KOACT 1000 (CO-AMOXICLAV TABLETS BP 875-125 MG)

Indications

• Bacterial infections
• Urinary tract infections
• Sinusitis
• Uncomplicated community-acquired pneumonia
• Salmonellosis
• Oral infections
• Lyme disease (under expert supervision)
• Acute exacerbation of bronchiectasis
• Anthrax (treatment and post-exposure prophylaxis)

Dosage

Children: 1 month–11 years: 30 mg/kg 3 times a day for 21 days; children 1–4 years: 250 mg 3 times a day; children 5–11 years: 500 mg 3 times a day.

Adults: 500 mg 3 times a day; increased if necessary up to 1 g 3 times a day in severe infections.

Mechanism of action

Amoxicillin works by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, interfering with the transpeptidation process necessary for cell wall integrity.

Pharmacodynamics

Amoxicillin exhibits bactericidal activity against susceptible bacteria. Its action is time-dependent, meaning that its effectiveness is related to the duration of time that the drug concentration remains above the minimum inhibitory concentration (MIC) for the target pathogen.

Pharmacokinetics

Amoxicillin is well absorbed from the gastrointestinal tract, with peak plasma concentrations achieved within 1-2 hours after oral administration. It is widely distributed in body tissues and fluids, and it is excreted primarily via the kidneys. The elimination half-life is approximately 1 hour, and renal impairment may necessitate dosage adjustments.

Adverse effects

• Skin rash
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Allergic reactions (including anaphylaxis)
• Superinfection (due to resistant organisms)

Interactions

• Allopurinol (increases risk of skin rash)

Precautions

• History of penicillin allergy
• Renal impairment (reduce dose)
• Use with caution in patients with mononucleosis

Pregnancy

Use only if clearly needed; no adequate studies in pregnant women.

Breast-feeding

Amoxicillin is excreted in breast milk; use with caution.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Phenoxymethylpenicillin 250mg/5ml oral solution
• Phenoxymethylpenicillin 250 mg tablets

Indications

• Infections caused by beta-lactamase producing bacteria
• Sinusitis
• Otitis media
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections

Dosage

Children: Refer to specific product guidelines for dosing information. Doses in children may vary based on age, weight, and type of infection.

Adults: Refer to specific product guidelines for dosing information. Doses may vary depending on the severity of the infection and the specific penicillin antibiotic used in combination.

Mechanism of action

Calvulanate binds to and inactivates various beta-lactamases. These enzymes normally hydrolyze the beta-lactam ring of penicillin antibiotics, leading to their inactivation. By inhibiting these enzymes, clavulanate protects penicillin antibiotics from degradation, thus extending their spectrum of activity against beta-lactamase-producing bacteria.

Pharmacodynamics

Clavulanate exhibits a time-dependent antibacterial effect. The inhibition of beta-lactamases enhances the effectiveness of co-administered beta-lactam antibiotics. The spectrum of activity of clavulanate is primarily against gram-negative bacteria that produce beta-lactamase, including Haemophilus influenzae, Escherichia coli, and Klebsiella pneumoniae, as well as some gram-positive bacteria like Staphylococcus aureus.

Pharmacokinetics

Clavulanate is well absorbed following oral administration, with peak plasma concentrations achieved within 1 hour. It is widely distributed throughout the body, with the ability to penetrate tissue and body fluids. The elimination half-life is approximately 1 hour, and it is primarily excreted via the kidneys, with a significant proportion appearing in the urine as unchanged drug. Renal impairment may prolong the half-life and necessitate dose adjustments.

Contra-indications

• Hypersensitivity to clavulanate or any component of the formulation
• History of cholestatic jaundice or hepatic dysfunction associated with clavulanate

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Hepatic enzyme elevation
• Allergic reactions

Interactions

• May enhance the anticoagulant effect of warfarin
• Probenecid may increase plasma concentrations of clavulanate
• May interact with other antibiotics

Precautions

• Caution in patients with renal impairment
• Monitor for signs of hepatic dysfunction
• Use with caution in individuals with a history of allergy to penicillins

Pregnancy

Clavulanate is generally considered safe for use during pregnancy, but should be used only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Clavulanate is excreted in breast milk, and caution should be exercised when administered to nursing women.

Storage

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

Formulations

• Clavulanate potassium tablets
• Clavulanate potassium oral suspension
• Clavulanate in combination with amoxicillin as a fixed-dose combination

Indications

• Pediatric dosing adjustments
• Intravenous therapy
• Intramuscular injections
• Topical applications
• Oral medications for easier swallowing

Dosage

Children: Refer to the BNF for Children for appropriate dosing adjustments based on age and weight.

Adults: Refer to specific drug guidelines for appropriate dilution and dosage based on the active ingredient.

Mechanism of action

The mechanism of action of a diluted drug depends on the specific active ingredient within the solution. Generally, when a drug is diluted, its pharmacological effects are proportional to its concentration. The active molecules interact with specific receptors or enzymes in the body, leading to a desired therapeutic effect. For example, an analgesic diluted for oral administration will still bind to pain receptors, albeit at a lower intensity compared to its concentrated form.

Pharmacodynamics

Pharmacodynamics refers to the relationship between drug concentration and its effect on the body. In diluted solutions, the pharmacodynamic properties of the active ingredient remain intact, though the therapeutic effect may be reduced due to the lower concentration. The efficacy of the drug is influenced by factors such as receptor affinity, intrinsic activity, and the presence of other substances in the formulation.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of drugs. For diluted drugs, absorption can be affected by the dilution medium, which may enhance or delay the onset of action. Distribution is generally influenced by the volume of distribution of the active ingredient. Metabolism occurs primarily in the liver, where the drug is biotransformed, and excretion is typically via the kidneys. The pharmacokinetic profile may differ based on the dilution level and formulation.

Pregnancy

Consult a healthcare provider, as the effects of diluted preparations can vary depending on the active ingredient.

Breast-feeding

Consult a healthcare provider, as the safety of diluted preparations during breastfeeding can depend on the active ingredient.

Storage

Store in a cool, dry place away from direct sunlight. Ensure that the specific active ingredient's storage requirements are followed.

Mechanism of action

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action. The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Amoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.

Pharmacodynamics

Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis. Amoxicillin has a long duration of action as it is usually given twice daily. Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity. Patients should be counselled regarding the risk of anaphylaxis, _Clostridium difficile_ infections, and bacterial resistance.