Polares 100 DT & 200 Tablets

Cefpodoxime Proxetil Dispersible Tablets / Cefpodoxime Proxetil Tablets IP

Polares-100 DT

Each uncoated dispersible tablet contains :

Cefpodoxime Proxetil IP

equivalent to Cefpodoxime 100 mg

Excipients

Colour : Quinoline Yellow

Flavour added

Polares-200

Each film coated tablet contains :

Cefpodoxime Proxetil IP

equivalent to Cefpodoxime 200 mg

Excipients q.s

Colours : Titanium Dioxide IP and

Quinoline Yellow

Dispersible tablet 100 mg, Film coated tablet 200 mg

4.1 Therapeutic indications

Acute bronchitis, exacerbations of chronic bronchitis, bronchiolitis pneumonia, sinusitis, recurrent chronic tonsillitis, pharyngitis, acute otitis.

4.2 Posology and method of administration

Polares - 100 DT Tablets

Direction for use

Disperse the tablet in one teaspoonful of previously boiled and cooled water before administration. Cefpodoxime Proxetil 100 DT, should be administered orally with food to enhance absorption. The recommended dosages, durations of treatment, and applicable patient population are as described in the following chart. Infants and Pediatric Patients (age 2 months through 12 years)

Polares-200 Tablets

Cefpodoxime Proxetil Tablets, should be administered orally with food to enhance absorption. The recommended dosages, durations of treatment, and applicable patient population are as described in the following chart. Adults and Adolescents (age 12 years and older)

Patients with Renal Dysfunction

For patients with severe renal impairment (<30 mL/min creatinine clearance), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.

Patients with Cirrhosis

Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population

4.3 Contraindications

• patients with a known allergy to cefpodoxime or to the cephalosporin group of antibiotics.

• previous history of immediate and / or severe hypersensitivity reaction (anaphylaxis) to penicillin or other betalactam antibiotic.

4.4 Special warnings and precautions for use

Before therapy with cefpodoxime proxetil is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefpodoxime, other cephalosporins, penicillins, or other drugs. If cefpodoxime is to be administered 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 cefpodoxime proxetil occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, and airway management, as clinically indicated.

General precautions

In patients with transient or persistent reduction in urinary output due to renal insufficiency, the total daily dose of cefpodoxime proxetil should be reduced because high and prolonged serum antibiotic concentrations can occur in such individuals following usual doses. Cefpodoxime, like other cephalosporins, should be administered with caution to patients receiving concurrent treatment with potent diuretics. As with other antibiotics, prolonged use of cefpodoxime proxetil may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient’s condition is essential. If superinfection occurs during therapy, appropriate measures should be taken. Prescribing Cefpodoxime Proxetil, in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.

4.5 Interaction with other medicinal products and other forms of interaction

Antacids

Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or H2 blockers reduces peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%, respectively. The rate of absorption is not altered by these concomitant medications. Oral anticholinergics (e.g., propantheline) delay peak plasma levels (47% increase in Tmax), but do not affect the extent of absorption (AUC).

Probenecid

As with other beta-lactam antibiotics, renal excretion of cefpodoxime was inhibited by probenecid and resulted in an approximately 31% increase in AUC and 20% increase in peak cefpodoxime plasma levels.

Nephrotoxic drugs

Although nephrotoxicity has not been noted when cefpodoxime proxetil was given alone, close monitoring of renal function is advised when cefpodoxime proxetil is administered concomitantly with compounds of known nephrotoxic potential.

Drug/Laboratory Test Interactions

Cephalosporins, including cefpodoxime proxetil, are known to occasionally induce a positive direct Coombs’ test

4.6 Fertility, pregnancy and lactation

Pregnancy

There are, however, no adequate and well-controlled studies of cefpodoxime proxetil use in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Cefpodoxime proxetil has not been studied for use during labor and delivery.

Lactation

Cefpodoxime is excreted in human milk. Because of the potential for serious reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

4.7 Effects on ability to drive and use machines

It may cause dizziness. Driving or operating machinery is to be avoided

4.8 Undesirable effects

In clinical trials using multiple doses of cefpodoxime proxetil granules for oral drop, 2128 pediatric patients (93% of whom were less than 12 years of age) were treated with the recommended dosages of cefpodoxime (10 mg/kg/day Q 24 hours or divided Q 12 hours to a maximum equivalent adult dose). There were no deaths or permanent disabilities in any of the patients in these studies. Twenty-four patients (1.1%) discontinued medication due to adverse events thought possibly- or probably-related to study drug. Primarily, these discontinuations were for gastrointestinal disturbances, usually diarrhea, vomiting, or rashes. Adverse events thought possibly- or probably-related, or of unknown relationship to cefpodoxime proxetil for oral drop in multiple dose clinical trials (N=2128 patients treated with cefpodoxime) were:

Incidence Greater Than 1% were:

Incidence Less Than 1%

Body: Localized abdominal pain, abdominal cramp, headache, monilla, generalized abdominal pain, asthenia, fever, fungal infection.

Digestive: Nausea, monilia, anorexia, dry mouth, stomatitis, pseudomembranous colitis. Hemic & Lymphatic: Thrombocythemia, positive direct

Coombs' test, eosinophilla, leukocytosis, leukopenia, prolonged partial thromboplastin time, thrombocytopenic purpura. Metabolic & Nutritional: Increased SGPT Musculo-Skeletal: Myalgia. Nervous: Hallucination, hyperkinesia, nervousness, somnolence. Respiratory: Epistaxis, rhinitis, Skin: Fixed drug eruption (FDE), skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, maculopapular rash. Special Senses: Taste perversion. Laboratory Changes Significant laboratory changes that have been reported in adult and pediatric patients in clinical trials of cefpodoxime proxetil, without regard to drug relationship, were: Hepatic: Transient Increases in AST (SGOT), ALT (SGPT), GGT, alkaline phosphatase, bilirubin, and LDH. Hematologic: Eosinophilia, leukocytosis, lymphocytosis, granulocytosis, basophilia, mono- cytosis, thrombocytosis, decreased hemoglobin, decreased hematocrit, leukopenia, neu- tropenia, lymphocytopenia, thrombocytopenia, thrombocythemia, positive Coombs' test, and prolonged PT, and PTT. Serum Chemistry: Hyperglycemia, hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, and hyponatremia. Renal: Increases in BUN and creatinine. Most of these abnormalities were transient and not clinically significant. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation 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  By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

In acute rodent toxicity studies, a single 5 g/kg oral dose produced no adverse effects. In the event of serious toxic reaction from overdosage, hemodialysis or peritoneal dialysis may aid in the removal of cefpodoxime from the body, particularly if renal function is compromised. The toxic symptoms following an overdose of beta-lactam antibiotics may include nausea, vomiting, epigastric distress, and diarrhea.

5.1 Mechanism of action

Cefpodoxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefpodoxime has activity in the presence of some betalactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

5.2 Pharmacodynamic properties

Resistance to Cefpodoxime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability. Cefpodoxime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections

Gram-positive Bacteria

Staphylococcus aureus (methicillin-susceptible strains, including those producing penicillinases) Staphylococcus saprophyticus Streptococcus pneumoniae (excluding penicillin-resistant isolates) Streptococcus pyogenes

Gram-negative Bacteria

Escherichia coli Klebsiella pneumoniae Proteus mirabilis Haemophilus influenzae (including beta-lactamase producing isolates) Moraxella catarrhalis Neisseria gonorrhoeae (including penicillinase-producing isolates) The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefpodoxime. However, the efficacy of cefpodoxime in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-positive Bacteria

Streptococcus agalactiae Streptococcus spp. (Groups C, F, G)

Gram-negative Bacteria

Citrobacter diversus Klebsiella oxytoca Proteus vulgaris Providencia rettgeri Haemophilus parainfluenzae

Anaerobic Gram-positive Bacteria

Peptostreptococcus magnus

5.3 Pharmacokinetic properties

In adult subjects, a 100 mg dose of oral suspension produced an average peak cefpodoxime concentration of approximately 1.5 mcg/mL (range: 1.1 to 2.1 mcg/mL), which is equivalent to that reported following administration of the 100 mg tablet. Time to peak plasma concentration and area under the plasma concentration-time curve (AUC) for the oral suspension were also equivalent to those produced with film-coated tablets in adults following a 100 mg oral dose. The pharmacokinetics of cefpodoxime were investigated in 29 patients aged 1 to 17 years. Each patient received a single, oral, 5 mg/kg dose of cefpodoxime oral suspension. Plasma and urine samples were collected for 12 hours after dosing. The plasma levels reported from this study are as follows:

Dose did not exceed 200 mg.

Distribution

Protein binding of cefpodoxime ranges from 22 to 33% in serum and from 21 to 29% in plasma

Effects of Decreased Renal Function

Elimination of cefpodoxime is reduced in patients with moderate to severe renal impairment (<50 mL/min creatinine clearance). In subjects with mild impairment of renal function (50 to 80 mL/min creatinine clearance), the average plasma half-life of cefpodoxime was 3.5 hours. In subjects with moderate (30 to 49 mL/min creatinine clearance) or severe renal impairment (5 to 29 mL/mincreatinine clearance), the half-life increased to 5.9 and 9.8 hours, respectively. Approximately 23% of the administered dose was cleared from the body during a standard 3-hour hemodialysis procedure.

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data

Cefpodoxime proxetil is an orally administered, extended spectrum, semisynthetic antibiotic of the cephalosporin class. The chemical name is (RS)-1(isopropoxycarbonyloxy) ethyl (+) (6R,7R)-7-[2-(2-amino-4-thiazolyl)-2- {(Z)methoxyimino} acetamido]-3-methoxymethyl-8-oxo-5-thia-1-azabicyclo [4.2.0]oct-2-ene-2-carboxylate. Its empirical formula is C₂₁H₂₇N₅O₉S₂ and its structural formula is represented below:

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

Polares 100 DT : A strip of 10 tablets each.

Polares 200 : A strip of 10 tablets each.

8.4 Storage and handing instructions

Polares 100 DT : Store below 30°C. Protect from moisture.

Polares 200 : Store protected from moisture, at a temperature not exceeding 30°C.

Keep out of reach of children

Patients should be counseled that antibacterial drugs including Cefpodoxime Proxetil, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefpodoxime Proxetil, 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 Cefpodoxime Proxetil, or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible