Clavpod Dt

Uses

Cefpodoxime is used for the treatment of patients infected with susceptible strains of micro-organisms which include a wide range of gram-positive & gram-negative bacteria. As it is highly stable in presence of b-lactamase enzyme, so it is more effective against gram-positive bacteria than other 3rd generation oral Cephalosporins.

The susceptible organisms include gram-positive bacteria eg. S. aureus (including penicillinase producing strains), S. saprophyticus, S. pneumoniae, S. pyogenes, S. agalactiae, P. magnus and gram-negative bacteria eg. E. coli, K. pneumoniae, H. influenzae (including b-lactamase producer & Ampicillin resistant strains), M. catarrhalis, N. gonorrhoeae (including penicillinase producing strains), P. mirabillis, C. diversus, H. parainfluenzae, K. oxytoca, P. vulgaris, P. rettgeri.

Ximeprox is used for the following diseases:-

(1) Lower respiratory tract infection: Acute community-acquired pneumonia, Acute bacterial exacerbation of chronic bronchitis; (2) Upper respiratory tract infection: Acute otitis media, Acute maxillary sinusitis, Pharyngitis, Tonsillitis; (3) Sexually transmitted diseases: Acute uncomplicated urethral & cervical gonorrhea, Acute ano-rectal infection in woman caused by N. gonorrhoeae; (4) Uncomplicated urinary tract infection: Cystitis, Pyuria; (5) Skin & soft tissue infections: Furuncle, Cellulitis, Subcutaneous abscess, infectious atheroma & periproctal abscess (6) Enteric fever.

Clavulanic acid is a beta lactamase inhibitor used to enhance the effectiveness of beta lactam antibiotics.

Clavulanic acid combined with other antibiotics is indicated to prevent the development of drug-resistant strains of bacteria and promotes their therapeutic antibacterial effects.

The following conditions, when they produced beta-lactamases, have been treated with a combination of amoxicillin and clavulanic acid or ticarcillin and clavulanic acid:

Acute otitis media caused by H. influenzae and M. catarrhalis

Sinusitis due to H. influenzae and M. catarrhalis

Lower respiratory tract infections due to Haemophilus influenzae, S.aureus, Klebsiella species, and Moraxella catarrhalis

Skin and skin structure infections caused by Staphylococcus aureus, Escherichia coli, and Klebsiella species

Urinary Tract Infections due to E. coli, Klebsiella species of bacteria, and Enterobacter species of bacteria, S.marcescens, or S.aureus

Gynecologic infections due to a variety of bacteria, including P.melaninogenicus, Enterobacter species, E.Coli species, Klebsiella species, S. aureus, S.epidermidis

Septicemia due to a variety of bacteria, including Klebsiella species, E.Coli species, S.aureus, or Pseudomonas species

Bone and joint infections due to S.aureus

Intraabdominal infections due to E.Coli, K.pnemoniae, or B.fragilis group

A note on susceptibility

It should be noted that it is only to be administered in infections that are confirmed or highly likely to be caused by susceptible bacteria. Culture and susceptibility tests should be performed if possible and used in selecting whether this antibiotic is prescribed. When beta-lactamase enzyme production is not detected during microbiological testing, clavulanic acid should not be used. When these tests are not available patterns of local infection and susceptibility may be used to determine the appropriateness of using clavulanic acid. Ticarcillin with clavulanate has shown particular efficacy in mixed infections in addition to empiric therapy before determining the susceptibility of causative organisms. The ticarcillin-clavulanic acid combination may prove to be an effective single-agent antibiotic therapy to treat infections where a regimen of several drugs may normally be used.

Clavpod Dt is also used to associated treatment for these conditions: Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Acute Otitis Media, Acute Sinusitis, Acute Tracheobronchitis, Acute maxillary sinusitis, Bacterial Infections, Bacterial Pneumonia, Community Acquired Pneumonia (CAP), Gonorrhea, Lower Respiratory Tract Infection (LRTI), Otitis Media (OM), Pharyngitis, Skin and Soft Tissue Infections, Streptococcal Pharyngitis, Streptococcal tonsillitis, Superinfection bacterial, Tonsillitis, Uncomplicated Urinary Tract Infections, Upper Respiratory Tract Infection, Uncomplicated Lower Respiratory Tract Infection (LRTI), Uncomplicated Upper Respiratory Tract Infection, Uncomplicated Urethritis gonococcal, Uncomplicated skin and subcutaneous tissue bacterial infectionsAcute Cystitis, Acute Uncomplicated Pyelonephritis, Bacterial Infections, Bacterial Pneumonia, Bacterial infection due to streptococcus, group A, Bloodstream Infections, Bone and Joint Infections, Bronchitis, Cysto-Urethritis, Gonorrhoea, Gynaecological infection, Haemophilus Influenzae, Infection Due to Escherichia Coli, Intraabdominal Infections, Lower Respiratory Infection, Lower Respiratory Tract Infection (LRTI), Moraxella catarrhalis, Otitis Media (OM), Pharyngitis, Proteus mirabilis, Sinusitis, Skin and skin structure infections, Streptococcus Pneumoniae, Tonsillitis, Upper Respiratory Tract Infection, Urinary Tract Infection, Skin and skin-structure infections, Susceptible Bacterial Infections

How Clavpod Dt works

Cefpodoxime is active against a wide spectrum of Gram-positive and Gram-negative bacteria. Cefpodoxime is stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and cephalosporins, due to their production of beta-lactamase, may be susceptible to cefpodoxime. Cefpodoxime is inactivated by certain extended spectrum beta-lactamases. The bactericidal activity of cefpodoxime results from its inhibition of cell wall synthesis. The active metabolite of cefpodoxime binds preferentially to penicillin binding protein 3, which inhibits production of peptidoglycan, the primary constituent of bacterial cell walls.

Clavulanic acid contains a beta-lactam ring in its structure that binds in an irreversible fashion to beta-lactamases, preventing them from inactivating certain beta-lactam antibiotics, with efficacy in treating susceptible gram-positive and gram-negative infections.

Dosage

Clavpod Dt dosage

Ximeprox should be administered orally with food to enhance absorption. Ximeprox suspension may be given without regard to food.

Child :

15 days - 6 months : 4 mg/kg every 12 hours

6 months - 2 years : 40 mg every 12 hours

3 - 8 years : 80 mg every 12 hours

over 9 years : 100 mg every 12 hours

Patients with renal dysfunction: For patients with severe renal impairment (creatinine clearance <30 ml/min) the dosing intervals should be increased to 24 hourly.

Patients with liver cirrhosis: Cefpodoxime proxetil pharmacokinetics in cirrhotic patients are similar to those in healthy subjects. Dose adjustment is not necessary in this population.

Direction for Reconstitution of suspension:

For 100 ml suspension : Add 50 ml (10 measuring spoonful) of boiled and cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

For 50 ml suspension : Add 25 ml (5 measuring spoonful) of boiled and cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

For 50 ml DS suspension : Add 25 ml (5 measuring spoonful) of boiled and cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place, preferably in refrigerator and unused portion should be discarded after 10 days.

Side Effects

Cefpodoxime has very few side effects. The side effects include diarrhea, nausea, skin & vaginal fungal infection, abdominal pain, headache, chest pain, myalgia, dyspepsia, dizziness, vertigo, cough etc. In children incidence of fungal skin rash is more than adults.

Toxicity

LD50 information

Clavulanic acid has demonstrated low oral acute toxicity in adult rodents, having an LD50 of more than 2000 mg/kg. The toxicity of clavulanic acid on pre-weaning rats was also studied. Gastrointestinal disturbance and mortality occurred, even at lower clavulanic acid doses of 125 mg/kg.

Overdose information

Overdose information has been obtained for the combination of amoxicillin and clavulanic acid, as these drugs are frequently administered together in a single product. Changes in fluid and electrolyte balances and gastrointestinal symptoms may occur in the case of an overdose. Offer symptomatic treatment or gastrointestinal disturbances, while considering the importance of fluid and electrolyte balance. This drug may be removed by a session of hemodialysis. When coadministered with amoxicillin, crystalluria causing renal failure has been observed. Seizures may also occur in a case of overdose, or in a patient with renal failure.

Precaution

In patients with transient or persistent reduction in urinary output due to renal insufficiency, the total daily dose of cefpodoxime proxetil should be reduced. Cefpodoxime, like other cephalosporins, should be administered with caution to patients receiving concurrent treatment with potent diuretics. As with other broad spectrum antibiotics, prolonged use of cefpodoxime proxetil may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential.

Interaction

Antacids or H2-blockers may decrease the absorption of cefpodoxime. Reduced renal excretion with probenecid.

Volume of Distribution

A study in 4 healthy volunteers administered a radiolabeled dose of clavulanic acid determined a volume of distribution of 12L.Clavulanic acid is distributed to various tissues and interstitial fluid. Clinically significant concentrations have been measured in the gallbladder, abdomen, skin, fat, and muscle tissues. Bile, pus, synovial and peritoneal fluids are also found to have therapeutic concentrations of clavulanic acid. Studies of animals have demonstrated that clavulanic crosses the placenta.

Elimination Route

Cefpodoxime proxetil is a prodrug that is absorbed from the gastrointestinal tract and de-esterified to its active metabolite, cefpodoxime. Following oral administration of 100 mg of cefpodoxime proxetil to fasting subjects, approximately 50% of the administered cefpodoxime dose was absorbed systemically.

Clavulanic acid, when taken orally, is well absorbed in the gastrointestinal tract. After administration of radiolabeled clavulanic acid to four human subjects, a minimum of 73% absorption and the average absolute bioavailability was calculated at 64%. The mean Cmax in a group of 8 healthy research volunteers was 2.098 ± 0.441 micrograms/ml in a pharmacokinetic study. The same study reported a mean Tmax of 1.042 ± 0.80 hours. Tmax is reported to be 40-120 minutes according to another pharmacokinetic study.

Half Life

2.09 to 2.84 hours

The half-life of clavulanic acid is reported to be similar to amoxicillin, and last 45-90 minutes. A study of radiolabeled clavulanic acid administered to 4 healthy volunteers determined a half-life of 0.8 h.

Clearance

The clearance of clavulanic acid in a pharmacokinetic study of 4 healthy volunteers administered a radiolabeled dose of clavulanic acid was 0.21 l/min. Another resource indicates the average clearance of clavulanic acid is 12.20 liters/h/70 kg. Dose adjustments may be required in patients with renal failure.

Elimination Route

Over the recommended dosing range (100 to 400 mg), approximately 29 to 33% of the administered cefpodoxime dose was excreted unchanged in the urine in 12 hours.

About 40 to 65% of the clavulanic acid is excreted as unchanged drug in urine during the first 6 hours following ingestion. The metabolites of clavulanic acid are found to be excreted in the urine and feces and as carbon dioxide in expired air. Clavulanate is cleared by both renal and non-renal processes. About 17% of radiolabeled dose of clavulanic acid was found to be exhaled in expired air and 8% of a dose was found to be excreted in the feces.

Pregnancy & Breastfeeding use

There are no adequate and well-controlled studies on Cefpodoxime proxetil use in pregnant woman, but it was found neither teratogenic nor embryocidal in animal trial. However, the drug should be used during pregnancy only if clearly needed. In nursing mother, Cefpodoxime is excreted in breast milk & there is potential risk of serious reactions in nursing infants, so a decision should be made whether to discontinue breast feeding or to discontinue the drug.

Contraindication

Cefpodoxime is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.

Renal Impairment: Patients with renal dysfunction: For patients with severe renal impairment (creatinine clearance <30 ml/min) the dosing intervals should be increased to 24 hourly.

Hepatic Impairment: The dosage does not require modification in cases of hepatic impairment.

Acute Overdose

Symptoms: Nausea, vomiting, epigastric distress and diarrhoea.

Management: Haemodialysis or peritoneal dialysis may be useful in the event of a serious toxic reaction particularly if renal function is compromised.

Storage Condition

Capsule: Store below 30° C, protected from light and moisture.

Powder for suspension: Store below 25° C, protected from light and moisture.

After reconstitution: The suspension can be used within 7 days if be kept at room temperature and within 14 days if be kept in refrigerator (2° to 8° C). Always keep the bottle tightly closed.

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