Zostum-O 200 Tablets

Cefditoren Pivoxil Tablets 200 mg

Each film coated tablet contains :

Cefditoren Pivoxil equivalent to Cefditoren 200 mg

Excipients q.s. Colours : Lake of Quinoline Yellow & Titanium Dioxide IP

Tablet 200 mg

4.1 Therapeutic indications

Cefditoren pivoxil tablet is indicated for the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of the designated microorganisms in the conditions listed below.

• Acute bacterial exacerbation of chronic bronchitis
• Pharyngitis /tonsillitis
• Uncomplicated skin and skin-structure infections

4.2 Posology and method of administration

Acute Bacterial Exacerbation of Chronic Bronchitis: 400 mg b.i.d. for 10 days

In Pharyngitis/Tonsillitis and Skin and Skin Structure infections: 200 mg b.i.d. for 10 days.

It is recommended to take dose with the meal.

Patients with Renal Insufficiency

No dose adjustment is necessary for patients with mild renal impairment (CLcr: 50-80 mL/min/1.73 m2). It is recommended that not more than 200 mg BID be administered to patients with moderate renal impairment (CLcr: 30-49 mL/min/1.73 m2) and 200 mg QD be administered to patients with severe renal impairment (CLcr: <30 mL/min/1.73 m2). The appropriate dose in patients with end-stage renal disease has not been determined.

Patients with Hepatic Disease

No dose adjustments are necessary for patients with mild or moderate hepatic impairment

4.3 Contraindications

Cefditoren is contraindicated in patients with known allergy to the Beta-lactam class of antibiotics or any of the components of the formulations.

4.4 Special warnings and precautions for use

Before therapy with cefditoren pivoxil is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefditoren pivoxil, other cephalosporins, penicillins, or other drugs. If cefditoren pivoxil is to be given to penicillin- sensitive patients, caution should be exercised because cross- hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.

If an allergic reaction to cefditoren pivoxil occurs, the drug should be discontinued. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated.

Cefditoren pivoxil is not recommended when prolonged antibiotic treatment is necessary, since other pivalate-containing compounds have caused clinical manifestations of carnitine deficiency when used over a period of months. With other antibiotics prolonged treatment may result in the possible emergence and overgrowth of resistant organisms. It should be taken with meals to enhance absorption. It may be taken concomitantly with oral contraceptives. It is not recommended when taken concomitantly with antacids or other drugs taken to reduce stomach acids

4.5 Interaction with other medicinal products and other forms of interaction

Antacids – Antacids reduces the oral absorption of a single 400 mg dose of Cefditoren pivoxil administered following a meal, by a 14% decrease in mean Cmax and an 11% decrease in mean AUC. H2-Receptor Antagonists like Famotidine reduce the oral absorption of a single 400 mg dose of Cefditoren pivoxil administered following a meal, by a 27% decrease in mean Cmax and a 22% decrease in mean AUC. Probenecid increases the plasma concentration of cefditoren pivoxil, with a 49% increase in mean Cmax, a 122% increase in mean AUC, and a 53% increase in t1/2

4.6 Use in special populations

Pregnancy

The safety of Cefditoren has not been established. Cefditoren should not be used in pregnant women unless the potential benefits to the mother outweigh the risk to the fetus.

Nursing mothers:

Many drugs are excreted in human breast milk so caution should be exercised when cefditoren pivoxil is administered to nursing women. Geriatric use:

No clinically significant differences in effectiveness or safety were observed between older and younger patients. No dose adjustments are necessary in geriatric patients with normal (for their age) renal function.

4.7 Effects on ability to drive and use machines

Cefditoren has no or negligible influence on the ability to drive or use machines. However, cefditoren may cause side effects influencing the capacity of reaction and the ability to drive and use machines.

4.8 Undesirable effects

Fixed Drug Eruption (FDE) has been associated with Cefditoren pivoxil use

In clinical trials, 4834 adult and adolescent patients have been treated with the recommended doses of cefditoren pivoxil tablets (200 mg or 400 mg BID). Most adverse events were mild and self-limiting. No deaths or permanent disabilities have been attributed to cefditoren. The following adverse events were thought by the investigators to be possibly, probably, or definitely related to cefditoren tablets in multiple-dose clinical trials:

 

The overall incidence of adverse events, and in particular diarrhea, increased with the higher recommended dose of Cefditoren Pivoxil. Treatment related adverse events experienced by <1% but >0.1% of patients who received 200 mg or 400 mg BID of cefditoren pivoxil were abnormal dreams, allergic reaction, anorexia, asthenia, asthma, coagulation time increased, constipation, dizziness, dry mouth, eructation, face edema, fever, flatulence, fungal infection, gastrointestinal disorder, hyperglycemia, increased appetite, insomnia, leukopenia, leukorrhea, liver function test abnormal, myalgia, nervousness, oral moniliasis, pain, peripheral edema, pharyngitis, pseudomembranous colitis, pruritus, rash, rhinitis, sinusitis, somnolence, stomatitis, sweating, taste perversion, thirst, thrombocythemia, urticaria, and vaginitis. Pseudomembranous colitis symptoms may begin during or after antibiotic treatment.

Sixty-one of 2675 (2%) patients who received 200 mg BID and 69 of 2159 (3%) patients who received 400 mg BID of cefditoren pivoxil discontinued medication due to adverse events thought by the investigators to be possibly, probably, or definitely associated with cefditoren therapy. The discontinuations were primarily for gastrointestinal disturbances, usually diarrhea or nausea. Diarrhea was the reason for discontinuation in 19 of 2675 (0.7%) patients who received 200 mg BID and in 31 of 2159 (1.4%) patients who received 400 mg BID of cefditoren pivoxil.

Changes in laboratory parameters of possible clinical significance, without regard to drug relationship and which occurred in ≥1% of patients who received cefditoren pivoxil 200 mg or 400 mg BID, were hematuria (3.0% and 3.1%), increased urine white blood cells (2.3% and 2.3%), decreased hematocrit (2.1% and 2.2%), and increased glucose (1.8% and 1.1%). Those events which occurred in <1% but >0.1% of patients included the following: increased/decreased white blood cells, increased eosinophils, decreased neutrophils, increased lymphocytes, increased platelet count, decreased hemoglobin, decreased sodium, increased potassium, decreased chloride, decreased inorganic phosphorus, decreased calcium, increased SGPT/ALT, increased SGOT/AST, increased cholesterol, decreased albumin, proteinuria, and increased BUN. It is not known if these abnormalities were caused by the drug or the underlying condition being treated.

Cephalosporin Class Adverse Reactions

In addition to the adverse reactions listed above which have been observed in patients treated with cefditoren pivoxil, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics: Adverse Reactions: Allergic reactions, anaphylaxis, drug fever, Stevens-Johnson syndrome, serum sickness-like reaction, erythema multiforme, toxic epidermal necrolysis, colitis, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, and superinfection. Altered Laboratory Tests: Prolonged prothrombin time, positive direct Coombs’ test, false-positive test for urinary glucose, elevated alkaline phosphatase, elevated bilirubin, levated LDH, increased creatinine, pancytopenia, neutropenia, and agranulocytosis. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Treat over-dosage symptomatically and institute supportive measures as required. In animals diarrhea and soft stool lasting for few days were observed. Gastric Lavage may be done to remove the excess drug from the stomach.

5.1 Mechanism of action

Cefditoren is bactericidal in nature and its activity results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). It has high affinity for penicillin binding protein (PBP) of various bacteria.

5.2 Pharmacodynamic properties

Antibacterial activity Cefditoren pivoxil is metabolized into cefditoren on absorption in the intestinal wall and shows its antibacterial activity. Cefditoren exerts broad spectrum antibacterial activity in vitro against gram-positive and gram-negative bacteria. Especially it showed strong antibacterial activity against gram-positive bacteria such as Staphylococcus sp., Streptococcus sp. and Streptococcus pneumoniae, and gram-negative bacteria such as Escherichia coli, Moraxella (Branhamella) catarrhalis, Klebsiella sp., Proteus sp. and Haemophilus influenzae, and against anaerobic bacteria such as Peptostreptococcus sp., Propionibacterium acnes, Bacteroides sp. and Prevotella sp. Cefditoren also showed antibacterial activity against -lactamase-non producing ampicillin resistant Haemophilus influenzae (BLNAR). In vitro, cefditoren was stable against -lactamases producing strains.

5.3 Pharmacokinetic Properties

Absorption

Following oral administration, cefditoren pivoxil is absorbed from the gastrointestinal tract and hydrolyzed to cefditoren by esterases. Maximal plasma concentrations (Cmax) of cefditoren under fasting conditions average 1.8 ± 0.6 µg/mL following a single 200 mg dose and occur 1.5 to 3 hours following dosing. Less than dose-proportional increases in Cmax and area under the concentration-time curve (AUC) were observed at doses of 400 mg and above. Cefditoren does not accumulate in plasma following twice daily administration to subjects with normal renal function. Under fasting conditions, the estimated absolute bioavailability of cefditoren pivoxil is approximately 14%. Administration of cefditoren pivoxil following a high fat meal resulted in a 70% increase in mean AUC and a 50% increase in mean Cmax compared to administration of cefditoren pivoxil in the fasted state.

Distribution

The mean volume of distribution at steady state (Vss) of cefditoren is 9.3 ± 1.6 L. Binding of cefditoren to plasma proteins averages 88% from in vitro determinations, and is concentration-independent at cefditoren concentrations ranging from 0.05 to 10 µg/mL.

Metabolism and Excretion

Cefditoren is eliminated from the plasma, with a mean terminal elimination half-life (t1/2) of 1.6 ± 0.4 hours in young healthy adults. Cefditoren is not appreciably metabolized. After absorption, cefditoren is mainly eliminated by excretion into the urine, with a renal clearance of approximately 4-5 L/h. Cefditoren renal clearance is reduced in patients with renal insufficiency.

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data.

Zostum-O contains cefditoren pivoxil, a semi-synthetic cephalosporin antibiotic for oral administration. It is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren.

Chemical name: 2, 2-Dimethylpropanoyloxymethyl (6R, 7R)-7-[(Z)-2- (2-aminothiazol-4-yl)-2-(methoxyimino) acetylamino]-3-[(1Z)- 2-(4-methylthiazol-5-yl) ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0] oct-2-ene -2-carboxylate.

Molecular formula: C₂₅H₂₈N₆O₇S₃

Molecular weight: 620.72

 

8.1 Incompatibilities

Not applicable.

8.2 Shelf Life

Refer on the pack.

8.3 Packaging Information

A strip of 6 tablets / A strip of 10 tablets.

8.4 Storage and handing Instructions

Store below 25°C. Protect from light & moisture.

Keep out of reach of children.

• Patients should be counseled that antibacterial drugs including Cefditoren Pivoxil should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold).
• When Cefditoren Pivoxil is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Cefditoren Pivoxil or other antibacterial drugs in the future.
• Cefditoren Pivoxil should be taken with meals to enhance absorption.
• Cefditoren Pivoxil may be taken concomitantly with oral contraceptives.
• It is not recommended that Cefditoren Pivoxil be taken concomitantly with antacids or other drugs taken to reduce stomach acids

07 April 2023