AMOXICLAV-DENK 1000/125

Indications

• Acute otitis media
• Sinusitis
• Pneumonia

Mechanism of action

Amoxicillin exerts its antibacterial effect by binding to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, leading to inhibition of peptidoglycan synthesis, which is essential for bacterial cell wall structural integrity. This results in cell lysis and death of the bacteria. Clavulanic acid inhibits beta-lactamase enzymes, which are responsible for the hydrolysis of beta-lactam antibiotics, thus protecting amoxicillin from degradation and allowing it to exert its effect more effectively against beta-lactamase-producing bacteria.

Pharmacodynamics

The pharmacodynamics of amoxiclav is characterized by its time-dependent killing mechanism. The efficacy of amoxicillin is influenced by the duration of time that plasma concentrations remain above the minimum inhibitory concentration (MIC) for the target organism. Clavulanic acid increases the spectrum of activity of amoxicillin, allowing for the treatment of infections caused by organisms that would be resistant to amoxicillin alone. The combination is effective against a wide range of Gram-positive and Gram-negative bacteria.

Pharmacokinetics

Amoxiclav is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours after oral administration. It is widely distributed in body tissues and fluids, including the lungs, skin, and urine. The presence of food can affect the absorption of amoxicillin but does not significantly affect clavulanic acid. Both components are primarily eliminated via renal excretion, with approximately 50-70% of a dose excreted unchanged in the urine. The half-life of amoxicillin is about 1 hour, while clavulanic acid has a slightly longer half-life.

Contra-indications

• History of hypersensitivity to amoxicillin, clavulanic acid, or any other component of the formulation
• Severe liver impairment
• History of cholestatic jaundice or hepatic dysfunction associated with amoxicillin/clavulanic acid

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Rash
• Allergic reactions
• Hepatic dysfunction
• Clostridium difficile-associated diarrhea
• Anemia
• Thrombocytopenia

Interactions

• Probenecid may increase the plasma concentration of amoxicillin
• Anticoagulants may have enhanced effects when used concurrently
• Methotrexate clearance may be reduced, leading to increased toxicity

Precautions

• Use with caution in patients with renal impairment
• Monitor liver function in patients with a history of liver disease
• Caution in patients with a history of allergy to penicillins or cephalosporins
• Monitor for signs of superinfection with prolonged use

Pregnancy

Amoxiclav is generally considered safe to use during pregnancy. However, it should only be used if clearly needed and after assessment of risks versus benefits.

Breast-feeding

Amoxiclav is excreted in breast milk in small amounts. Caution is advised, and benefits should be weighed against potential risks.

Storage

Store at room temperature away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension
• Injection

Indications

• Bacterial infections caused by beta-lactamase producing organisms
• Community-acquired pneumonia
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing of clavulanate should be determined based on the specific indication and the formulation used. Refer to the BNF for

Adults: The usual adult dose of clavulanate varies depending on the specific antibiotic it is combined with, generally ranging from 125 mg to 250 mg, taken every 8 hours when combined with amoxicillin.

Mechanism of action

Clavulanate works by irreversibly binding to the active site of beta-lactamase enzymes. By inhibiting these enzymes, clavulanate protects beta-lactam antibiotics from degradation, allowing them to exert their antibacterial effects effectively. This mechanism enhances the spectrum of activity of the co-administered antibiotic, thereby improving clinical outcomes in infections caused by beta-lactamase producing organisms.

Pharmacodynamics

Clavulanate exhibits a time-dependent antibacterial effect, characterized by its ability to maintain effective concentrations against beta-lactamase producing bacteria. Its pharmacodynamic properties are mainly influenced by its interaction with beta-lactam antibiotics, enhancing their efficacy in treating infections. The overall effect is a synergistic relationship that increases the potency of the antibiotic treatment.

Pharmacokinetics

Clavulanate is usually administered orally or parenterally, and it is rapidly absorbed from the gastrointestinal tract. It reaches peak plasma concentrations within 1 to 2 hours after administration. The drug is widely distributed in body tissues, with a volume of distribution indicative of good tissue penetration. Clavulanate undergoes hepatic metabolism, primarily by conjugation, and is excreted largely in the urine as metabolites. The elimination half-life is approximately 1 hour, necessitating frequent dosing for optimal therapeutic effect.

Contra-indications

• Hypersensitivity to clavulanate or any component of the formulation
• History of jaundice or hepatic impairment related to previous use of beta-lactam antibiotics

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Hepatic dysfunction
• Allergic reactions

Interactions

• Probenecid may increase concentrations of clavulanate
• Anticoagulants may have altered effects due to changes in gut flora

Precautions

• Monitor liver function during prolonged therapy
• Use cautiously in patients with renal impairment
• Assess for history of allergy to penicillins or cephalosporins

Pregnancy

Clavulanate is classified as category B. Animal studies have not shown teratogenic effects, but adequate and well-controlled studies in pregnant women are lacking.

Breast-feeding

Clavulanate is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Clavulanate potassium 125 mg/5 mL
• Clavulanate potassium 250 mg/5 mL