to penicillin binding protein (PBPs) in various bacteria, showing a bactericidal effect. | ||
| 3 | Therapeutic efficacy on experimental infections 30, 31, 33) 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. | ||
PHYSICOCHEMISTRY
Nonproprietary name :
Cefditoren pivoxil (JAN), Cefditoren (INN)
Chemical name :
(-)-(6R,7R)-2, 2-dimethylpropionyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(Z)-2-(4-methylthiazol-5-yl)ethenyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]
oct-2-ene-2-carboxylate
Abbreviation : CDTR-PI
Molecular formula : C25H28N6O7S3
Molecular weight: 620.73
Structural formula :
Description :
Cefditoren pivoxil, The Minimum Requirements for Antibiotic Products of Japan (MRAPJ) occurs as a light yellowish white to light yellow crystalline powder. It is freely soluble in diluted hydrochloric acid, sparingly soluble in methanol, slightly soluble in acetonitrile and in ethanol, very slightly soluble in ether and practically insoluble in water.
Melting point: 196-201°C (decomposition)
Partition coefficient: -
(log101-octanol layer/water layer, 25 ± 2°C)
| pH 2.0 | pH 4.0 - 6.0 |
| 0.92 | › 3.0 |
Potency :
Indicated as the weight (potency) of cefditoren (C19H18O5S3).
1.225 mg of Cefditoren pivoxil contains 1 mg (potency) of cefdiotren.
STORAGE CONDITION
Store at below 25°C, protect from moisture and direct light.
HOW SUPPLIED
MEIACT 100 Tablet, Box 3 blisters @ 10 tablets, Reg. No DKI 0463200317A1
MEIACT 200 Tablet, Box 2 blisters @ 10 tablets, Reg. No DKI 0665600217A1
MEIACT 400 Tablet, Box 2 blisters @ 5 tablets, Reg. No DKI 0665600217B1
HARUS DENGAN RESEP DOKTER
Manufactured by
MEIACT 100 Tablet: Meiji Seika Kaisha Ltd., Tokyo - Japan
MEIACT 200 Tablet and MEIACT 400 Tablet: Tedec Meiji Farma, S.A, Madrid - Spain
Imported by
PT MEIJI INDONESIAN
PHARMACEUTICAL INDUSTRIES
BANGIL - PASURUAN, JAWA TIMUR - INDONESIA
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