COMPOSITION :

 

Cefixime is a semi-synthetic broad spectrum third generation cephalosporin antibiotic for oral administration. Cefixime, one of the three oral third generation cephalosporins has the most activity of all oral cephalosporins against Streptococcus pyogens, S. pneumonia and all Gram negative bacilli, including betalactamase producing strains of H. influenza, Moraxella catarrhalis and N. gonorrhea.Cefixime has little activity against Staphylococci.

MECHANISM OF ACTION: CEFIXIME act by inhibiting the bacterial cell wall synthesis and are bactericidal. Also the autolytic enzymes in cell wall may be activated leading to bacterial death.

Pharmacology: When given orally, about 40 -50 % is absorbed with or without food; Cmax is increased by 0.8 hrs when given with food. A tablet of 200 mg produces serum concentration of about 2mcg/ml and that of 400 mg about 3.7 mcg/ml. The oral suspension produces peak concentrations of 25 -50 % higher than tablets and bioavailability of 10 -25 % higher than tablets as compared to tablets in adult volunteers. Because of lack of bioequivalence, tablet should not be substituted for oral suspension. The comparative study in children is not reported.

Approximately 50 % of the absorbed dose is excreted unchanged in the urine in 24 hrs. Serum half life in healthy subjects is 3-4 hrs but may range up to 9 hrs in some volunteers. The half life is significantly increased in renal impairment. The drug is not significantly cleared from the blood by haemodialysis or peritoneal dialysis. There is no evidence of metabolism in vivo.

MICROBIOLOGY: As with other cephalosporins, bactericidal action of CEFIXIME results from inhibition of cell wall synthesis.CEFIXIME is highly stable in the presence of beta-lactamse enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to Cefixime. CEFIXIME has been shown to be active against most strains of the following organisms both in vitro and in clinical infections:

Gram -Positive Organisms
Streptococcus pneumonia
Streptococcus pyogenes

Gram -Negative Organisms
Haemophilus influenza (beta-lactamase positive and negative strains )
Moraxella (Branhamella) catarrhalis ( most of which are beta-lactamase positive)
Escherichia coli
Proteus mirabilis
Neisseria gonorrhoeae (including penicillinase and non-penicillinase- producing strains.

INDICATIONS AND USAGE: CEFIXIME is indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms:

• Otitis Media caused by Haemophilus influenza (beta- lactamase positive and negative strains), Moraxella ( Branhamella) catarrhalis, (most of which are beta-lactamase positive) and S. pyogenes.
• Pharyngitis and Tonsilitis
• Acute Bronchitis and Acute Exacerbations of Chronic Brochitis caused by Streptococcus pneumonia and Haemophilus influenza(beta-lactamase positive and negative strains).
• Uncomplicated Urinary Tract Infections caused by E. Coli and Proteus mirabilis.
• Uncomplicated Gonorrhea(Cervical/ Urethral), caused by Neisseria gonorrhoeae (penicilinase- and nonpenicilinase- producing strains).
• Typhoid Fever.

DOSAGE AND ADMINISTRATION: Adults: The recommended dose of Cefixime is 400 mg daily. This may be given as a 400mg tablet daily or as 200 mg tablet every 12 hours. For the treatment of Uncomplicated cervical/urethral gonococcal infections, a single oral dose of 400 mg is recommended.

Children : The recommended dose is 8 mg/ kg/ day of the suspension. This may be administered as a single daily dose or may be given in two divided doses, as 4 mg/kg every 12 hours. In Typhoid the dose is 20 mg/ kg/ day in two divided doses or as a single dose.

Infants : Up to 6 months of age – dosage has not been established.
Children weighing more than 50 kg or older than 12 years should be treated with the recommended adult dose.

Otitis media should be treated with the suspension.Clinical studies of Otitis media were conducted with the suspension, and the suspension results in higher peak blood levels than the tablet when administered at the same dose. Therefore, the tablet should not be substituted for the suspension in the treatment of Otitis media.

DRUG INTERACTIONS: Probenecid may increase the blood concentration of Cefixime by decreasing removal of Cefixime by the kidney. This interaction sometimes is used to enhance the effect of cephalosporins.

Combining Cefixime with aminoglycosides for example, tobramycin produces additive bacterial killing effects but also may increase the risk of harmful effects to the kidney.

Cefixime may cause a false positive urine ketone test.

PREGNANCY: Safety in pregnancy has not been established for Cefixime. There are no adequate studies in pregnant women; however, studies in animals suggest no important effects on the fetus.

NURSING MOTHERS: Safety in nursing mothers has not been established. It is not known if Cefixime is excreted in breast milk.

SIDE EFFECTS: Cefixime is generally well tolerated, and side effects usually are transient. Reported side effects include diarrhea, nausea, abdominal pain, vomiting, skin rash, fever, joint pain and arthritis, abnormal liver tests, vaginitis, itching, headaches, and dizziness.

Cefixime should be avoided by patients with a known allergy to cephalosporin type antibiotics. Since Cefixime is chemically related to penicillin, an occasional patient can have an allergic reaction (sometimes even life-threatening anaphylaxis) to both medications.

Cefixime is used to treat a wide variety of bacterial infections. This medication is known as a cephalosporin antibiotic. It works by stopping the growth of bacteria. This antibiotic treats only bacterial infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or overuse of any antibiotic can lead to its decreased effectiveness.

PRECAUTIONS: General : The possibility of the emergency of resistant organisms, which might result in overgrowth should be kept in mind, particularly during prolonged treatment. In such use, careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

The dose of CEFIXIME should be adjusted in patients with renal impairment as well as those undergoing continous ambulatory peritoneal dialysis ( CAPD) and hemodialysis (HD). Patients on dialysis should be monitored carefully.

CEFIXIME should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

ADVERSE REACTIONS: Most of the adverse reactions observed in clinical trials were of a mild and transient nature.

Gastrointestinal : Diarrhea, loose stools, abdominal pain, Dyspepsia, Nausea, and Vomiting. Several cases of documented pseudomembranous colitis were identified during the studies. The onset of pseudomembranous colitis symptons may occur during or after therapy.

Hypersensitivity Reactions : Skin rashes, Urticaria, drug fever, and Pruritus. Erythema multiforme, Stevens- Johnson syndrome, and serum sickness- like reactions have been reported.

Hepatic : Transient elevations in SGPT, SGOT, and alkaline phosphatase.
Renal : Transient elevations in BUN or creatinine.
Central Nervous System : Headache or dizziness.
Hemic & Lymphatic Systems : Transient thrombocytopenia, Leukopenia, and eosinophilia. Prolongation in prothrombin time was seen rarely.
Other : Genital pruritus, vaginitis, candidiasis.

PACKAGING INFORMATION: Sorafix -100 : Cefixime 100 mg dispersible tablets : Strip of 10 Tabs.
Sorafix -200 : Cefixime 200 mg dispersible tablets : Strip of 10 Tabs.