C Tax-O Drops

Cefixime oral suspension IP

Each ml of reconstituted suspension contains:

Cefixime IP (as Trihydrate)

equivalent to Cefixime (Anhydrous) 25 mg

Excipients q.s.

Colour: Quinoline Yellow WS

Oral Suspension

25mg/ml

4.1 Therapeutic indication

• Uncomplicated Urinary Tract Infections
• Otitis Media
• Pharyngitis and Tonsillitis
• Acute Exacerbations of Chronic Bronchitis
• Uncomplicated Gonorrhea (cervical/urethral)
• For the treatment of enteric (typhoid) fever

4.2 Posology and method of administration

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.

Children weighing more than 45 kg or older than 12 years should be treated with the recommended adult dose, 200 to 400 mg daily depending on the severity of infection.

In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of cefixime should be administered for at least 10 days.

Safety and effectiveness of cefixime in children aged less than 6 months old have not been established.

Suggested Doses for Pediatric Patients

Renal Impairment

Cefixime may be administered in the presence of impaired renal function. Doses for patients with renal impairment is shown in the table 1.

Table 1: Doses for Patient with Renal Impairment

In patients whose creatinine clearance is less than 20 ml/min, it is recommended that a dose of 200 mg once daily should not be exceeded. The dose and regimen for patients who are maintained on chronic ambulatory peritoneal dialysis or haemodialysis should follow the same recommendation as that for patients with creatinine clearance of less than 20 ml/min. Neither haemodialysis nor peritoneal dialysis removes significant amounts of drug from the body.

Directions for reconstitution

• Shake the bottle well to loosen the powder.
• Slowly add part quantity of SWFI provided with this pack up to the ring mark on the bottle & shake well.
• Add more SWFI if necessary to adjust the volume up to the ring mark on the bottle.
• This makes 10 ml of the suspension.
• The reconstituted suspension should be consumed within 5 days of preparation.

4.3 Contraindications

Known allergy to cefixime or other cephalosporins.

4.4 Special warnings and precautions for use

Hypersensitivity Reactions

Anaphylactic/anaphylactoid reactions (including shock and fatalities) have been reported with the use of cefixime. If this product is to be given to penicillin sensitive patients, caution should be exercised because cross hypersensitivity among beta-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 for oral suspension occurs, discontinue the drug.

Clostridium difficile-Associated Diarrhea

Clostridium difficile associated diarrhea has been reported with use of Cefixime oral suspension. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.difficile, and surgical evaluation should be instituted as clinically indicated.

Coagulation Effects

Cephalosporins, including Cefixime for oral suspension may be associated with a fall in prothrombin activity. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.

4.5 Drugs interactions

Carbamazepine

Elevated carbamazepine levels have been reported in postmarketing 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.

4.6 Use in special populations

Pregnancy

Pregnancy Category B

Reproduction studies have been performed in mice and rats at doses up to 40 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.

Labor and Delivery

Cefixime has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.

Nursing Mothers

It is not known whether cefixime is excreted in human milk. Consideration should be given to discontinuing nursing temporarily during treatment with this drug.

4.7 Effects on ability to drive and use machines

Cefixime has no or negligible influence on the ability to drive or use machines. However, cefixime may cause side effects influencing the capacity of reaction and the ability to drive and use machines.

4.8 Undesirable effects

Acute generalized exanthematous pustulosis and Mouth Ulceration has been seen with Cefixime use.

The most commonly seen adverse reactions were gastrointestinal events, which were reported in 30% of adult

patients on either the twice-daily or the once daily regimen. Individual adverse reactions included diarrhoea (16%), loose or frequent stools (6%), abdominal pain (3%), nausea (7%), dyspepsia (3%), and flatulence (4%).

Diarrhoea has been more commonly associated with higher doses. Other gastrointestinal side effects seen less frequently are vomiting and flatulence. The incidence of gastrointestinal adverse reactions, including diarrhoea and loose stools, in paediatric patients receiving the suspension was comparable with the incidence seen in adult patients receiving tablets.

The following adverse reactions have been reported following the post-approval use of cefixime. Incidence rates were less than 1 in 50 (less than 2%).

Gastrointestinal: pseudomembranous colitis; 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 System : Transient thrombocytopenia, leukopenia, neutropenia, prolongation in prothrombin time, elevated LDH, pancytopenia, agranulocytosis, and eosinophilia; Abnormal Laboratory Tests : Hyperbilirubinemia; Other Adverse Reactions : Genital pruritus, vaginitis, candidiasis, toxic epidermal necrolysis.

Adverse Reactions Reported for Cephalosporin-class Drugs: Allergic reactions, superinfection, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, and colitis. 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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

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 reactions 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.

5.1 Mechanism of Action

Pharmacotherapeutic group: third generation cephalosporin, ATC code: J01DD08

Cefixime is an oral third generation cephalosporin which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms.

Clinical efficacy has been demonstrated in infections caused by commonly occurring pathogens including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and negative), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacter species. It is highly stable in the presence of beta-lactamase enzymes.

Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase positive and negative strains and methicillin-resistant strains) are resistant to cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to cefixime.

5.2 Pharmacodynamic properties

Cefixime is an oral third generation cephalosporin which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms. Comparative clinical trials of otitis media were conducted in nearly 400 children between the ages of 6 months to 10 years. Streptococcus pneumoniae was isolated from 47% of the patients, Haemophilus influenzae from 34%, Moraxella catarrhalis from 15% and S. pyogenes from 4%. The overall response rate of Streptococcus pneumoniae to cefixime was approximately 10% lower and that of Haemophilus influenzae or Moraxella catarrhalis approximately 7% higher (12% when beta-lactamase positive isolates of H. influenzae are included) than the response rates of these organisms to the active control drugs. In these studies, patients were randomized and treated with either cefixime at dose regimens of 4 mg/kg twice a day or 8 mg/kg once a day, or with a comparator. Sixty-nine to 70% of the patients in each group had resolution of signs and symptoms of otitis media when evaluated 2 to 4 weeks’ post-treatment, but persistent effusion was found in 15% of the patients. When evaluated at the completion of therapy, 17% of patients receiving cefixime and 14% of patients receiving effective comparative drugs (18% including those patients who had Haemophilus influenzae resistant to the control drug and who received the control antibacterial drug) were considered to be treatment failures. By the 2 to 4-week follow-up, a total of 30%-31% of patients had evidence of either treatment failure or recurrent disease.

5.3 Pharmacokinetic properties

Absorption: Cefixime suspension, given orally, absorbed about 40% to 50% whether administered with or without food; however, time to maximal absorption is increased approximately 0.8 hours when administered with food. The oral suspension produces average peak concentrations approximately 25% to 50% higher than the tablets, when tested in normal adult volunteers. Two hundred and 400 mg doses of oral suspension produce average peak concentrations of 3 mcg/mL (range 1 to 4.5 mcg/mL) and 4.6 mcg/mL (range 1.9 to 7.7 mcg/mL), respectively, when tested in normal adult volunteers. AUC is greater by approximately 10% to 25% with the oral suspension than with the tablet after doses of 100 to 400 mg, when tested in normal adult volunteers. This increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet.

Because of the lack of bioequivalence, tablets should not be substituted for oral suspension in the treatment of otitis media. 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.

Distribution: Serum protein binding is concentration independent with a bound fraction of approximately 65%. In a multiple dose study conducted with a research formulation which is less bioavailable than the tablet or suspension, there was little accumulation of drug in serum or urine after dosing for 14 days. Adequate data on CSF levels of cefixime are not available.

Metabolism and Excretion: There is no evidence of metabolism of cefixime in vivo. 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. 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.

6.1 Animal Toxicology or Pharmacology

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 25 times the adult therapeutic dose.

Cefixime is a semisynthetic, cephalosporin antibacterial 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-(carboxy methyl) oxime]trihydrate. Molecular weight- 507.50 as the trihydrate.

Chemical Formula is C₁₆H₁₅N₅O₇S₂.3H₂O

The structural formula for cefixime is:

8.1 Incompatibilities

Not Applicable

8.2 Shelf-life

Refer on pack

8.3Packaging information

C Tax-O drops: A bottle of 10 ml. For pediatric use only.

8.4 Storage and handing instructions

Shake well before use. Store in a cool & dry place. Protect from light. Keep out of reach of children. Store the reconstituted oral suspension in a refrigerator (at 2°C to 8°C).

Counsel patients that antibacterial drugs, including cefixime, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefixime is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.

Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefixime for oral suspension or other antibacterial drugs in the future.

Advise patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible.

20th September 2024