Description and Composition of Cefixime & Clavulanic Acid
Cefixime & Clavulanic Acid is an antibacterial antibiotic that is formulated to have a broader spectrum of activity than ordinary cefixime. It is a third generation cephalosporin. Ordinarily, it is highly stable in the presence of Beta lactam enzymes. It contains as its active pharmaceutical ingredient cefixime and clavulanic acid. The cefixime is the main active ingredient as the clavulanic acid there is to protect it from beta lactamase enzymes produced by some bacteria. Cefixime is a cell-wall synthesis inhibitor while Clavulanic Acid is naturally derived B-lactamase inhibitor.
Pharmacology of Cefixime Clavulanic Acid
Cefixime is a semisynthetic, oral, third generation cephalosporin antibiotic. It is effective against gram positive gram-negative and anaerobic bacteria induding B-lactamase producing strains. It acts by inhibition of bacterial cell wall synthesis.
Clavulanic acid is a B-lactamase inhibitor produced by Streptomyces clavuligerus. Clavulanic acid is an irreversible inhibitor of intracellular and extracellular B-lactamases. The combination of Cefixime & Clavulanic acid is useful in treatment of bacterial infections caused by Beta lactam resistant strains.
Mechanism of action of Cefixime Clavulanic Acid
Cefixime is a semi-synthetic (partially man-made), oral antibiotic in the cephalosporin family of antibiotics Cefone stops bacteria from multiplying by preventing bacteria from forming the walls that surround them. The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together, bacteria cannot survive without a cell wall. Activity of cefixime enhance In presence of Clavulanic Acid
As with other cephalosporins, bactericidal action of cefixime results from inhibition of cell wall synthesis. Cefixime is highly stable in the presence of B-lactamase enzymes. As a result, many organism resistant to penicillin and some cephalosporins due to the presence of B-lactamase, may be susceptible to cefixime: Cefixime has been shown to be active against most strains of the following organism both in vitro and in clinical infections. These include:
- Streptococcus pneumoniae
- Streptococcus agalactiae
- Streptococcus pyogenes
- Haemophilus influenzae
- Morarella (Branhamella) catarrhalis (most which are B-lactamase positive).
- Escherichia coli
- Proteus mirabilis
- Neisseria gonorrhoeae (including penicilinase and nonpencillinase producing strains)
Cefixime has been shown to be active in vitro against most strains of the following organism enlisted below; however, clinical efficacy has not been established.
- Haemophilus parainfuenzao (B-lactamase positive and negative strains)
- Proteus vulgaris
- Klebsiella pneumonia
- Klebsiella oxytoca
- Pasteurella multocida
- Providencia species
- Salmonella species
- Shigella species
- Citrobacter amalonaticus
- Citrobacter diversus
- Serratia marcescens
Note: Pseudomonas species, strains of group D Streptococci (including Enterococa, Listeria monocytogenes, most strains of Staphylococci (includung 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.
Approximately 30-50% of a single dose of cefixime is absorbed following oral administration, in-vivo studies indicate that the drug is absorbed from the upper and middle part of the small intestine and probably transported across the intestinal membrane by a dipeptide carrier system. Presence of food in the GI tract decreases the rate of absorption of ceforme but generally does not affect the extent of absorption of the drug. The time to peak concentrations is increased approximately 0.8 hours by administration with food. Glabsorption of cefixime is not affected by concomitant administration of antacids. There is no evidence that cefixime accumulates in serum or urine of patients with nomal renal function following multiple doses of the drug given once or twice daily
Indications and Uses
Cefixime & Clavulanate Potassium Tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Cefixime & Clavulanate Potassium Tablets is indicated for treatment of:
- Uncomplicated Urinary Tract Infections caused by Escherichia coli and Proteus mirabilis
- Otitis Media caused by Haemophilus Influenzae (-lactamase positive and negative strains), Moraxella (Branhamento) catanhalis, (mostol which are -lactamase positive) andS. pyogenes
- Pharyngitis and Tonsillitis, caused by S. pyogenes.
- Acute Bronchitis and Acute Exacerbations of Chronic Bronchitis, caused by Streptococcus pneumoniae and Haemophilus influenzae (B-lactamase positive and negative strains)
- Uncomplicated gonorrhea (cervical/urethral), caused by Neisseria gonorrhoeae (penicilinase and non- penicillinase producing strains)
Contraindicated in patients hypersensitivity to the cephalosporin group of antibiotics,
Precautions and Warnings
- Before therapy with Cefixime Clavulanate Potassium is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs.
- Cefixime as with other broad-spectrum antibiotics should be prescribed with caution in individuals with a history of colitis,
- Increases in prothrombin times may occur and therefore care should be taken in patients receiving anticoagulant therapy.
- No adequate and well-controlled studies in pregnant women have been reported so Cefixime-Clavulanate Potassium should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.
Use In Pregnancy & Lactation:
There are no adequate and well controlled studies in pregnant women Cefixime & Potassium Clavulanate Tablets should therefore not be used in pregnancy or in nursing mothers unless considered by the physician
Effects on ability to drive and use machines:
Cefixime is not known to affect the ability to drive or use machines, still physicians advice is mandatory.
- Carbamazepine: Elevated carbamazepine levels have been reported when cefixime is administered concomitantly,
- Warfarin and Anticoagulants: Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly
- Oral Contraceptives: Cefixime may interfere with the effectiveness of birth control pills.
- Glucose Test: A false positive reaction for glucose in the urine may occur with Benedict’s or Fehling’s solutions sulphate test tablets or with copper
- Coombs test: A false positive direct Coombs test has been reported during treatment with cephalosporin antibiotics.
The most frequent side effects seen with Cefixime-Clavulanate Potassium are diarrhoea and stool changes Events like nausea vomiting, transient elevation in liver transaminases, alkaline phosphatase and jaundice can also occur. Thrombocytosis, thrombocytopenia leucopenia, hypereosinophilia, neutropenia and agranulocytosis may also occur. Other adverse events that may occur are abdominal pain, abdominal cramps, flatulence, indigestion, headache, vaginitis, vulvar itch, rash, hives, itch, dysuria, chills, chest pain, shortness of breath, mouth ulcers, swollen tongue, sleepiness, thirst, anorexia.
Dosage and administration
The dose is determined of by the Cefixime base.
The recommended dose of cefixime is 400 mg daily. This may be given as a 400 mg tablet or capsule daily or the 400 mg tablet may be split and given as one half tablet every 12 hours. For the treatment of uncomplicated cervical/urethral gonococcal infections, a single oral dose of 400 mg is recommended. The capsule and tablet may be administered without regard to food.
Pediatric Patients (6 Months Or Older)
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.
Overdosage of cephalosporins can lead to cerebral irritation and seizures With selzures the drug should be discontinued and appropriate anticonvulsive and supportive therapy administered. Serum levels of Cefixime can be reduced by haemodialysis or peritoneal dialysis.
Store below 30*C Protect from light.
KEEP MEDICINE OUT OF REACH OF CHILDREN
- CFXCLAV 325, Aquatix Pharmaceutical limited, Lagos, Nigeria