Z-Fix 400

Each orodispersible tablet contains: Cefixime (as trihydrate) USP 400 mg.
Colour: FD&C Yellow No. 6.
CEFIXIME (Z-FIX 400) 400 mg dispersible tablet is a semisynthetic, cephalosporin antibiotic for oral administration. Chemically, it is (6R,7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 72-(Z)-[O-(carboxymethyl) oxime] trihydrate. Molecular weight= 507.50 as the trihydrate. Chemical Formula is C₁₆H₁₅N₅O₇S₂·3H₂O.
CEFIXIME (Z-FIX 400) 400 mg dispersible tablet are available off-white coloured, elongated, biconvex, dispersible tablet having break line on one side and plain on other side, for oral administration. It contains the following inactive ingredients: microcrystalline cellulose (PH-102), maize starch, purified talc, magnesium stearate, colloidal anhydrous silica, croscarmellose sodium, tulsion 339, aspartame, sunset yellow, flavour dry sweet orange, starch glycolate (Type-A) and Aspartame.

Pharmacology: Pharmacodynamics: Cefixime exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. It binds to specific penicillin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves completion of the cross-linking of the terminal glycine residue of the pentaglycine bridge to the fourth residue of the pentapeptide. The transpeptidase that catalyzes this step is inhibited by cephalosporins. Thus, inhibition of the transpeptidase interrupts peptidoglycan synthesis, causing formation of defective cell walls and osmotically unstable spheroplasts and lysis of the bacteria.
Pharmacokinetics: CEFIXIME (Z-FIX 400) dispersible tablets, given orally, are about 40%-50% absorbed from gastrointestinal tract whether administered with or without food; although the rate of absorption may be decreased in the presence of food. Absorption is fairly slow; peak plasma concentrations of 2 to 3 micrograms/ml and 3. 7 to 4.6 micrograms/ml have been reported between 2 and 6 hours after single doses of 200 and 400 mg, respectively. About 65% of cefixime is bound to plasma proteins. The plasma half-life is usually about 3 to 4 hours and may be prolonged when there is renal impairment. Information on the distribution of cefixime in body tissues and fluids is limited. It crosses the placenta. Relatively high concentrations may be achieved in bile and urine. About 20% of an oral dose (or 50% of an absorbed dose) is excreted unchanged in the urine within 24 hours. Up to 60% may be eliminated by non-renal mechanisms; there is no evidence of metabolism but some is probably excreted into the faeces from bile. It is not substantially removed by dialysis.
Microbiology: Antimicrobial Action: As with other cephalosporins, bactericidal action of cefixime results from inhibition of cell-wall synthesis. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamase may be susceptible to cefixime. Cefixime has been shown to be active against many strains of the gram-positive and gram negative both in vitro and in clinical infections. It has a mode of action and spectrum of activity similar to those of the third-generation cephalosporin cefotaxime, but some Enterobacteriaceae are less susceptible to cefixime. Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis), and Neisseria gonorrhoeae are sensitive, including penicillinase-producing strains of the Gram positive bacteria, Streptococci are sensitive to cefixime but most strains of staphylococci, enterococci, and Listeria spp. are not Enterobacter spp., Pseudomonas aeruginosa, and Bacteroides spp. are resistant to cefixime.

To reduce the development of drug resistant bacteria and maintain the effectiveness cefixime should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
CEFIXIME (Z-FIX 400) dispersible tablets are indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Uncomplicated Urinary Tract Infections caused by Escherichia coli and Proteus mirabilis.
Uncomplicated gonorrhea caused by N. gonorrhoeae, Otitis Media caused by Haemophilus influenzae (beta-lactamase positive and negative strains), Moraxella (Branhamella) catarrhalis (most of which are beta-lactamase positive) and S. pyogenes.
Pharyngitis and Tonsillitis, caused by S. pyogenes. Acute Bronchitis and Acute Exacerbations of Chronic Bronchitis, caused by Streptococcus pneumoniae and Haemophilus influenzae (beta-lactamase positive and negative strains).

Adults: It is given orally 200 to 400 mg daily as a single dose or in two divided doses. 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 cefixime. This may be administered as a single daily dose or may be given in two divided doses. Children weighing more than 50 kg or older than 12 years should be treated with the recommended adult dose.
Renal Impairment: Cefixime tablets may be administered in the presence of impaired renal function. Normal dose and schedule may be employed in patients with creatinine clearances of 60 mL/min or greater. Patients whose clearance is between 21 and 60 mL/min or patients who are on renal hemodialysis may be given 75% of the standard dosage at the standard dosing interval (300 mg daily). Patients whose clearance is < 20 mL/min or patients who are on continuous ambulatory peritoneal dialysis may be given half the standard dosage at the standard dosing interval (200 mg daily).

Gastric lavage may be indicated; otherwise, no specific antidote exists. Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis. Adverse effects in small numbers of healthy adult volunteers receiving single doses up to 2 g of cefixime did not differ from the profile seen in patients treated at the recommended doses.

CEFIXIME (Z-FIX 400) dispersible tablets are contraindicated in patients with known allergy to the cephalosporin group of antibiotics. Anaphylactic/anaphylactoid reactions have been reported with the use of cefixime. Antibiotics, including cefixime, should be administered cautiously to any patient who has demonstrated some form of allergy, particularly to treatment with broad spectrum antibiotics, including cefixime tablets, alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of severe antibiotic associated diarrhea including pseudomembranous colitis. Pseudomembranous colitis has been reported with the use of cefixime chewable tablets and other broad spectrum antibiotics; therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with the use of antibiotics. Symptoms of pseudomembranous colitis may occur during or after antibiotic treatment and may range in severity from mild to life-threatening. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, management should include fluids, electrolytes, and protein supplementation. If the colitis does not improve after the drug has been discontinued, or if the symptoms are severe, oral vancomycin is the drug of choice for antibiotic-associated pseudomembranous colitis produced by C. difficile. Other causes of colitis should be excluded.

This product contains aspartame which may cause allergic type of reaction including anaphylactic symptoms and life-threatening episodes in certain susceptible persons.

General: CEFIXIME (Z-FIX 400) dispersible tablets in the absence of a proven or strongly suspected bacterial infection of a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.
The possibility of the emergence 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 continuous 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. Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic. impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.
Use in Children: Safety and effectiveness of cefixime in children aged less than six months old have not been established.

Pregnancy: Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Potential benefit should justify the potential risk when cefixime is used during pregnancy.
Labor and Delivery: The effect of cefixime in labor and delivery is unknown.
Lactation: It is not known whether cefixime is excreted in human milk. Consideration should be given to discontinuing breastfeeding temporarily during treatment with cefixime.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Lifetime studies in animals to evaluate carcinogenic potential have not been conducted. Cefixime did not cause point mutations in bacteria or mammalian cells, DNA damage, or chromosome damage in vitro and did not exhibit clastogenic potential in vivo in the mouse micronucleus test. In rats, fertility and reproductive performance were not affected by cefixime at doses up to 125 times the adult therapeutic dose.
Usage in Pregnancy: Reproduction studies have been performed in mice and rats at doses up to 400 times the human dose and have revealed no evidence of harm to the fetus due to cefixime.
There are no adequate and well-controlled studies 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.

Most of adverse effects observed in clinical trials were of a mild and transient nature. Five percent (5%) of patients discontinued therapy because of drug-related adverse effects. The most commonly seen adverse effects were gastrointestinal events, which were reported in 30% of adult patients on either the BID or the QD regimen. Clinically mild gastrointestinal symptoms occurred in 20% of all patients, moderate events occurred in 9% of all patients and severe adverse effects occurred in 2% of all patients. Individual event rates included diarrhea 16%, loose, or frequent stools 6%, abdominal pain 3%, nausea 7%, dyspepsia 3%, and flatulence 4%. These symptoms usually responded to symptomatic therapy or ceased when cefixime was discontinued. Several patients developed severe diarrhea and/or documented pseudomembranous colitis, and a few required hospitalization.
The following adverse effects have been reported following the use of cefixime. Incidence rates were less than 1 in 50 (less than 2%), except as noted previously mentioned for gastrointestinal events.
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 symptoms may occur during or after therapy.
Hypersensitivity Reactions: Anaphylactic/anaphylactoid reactions (including shock and fatalities), skin rashes, urticaria, drug fever, pruritus, angioedema, and facial edema. Erythema multiforme, Stevens-Johnson syndrome, and serum sickness like reactions have been reported.
Hepatic: Transient elevations in SGPT, SGOT, alkaline phosphatase, hepatitis, jaundice.
Renal: Transient elevations in BUN or creatinine, acute renal failure.
Central Nervous System: Headaches, dizziness, seizures.
Hemic and Lymphatic Systems: Transient thrombocytopenia, leukopenia, neutropenia, and eosinophilia. Prolongation in prothrombin time was seen rarely.
Abnormal Laboratory Tests: Hyperbilirubinemia.
Other: Genital pruritus, vaginitis, candidiasis, toxic epidermal necrolysis.

Carbamazepine: Elevated carbamazepine levels have been reported in post marketing experience when cefixime is administered concomitantly. Drug monitoring may be of assistance in detecting alterations in carbamazepine plasma concentrations.
Warfarin and Anticoagulants: Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly.
Drug/Laboratory Test Interactions: A false-positive reaction for ketones in the urine may occur with tests using nitroprusside but not with those using nitroferricyanide. The administration of cefixime may result in a false-positive reaction for glucose in the urine using Clinitest, Benedict's solution, or Fehling's solution. A false-positive direct Coombs test has been reported during treatment with other cephalosporin antibiotics; therefore, it should be recognized that a positive Coombs test may be due to the drug.

Store at temperatures not exceeding 30°C.

Cephalosporins

J01DD08 - cefixime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

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