AUGPEN 375 TABLETS

Indications

• Bacterial infections of the respiratory tract, such as pneumonia and bronchitis
• Otitis media (middle ear infections)
• Sinusitis
• Skin and soft tissue infections
• Urinary tract infections
• Gonorrhea
• Helicobacter pylori eradication (as part of combination therapy for peptic ulcer disease)

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on the child's age, weight, and clinical condition.

Adults: Refer to specific guidelines or the BNF for appropriate adult dosing based on the indication and severity of the infection.

Mechanism of action

Amoxicillin exerts its antibacterial effect by binding to penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding inhibits the transpeptidation enzyme necessary for cross-linking peptidoglycan layers, ultimately disrupting cell wall synthesis and leading to cell death.

Pharmacodynamics

The pharmacodynamic properties of amoxicillin include its ability to exhibit time-dependent killing, with its efficacy linked to the time that serum concentrations remain above the minimum inhibitory concentration (MIC) for the target organism. Resistance can occur through the production of beta-lactamases, which hydrolyze the beta-lactam ring, rendering the antibiotic ineffective.

Pharmacokinetics

Amoxicillin is well absorbed from the gastrointestinal tract, with bioavailability ranging from 70% to 90%. It is widely distributed in body tissues and fluids, including the lungs, liver, and kidneys. Amoxicillin is minimally metabolized in the liver, with approximately 50-70% of the drug excreted unchanged in the urine. Its half-life is approximately 1 to 1.5 hours, necessitating multiple dosing to maintain effective plasma levels.

Contra-indications

• Hypersensitivity to penicillins
• History of severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Rash
• Allergic reactions
• Anaphylaxis
• Clostridium difficile-associated diarrhea

Interactions

• Probenecid may increase amoxicillin plasma levels
• Oral contraceptives may have reduced efficacy when used with amoxicillin
• Anticoagulants may have increased effects when used with amoxicillin

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of an allergic reaction
• Consider alternative therapy in patients with a history of gastrointestinal disease

Pregnancy

Amoxicillin is generally considered safe during pregnancy and is often used to treat infections in pregnant women.

Breast-feeding

Amoxicillin is excreted in breast milk, but is usually considered safe for use during breastfeeding.

Storage

Store at room temperature, away from moisture and heat. Reconstituted solutions should be refrigerated and used within a specified time frame.

Formulations

• Capsules
• 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