Kefuclav(125 mg+31.25 mg)/5 ml

Kefuclav (125 mg+31.25 mg)/5 ml is a combination oral antibiotic used to treat bacterial infections caused by susceptible organisms, including many beta-lactamase-producing strains that would otherwise resist cefuroxime alone.

Established / commonly used indications

• Pharyngitis and tonsillitis
• Acute bacterial otitis media
• Acute bacterial sinusitis
• Acute bacterial exacerbations of chronic bronchitis and other lower respiratory tract infections
• Uncomplicated skin and skin-structure infections
• Uncomplicated urinary tract infections

Uses requiring specialist/combination therapy or supported mainly by local prescribing practice

• ENT infections in patients with a history of, or risk factors for, beta-lactamase-producing resistant organisms
• As oral step-down therapy for lower respiratory tract infections after an initial course of parenteral antibiotics, under physician guidance

Kefuclav (125 mg+31.25 mg)/5 ml should be used only for infections proven or strongly suspected to be caused by susceptible bacteria, based on culture and sensitivity data or local resistance patterns, to reduce the development of drug-resistant bacteria. It is not effective against viral infections such as the common cold or flu.

Kefuclav (125 mg+31.25 mg)/5 ml is available in Bangladesh as tablets containing cefuroxime axetil equivalent to 125 mg, 250 mg, or 500 mg of cefuroxime combined with 31.25 mg, 62.5 mg, or 125 mg of clavulanic acid (as potassium clavulanate) respectively, and as a powder for oral suspension providing cefuroxime 125 mg with clavulanic acid 31.25 mg per 5 mL after reconstitution. Cefuroxime axetil is the 1-acetoxyethyl ester (prodrug) of cefuroxime; clavulanic acid is derived from fermentation of Streptomyces clavuligerus.

Kefuclav (125 mg+31.25 mg)/5 ml is a fixed-dose combination antibiotic that pairs cefuroxime axetil, a semi-synthetic second-generation cephalosporin prodrug, with clavulanic acid, a beta-lactamase inhibitor. After oral absorption, cefuroxime axetil is hydrolyzed to release active cefuroxime, which is bactericidal against a broad range of Gram-positive and Gram-negative bacteria. Clavulanic acid itself has weak intrinsic antibacterial activity but irreversibly inactivates many bacterial beta-lactamase enzymes, protecting cefuroxime from degradation and extending its effective spectrum to include some beta-lactamase-producing organisms that would otherwise be resistant.

Kefuclav (125 mg+31.25 mg)/5 ml is used to treat respiratory tract infections, ear and sinus infections, urinary tract infections, and skin infections caused by organisms susceptible to this combination.

Kefuclav (125 mg+31.25 mg)/5 ml belongs to the second-generation cephalosporin class of beta-lactam antibiotics, combined with a beta-lactamase inhibitor.

Kefuclav (125 mg+31.25 mg)/5 ml combines an orally-absorbed cephalosporin prodrug with a beta-lactamase inhibitor to achieve bactericidal activity against a broadened range of bacteria.

Mechanism of action

Cefuroxime axetil is hydrolyzed during and after absorption to cefuroxime, the pharmacologically active moiety, which binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, inhibiting the final transpeptidation (cross-linking) step of peptidoglycan synthesis. This weakens the bacterial cell wall, causing cell lysis and death. Clavulanic acid has a beta-lactam ring structure similar to penicillins but only weak antibacterial activity on its own; instead, it binds irreversibly to and inactivates many bacterial beta-lactamase enzymes, preventing them from destroying cefuroxime and thereby restoring cefuroxime's activity against some beta-lactamase-producing resistant strains.

Spectrum of activity

Kefuclav (125 mg+31.25 mg)/5 ml is active against many Gram-positive organisms (e.g., Streptococcus pyogenes, Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus) and Gram-negative organisms (e.g., Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae), including a number of beta-lactamase-producing strains that are resistant to cefuroxime alone.

Pharmacokinetics

Absorption of the cefuroxime axetil component of Kefuclav (125 mg+31.25 mg)/5 ml is enhanced when taken with food; peak plasma concentrations occur approximately 2-3 hours after dosing. Cefuroxime is eliminated primarily unchanged by the kidneys via glomerular filtration and tubular secretion; clavulanic acid is also substantially renally eliminated.

Kefuclav (125 mg+31.25 mg)/5 ml tablets should be swallowed whole with water and not crushed or chewed, as crushing exposes the bitter-tasting active drug. Kefuclav (125 mg+31.25 mg)/5 ml is best taken with food, which increases absorption of the cefuroxime component and helps reduce stomach upset. If the oral suspension formulation of Kefuclav (125 mg+31.25 mg)/5 ml is used, shake well before each dose and use the measuring device provided; tablets and suspension are not necessarily interchangeable on a milligram-for-milligram basis, so use the formulation and dose prescribed by the physician.

The following interactions with Kefuclav (125 mg+31.25 mg)/5 ml are clinically significant:

• Gastric acid-reducing agents (antacids, H2-receptor antagonists, proton pump inhibitors): Reduced gastric acidity can lower the absorption and peak plasma concentration of the cefuroxime component of Kefuclav (125 mg+31.25 mg)/5 ml. If an antacid is required, it should be taken at least 1 hour before or 2 hours after Kefuclav (125 mg+31.25 mg)/5 ml.
• Probenecid: Competitively inhibits renal tubular secretion of cefuroxime, increasing and prolonging its plasma concentration; concurrent use with Kefuclav (125 mg+31.25 mg)/5 ml is generally not recommended unless specifically directed by a physician.
• Oral contraceptives: As with other antibiotics, Kefuclav (125 mg+31.25 mg)/5 ml may theoretically reduce the efficacy of estrogen-containing oral contraceptives; an additional non-hormonal method of contraception may be advised during treatment.
• Anticoagulants (e.g., warfarin): Beta-lactam/beta-lactamase-inhibitor combinations, including Kefuclav (125 mg+31.25 mg)/5 ml, have rarely been associated with prolonged prothrombin time; monitor closely if co-administered.
• Laboratory test interference: Kefuclav (125 mg+31.25 mg)/5 ml may cause false-positive results in some urine glucose tests using copper-reduction methods and may interfere with certain assays for serum/urine creatinine.

Kefuclav (125 mg+31.25 mg)/5 ml is generally well tolerated. Reported adverse effects include:

Common

• Diarrhea
• Nausea and vomiting
• Abdominal discomfort
• Headache
• Vaginal itching or vaginitis (in females)

Less common

• Skin rash or urticaria
• Transient elevation of liver enzymes
• Eosinophilia

Rare but serious

• Severe hypersensitivity/anaphylaxis
• Stevens-Johnson syndrome and toxic epidermal necrolysis
• Clostridioides difficile-associated diarrhea/colitis (see Precautions and Warnings)
• Cholestatic jaundice/hepatitis, mainly attributed to the clavulanic acid component, usually reversible on stopping treatment (see Contraindications)
• Seizures (typically with very high doses or in renal impairment)

Patients should seek prompt medical attention for any severe rash, difficulty breathing, swelling, yellowing of the skin/eyes, or persistent diarrhea while taking Kefuclav (125 mg+31.25 mg)/5 ml.

Pregnancy: Kefuclav (125 mg+31.25 mg)/5 ml should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus. Available data on cephalosporins and clavulanic acid have not shown an increased risk of major birth defects, and this combination has been used later in pregnancy to treat urinary and other infections under medical supervision, but there are no adequate, well-controlled studies to confirm safety definitively. A physician should always be consulted before using Kefuclav (125 mg+31.25 mg)/5 ml during pregnancy.

Lactation: Small amounts of cefuroxime and clavulanic acid are excreted into human breast milk. Kefuclav (125 mg+31.25 mg)/5 ml should be used with caution in breastfeeding women, and only under medical advice, with the infant monitored for gastrointestinal effects such as diarrhea, rash, or oral thrush.

Hypersensitivity: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported with cephalosporins; discontinue Kefuclav (125 mg+31.25 mg)/5 ml immediately if a reaction occurs. Use with caution in patients with a history of penicillin allergy due to possible cross-reactivity (see Contraindications).

Clostridioides difficile-associated diarrhea (CDAD): Kefuclav (125 mg+31.25 mg)/5 ml, like nearly all antibacterial agents, can cause CDAD ranging from mild diarrhea to fatal colitis. Evaluate patients who develop diarrhea during or after treatment.

Hepatic effects: Cholestatic jaundice and hepatitis have rarely been reported with beta-lactam/clavulanic acid combinations, usually reversible after stopping the drug; use with caution in patients with pre-existing liver disease and discontinue Kefuclav (125 mg+31.25 mg)/5 ml promptly if signs of hepatic dysfunction develop (see Contraindications).

Absorption and food: Absorption of the cefuroxime component of Kefuclav (125 mg+31.25 mg)/5 ml is enhanced by food; taking it with meals is recommended, particularly for higher doses.

Superinfection: Prolonged use of Kefuclav (125 mg+31.25 mg)/5 ml may result in overgrowth of non-susceptible organisms, including fungi.

Renal impairment: Dose or interval adjustment of Kefuclav (125 mg+31.25 mg)/5 ml may be required in patients with significant renal impairment.

Antibiotic stewardship: Take Kefuclav (125 mg+31.25 mg)/5 ml exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice, as inappropriate use promotes antibiotic resistance.

Laboratory interference: Kefuclav (125 mg+31.25 mg)/5 ml may cause false results in certain glucose and Coombs' tests (see Interactions).

Overdosage with Kefuclav (125 mg+31.25 mg)/5 ml may cause gastrointestinal disturbance (nausea, vomiting, diarrhea) and, particularly with the cefuroxime component in patients with renal impairment, central nervous system effects including increased cerebral irritability and seizures/convulsions. There is no specific antidote. If an overdose of Kefuclav (125 mg+31.25 mg)/5 ml is suspected, seek immediate medical attention or contact a poison control center; supportive care should be provided, and hemodialysis may help reduce serum concentrations of both components in severe cases. Do not attempt to manage a suspected overdose of Kefuclav (125 mg+31.25 mg)/5 ml at home without medical guidance.

Store Kefuclav (125 mg+31.25 mg)/5 ml tablets at room temperature (below 30°C), away from light and moisture. Keep out of reach of children. If using the reconstituted oral suspension of Kefuclav (125 mg+31.25 mg)/5 ml, store in a refrigerator and discard any unused portion after the period stated on the product label (commonly 7-10 days).

Pediatric use: Kefuclav (125 mg+31.25 mg)/5 ml may be used in children per approved weight-based dosing for specific indications; safety and efficacy have not been established in very young infants (consult the product label and a pediatrician). Tablets are not recommended for children unable to swallow them whole; use the oral suspension instead (see Pediatric Uses).

Geriatric use: No overall differences in safety or effectiveness have been observed with Kefuclav (125 mg+31.25 mg)/5 ml in elderly patients compared to younger adults, but elderly patients are more likely to have reduced renal function, requiring dose adjustment.

Renal impairment: The dose or dosing interval of Kefuclav (125 mg+31.25 mg)/5 ml should be adjusted in patients with significant renal impairment (e.g., creatinine clearance below 30 mL/min); consult a physician for individualized dosing.

Hepatic impairment: No formal dose adjustment of Kefuclav (125 mg+31.25 mg)/5 ml is established, but it should be used with caution and liver function monitored, given the rare association of the clavulanic acid component with hepatic effects (see Precautions and Warnings).

Pregnancy and lactation: See Pregnancy and Lactation section.

The duration of Kefuclav (125 mg+31.25 mg)/5 ml therapy depends on the infection being treated, generally ranging from 5 to 14 days for most common infections. Patients should complete the full prescribed course of Kefuclav (125 mg+31.25 mg)/5 ml even if symptoms improve early, to ensure eradication of the infection and reduce the risk of antibiotic resistance and relapse.

Kefuclav (125 mg+31.25 mg)/5 ml tablets do not require reconstitution. The Kefuclav (125 mg+31.25 mg)/5 ml powder for oral suspension must be reconstituted by adding the specified amount of water to the bottle as directed on the product label, then shaking well to form a uniform suspension (typically providing cefuroxime 125 mg with clavulanic acid 31.25 mg per 5 mL). The reconstituted suspension of Kefuclav (125 mg+31.25 mg)/5 ml should be shaken before each use, stored as directed on the label (commonly refrigerated), and any unused portion discarded after the period stated on the label (commonly 7-10 days).

Cephalosporins (second-generation); Beta-lactamase inhibitors; Beta-lactam antibiotic combinations.

Kefuclav (125 mg+31.25 mg)/5 ml combines cefuroxime axetil, an inactive ester prodrug hydrolyzed during absorption to release active cefuroxime, with clavulanic acid, a beta-lactamase inhibitor. Cefuroxime exerts a bactericidal effect by binding to penicillin-binding proteins (PBPs) in the bacterial cell wall, inhibiting the transpeptidation step of peptidoglycan (cell wall) biosynthesis and causing bacterial cell lysis and death. Clavulanic acid irreversibly binds and inactivates many bacterial beta-lactamase enzymes that would otherwise destroy cefuroxime, thereby protecting cefuroxime and broadening its effective spectrum to include some beta-lactamase-producing resistant organisms.

B

Kefuclav (125 mg+31.25 mg)/5 ml is used in children for specific indications such as pharyngitis/tonsillitis and acute otitis media, using weight-based dosing of the cefuroxime component (typically around 20-30 mg/kg/day in two divided doses, not exceeding the adult dose), per the product label and physician guidance. Safety and efficacy in very young infants have not been established, and a pediatrician should confirm appropriateness before use in this age group. Because the tablet form has a bitter taste when crushed, children who cannot swallow tablets whole should receive the oral suspension formulation of Kefuclav (125 mg+31.25 mg)/5 ml rather than a crushed tablet. Tablets and oral suspension are not necessarily interchangeable on a milligram-per-milligram basis, so a physician's specific formulation and dose should be followed.