Amoxicillin + Clavulanic acid: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Indonesia prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous
Prophylaxis of surgical infections

Adult: Available preparations:
Amoxicillin 500 mg and clavulanic acid 100 mg powder for solution for inj or infusion
Amoxicillin 1,000 mg and clavulanic acid 200 mg powder for solution for inj or infusion

In major surgical procedures involving the head and neck, cardiac, gastrointestinal tract, biliary tract, renal, joint replacement, and pelvic cavity: For procedures <1 hour duration: 1,000 mg/200 mg to 2,000 mg/200 mg given at induction of anaesthesia; For procedures >1 hour duration: 1,000 mg/200 mg to 2,000 mg/200 mg given at induction of anaesthesia, then up to 3 more 1,000 mg/200 mg doses in 24 hours. Administer normal IV or oral treatment course post-operatively, if clear signs of infection at operation is observed.

Intravenous
Acute exacerbations of chronic bronchitis, Bone and joint infections, Community-acquired pneumonia, Cystitis, Ear, nose and/or throat infections, Genitourinary infections, Infected animal bites, Intra-abdominal infections, Lower respiratory tract infections, Osteomyelitis, Pyelonephritis, Skin and soft tissue infections, Upper respiratory tract infections

Adult: Available preparations:
Amoxicillin 500 mg and clavulanic acid 100 mg powder for solution for inj or infusion
Amoxicillin 1,000 mg and clavulanic acid 200 mg powder for solution for inj or infusion

Individualise dosing based on expected susceptible pathogens, severity and site of infection, age, weight and renal function of the patient. 1,000 mg/200 mg 8 hourly via slow inj over 3-4 minutes or via drip or infusion over 30-40 minutes. In more serious infections, frequency may be increased to 6 hourly intervals. Treatment duration: Up to 14 days without review; osteomyelitis may require longer periods of treatment. Consider local guidelines on appropriate dosing frequencies and recommendations.
Child: Available preparations:
Amoxicillin 500 mg and clavulanic acid 100 mg powder for solution for inj or infusion
Amoxicillin 1,000 mg and clavulanic acid 200 mg powder for solution for inj or infusion

<3 months or weighing <4 kg: 25 mg/5 mg/kg 12 hourly via infusion only over 30-40 minutes; ≥3 months <40 kg: 25 mg/5 mg/kg 8 hourly via slow IV inj over 3-4 minutes or via drip or infusion over 30-40 minutes; ≥40 kg: Same as adult dose.

Oral
Acute bacterial sinusitis, Cystitis, Ear, nose and/or throat infections, Genitourinary infections, Infected animal bites, Intra-abdominal infections, Pyelonephritis, Skin and soft tissue infections, Upper respiratory tract infections

Adult: Available preparations:
Amoxicillin 250 mg and clavulanic acid 125 mg conventional tab
Amoxicillin 500 mg and clavulanic acid 125 mg conventional tab
Amoxicillin 875 mg and clavulanic acid 125 mg conventional tab
Amoxicillin 1,000 mg and clavulanic acid 62.5 mg extended-release tab
Amoxicillin 125 mg and clavulanic acid 31.25 mg per 5 mL oral susp
Amoxicillin 250 mg and clavulanic acid 62.5 mg per 5 mL oral susp

Individualise dosing based on expected susceptible pathogens, severity and site of infection, age, weight and renal function of the patient. As conventional tab: 250 mg/125 mg tid, or 500 mg/125 mg tid, or 875 mg/125 mg bid. As oral susp: 500 mg/125 mg tid. Treatment duration: Up to 14 days. without review. For treatment of acute bacterial sinusitis only: As extended-release tab: 2,000 mg/125 mg 12 hourly for 10 days.
Child: Available preparations:
Amoxicillin 125 mg and clavulanic acid 31.25 mg per 5 mL oral susp
Amoxicillin 250 mg and clavulanic acid 62.5 mg per 5 mL oral susp
≤6 years <40 kg: 20 mg/5 mg/kg daily to 60 mg/15 mg/kg daily given in 3 divided doses; ≥40 kg: Same as adult dose.

Amoxicillin 400 mg and clavulanic acid 57 mg per 5 mL oral susp
≤6 years <40 kg: 25 mg/3.6 mg/kg daily to 45 mg/6.4 mg/kg daily given in 2 divided doses. For sinusitis: Up to 70 mg/10 mg/kg daily may be given in 2 divided doses.

Amoxicillin 250 mg and clavulanic acid 125 mg conventional tab
≥40 kg: Same as adult dose.

Amoxicillin 500 mg and clavulanic acid 125 mg conventional tab
25-<40 kg: 20 mg/5 mg/kg daily to 60 mg/15 mg/kg daily given in 3 divided doses; ≥40 kg: Same as adult dose.

Amoxicillin 1,000 mg and clavulanic acid 62.5 mg extended-release tab
For treatment of acute bacterial sinusitis only: ≥40 kg: Same as adult dose.

Oral
Acute exacerbations of chronic bronchitis, Acute otitis media, Bone and joint infections, Community-acquired pneumonia, Lower respiratory tract infections, Osteomyelitis

Adult: Available preparations:
Amoxicillin 500 mg and clavulanic acid 125 mg conventional tab
Amoxicillin 875 mg and clavulanic acid 125 mg conventional tab
Amoxicillin 1,000 mg and clavulanic acid 62.5 mg extended-release tab
Amoxicillin 125 mg and clavulanic acid 31.25 mg per 5 mL oral susp
Amoxicillin 250 mg and clavulanic acid 62.5 mg per 5 mL oral susp

Individualise dosing based on expected susceptible pathogens, severity and site of infection, age, weight and renal function of the patient. As conventional tab: 500 mg/125 mg tid, or 875 mg/125 mg 2 or 3 times daily. As oral susp: 500 mg/125 mg tid. Treatment duration: Up to 14 days without review; osteomyelitis may require longer periods of treatment. For treatment of community-acquired pneumonia only: As extended-release tab: 2,000 mg/125 mg 12 hourly for 7-10 days.
Child: Available preparations:
Amoxicillin 125 mg and clavulanic acid 31.25 mg per 5 mL oral susp
Amoxicillin 250 mg and clavulanic acid 62.5 mg per 5 mL oral susp
≤6 years <40 kg: 20 mg/5 mg/kg daily to 60 mg/15 mg/kg daily given in 3 divided doses; ≥40 kg: Same as adult dose.

Amoxicillin 400 mg and clavulanic acid 57 mg per 5 mL oral susp
≤6 years <40 kg: 25 mg/3.6 mg/kg daily to 45 mg/6.4 mg/kg daily given in 2 divided doses. For otitis media and lower respiratory tract infections: Up to 70 mg/10 mg/kg daily may be given in 2 divided doses.

Amoxicillin 500 mg and clavulanic acid 125 mg conventional tab
25-<40 kg: 20 mg/5 mg/kg daily to 60 mg/15 mg/kg daily given in 3 divided doses; ≥40 kg: Same as adult dose.

Amoxicillin 1,000 mg and clavulanic acid 62.5 mg extended-release tab
For treatment of community-acquired pneumonia only: ≥40 kg: Same as adult dose.

Renal Impairment

Oral:
Upper respiratory tract infections; Ear, nose and/or throat infections; Acute bacterial sinusitis; Genitourinary infections; Cystitis; Pyelonephritis; Skin and soft tissue infections; Infected animal bites; Intra-abdominal infections:
Haemodialysis: Adults and children ≥40 kg: As 250 mg/125 mg conventional tab: 500 mg/250 mg 24 hourly, then 500 mg/250 mg dose during and repeated at the end of dialysis; As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 500 mg/125 mg 24 hourly, then 500 mg/125 mg dose during and repeated at the end of dialysis; Children <40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 15 mg/3.75 mg/kg once daily. Give 15 mg/3.75 mg/kg dose prior to and after dialysis. As extended-release tab: Contraindicated.

CrCl (mL/min)	Dosage
<10	Adults and children ≥40 kg: As 250 mg/125 mg conventional tab: 250 mg/125 mg once daily; As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 500 mg/125 mg once daily; Children <40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 15 mg/3.75 mg/kg given as single daily dose. Max: 500 mg/125 mg daily.
10-30	Adults and children ≥40 kg: As 250 mg/125 mg conventional tab: 250 mg/125 mg bid; As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 500 mg/125 mg bid; Children <40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 15 mg/3.75 mg/kg bid. Max: 500 mg/125 mg bid.
<30	As extended-release tab: Contraindicated.

Acute otitis media; Lower respiratory tract infections; Acute exacerbations of chronic bronchitis; Community-acquired pneumonia; Bone and joint infections; Osteomyelitis:
Haemodialysis: Adults and children ≥40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 500 mg/125 mg 24 hourly, then 500 mg/125 mg dose during and repeated at the end of dialysis; Children <40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 15 mg/3.75 mg/kg once daily. Give 15 mg/3.75 mg/kg dose prior to and after dialysis. As extended-release tab: Contraindicated.

CrCl (mL/min)	Dosage
<10	Adults and children ≥40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 500 mg/125 mg once daily; Children <40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 15 mg/3.75 mg/kg given as single daily dose. Max: 500 mg/125 mg daily.
10-30	Adults and children ≥40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 500 mg/125 mg bid; Children <40 kg: As 500 mg/125 mg conventional tab, 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL oral susp: 15 mg/3.75 mg/kg bid. Max: 500 mg/125 mg bid.
<30	As extended-release tab: Contraindicated.

Intravenous:
Upper respiratory tract infections; Ear, nose and/or throat infections; Lower respiratory tract infections; Acute exacerbations of chronic bronchitis; Community-acquired pneumonia; Genitourinary infections; Cystitis; Pyelonephritis; Skin and soft tissue infections; Infected animal bites; Bone and joint infections; Osteomyelitis; Intra-abdominal infections:
Haemodialysis: Adults and children ≥40 kg: Initially, 1,000 mg/200 mg via slow inj or infusion, followed by 500 mg/100 mg 24 hourly, then 500 mg/100 mg dose at the end of dialysis; Children <40 kg: 25 mg/5 mg/kg 24 hourly, then 12.5 mg/2.5 mg/kg dose at the end of dialysis.

CrCl (mL/min)	Dosage
<10	Adults and children ≥40 kg: Initially, 1,000 mg/200 mg via slow inj or infusion, followed by 500 mg/100 mg 24 hourly; Children <40 kg: 25 mg/5 mg/kg 24 hourly.
10-30	Adults and children ≥40 kg: Initially, 1,000 mg/200 mg via slow inj or infusion, followed by 500 mg/100 mg 12 hourly; Children <40 kg: 25 mg/5 mg/kg 12 hourly.

Administration

extended-release: Should be taken with food. Must be taken at the start of meals.
May be taken with or without food. May be given w/o regard to meals. Best taken at the start of meals for better absorption & to reduce GI discomfort.

Reconstitution

Powder for oral susp: Reconstitute with the appropriate volume of water as indicated on the label. Invert and shake well until suspended. Powder for solution for IV inj: Dissolve vial labelled as 500 mg/100 mg and 1,000 mg/200 mg with 10 mL and 20 mL of water for inj to yield approx 10.5 mL and approx 20.9 mL reconstituted solution, respectively. Powder for solution for IV infusion: Add the 500 mg/100 mg and 1,000 mg/200 mg reconstituted solution to 50 mL and 100 mL of infusion fluid (e.g. water for inj, 0.9% NaCl inj), respectively. IV reconstituted solutions should be administered or diluted for infusion within 20 minutes. Refer to detailed product guideline for further appropriate infusion fluids and their stability.

Incompatibility

Powder for solution for inj or infusion: Incompatible with blood products, other proteinaceous fluids (e.g. protein hydrolysates), IV lipid emulsions, aminoglycosides, and infusions containing glucose, dextran, or bicarbonate.

Contraindications

Hypersensitivity or history of hypersensitivity reactions (e.g. anaphylaxis, Stevens-Johnson syndrome) to amoxicillin, clavulanic acid, or other β-lactam antibacterials (e.g. penicillin, cephalosporin, carbapenem, monobactam). History of cholestatic jaundice or hepatic dysfunction associated with amoxicillin/clavulanic acid treatment. As extended-release tab: Severe renal impairment (CrCl <30 mL/min) and patients undergoing haemodialysis.

Special Precautions

Patients with infectious mononucleosis; reduced urine output. Atopic individuals. Renal (including haemodialysis patients) and hepatic impairment. Children. Pregnancy and lactation.

Adverse Reactions

Significant: Diarrhoea, fungal or bacterial superinfection, convulsions (at high doses or in patients with renal impairment), morbilliform rash (in patients with mononucleosis). Rarely, crystalluria (IV), prothrombin time prolongation.
Blood and lymphatic system disorders: Haemolytic anaemia, reversible agranulocytosis. Rarely, thrombocytopenia, reversible leucopenia or neutropenia.
Gastrointestinal disorders: Nausea, vomiting, indigestion, black hairy tongue.
Immune system disorders: Serum sickness-like syndrome, urticaria, hypersensitivity vasculitis.
Infections and infestations: Mucocutaneous candidosis.
Investigations: Increased AST/ALT.
Nervous system disorders: Headache, dizziness, reversible hyperactivity.
Renal and urinary disorders: Interstitial nephritis.
Reproductive system and breast disorders: Vaginal mycosis.
Skin and subcutaneous tissue disorders: Rash, pruritus, Stevens-Johnson syndrome. Rarely, erythema multiforme.
Potentially Fatal: Severe hypersensitivity reactions, including anaphylactoid and severe cutaneous reactions (e.g. acute generalised exanthematous pustulosis); Clostridium difficile-associated diarrhoea or pseudomembranous colitis. Rarely, hepatic dysfunction (e.g. cholestatic jaundice, hepatitis).

Pregnancy Category (US FDA)

Parenteral/PO: B

Patient Counseling Information

Do not switch between different formulations unless instructed by your doctor.

Monitoring Parameters

Perform culture and sensitivity tests. Monitor CBC with differential, renal function tests, and LFTs periodically especially with prolonged treatment; LFTs at regular intervals in patients with hepatic impairment. Assess for signs of infection at baseline and throughout the treatment; anaphylaxis during 1st dose.

Overdosage

Symptoms: Gastrointestinal effects (e.g. stomach or abdominal pain, vomiting, and diarrhoea), rash, hyperactivity, drowsiness, fluid and electrolyte imbalance, crystalluria resulting in renal failure, and convulsions (in patients with renal impairment). Management: Symptomatic and supportive treatment. Focus on water/electrolyte balance.

Drug Interactions

Reduced pre-dose concentrations of mycophenolate mofetil active metabolite. May reduce the efficacy of combined oral oestrogen/progesterone contraceptives.
Amoxicillin: Increased risk of allergic skin reactions with allopurinol. Probenecid increases and prolongs plasma concentrations of amoxicillin. May increase INR in patients maintained with oral anticoagulants (e.g. acenocoumarol, warfarin). May reduce the excretion and increase the risk of methotrexate toxicity.

Food Interaction

Increased amoxicillin absorption and decreased gastrointestinal upset with food. Decreased clavulanic acid absorption with high-fat meals.

Lab Interference

May cause false-positive result for Platelia Aspergillus EIA test.
Amoxicillin: Non-enzymatic methods for urinary glucose testing (e.g. Benedict’s solution, Fehling’s solution) may lead to false-positive reactions. May transiently decrease plasma levels of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone, and oestradiol in pregnant women.
Clavulanic acid: May result in false-positive Coombs test.

Action

Description:
Mechanism of Action: Amoxicillin, a semi-synthetic penicillin, inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs), thereby blocking the final transpeptidation step of peptidoglycan synthesis in the bacterial cell walls. It is susceptible to degradation by β-lactamases which are produced by certain resistant bacteria.
Clavulanic acid, a β-lactam structurally related to penicillin, binds and inhibits β-lactamases, thereby preventing amoxicillin inactivation and expands the amoxicillin spectrum of activity. It does not exert clinically significant antibacterial effect alone.
Synonym: Co-amoxiclav
Pharmacokinetics:
Absorption: Amoxicillin: Rapidly and well absorbed from the gastrointestinal tract. Increased absorption and decreased gastrointestinal upset with food. Bioavailability: Approx 70%. Time to peak plasma concentration: Approx 1-2 hours.
Clavulanic acid: Rapidly and well absorbed from the gastrointestinal tract. Decreased absorption with high-fat meals. Bioavailability: Approx 70%. Time to peak plasma concentration: 1.5 hours.
Distribution: Amoxicillin: IV: Readily distributed into body tissues and fluids (e.g. gall bladder, abdominal or muscle tissues, skin, fat, synovial and peritoneal fluids, bile, pus) except the brain and CSF. Crosses placenta and enters breast milk. Volume of distribution: Approx 0.3-0.4 L/kg. Plasma protein binding: Approx 18%.
Clavulanic acid: IV: Well distributed into body tissues and fluids (e.g. gall bladder, abdominal or muscle tissues, skin, fat, synovial and peritoneal fluids, bile, pus). Crosses placenta and enters breast milk. Volume of distribution: Approx 0.2 L/kg. Plasma protein binding: Approx 25%.
Metabolism: Amoxicillin: Metabolised to a limited extent to form inactive penicilloic acid.
Clavulanic acid: Extensively metabolised.
Excretion: Amoxicillin: Mainly via urine (approx 60-80% as unchanged drug). Elimination half-life: Approx 1.3 hours.
Clavulanic acid: Via urine (approx 25-40% as unchanged drug); faeces; expired air. Elimination half-life: Approx 1 hour.

Chemical Structure

Storage

Tab/susp: Store below 25°C. Protect from moisture. Reconstituted oral susp: Store between 2-8°C. Do not freeze. Vial: May be stored either below 25°C, or between 2-8°C. Protect from moisture. Storage conditions may vary according to individual product or country of use. Do not freeze reconstituted IV solution.

MIMS Class

Penicillins

ATC Classification

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

References

Amoxicillin and Clavulanate Potassium Extended Release Tablet (Dr. Reddy's Laboratories Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 9/12/2019.

Anon. Amoxicillin and Clavulanate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 9/12/2019.

Augmentin 125/31 Suspension (GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk/. Accessed 17/04/2020.

Augmentin 375 mg Tablets (GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk/. Accessed 17/04/2020.

Augmentin 625 mg Tablets (GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk/. Accessed 17/04/2020.

Augmentin Duo 400/57 mg Powder for Oral Suspension (GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk/. Accessed 17/04/2020.

Augmentin Intravenous (GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk/. Accessed 17/04/2020.

Augmentin Oral Preparations (GlaxoSmithKline Philippines Inc). MIMS Philippines. http://www.mims.com/philippines. Accessed 11/12/2019.

Augmentin Powder for Injection (GlaxoSmithKline Philippines Inc). MIMS Philippines. http://www.mims.com/philippines. Accessed 11/12/2019.

Buckingham R (ed). Amoxicillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 9/12/2019.

Buckingham R (ed). Clavulanic acid. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 9/12/2019.

Co-amoxiclav 250 mg/62.5 mg/5 mL Powder for Oral Suspension (Medereich Plc). MHRA. https://products.mhra.gov.uk/. Accessed 17/04/2020.

Disclaimer: This information is independently developed by MIMS based on Amoxicillin + Clavulanic acid from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com

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