Zifex Plus

Zifex Plus

Manufacturer:

Zifam Pinnacle

Distributor:

Pinnacle House
Full Prescribing Info
Contents
Cefixime trihydrate, potassium clavulanate.
Description
Each tablet contains cefixime 200 mg and potassium clavulanate 125 mg.
Each 5 mL of dry syrup contains cefixime 50 mg and potassium Clavulanate 31.25 mg.
Action
Pharmacology: Cefixime is a semisynthetic, 3rd-generation cephalosporin antibiotic, effective against a wide spectrum of sensitive gram-positive, gram-negative and anaerobic bacterial pathogens including β-lactamase-producing strains. It has high affinity for penicillin-binding proteins with varying site of activity. It acts by inhibition of bacterial cell wall synthesis. The elimination half-life is about 3 hrs with little variation over the usual therapeutic dosage range.
Clavulanic acid is a naturally derived β-lactamase inhibitor produced by Streptomyces clavuligerus. Clavulanic acid is an irreversible inhibitor of intracellular and extracellular β-lactamases, demonstrating concentration-dependent and competitive inhibition.
Cefixime is found to be ineffective against bacteria which produces extended-spectrum β-lactamases (ESBL) enzyme and resistance is seen in such types of bacteria. The combination of cefixime and clavulanic acid (β-lactamase inhibitor) provides a solution for treatment of bacterial infections caused by β-lactam resistant pathogens.
Pharmacokinetics: Combining clavulanic acid with β-lactam antibiotic causes no appreciable alteration of the pharmacokinetics of either drug compared with their separate administration. About 40-50% of cefixime is absorbed slowly following oral administration from gastrointestinal. Absorption is not significantly modified by the presence of food. After a 200-mg oral dose, peak plasma level on an average of 2.7 mg/L are achieved, between 3-4 hrs post-dose in fasting volunteers. Cephalosporins are widely distributed in most tissues and fluids. The mean volume of distribution of cefixime is 0.11 L/kg. Penetration into tissue fluid is slow (mean tmax 6.7 hrs) but peak concentrations similar to those of plasma have been achieved.
From in vitro studies, serum or urine concentrations of 1 mcg/mL or greater were considered to be adequate for most common pathogens against which cefixime is active. Typically, the peak serum levels following the recommended adult or pediatric doses are between 1.5 and 3 mcg/mL.
Cefixime is mainly excreted unchanged in bile and urine. The mean elimination half-life (t½) is 3 hrs. Urinary excretion accounts for about 40% of an orally administered dose, the rest of the excretion takes place through the biliary tract. Glomerular filtration is considered the predominant mechanism. Metabolites of cefixime have not been isolated from human serum or urine.
Serum protein-binding is well characterized for human and animal sera; cefixime is almost exclusively bound to the albumin fraction, the mean free fraction being approximately 30%. Protein-binding of cefixime is only concentration-dependent in human serum at very high concentrations which are not seen following clinical dosing.
Clavulanic acid is well absorbed from the gastrointestinal tract after oral administration. On administration of clavulanate potassium 57 mg, the maximum plasma concentration obtained is 1.03 mcg/mL and the area under the plasma concentration-time curve (AUC) for 24 hr is 2.17 mcg·hr/mL.
Microbiology: As with other cephalosporins, the bactericidal action of cefixime results from the inhibition of cell wall synthesis. Being a 3rd-generation cephalosporin, cefixime is highly stable in the presence of β-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins, due to the presence of β-lactamase, may be susceptible to cefixime. Cefixime has been shown to be active against most strains of both in vitro and in clinical infections.
Gram-Positive: Streptococcus pneumoniae, Streptococcus pyogenes.
Gram-Negative: Haemophilus influenzae (β-lactamase-positive and -negative strains), Moraxella (Branhamella) catarrhalis (most of which are β-lactamase positive), Escherichia coli, Proteus mirabilis, Neisseria gonorrhoeae (including penicillinase- and nonpenicillinase-producing strains).
Note: Pseudomonas spp, strains of group D streptococci (including enterococci), Listeria monocytogenes, most strains of staphylococci (including methicillin-resistant strains) and most strains of Enterobacter are resistant to cefixime. In addition, most strains of Bacteroides fragilis and Clostridia are resistant to cefixime.
Indications/Uses
Treatment of the Following Infections: Urinary tract infections caused by Escherichia coli and Proteus mirabilis; otitis media caused by Haemophilus influenzae (β-lactamase-positive and -negative strains), Moraxella (Branhamella) catarrhalis (most of which are β-lactamase positive) and Streptococcus pyogenes; pharyngitis and tonsillitis caused by Streptococcus pyogenes; acute bronchitis and acute exacerbations of chronic bronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae (β-lactamase-positive and -negative strains); gonorrhoea (cervical/urethral) caused by Neisseria gonorrhoeae (penicillinase and non-penicillinase-producing strains); typhoid fever.
Dosage/Direction for Use
Dosage should be adjusted according to age, body weight and condition of the patients.
Adults: Recommended Dose: One tablet twice daily for 7 days. This may be continued for up to 14 days if required.
Children: Recommended Dose: 8 mg/kg daily as a single dose, or may be in 2 divided doses as 4 mg/kg every 12 hrs. 5 years: 7.5 mL twice daily; 3 years: 6 mL twice daily; 2 years: 5 mL twice daily; 1 year: 4 mL twice daily; 6 months: 2.5 mL twice daily.
>12 years (>50 kg): Same as recommended adult dose.
Renal Impairment: Zifex Plus 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. 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 (ie, 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 (ie, 200 mg daily). Neither hemodialysis nor peritoneal dialysis removes significant amounts of drug from the body.
Overdosage
No human data are available. Adverse reactions seen at a dose level up to 2 g in normal subjects did not differ from the profile seen in patients treated at the recommended doses. Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis.
Contraindications
Patients with known hypersensitivity to the cephalosporin group of antibiotics.
Warnings
Before therapy with Zifex Plus is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs.
Cefixime should be prescribed with caution in individuals with a history of gastrointestinal disease particularly colitis.
Increased prothrombin time may occur; therefore, care should be taken in patients receiving anticoagulant therapy.
Special Precautions
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.
Use in pregnancy & lactation: No adequate and well-controlled studies in pregnant women have been reported. Therefore, Zifex Plus should not be used in pregnancy or nursing mothers unless considered essential by the physician.
Use in children: Safety and effectiveness of this combination in children <6 months have not been established.
Neonates: No data are available on the use of the drug in neonates.
Use In Pregnancy & Lactation
No adequate and well-controlled studies in pregnant women have been reported. Therefore, Zifex Plus should not be used in pregnancy or nursing mothers unless considered essential by the physician.
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 symptoms may occur during or after therapy.
Hypersensitivity: Skin rashes, urticaria, drug fever and pruritus. Erythema multiforme, Stevens-Johnson syndrome and serum sickness-like reactions have been reported.
Hepatic: Transient elevations in serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase.
Renal: Transient elevations in blood urea nitrogen (BUN) or creatinine.
Central Nervous System: Headaches or dizziness.
Hemic and Lymphatic Systems: Transient thrombocytopenia, leukopenia and eosinophilia. Prolongation in prothrombin time was seen rarely. Others: Genital pruritus, vaginitis and candidiasis.
Drug Interactions
Carbamazepine: Elevated carbamazepine levels have been reported in post-marketing experience when Zifex Plus is administered concomitantly. Drug monitoring may be of assistance in detecting alterations in carbamazepine plasma concentrations.
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, Benedicts' solution or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (eg, Clinistix or Tes-Tape) be used.
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 cefixime.
Storage
Store at temperatures below 25°C. Protect from light.
MIMS Class
ATC Classification
J01DD08 - cefixime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
Tab 325 mg x 10's. Dry syr 81.25 mg/5 mL x 30 mL.
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