Co-amoxiclav (amoxicillin and clavulanic acid) oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing amoxicillin (as amoxicillin trihydrate) and clavulanic acid (as potassium clavulanate).
Drugs List
Therapeutic Indications
Uses
Infections due to amoxicillin-resistant beta-lactamase producing bacteria
Treatment of the following bacterial infections when caused by organisms that are resistant to amoxicillin but susceptible to amoxicillin with clavulanic acid:
Respiratory tract infections: e.g. acute bacterial sinusitis (adequately diagnosed), acute otitis media, acute exacerbations of chronic bronchitis (adequately diagnosed), community acquired pneumonia
Genito-urinary tract infections: e.g. cystitis, pyelonephritis
Skin and soft tissue infections: in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis
Bone and joint infections: in particular osteomyelitis
Abdominal infections
Dosage
Duration of therapy should be appropriate to the indication and should not exceed 14 days without review.
Adults
Infections
One tablet (250mg+125mg) every 8 hours.
Severe infections
One tablet (500mg+125mg) every 8 hours.
Alternatively, one tablet (875mg+125mg) twice a day.
Otitis media, sinusitis, lower respiratory tract infections and urinary tract infections
One tablet (875mg+125mg) two to three times a day.
Children
Children aged 6 to 18 years and weighing 40kg or more
(See Dosage; Adult)
Children 6 years and younger or weighing less than 40kg
It is recommended to use oral suspension or paediatric sachets.
20mg+5mg/kg to 60mg+15 mg/kg a day, given in three divided doses.
If considered necessary, for some infections dose may be increased up to 70mg+10mg/kg per day, given in two divided doses.
The following alternate dosing schedule may be suitable:
Children aged 12 to 18 years
(See Dosage; Adult)
Children aged 12 to 18 years weighing 41kg or more
10ml (of 400mg+57mg) oral suspension twice a day. May be increased up to three times a day based on severity of the infection.
Children aged 6 to 12 years
5ml (of 250mg+62mg) oral suspension three times a day. Doses may be increased based on severity of the infection.
Children aged 6 to 12 years weighing 22kg to 41kg
5ml (of 400mg+57mg) oral suspension twice a day. Doses may be doubled based on severity of the infection.
Children aged 1 to 6 years
5ml (of 125mg+31mg) oral suspension three times a day. Doses may be doubled based on severity of the infection.
Children aged 2 to 6 years weighing 13kg to 22kg
2.5ml (of 400mg+57mg) oral suspension twice a day. Doses may be doubled based on severity of the infection.
Children aged 1 month to 1 year
0.25ml/kg of 125mg+31mg oral suspension three times a day. Doses may be doubled based on severity of the infection.
Neonates
The following dosing schedule may be suitable:
0.25ml per kg (of 125mg+31mg) oral suspension three times a day.
Patients with Renal Impairment
In patients with renal impairment, the dose should be adjusted according to the degree of impairment. Convulsions may occur in patients with impaired renal function or in those receiving high doses. Dosage adjustments are based on the maximum recommended level of amoxicillin.
No adjustment in dose is required in patients with creatinine clearance above 30 ml/minute.
Adults and children weighing 40kg or more
Creatinine clearance between 10 and 30ml/minute
One tablet (250mg+125mg or 500mg+125mg) twice a day.
Creatinine clearance less than 10ml/minute
One tablet (250mg+125mg or 500mg+125mg) once a day.
Haemodialysis
500mg+125mg every 24 hours, plus 500mg+125mg during dialysis, to be repeated at the end of dialysis.
Some manufacturers support using multiple doses of 250mg+125mg tablet.
In patients with creatinine clearance less than 30ml/minute, the use of co-amoxiclav preparations with amoxicillin to clavulanic acid ratio of 7:1 is not recommended.
Children weighing less than 40kg
Creatinine clearance between 10 and 30 ml/minute
15mg+3.75mg/kg twice a day (maximum 500mg+125mg twice a day).
Creatinine clearance less than 10 ml/minute
15mg+3.75mg/kg as a single daily dose (maximum 500mg+125mg).
Haemodialysis
15mg+3.75mg/kg per day once daily.
Give 15mg+3.75mg/kg prior to dialysis. The same amount of co-amoxiclav should be administered after haemodialysis to restore circulating drug levels.
In children weighing less than 40kg with creatinine clearance less than 30ml/minute, the use of co-amoxiclav presentations with amoxicillin to clavulanic acid ratios of 2:1 and 7:1 is not recommended.
Contraindications
Infectious mononucleosis
History of drug induced hepatic impairment
History of drug induced jaundice
Precautions and Warnings
Allergic disposition
Atopy
Children under 2 years
Cytomegalovirus infection
Asthma
Breastfeeding
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
Lymphatic leukaemia
Phenylketonuria
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Reduce dose in patients with creatinine clearance below 30ml/min
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Before initiating therapy enquire about previous hypersensitivity reactions
Consult national/regional policy on the use of anti-infectives
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain glucose
Some presentations may contain benzyl alcohol
Dose should be administered just before or after food
Consider pseudomembranous colitis if patient presents with severe diarrhoea
Maintain hydration and urinary output
Monitor hepatic function in patients with hepatic impairment
Monitor liver function on prolonged therapy
Monitor patency of urinary catheters regularly, precipitation may occur
Monitor renal function during prolonged/high dose therapy
Perform blood counts on prolonged use of this treatment
Review treatment after 14 days, and frequently thereafter
Cholestatic jaundice may occur during or after treatment
Erythematous rash common in glandular fever, CMV inf, lymphocytic leukaemia
May cause convulsions
Prolonged use may result in superinfection with non-susceptible organisms
May affect results of some laboratory tests
May cause false positive Coomb's test and glycosuria test
Discontinue at once if pseudomembranous colitis occurs
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if generalised rash or erythema occurs
The occurrence at the initiation of treatment of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP). This reaction requires co-amoxiclav discontinuation and contraindicates any subsequent administration of amoxicillin.
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been rarely reported in children. Signs and symptoms usually occur during or shortly after treatment, in some cases these may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events can be severe, and very rarely, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects.
The flavouring in some presentations of co-amoxiclav contains traces of benzyl alcohol. Benzyl alcohol may cause allergic reactions.
Pregnancy and Lactation
Pregnancy
Use co-amoxiclav with caution during pregnancy.
The manufacturers suggest that co-amoxiclav should be avoided during pregnancy unless considered essential. At the time of writing, there is limited experience with the use of co-amoxiclav during human pregnancy. Available data do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with co-amoxiclav may be associated with an increased risk of necrotising enterocolitis in neonates.
Lactation
Use co-amoxiclav with caution during breastfeeding.
The manufacturers suggest that co-amoxiclav should only be used during breastfeeding after an assessment of the risks and benefits. The Drugs and Lactation Database (LactMed) suggests that co-amoxiclav is acceptable for use during breastfeeding. At the time of writing limited information indicates that serious reactions in infants are uncommon during the use of co-amoxiclav during nursing, with restlessness, diarrhoea and rash occurring occasionally. The infant should be monitored for these reactions during breastfeeding. Both amoxicillin and potassium clavulanate are excreted into breast milk, consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breastfeeding might have to be discontinued.
Side Effects
Acute generalised exanthematous pustulosis
Agranulocytosis
Anaphylaxis
Angioedema
Antibiotic-associated colitis
Aseptic meningitis
Black tongue
Candida mucocutaneous
Cholestatic jaundice
Convulsions
Crystalluria
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Erythema multiforme
Erythematous rash
Exfoliative dermatitis
Haemolytic anaemia
Haemorrhagic colitis
Headache
Hepatitis
Hyperactivity
Hypersensitivity reactions
Increase in serum ALT/AST
Indigestion
Interstitial nephritis
Leucopenia
Nausea
Neutropenia
Overgrowth by non-susceptible organisms
Prolonged bleeding
Prothrombin time increased
Pruritus
Pseudomembranous colitis
Rash
Serum sickness-like reactions
Severe cutaneous adverse reactions
Stevens-Johnson syndrome
Superficial tooth discolouration
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Vasculitis (allergic)
Vomiting
Effects on Laboratory Tests
Enzymatic glucose oxidase methods should be used during amoxicillin therapy whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
The presence of clavulanic acid may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving co-amoxiclav who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving co-amoxiclav should be interpreted cautiously and confirmed by other diagnostic methods.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: February 2021
Reference Sources
Summary of Product Characteristics: Augmentin 125/31 SF Suspension. GlaxoSmithKline UK. Revised September 2020.
Summary of Product Characteristics: Augmentin 250/62 SF Suspension. GlaxoSmithKline UK. Revised September 2020.
Summary of Product Characteristics: Co-Amoxiclav 400mg/57mg/5ml Powder for Oral Suspension. Sandoz Limited. Revised May 2020.
Summary of Product Characteristics: Co-amoxiclav 125mg/31.25mg/5ml Powder for Oral Suspension. Generics (UK) Limited. Revised March 2020.
Summary of Product Characteristics: Co-amoxiclav 250mg/62mg/5ml Powder for Oral Suspension. Generics (UK) Limited. Revised March 2020.
Summary of Product Characteristics: Co-amoxiclav 125mg/31.25mg/5ml Powder for Oral Suspension. Sandoz Limited. Revised September 2020.
Summary of Product Characteristics: Co-amoxiclav 250mg/62mg/5ml Powder for Oral Suspension. Sandoz Limited. Revised September 2020.
Summary of Product Characteristics: Co-amoxiclav 400/57mg/5ml Powder for Oral Suspension. Sandoz Limited. Revised May 2020.
Summary of Product Characteristics: Co-amoxiclav 250/125mg film-coated tablets. Sandoz Limited. Revised December 2017.
Summary of Product Characteristics: Co-amoxiclav 500/125mg Tablets. Sandoz Limited. Revised December 2017.
Summary of Product Characteristics: Co-amoxiclav 875mg/125mg tablets. Brown and Burk Ltd. Revised December 2018.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 August 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Amoxicillin and Clavulanic Acid Last revised: 31 October 2018
Last accessed: 13 August 2020
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.