Ixime

Ixime

cefixime

Manufacturer:

BioCare

Distributor:

BioCare
Full Prescribing Info
Contents
Cefixime.
Description
Cefixime is a semisynthetic, cephalosporin antibiotic for oral administration.
FC tab: Each film coated IXIME Tablet contains Cefixime equivalent to Cefixime Anhydrous 400 mg.
Oral susp: Each 5 ml of reconstituted suspension contains Cefixime equivalent to anhydrous Cefixime 100 mg.
Action
Pharmacology: Pharmacokinetics: Cefixime given orally are about 40-50% absorbed whether administered with or without food, however, time to maximal absorption is increased approximately 0.8 hours when administered with food.
The oral suspension produced an average peak concentration approximately 25-50% higher than the tablets, when tested in normal adult volunteers.
200 and 400 mg doses of the oral suspension produced average peak concentrations of 3 μg/ml (range of 1 to 4.5 μg/ml) and 4.6 μg/ml (range of 1.9 to 7.7 μg/ml) respectively when tested in normal adult volunteers.
The area under the Time versus Concentration Curve is greater by approximately 10% - 25% with the oral suspension than with the tablet after doses of 100 to 400 mg in normal adult volunteers.
This increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet.
Tablets should not be substituted for oral suspension in the treatment of Otitis media because of the lack of bioequivalence.
Cross over studies of tablet versus suspension have not been performed in children.
Peak serum concentrations occur between 2 and 6 hours following the administration of a single 200 mg Tablet or a single 400 mg tablet. (See Tables 1 and 2.)

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Click on icon to see table/diagram/image

Oral susp: Peak serum concentrations occur between 2 and 6 hours following oral administration of 400 mg of Cefixime suspension.
Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of suspension. (See Table 3.)

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Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours.
In animal studies it was noted that Cefixime is also excreted in the bile in excess of 10% of the administered dose.
Serum protein binding is concentration independent with a bound fraction of approximately 65%.
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.
In a multiple dose study conducted with a research formulation which was less bioavailable than the tablet or suspension, there was little accumulation of drug in serum or urine after dosing for 14 days.
The serum half-life of Cefixime in healthy subjects is independent of dosage form and averages 3 to 4 hours but may range up to 9 hours in some normal volunteers.
Average AUCs at steady state in elderly patients are approximately 40% higher than average AUCs in other healthy adults.
In subjects with moderate impairment of renal function (20 to 40 mL/min Creatinine Clearance), the average serum half-life of Cefixime is prolonged to 6.4 hours.
In severe renal impairment (5 to 20 mL/min Creatinine Clearance), the half-life increased to an average of 11.5 hours.
Cefixime is predominantly eliminated as the unchanged drug in the urine.
Glomerular filtration is the predominant mechanism of elimination and metabolites have not been isolated either from human serum or urine.
Cefixime is not cleared significantly from the blood by hemodialysis or peritoneal dialysis.
However, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar blood profiles as subjects with Creatinine Clearances of 21-60 mL/min.
There is no evidence of metabolism of Cefixime in vivo.
Adequate data on CSF levels of Cefixime are not available.
FC tab: A single 200 mg tablet of Cefixime produced an average peak serum concentration of approximately 2 μg/ml (range of 1 to 4 μg/ml) where as a single 400 mg tablet produced an average peak concentration of approximately 3.7μg/ml (range of 1.3 to 7.7 μg/ml).
Toxicology: FC tab: Carcinogenesis, mutagenesis, impairment of fertility: Cefixime did not cause point mutations in bacteria or mammalian cells, damage to DNA and chromosomes in vitro and did not exhibit clastogenic potential in vivo in the mouse micronucleus test.
Cefixime did not affect fertility and reproductive performance in rats at doses upto 125 times the adult therapeutic dose.
Microbiology: The bactericidal action of Cefixime, as with other Cephalosporins results from inhibition of cell wall synthesis. 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 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 pneumoniae, Streptococcus pyogenes.
Gram-negative organisms: Haemophilus influenzae (β lactamase positive & negative strains), Moraxella catarrhalis (mostly β lactamase positive), Escherichia coli, Proteus mirabilis, Salmonella typhi, Neisseria gonorrhoeae (including Penicillinase & Non Penicillinase Producing strains).
CEFIXIME has been shown to be active in vitro against most strains of the following organisms, however, clinical efficacy has not been established.
Gram-positive organisms: Streptococcus agalactiae.
Gram-negative organisms: Haemophilus parainfluenzae (β lactamase positive & negative strains), Proteus vulgaris, Klebsiella pneumoniae, Klebsiella oxytoca, Pasteurella multocida, Providencia species, Shigella species, Citrobacter amalonaticus, Citrobacter diversus, Serratia marcescens.
Note: Pseudomonas species, 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
IXIME is 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 & Proteus mirabilis.
Otitis Media caused by Haemophilus influenzae (β lactamase positive & negative strains), Moraxella catarrhalis (most of which are β lactamase positive) and Streptococcus pyogenes.
Pharyngitis and Tonsillitis caused by Streptococcus pyogenes.
Note: Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections, including the prophylaxis of Rheumatic Fever. Cefixime is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx, however, data establishing the efficacy of Cefixime in the subsequent prevention of Rheumatic Fever are not available.
Acute Bronchitis and Acute Exacerbations of Chronic Bronchitis, caused by Streptococcus pneumoniae & Haemophilus influenzae (β lactamase positive and negative strains).
Uncomplicated Multidrug Resistant and Quinolone Resistant Typhoid Fever caused by Salmonella typhi.
Uncomplicated Gonorrhea (cervical/urethral) caused by both Penicillinase and Non Penicillinase Producing Strains of Neisseria gonorrhoeae.
Dosage/Direction for Use
FC tab: Adult: The recommended dose of Cefixime is 400 mg once daily.
The recommended dose of Cefixime for Uncomplicated Multidrug Resistant Typhoid Fever is 15 to 20mg/kg bodyweight / 24 hours for 7 to 14 days and for Quinolone Resistant Typhoid Fever is 20mg /kg bodyweight / 24 hours for 7 to 14 days.
A single oral dose of 400 mg of Cefixime is recommended for the treatment of Uncomplicated Cervical /Urethral Gonococcal Infections.
Children: Children weighing more than 50 kg or older than 12 years should be treated with the recommended adult dose.
In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of Cefixime should be given for at least 10 days.
Renal impairment: Cefixime may be administered in the presence of impaired renal function as follows: See Table 4.

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Oral susp: Children: The recommended dose of the suspension is 8mg/kg bodyweight/day which may be administered as a single daily dose or may be given in two divided doses, as 4 mg/kg every 12 hours.
Children weighing more than 50 kg or older than 12 years should be treated with the recommended adult dose. (See Table 5.)

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The recommended dose of Cefixime for Uncomplicated Multidrug Resistant and Quinolone Resistant Typhoid Fever is 20mg /kg body weight / 24 hours in divided BID doses for 7 days.
In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of Cefixime should be given for at least 10 days.
Renal impairment: Cefixime may be administered in the presence of impaired renal function as follows: See Table 6.

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Reconstitution directions for oral suspension: Tap the bottle several times to loosen the powder contents prior to reconstitution.
Add freshly boiled and cooled water.
Swirl to dissolve the granules.
Add more water up to the mark on the label.
Shake the bottle to ensure uniformity.
After reconstitution the suspension may be kept for 14 days either at room temperature, or under refrigeration, without significant loss of potency.
Keep the bottle tightly closed.
Shake well before using.
Discard unused portion after 14 days.
Overdosage
Gastric lavage may be indicated; otherwise there is no specific antidote.
Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis.
Contraindications
Cefixime is contraindicated in patients with known allergy to the Cephalosporin group of antibiotics.
Warnings
Before therapy with Cefixime is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs.
FC tab: If this product has to be given to penicillin sensitive patients, caution should be exercised because cross hypersensitivity among β 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 cefixime occurs, discontinue the drug.
Serious acute hypersensitivity reactions may require treatment with emergency measures including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines and airway management as clinically indicated.
Special Precautions
Prescribing Cefixime 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 cases, careful observation of the patient is essential and 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.
Use in Children: Safety and Effectiveness of Cefixime in children aged less than 6 months have not been determined.
The incidence of gastrointestinal adverse reactions, including diarrhea and loose stools in pediatric patients receiving the suspension was comparable to the incidence seen in adult patients on tablets.
FC tab: Pseudomembraneous colitis has been reported with the use of Cefixime and other broad spectrum antibiotics including Macrolides, Semisynthetic Penicillins and Cephalosporins, therefore it is important to consider this diagnosis in patients who develop diarrhea in association with the use of antibiotics.
Symptoms of Pseudomembraneous Colitis may occur during or after antibiotic treatment and may range in severity from mild to life threatening.
Use In Pregnancy & Lactation
FC tab: Usage in pregnancy: Reproduction studies with Cefixime have been done in mice and rats at doses up to 400 times the human dose and revealed no evidence of harm to the fetus.
Animal Reproduction Studies are not always predictive of human response and Cefixime should be used during pregnancy only if clearly needed.
Labour and delivery: Cefixime has not been studied for use during labour and delivery and should be administered only if clearly needed.
Nursing mothers: Consideration should be given to discontinuing nursing temporarily during treatment with Cefixime as it is not known whether it is excreted in human milk.
Side Effects
Cefixime is generally well tolerated.
The majority of adverse reactions observed in clinical trials were mild and self-limiting in nature.
Gastrointestinal Disturbances: The most frequent side effects seen with Cefixime are diarrhoea and stool changes with diarrhoea being been more commonly associated with higher doses.
Some cases of moderate to severe diarrhoea have been reported; this has occasionally warranted cessation of therapy. Ixime should be discontinued if marked diarrhoea occurs. Other gastrointestinal side effects seen less frequently are nausea, abdominal pain, dyspepsia, vomiting and flatulence.
Pseudomembranous colitis has been reported.
Central Nervous System: Headache and dizziness.
Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced.
If seizures associated with drug therapy occur, the drug should be discontinued.
Anticonvulsant therapy can be given if clinically indicated.
Hypersensitivity Reactions: Allergies in the form of rash, pruritus, urticaria, drug fever and arthralgia have been observed.
These reactions usually subsided upon discontinuation of therapy.
Rarely Erythema multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis have been reported.
Haematological and Clinical Chemistry: Thrombocytopenia, leukopenia and eosinophilia have been reported though these reactions were infrequent and reversible.
Mild transient changes in liver and renal function tests too have been observed.
Hepatic Disorders: Transient rises in liver transaminases, alkaline phosphatase and jaundice can also occur.
Miscellaneous: Other possible reactions include genital pruritus and vaginitis.
Drug Interactions
Carbamazepine: Elevated carbamazepine levels have been reported in postmarketing experience when Cefixime was 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 was administered concomitantly.
Care should therefore be taken in patients receiving anticoagulation therapy.
Probenecid: Concomitant administration of Probenecid increases peak serum concentrations and the AUC while decreasing the renal clearance and volume of distribution of Cefixime.
Other drugs: Concomitant administration of Cefixime and Nifedipine increases the oral bioavailability of Cefixime as a result of higher peak plasma concentrations and area under the plasma concentration time curve.
In vitro, in pooled serum, Acetaminophen, Heparin, Phenytoin, Diazepam, Ibuprofen or Furosemide had no clinically important effects on the protein binding of Cefixime.
Laboratory test interferences: Tests for urinary glucose: Cefixime, like most Cephalosporins may cause false positive results in urinary glucose determinations, using cupric sulphate as in Benedict's solution, Clinitest or Fehling's slolution, but enzymatic Glucose Oxidase methods are unaffected.
Immunohematology tests: A false positive direct Coombs test has been reported during treatment with Cephalosporin antibiotics, therefore it should be recognised that this reaction may interfere with hematologic studies or transfusion cross matching procedures and should be considered in patients receiving Cefixime.
Urinary ketones: Cefixime may cause false positive results for urinary ketones when tests using nitroprusside are used but not with tests using nitroferricyanide.
FC tab: General: A false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.
A false positive direct Coombs test has been reported during treatment with cephalosporin antibiotics, therefore it should be recognized that a positive Coombs test may be due to the drug.
In common with other cephalosporins, increases in prothrombin times have been noted in a few patients. Care should therefore be taken in patients receiving anticoagulation therapy.
Storage
FC tab: Store in a cool dry place below 25°C and protect from light, heat and moisture.
Oral susp: Prior to reconstitution: Store the drug powder at 20-25°C.
After reconstitution: Store at room temperature or under refrigeration.
Keep the bottle tightly closed.
Shelf-Life: 24 months.
MIMS Class
ATC Classification
J01DD08 - cefixime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 400 mg (white to off-white, capsule shaped, with "LUPIN" debossed on one side and scored on the other) x 6's. Oral susp 100 mg/5 mL x 50 mL.
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