Composition

CEFORENZ-200 Tablet

 Each Tablet contains:

 Cefpodoxime Proxetil eq. to Cefpodoxime ………………… 500 mg

CEFORENZ-50 Dry syrup

 Each Dry syrup contains:

Cefpodoxime Proxetil eq. to Cefpodoxime   ………………….50 mg

Mechanism of action
Cefpodoxime proxetil is a semi-synthetic beta-lactam antibiotic belonging to the third generation oral cephalosporin group. Cefpodoxime proxetil is the prodrug of the bactericidal antibiotic cefpodoxime. The antibacterial action of cefpodoxime is through inhibition of bacterial cell wall synthesis probably by acylation of membrane bound transpeptidase enzymes; this prevents cross linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity.
Antibacterial spectrum
In vitro studies have demonstrated the susceptibility of most strains of the following micro-organisms to cefpodoxime proxetil. However, such in vitro activity does not necessarily imply in vivo efficacy.
Gram-positive organisms
Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. mitis, S. sanguis and S. salivarius; Propionibacterium acnes; Corynebacterium diphtheriae; methicillin-sensitive penicillinase and non-penicillinase producing strains of S. aureus.
Gram negative organisms
Beta-lactamase and non-beta-lactamase producing strains of Haemophilus influenzae, Haemophilus para-influenzae, Moraxella catarrhalis (Branhamella catarrhalis) and Neisseria gonorrhoea; Escherichia coli; Klebsiella pneumoniae; Klebsiella oxytoca; Proteus mirabilis.
The following organisms are not sensitive: Group D streptococci, Methicillin-resistant staphylococci (S. aureus and S. epidermidis), Staphylococcus saprophyticus, Corynebacteria, groups J and K, Listeria monocytogenes,Pseudomonas aeruginosa and Pseudomonas spp., Acinetobacter baumanii, Clostridium difficile, Bacteroides fragilis and related species.

Pharmacokinetics
Cefpodoxime proxetil is absorbed orally and rapidly hydrolysed by non-specific esterases in the gastro-intestinal wall to cefpodoxime, the active acid. Absorption is decreased in conditions of low gastric acidity. After oral administration of a single dose of 200 mg of cefpodoxime, the maximum plasma concentration (Cmax) obtained is 2,23 mg/L. After oral administration of a single 5 mg/kg (200 mg maximum) dose of cefpodoxime proxetil suspension in children, the maximum plasma concentration (Cmax) obtained is on average 2,6 mg/L. With cefpodoxime proxetil tablets the time taken to reach the maximum concentration (Tmax) is about 2,7 hours. With the suspension the time taken to reach the maximum concentration (Tmax) is about 2 to 4 hours. The drug diffuses well into respiratory tissues. The serum half-life is about 2,46 hours. About 27% of cefpodoxime in the plasma is bound to plasma proteins. The volume of distribution is about 0,46 L/kg and the clearance is around 2,4 mL/min/kg. About 81% of unchanged cefpodoxime is excreted in the urine.

Cefpodoxime proxetil 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 -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.

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

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).

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

Acute maxillary sinusitis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus.

Uncomplicated urinary tract infections (cystitis)

Ceforenz 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)

Diarrhea, nausea/vomiting, or headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: swelling of the ankles/feet, tiredness, fast/pounding heartbeat, trouble breathing, new signs of infection (e.g., fever, persistent sore throat), dark urine, persistent nausea/vomiting, yellowing eyes/skin, easy bruising/bleeding, change in the amount of urine.

Seek immediate medical attention if any of these rare but very serious side effects occur: vision changes, slurred speech, mental/mood changes (such as confusion).

This medication may rarely cause a severe intestinal condition (Clostridium difficile-associated diarrhea) due to a type of resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool. Do not use anti-diarrhea products or narcotic pain medications if you have any of these symptoms because these products may make them worse.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

The following drugs are found to be interacted with cefpodoxime (CEFORENZ) as it following drug should be  avoided with it.

·         with lithium (Lithobid);

·         probenecid (Benemid);

·         methotrexate (Rheumatrex, Trexall);

·         antiviral medicines such as adefovir (Hepsera), cidofovir (Vistide), or foscarnet (Foscavir);

·         cancer medicine such as aldesleukin (Proleukin), carmustine (BiCNU, Gliadel), cisplatin (Platinol), ifosfamide (Ifex), oxaliplatin (Eloxatin), plicamycin (Mithracin), streptozocin (Zanosar), or tretinoin (Vesanoid);

·         a diuretic (water pill) such as bumetanide (Bumex), furosemide (Lasix), indapamide (Lozol), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Lopressor, Vasoretic, Zestoretic), metolazone (Mykrox, Zarxolyn), spironolactone (Aldactazide, Aldactone), torsemide (Demadex), and others;

·         a medication that reduces stomach acid, such as an antacid, or cimetidine (Tagamet), famotidine (Pepcid), omeprazole (Prilosec), ranitidine (Zantac), and others;

·         IV antibiotics such as amphotericin B (Fungizone, AmBisome, Amphotec, Abelcet), amikacin (Amikin), bacitracin (Baci-IM), capreomycin (Capastat), gentamicin (Garamycin), kanamycin (Kantrex), streptomycin, or vancomycin (Vancocin, Vancoled);

·         medicines used to prevent organ transplant rejection, such as sirolimus (Rapamune) or tacrolimus (Prograf);

·         medicines used to treat ulcerative colitis, such as mesalamine (Pentasa) or sulfasalazine (Azulfidine); or

·         pain or arthritis medicines such as aspirin (Anacin, Excedrin), acetaminophen (Tylenol), diclofenac (Cataflam, Voltaren), etodolac (Lodine), ibuprofen (Advil, Motrin), indomethacin (Indocin), naproxen (Aleve, Naprosyn), and others.

This list is not complete and there may be other drugs that can interact cefpodoxime.

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.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including CEFORENZ, and may range in severity from mild diarrhea to fatal colitis.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

A concerted effort to monitor for C. difficile in cefpodoxime-treated patients with diarrhea was undertaken because of an increased incidence of diarrhea associated with C. difficile in early trials in normal subjects. C. difficileorganisms or toxin was reported in 10% of the cefpodoxime-treated adult patients with diarrhea; however, no specific diagnosis of pseudomembranous colitis was made in these patients.

In post-marketing experience outside the United States, reports of pseudomembranous colitis associated with the use of cefpodoxime proxetil have been received.

Precaution

General

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 super infection occurs during therapy, appropriate measures should be taken.

Prescribing CEFORENZ 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal carcinogenesis studies of cefpodoxime proxetil have not been performed. Mutagenesis studies of cefpodoxime, including the Ames test both with and without metabolic activation, the chromosome aberration test, the unscheduled DNA synthesis assay, mitotic  recombination and gene conversion, the forward gene mutation assay and the in vivo micronucleus test, were all negative. No untoward effects on fertility or reproduction were noted when 100 mg/kg/day or less (2 times the human dose based on mg/m²) was administered orally to rats.

Pregnancy

Teratogenic Effects - Pregnancy Category B

Cefpodoxime proxetil was neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day (2 times the human dose based on mg/m²) or to rabbits at doses up to 30 mg/kg/day (1–2 times the human dose based on mg/m²).

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. Treatment should only be given if clearly needed.

Nursing Mothers

Cefpodoxime is excreted in human milk. In a study of 3 lactating women, levels of cefpodoxime in human milk were 0%, 2% and 6% of concomitant serum levels at 4 hours following a 200 mg oral dose of cefpodoxime proxetil. At 6 hours post-dosing, levels were 0%, 9% and 16% of concomitant serum levels. 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.

Pediatric Use

Safety and efficacy in infants less than 2 months of age have not been established.

Geriatric Use

Of the 3338 patients in multiple-dose clinical studies of cefpodoxime proxetil film-coated tablets, 521 (16%) were 65 and over, while 214 (6%) were 75 and over. No overall differences in effectiveness or safety were observed between the elderly and younger patients. In healthy geriatric subjects with normal renal function, cefpodoxime half-life in plasma averaged 4.2 hours and urinary recovery averaged 21% after a 400 mg dose was given every 12 hours for 15 days. Other pharmacokinetic parameters were unchanged relative to those observed in healthy younger subjects.

Dose adjustment in elderly patients with normal renal function is not necessary.

Ceforenz (Cefpodoxime proxetil) is contra-indicated in patients who are allergic to the cephalosporin group of antibiotics. Safety of cefpodoxime proxetil for use in pregnancy and lactation has not been established.