Cefixime

Introduction Overview

Generic Name

cefixime

Brand Name

Suprax

Dosage Form

oral capsule, oral powder for reconstitution, oral tablet, oral chewable tablet

Drug Class

Third generation cephalosporins

Pharmacokinetics

Absorption: Cefixime exhibits variable oral absorption with bioavailability ranging broadly between 40% to 50%. It is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations in approximately 2 to 6 hours post-administration. Food intake does not significantly affect the absorption of cefixime, allowing flexibility in dosing with or without food. The oral suspension and chewable tablets demonstrate good systemic availability, making cefixime effective for outpatient therapy. Absorption may be influenced by gastrointestinal pH and motility, but overall, cefixime maintains consistent bioavailability across formulations.

Distribution: After absorption, cefixime is widely distributed throughout body tissues and fluids, including respiratory tract secretions, tonsillar tissue, middle ear fluid, and the urinary tract, which are common sites of infection. It achieves therapeutic concentrations in these compartments, which supports its clinical efficacy. Plasma protein binding of cefixime is moderate, approximately 65%, which influences its free active concentrations. Cefixime crosses the placenta, but fetal exposure data remains limited. It is unknown to what extent cefixime distributes into cerebrospinal fluid; therefore, its utility in central nervous system infections is limited without adjunctive therapies.

Metabolism: Cefixime is minimally metabolized in the human body. Majority of the active compound remains unchanged, reflecting limited hepatic biotransformation. This minimal metabolism reduces the risk of active metabolite accumulation or hepatotoxicity, enhancing cefixime's safety profile. The drug is stable under physiological conditions, and there is no significant involvement of cytochrome P450 enzymes, which lowers the potential for metabolic drug-drug interactions.

Elimination: Cefixime is primarily eliminated by renal excretion, with approximately 50% of an oral dose excreted unchanged in the urine within 24 hours. The elimination half-life averages 3 to 4 hours in healthy adults but may be prolonged in patients with renal impairment. Biliary excretion contributes to fecal elimination. Due to the renal clearance pathway, dose adjustment is critical in patients with reduced kidney function to prevent toxicity. Renal clearance correlates well with creatinine clearance, providing guidance for dosage modifications. Studies have shown that up to 30% of cefixime may be excreted via the feces through biliary excretion, contributing to treatment of some gastrointestinal infections.

Dosage Forms

Available Dosage Forms: Cefixime is commercially available in several oral formulations to accommodate different patient needs, including:
- Oral capsule (commonly 400 mg)
- Oral tablet (also typically 400 mg)
- Oral chewable tablet (available in 200 mg dosing, designed for pediatric use and patients with difficulty swallowing)
- Oral powder for reconstitution (available as 100 mg/5 mL, 50 mg/5 mL suspensions for flexible pediatric dosing)

Dosages for Adults and Adolescents: Typical adult dosing for cefixime varies according to infection severity and site, with common regimens including 400 mg once daily or divided doses of 200 mg twice daily. For uncomplicated urinary tract infections and pharyngitis, 400 mg daily for 7 to 14 days is usually sufficient. In more severe or complicated infections, higher or prolonged dosing may be necessary under clinical supervision. For gonorrhea, a single 400 mg dose is standard. The dosing interval and duration should be individualized based on clinical response and pathogen susceptibility.

Specific Patient Populations: In pediatric patients, dosing is weight-based, with recommended doses ranging typically from 8 mg/kg/day divided into two doses, ensuring safety and efficacy for children as young as 6 months. For patients with renal impairment, dose adjustment to extend the dosing interval or reduce the dose amount is essential due to decreased clearance. Elderly patients often receive standard dosing unless renal function is compromised. The chewable tablet formulation requires careful consideration in patients with phenylketonuria (PKU) due to phenylalanine content. The liquid suspension contains sucrose, necessitating caution in diabetic patients. There are limited data on use during pregnancy and lactation; thus, risk-benefit assessment is advised.

Mechanism Of Action

Cefixime is a bactericidal antibiotic belonging to the third generation cephalosporin class that exerts its action by interfering with bacterial cell wall synthesis. Its primary molecular mechanism targets the penicillin-binding proteins (PBPs), which are enzymes critical for cross-linking peptidoglycan chains that confer mechanical strength and structural integrity to the bacterial cell wall. Binding to PBPs results in inhibition of their transpeptidase activity, leading to defective cell wall assembly.

At a cellular level, cefixime's interaction with PBPs induces the formation of weak or incomplete cell walls, causing osmotic imbalance and eventual lysis of susceptible bacteria. This bacteriolytic effect is most effective during active bacterial growth phases when cell wall production is highest. Cefixime exhibits enhanced affinity for PBPs in many gram-negative pathogens compared to earlier generations of cephalosporins, thus offering broader coverage, particularly against resistant strains.

Biochemically, cefixime is stable against many beta-lactamases produced by gram-negative bacteria, which hydrolyze and inactivate other beta-lactam antibiotics. This stability stems from structural modifications in the cefixime molecule, allowing it to evade enzymatic degradation, thus preserving its antibacterial efficacy.

Clinically, this mechanism translates to cefixime’s ability to treat respiratory tract infections, uncomplicated urinary tract infections, and certain sexually transmitted infections caused by susceptible bacteria. It offers advantages over first- and second-generation cephalosporins due to its extended gram-negative spectrum. Comparative studies with drugs like ceftriaxone demonstrate cefixime’s utility as an oral alternative with similar mechanisms but different pharmacokinetic profiles, thus influencing treatment strategies and patient compliance.

Pharmacological Actions

Bactericidal activity by inhibition of bacterial cell wall synthesis.
High affinity binding to penicillin-binding proteins (PBPs) in susceptible bacteria.
Effective against a broad spectrum of gram-negative pathogens including Haemophilus influenzae, Escherichia coli, and Neisseria gonorrhoeae.
Moderate activity against certain gram-positive bacteria compared to earlier cephalosporins.
Resistance to degradation by many beta-lactamases produced by gram-negative bacteria.
Ability to penetrate bacterial outer membranes facilitating efficacy against resistant organisms.
Enhanced stability and oral bioavailability relative to earlier cephalosporins.
Exhibits concentration-dependent killing at therapeutic dosages.
Limited impact on anaerobic bacteria due to spectrum limitations.
Minimal metabolism leads to predictable pharmacokinetics and steady systemic exposure.

Therapeutic Or Clinical Uses

Treatment of uncomplicated urinary tract infections caused by susceptible bacteria.
Management of acute otitis media in pediatric patients.
Therapy for pharyngitis and tonsillitis caused by Streptococcus pyogenes.
Treatment of community-acquired respiratory tract infections including bronchitis and pneumonia.
Treatment of uncomplicated gonorrhea caused by Neisseria gonorrhoeae.
Used in infections caused by susceptible strains of Escherichia coli, Klebsiella, and Proteus species.
Management of uncomplicated skin and soft tissue infections.
Alternative therapy in patients intolerant or allergic to penicillins (non-cross allergic cephalosporins).
Empirical treatment for mixed infections where gram-negative coverage is important.
Second-line agent in some cases of Enterobacteriaceae infections.

Side Or Adverse Effects

Gastrointestinal disturbances such as indigestion, nausea, vomiting, and abdominal pain.
Diarrhea, including antibiotic-associated and potential Clostridioides difficile-associated diarrhea.
Hypersensitivity reactions including rash, urticaria, and rarely anaphylaxis.
Potential for severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (rare).
Allergic cross-reactivity in patients with penicillin allergy.
Transient elevation of hepatic enzymes (ALT, AST) noted in some patients.
Hematologic abnormalities including neutropenia, thrombocytopenia, and eosinophilia (uncommon).
Potential for superinfection or secondary infections including fungal overgrowth.
Headache and dizziness reported infrequently.
Renal function impairment is rare but should be monitored in predisposed patients.
Local reactions at injection (if administered parenterally, although cefixime is primarily oral).
Vaginal candidiasis presenting with itching or discharge.
Rare but serious side effects include seizures in patients with renal impairment or high dosages.
Positive Coombs test without hemolytic anemia in some cases.

Precautions

Assess history of hypersensitivity to cephalosporins or penicillins before administration.
Use cautiously in patients with severe renal impairment; adjust dosing accordingly.
Monitor for signs of superinfection during or following therapy.
Avoid use in patients with known phenylketonuria when administering chewable tablets due to phenylalanine content.
Caution advised in diabetic patients when using oral suspension containing sucrose.
Evaluate hepatic and renal function prior to and during therapy especially in prolonged treatments.
Educate patients on importance of completing the full course even if symptoms improve early.
Be alert for possible cross-allergenicity in patients allergic to other beta-lactams.
Use judiciously to reduce the emergence of antibiotic-resistant bacteria.
Pregnancy risk assessment required due to limited data; use only if clearly needed.
Advise breastfeeding mothers to consult physicians prior to use, as safety during lactation is not established.
Monitor for gastrointestinal symptoms during therapy, particularly in the elderly or debilitated patients.
Laboratory interference: cefixime may cause false-positive urine glucose tests; inform clinicians accordingly.

Warnings

Do not administer to patients with known allergy to cefixime or other cephalosporin antibiotics.
Potential for severe allergic reactions including anaphylaxis; immediate medical attention required if they occur.
Risk of Clostridioides difficile-associated diarrhea with antibiotic use; discontinue cefixime if severe diarrhea occurs.
May cause serious hypersensitivity reactions in penicillin-sensitive individuals due to cross-reactivity.
Use with caution in patients with a history of gastrointestinal disease, particularly colitis.
Not effective against viral infections; misuse may promote resistance.
Potential risk of hemolytic anemia, though rare; monitor hematologic parameters in prolonged use.
Oral suspension contains sucrose; contraindicated or used with caution in patients with hereditary fructose intolerance.
Phenylalanine content in chewable tablets may be harmful in patients with phenylketonuria.
Safety and efficacy in pediatric patients under 6 months of age have not been established.
Cefixime may cause false-positive urine glucose test results; alternative testing methods recommended.
Use caution in patients with seizure history; high doses in renal impairment could precipitate convulsions.
Discontinue if severe cutaneous adverse reactions are suspected.

Contraindication

Known hypersensitivity to cefixime or other cephalosporin antibiotics.
History of immediate hypersensitivity reactions (e.g., anaphylaxis) to penicillins and/or cephalosporins.
Use contraindicated in patients with phenylketonuria when prescribing chewable tablet formulation due to phenylalanine content.
Contraindicated in patients with prior severe allergic reactions to beta-lactam antibiotics.
Should not be used in neonates or infants under 6 months as safety and efficacy are not established.
Avoid in patients with documented hypersensitivity to any component of the formulation.
Caution advised in patients with history of antibiotic-associated colitis.
Avoid concomitant use with bacteriostatic antibiotics as efficacy may be reduced.
Not recommended in severe renal impairment without dosage adjustment.
Contraindicated during lactation unless benefit outweighs risk; careful monitoring required.

Drug Interactions

Concomitant use with aminoglycosides or loop diuretics may increase nephrotoxicity risk.
Probenecid co-administration can decrease renal tubular secretion of cefixime, increasing plasma concentrations.
Concurrent use with warfarin may increase anticoagulant effect and risk of bleeding; monitor INR frequently.
May interfere with urinary glucose tests, resulting in false-positive results.
Concomitant use with bacteriostatic antibiotics (e.g., tetracyclines, macrolides) may reduce bactericidal efficacy.
Antacids, H2-receptor antagonists, or proton pump inhibitors do not significantly affect cefixime absorption.
Concurrent use of live bacterial vaccines may result in diminished vaccine efficacy.
Oral contraceptives’ effectiveness may be reduced; advise additional contraception methods.
No significant cytochrome P450 interactions as cefixime is minimally metabolized hepatically.
Concurrent administration with other nephrotoxic drugs requires careful monitoring of renal function.
Potential enhancement of neuromuscular blocking agents leading to increased effects.
Caution advised when used with other medications affecting hematologic parameters.

Preparations Of The Drug

Suprax (brand name preparation) available as 400 mg oral capsules and 200 mg chewable tablets.
Oral powder for suspension: 100 mg/5 mL and 50 mg/5 mL, allowing flexible dosing especially for pediatric use.
Standard oral tablets available in 400 mg strength for adults and adolescents.
Chewable tablets formulated with phenylalanine, intended for pediatric patients who can chew.
Oral suspension contains sucrose, requiring caution in diabetic patients or patients on sucrose-restricted diets.
Packaging includes dosing syringe or calibrated spoon for liquid formulations to ensure accurate dosing.
Stability noted for up to 14 days post-reconstitution for suspensions when stored refrigerated.
Capsules designed for ease of swallowing and optimized release in the gastrointestinal tract.
All formulations designed to maintain adequate bioavailability and patient adherence.
Available in multiple generic formulations worldwide, meeting FDA and EMA standards.