Curocef

Cefpodoxime proxetil tablets

Composition

CUROCEF -100 DT
Each dispersible uncoated tablet contains
Cefpodoxime proxetil USP equivalent to
Cefpodoxime 100 mg
In a flavoured base

CUROCEF - 200 Tablets
Each film coated tablet contains
Cefpodoxime proxetil equivalent to
Cefpodoxime 200 mg

CUROCEF 50 Oral suspension
Each 5ml of reconstituted suspension contains
Cefpodoxime proxetil USP equivalent to
Cefpodoxime 50 mg

Pharmacology

 

Pharmacodynamics

Cefpodoxime proxetil is an orally administered, extended spectrum, semi-synthetic antibiotic of the cephalosporin class. 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.

Microbiology
Cefpodoxime is active against a wide-spectrum of Gram-positive and Gram-negative bacteria. Cefpodoxime has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections.

Aerobic Gram-positive microorganisms:
Staphylococcus aureus (including penicillinase-producing strains)
NOTE: Cefpodoxime is inactive against methicillin-resistant staphylococci.
Staphylococcus saprophyticus
Streptococcus pneumoniae (excluding penicillin-resistant strains)
Streptococcus pyogenes

Aerobic Gram-negative microorganisms:
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Haemophilus influenzae (including beta-lactamase producing strains)
Moraxella (Branhamella) catarrhalis
Neisseria gonorrhoeae (including penicillinase-producing strains)
The following in vitro data are available, but their clinical significance is unknown. Cefpodoxime exhibits in vitro minimum inhibitory concentrations (MICs) of </= 2.0 mcg/mL against most (>/=90%) of isolates of the following microorganisms. However, the safety and efficacy of cefpodoxime in treating clinical infections due to these microorganisms have not been established in adequate and well controlled clinical trials.

Aerobic Gram-positive microorganisms:
Streptococcus agalactiae
Streptococcus spp. (Groups C, F, G)
NOTE: Cefpodoxime is inactive against enterococci.

Aerobic Gram-negative microorganisms:
Citrobacter diversus
Klebsiella oxytoca
Proteus vulgaris
Providencia rettgeri
Haemophilus parainfluenzae
NOTE: Cefpodoxime is inactive against most strains of Pseudomonas and Enterobacter.
Anaerobic Gram-positive microorganisms:
Peptostreptococcus magnus

Pharmaco Kinetics

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. A 100 mg dose of oral suspension produced an average peak cefpodoxime concentration of approximately 1.5 mcg/mL.

When a 200 mg dose of the suspension was taken with food, the extent of absorption (mean AUC) and mean peak plasma concentration in fed subjects were not significantly different from fasted subjects, but the rate of absorption was slower with food (48% increase in T max ). Protein binding of cefpodoxime ranges from 22 to 33% in serum and from 21 to 29% in plasma. 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. There is minimal metabolism of cefpodoxime in vivo.

Indication

CUROCEF is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

Acute otitis media caused by Streptococcus pneumoniae, (excluding penicillin-resistant strains), Streptococcus pyogenes, Haemophilus influenzae (including beta-lactamase-producing strains), or Moraxella (Branhamella) catarrhalis (including beta-lactamase producing strains).

Pharyngitis and/or tonsillitis caused by Streptococcus pyogenes.

NOTE:  Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Cefpodoxime proxetil is generally effective in the eradication of streptococci from the oropharynx. However, data establishing the efficacy of cefpodoxime proxetil for the prophylaxis of subsequent rheumatic fever are not available.

Community-acquired pneumonia caused by S. pneumoniae or H. influenzae (including beta-lactamase-producing strains).
Acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae, H. influenzae (non-beta-lactamase-producing strains only), or M. catarrhalis. Data are insufficient at this time to establish efficacy in patients with acute bacterial exacerbations of chronic bronchitis caused by beta-lactamase-producing strains of H. influenzae.

Acute, uncomplicated urethral and cervical gonorrhea caused by Neisseria gonorrhoeae (including penicillinase-producing strains).

Acute, uncomplicated ano-rectal infections in women due to Neisseria gonorrhoeae (including penicillinase-producing strains).

NOTE: The efficacy of cefpodoxime in treating male patients with rectal infections caused by N. gonorrhoeae has not been established. Data do not support the use of cefpodoxime proxetil in the treatment of pharyngeal infections due to N. gonorrhoeae in men or women.

Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains) or Streptococcus pyogenes. Abscesses should be surgically drained as clinically indicated.

NOTE:  In clinical trials, successful treatment of uncomplicated skin and skin structure infections was dose-related. The effective therapeutic dose for skin infections was higher than those used in other recommended indications.

Acute maxillary sinusitis caused by Haemophilus influenzae (including beta-lactamase producing strains), Streptococcus pneumoniae, and Moraxella catarrhalis.

Uncomplicated urinary tract infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus.

NOTE: In considering the use of cefpodoxime proxetil in the treatment of cystitis, cefpodoxime proxetil's lower bacterial eradication rates should be weighed against the increased eradication rates and different safety profiles of some other classes of approved agents.

Dosage and Administration

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):
Type of Infection
Total Daily Dose
Dose Frequency
Duration
Pharyngitis and/or tonsillitis
200 mg
100 mg Q 12 hours
5 to 10 days
Acute community-acquired pneumonia
400 mg
200 mg Q 12 hours
14 days
Acute bacterial exacerbations of chronic bronchitis
400 mg
200 mg Q 12 hours
10 days
Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women)
200 mg
single dose
 
Skin and skin structure
800 mg
400 mg Q 12 hours
7 to 14 days
Acute maxillary sinusitis
400 mg
200 mg Q 12 hours
10 days
Uncomplicated urinary tract infection
200 mg
100 mg Q 12 hours
7 days

Infants and Pediatrics (Age: 2 months through 12 years)
Acute maxillary sinusitis
5 mg/kg (max 200 mg/dose) 12-hourly for 10 days
Acute otitis media
5 mg/kg (max 200 mg/dose) 12-hourly for 5 days
Pharyngitis and/or tonsillitis
5 mg/kg/dose (max 100 mg/dose) 12-hourly for 5 to 10 days

CUROCEF is provided in the form of a dry powder for constitution. Tap the bottle to loosen the powder. Add 2/3 rd of the sterile water (provided with this pack) and shake the bottle vigorously. Add more water up to the mark on the bottle and shake well. Allow the suspension to stand for 5 minutes. After mixing, the suspension should be stored in a refrigerator, 2° to 8°C (36° to 46°F). Shake well before using. Keep container tightly closed. The mixture may be used for 14 days. Discard unused portion after 14 days.

Contraindications
Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to the cephalosporin group of antibiotics.
Warnings and Precautions
Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to the cephalosporin group of antibiotics.

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. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefpodoxime, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an oral antibacterial drug effective against C. difficile.

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.

Drug interactions
Antacids: Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or H 2 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 anti-cholinergics (e.g., propantheline) delay peak plasma levels (47% increase in T max ), 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.
Renal impairment 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 haemodialysis, the dose frequency should be 3 times/week after haemodialysis.
Hepatic Impairment No dose adjustment is recommended for patients with hepatic insufficiency.
Pregnancy Used during pregnancy only if clearly needed.
Lactation 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.
Paediatric use Safety and efficacy in infants less than 2 months of age have not been established.
Geriatric Use Dose adjustment in elderly patients with normal renal function is not necessary.
Undesirable Effects
Adverse events thought possibly- or probably-related, or of unknown relationship to cefpodoxime proxetil for oral suspension in multiple dose clinical trials (N=2128 patients treated with cefpodoxime) were:
Incidence Greater Than 1%:
Diarrhea 6.0%
The incidence of diarrhea in infants and toddlers (age 1 month to 2 years) was 12.8%.
Diaper rash/Fungal skin rash      2.0%
(includes moniliasis)
The incidence of diaper rash in infants and toddlers was 8.5%.
Other skin rashes 1.8%
Vomiting  2.3%
Incidence Less Than 1%:
Body: Localized abdominal pain, abdominal cramp, headache, monilia, generalized abdominal pain, asthenia, fever, fungal infection.
Digestive: Nausea, monilia, anorexia, dry mouth, stomatitis, pseudomembranous colitis.
Hemic & Lymphatic: Thrombocythemia, positive direct Coombs' test, eosinophilia, leukocytosis, leukopenia, prolonged partial thromboplastin time, thrombocytopenic purpura.
Metabolic & Nutritional: Increased SGPT.
Musculo-Skeletal: Myalgia.
Nervous: Hallucination, hyperkinesia, nervousness, somnolence.
Respiratory: Epistaxis, rhinitis.
Skin: Skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, maculopapular rash.
Special Senses: Taste perversion.
Overdosage
In the event of serious toxic reaction from overdosage, haemodialysis 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 diarrhoea.
Shelf-Life
See on pack
Storage and Handling Instructions
CUROCEF-100 DT & 200 Store in a cool dry place
CUROCEF 50 Oral suspension Store in a cool dry place
Protect from light
Packaging Information
CUROCEF – 100 DT & 200 (Strip of 10 Tablets)
CUROCEF 50 Oral suspension Bottle of 30ml