Augmentin/Augmentin ES

Augmentin/Augmentin ES

amoxicillin + clavulanic acid

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig
Full Prescribing Info
Contents
Co-amoxiclav: Amoxicillin and clavulanic acid.
Description
Augmentin: Powder for Suspension (in bottles): Co-amoxiclav (Augmentin) 156.25 mg/5 mL: Powder for Suspension: Bottles of powder for the preparation of fruit flavoured suspension. When reconstituted, each 5 mL contains 125 mg amoxicillin and 31.25 mg clavulanic acid.
Co-amoxiclav (Augmentin DS) 312.5 mg/5 mL: Powder for Suspension: Bottles of powder for the preparation of fruit flavoured suspension. When reconstituted, each 5 mL contains 250 mg amoxicillin and 62.5 mg clavulanic acid.
Co-amoxiclav (Augmentin) 228.5 mg/5 mL: Powder for Suspension: Bottles of powder for the preparation of fruit flavoured suspension. When reconstituted, each 5 mL contains 200 mg amoxicillin and 28.5 mg clavulanic acid.
Co-amoxiclav (Augmentin) 457 mg/5 mL: Powder for Suspension: Bottles of powder for the preparation of mixed fruit flavoured suspension. When reconstituted, each 5 mL contains 400 mg amoxicillin and 57 mg clavulanic acid.
Tablets: Co-amoxiclav (Augmentin) 375 mg Tablet: White, oval film-coated tablets with "AUGMENTIN" engraved on one side. Each tablet contains 250 mg amoxicillin and 125 mg clavulanic acid.
Co-amoxiclav (Augmentin) 625 mg Tablet: A white to off-white oval- shaped film-coated debossed tablet, with a score line on one side and plain on the other side. Each tablet contains 500 mg amoxicillin and 125 mg clavulanic acid.
Co-amoxiclav (Augmentin) 1 g Tablet: A white to off-white capsule shaped, film coated tablet, debossed with "AC" on both sides with a score line on one side. Each tablet contains 875 mg amoxicillin and 125 mg clavulanic acid.
Co-amoxiclav (beta-lactam antibacterial penicillin coformulated with a beta-lactamase inhibitor) is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The beta-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other beta-lactam antibiotics.
Injection: Co-Amoxiclav (Augmentin 600) 500 mg/100 mg Injection: Each vial contains 500 mg amoxicillin and 100 mg potassium clavulanate for reconstitution as an intravenous injection or infusion.
Co-Amoxiclav (Augmentin 1.2) 1 g/200 mg Injection: Each vial contains 1 g amoxicillin and 200 mg potassium clavulanate for reconstitution as an intravenous injection or infusion.
Augmentin ES: Co-amoxiclav (Augmentin ES) 600 mg/42.9 mg per 5mL Powder for Suspension: Bottles of Off-white powder with a characteristic strawberry odour, which, when reconstituted in water at time of dispensing, yields an off-white suspension. Each 5 mL of reconstituted suspension contains 600 mg amoxicillin and 42.9 mg clavulanic acid. The amoxicillin is present as amoxicillin trihydrate and the clavulanic acid is present as potassium clavulanate in a ratio of 14:1.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by β-lactamases and, therefore, the spectrum of activity does not include organisms which produce these enzymes.
Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated β-lactamases frequently responsible for transferred drug resistance.
Thus, Co-amoxiclav possesses the distinctive properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.
In the list as follows, organisms are categorised according to their in vitro susceptibility to Co-amoxiclav (see Table 1).

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Augmentin: It is generally less effective against chromosomally-mediated type 1 beta-lactamases.
The presence of clavulanic acid in co-amoxiclav formulations protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other penicillins and cephalosporins. Thus amoxicillin-clavulanate possesses the distinctive properties of a broad spectrum antibiotic and a beta-lactamase inhibitor.
Augmentin ES: The clavulanate component in Co-amoxiclav (Augmentin ES) protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics.
Injection: Augmentin: Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in Co-amoxiclav (Augmentin) anticipates this defense mechanism by blocking the β-lactamase enzymes, thus rendering the organisms sensitive to amoxicillin's rapid bactericidal effect at concentrations readily attainable in the body.
Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as Co-Amoxiclav (Augmentin), it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.
Pharmacokinetics: Augmentin: Tablet/Oral Suspension: Absorption: The two components of co-amoxiclav, amoxicillin and clavulanic acid, are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of Co-amoxiclav (Augmentin) is optimised when taken at the start of a meal.
The pharmacokinetic results for the two separate studies, in which co-amoxiclav 250/125 (375) or 2 x 250/125 and 500/125 (625) mg tablets (in comparison with the two components given separately) were administered in the fasting state to groups of healthy volunteers, are presented in Table 2. (See Table 2.)

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Amoxicillin serum concentrations achieved with co-amoxiclav are similar to those produced by the oral administration of equivalent doses of amoxicillin alone.
Distribution: Following IV administration, therapeutic concentrations of both amoxicillin and clavulanic acid may be detected in the tissues and interstitial fluid. Therapeutic concentrations of both drugs have been found in the gall bladder, abdominal tissue, skin, fat, and muscle tissues; fluids found to have therapeutic levels include synovial and peritoneal fluids, bile and pus.
Neither amoxicillin nor clavulanic acid is highly protein bound, studies show that about 25% for clavulanic acid and 18% for amoxicillin of total plasma drug content is bound to protein.
From animal studies, there is no evidence to suggest that either component accumulates in any organ.
Amoxicillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanate can also be detected in breast milk. With the exception of the risk of sensitisation associated with this excretion, there are no known detrimental effects for the breast-fed infant.
Reproduction studies in animals have shown that both amoxicillin and clavulanic acid penetrate the placental barrier.
However, no evidence of impaired fertility or harm to the foetus was detected.
Metabolism: Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized in man to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and eliminated in urine and faeces as carbon dioxide in expired air.
Elimination: As with other penicillins, the major route of elimination for amoxicillin is via the kidney, whereas for clavulanate it is by both renal and non-renal mechanisms.
Approximately 60 to 70% of the amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single 250/125 mg or a single 500/125 mg tablet.
Concomitant use of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid (see Interactions).
Injection: The pharmacokinetics of the two components of Co-amoxiclav (Augmentin) are closely matched. In Infant Drops, peak serum levels of both occur about 1 hour after oral administration. Absorption of Co-amoxiclav (Augmentin) is optimised at the start of a meal.
Both clavulanate and amoxicillin have low levels of serum-binding; about 70% remains free in the serum.
Doubling the dosage of Co-amoxiclav (Augmentin) approximately doubles the serum levels achieved.
Augmentin ES: Pharmacokinetic parameters are given as follows for Co-amoxiclav (Augmentin ES) administered at 45 mg/kg every 12 hours to paediatric patients (see Table 3).

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The pharmacokinetics of the two components of Co-amoxiclav (Augmentin ES) are closely matched. Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Toxicology: Pre-clinical Safety Data: No further information of relevance.
Indications/Uses
Augmentin: Amoxicillin-clavulanate should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data. Adult Formulations: Co-amoxiclav is indicated for short term treatment of bacterial infections at the following sites when caused by amoxicillin-clavulanate-susceptible organisms: Upper respiratory tract infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media, typically caused by Streptococcus pneumoniae, Haemophilus influenzae#, Moraxella catarrhalis# and Streptococcus pyogenes.
Lower respiratory tract infections e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia, typically caused by Streptococcus pneumoniae, Haemophilus influenzae# and Moraxella catarrhalis#. Genitourinary tract infections e.g. cystitis, urethritis, pyelonephritis and female genital infections typically caused by Enterobacteriaceae# (mainly Escherichia coli#), Staphylococcus saprophyticus and Enterococcus species and gonorrhea caused by Neisseria gonnorhoeae#.
Skin and soft tissue infections typically caused by Staphylococcus aureus#, Streptococcus pyogenes and Bacteroides species#.
Bone and joint infections e.g. osteomyelitis typically caused by Staphylococcus aureus#, where more prolonged therapy may be appropriate.
Other infections e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis.
Pediatric Formulations: Co-amoxiclav is indicated for short term treatment of bacterial infections at the following sites when caused by amoxicillin-clavulanate sensitive organisms: Upper respiratory tract infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media typically caused by Streptococcus pneumoniae, Haemophilus influenzae#, Moraxella catarrhalis# and Streptococcus pyogenes.
Lower respiratory tract infections e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia typically caused by Streptococcus pneumoniae, Haemophilus influenzae# and Moraxella catarrhalis#.
Genitourinary tract infections e.g. cystitis, urethritis, pyelonephritis, female genital infections typically caused by Enterobacteriaceae# (mainly Escherichia coli#), Staphylococcus saprophyticus and Enterococcus species and gonorrhea caused by Neisseria gonorrhoeae#.
Skin and soft tissue infections typically caused by Staphylococcus aureus#, Streptococcus pyogenes and Bacteroides species#.
Amoxicillin-Clavulanate Pediatric Three Times Daily: The pediatric three times daily dosing regimen is also indicated for the following infections: Bone and joint infections e.g. osteomyelitis typically caused by Staphylococcus aureus#, where more prolonged therapy may be appropriate.
Other infections e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis.
All Formulations: A comprehensive list of sensitive organisms is provided in Microbiology under Actions.
#Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone (see Pharmacology: Pharmacodynamics under Actions).
Susceptibility to amoxicillin-clavulanate will vary with geography and time. Local susceptibility data should be consulted where available, and microbiological sampling and susceptibility testing performed where necessary.
Infection caused by amoxicillin-susceptible organisms are amenable to Co-amoxiclav (Augmentin) treatment due to its amoxicillin content. Mixed infections caused by amoxicillin-susceptible organisms in conjunction with amoxicillin-clavulanate-susceptible beta-lactamase-producing organisms may therefore be treated with Co-amoxiclav (Augmentin).
Injection: Co-amoxiclav (Augmentin) intravenous is also indicated for prophylaxis against infection which may be associated with major surgical procedures such as gastrointestinal, pelvic, head and neck, cardiac, renal, joint replacement and biliary tract.
Augmentin ES: Co-amoxiclav (Augmentin) should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.
Co-amoxiclav (Augmentin ES) is indicated for the short-term treatment of bacterial infections in paediatric patients at the following sites when caused by Co-amoxiclav (Augmentin)-susceptible organisms: Upper respiratory tract infections (including ENT) e.g. recurrent or persistent acute otitis media due to Streptococcus pneumoniae (penicillin minimum inhibitory concentration (MIC) less than or equal to 4 μg/mL), Haemophilus influenzae# and Moraxella catarrhalis#. Such patients are often characterised by antibiotic exposure for acute otitis media within the preceding 3 months, and are either aged ≤2 years or attend daycare; tonsillo-pharyngitis and sinusitis, typically caused by Streptococcus pneumoniae, Haemophilus influenzae#, Moraxella catarrhalis# and Streptococcus pyogenes.
Lower respiratory tract infections e.g. lobar and bronchopneumonia typically caused by Streptococcus pneumoniae, Haemophilus influenzae# and Moraxella catarrhalis#.
Skin and soft tissue infections typically caused by Staphylococcus aureus# and Streptococcus pyogenes.
Other Co-amoxiclav (Augmentin) formulations are indicated for short-term treatment of bacterial infections at the following sites when caused by Co-amoxiclav (Augmentin)-susceptible organisms: Upper respiratory tract infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media typically caused by Streptococcus pneumoniae, Haemophilus influenzae#, Moraxella catarrhalis# and Streptococcus pyogenes.
Lower respiratory tract infections e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia typically caused by Streptococcus pneumoniae, Haemophilus influenzae# and Moraxella catarrhalis#.
Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis, female genital infections typically caused by Enterobacteriaceae# (mainly Escherichia coli#) Staphylococcus saprophyticus and Enterococcus species, and gonorrhoea caused by Neisseria gonorrhoeae#.
Skin and soft tissue infections typically caused by Staphylococcus aureus#, Streptococcus pyogenes and Bacteroides species#.
#Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone (see Pharmacologic Properties: Pharmacodynamics under Actions).
Susceptibility to Co-amoxiclav (Augmentin) will vary with geography and time. Local susceptibility data should be consulted where available, and microbiological sampling and susceptibility testing performed where necessary.
Dosage/Direction for Use
Augmentin: Tablet/Powder Suspension: Dosage depends on the age, weight and renal function of the patient and the severity of the infection.
Dosages are expressed throughout in terms of co-amoxiclav content except when doses are stated in terms of an individual component.
Therapy can be started parenterally and continued with an oral preparation. (See Table 4.)

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Two co-amoxiclav 250/125 mg tablets should not be substituted for one co-amoxiclav 500/125 mg tablet since they are not equivalent.
Children: Dosage should be expressed in terms of the age of the child and either in mg/kg/day (given in 2 or 3 divided doses) or mL of suspension per dose or equivalent for other presentations.
Children weighing 40 kg and over should be dosed according to the adult recommendations. (See Table 5.)

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The lower dose is recommended for infections such as skin and soft tissue and recurrent tonsillitis.
The higher dose is recommended for infections such as otitis media, sinusitis, lower respiratory tract infections and urinary tract infections.
No clinical data are available on doses of these formulations higher than 40/10 mg/kg/day (4:1) or 45/6.4 mg/kg/day (7:1) in children under 2 years.
There are no clinical data for the 7:1 formulation in patients under 2 months of age. Dosing recommendations in this population therefore cannot be made.
The 8:1 ratio formulation is recommended for dosing at 40/50 to 80/10 mg/kg/day (in three divided doses) in children aged 1 to 30 months, depending upon severity of infection.
Premature: No dosage recommendation can be made for this category.
Elderly: No adjustment needed; dose as for adults. If there is evidence of renal impairment, dose should be adjusted as for renally impaired adults.
Haemodialysis: Adults: 1 times 500/125 mg or 2 times 250/125 mg every 24 hours, plus 1 dose during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased)(+).
(+)The 875/125 mg and 1000/125 mg presentations should only be used in patients with a creatinine clearance of more than 30 mL/min.
Children: 15/3.75 mg/kg/day given as a single daily dose.
Prior to haemodialysis one additional dose of 15/3.75 mg/kg should be administered. In order to restore circulating drug levels, another dose of 15/3.75 mg/kg should be administered after haemodialysis.
Injection: Treatment of Infection: Adults and Children over 12 Years: Usually 1.2 g eight hourly. In more serious infections, increase frequency to six-hourly intervals.
Children 3 months-12 years: Usually 30 mg/kg* Co-amoxiclav (Augmentin) eight hourly. In more serious infections, increase frequency to six-hourly intervals.
0-3 months: 30 mg/kg* Co-amoxiclav (Augmentin) every 12 hours in premature and in full term infants during the perinatal period, increasing to eight hours thereafter.
*Each 30 mg Co-amoxiclav (Augmentin) contains 25 mg amoxicillin and 5 mg clavulanate.
Adult Dosage for Surgical Propyhlaxis: The usual dose is 1.2 g Co-amoxiclav (Augmentin) intravenous given at the induction of anaesthesia.
Operations where there is a high risk of infection e.g. colorectal surgery, may require three, and up to four doses of 1.2 g Co-amoxiclav (Augmentin) intravenous in a 24-hour period. These doses are usually given at 0, 8, 16 (and 24) hours. This regimen can be continued for several days if the procedure has a significantly increased risk of infection.
Clear clinical signs of infection at operation will require a normal course of intravenous or oral Co-amoxiclav (Augmentin) therapy post-operatively.
Renal Impairment: Tablet/Powder for Suspension: Dosage adjustments are based on the maximum recommended level of amoxicillin. (See Tables 6 and 7.)

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In the majority of cases, parenteral therapy, where available, may be preferred.
Injection: See Table 8.

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Children: Similar reduction in dosage should be made for children.
Infant Drops: Dosage in Renal Impairment: Mild Impairment (Creatinine clearance >30 mL/min): No change in dosage, ie The recommended dose given three times daily.#
Moderate Impairment (Creatinine clearance 10-30 mL/min): The recommended dose given twice daily instead of three times per day.#
Severe Impairment (Creatinine clearance <10 mL/min): The recommended dose given once daily instead of three times per day.#
#In more serious cases this dose may be doubled.
Hepatic Impairment: Tablet: Dose with caution; monitor hepatic function at regular intervals. There are insufficient data on which to base a dosage recommendation.
Injection: Each 1.2 g vial of Co-amoxiclav (Augmentin) contains 1.0 mmoL of potassium and 3.1 mmoL of sodium (approx.).
Administration: Tablet/Powder for Suspension: To minimise potential gastrointestinal intolerance, administer at the start of a meal.
The absorption of Co-amoxiclav (Augmentin) is optimised when taken at the start of a meal.
Treatment should not be extended beyond 14 days without review.
Injection: Co-amoxiclav (Augmentin) intravenous may be administered either by intravenous injection or by intermittent infusion. It is not suitable for intramuscular administration.
Augmentin ES: Paediatric patients 3 months and older: The recommended dose for Co-amoxiclav (Augmentin ES) is 90/6.4 mg/kg/day in 2 divided doses at 12-hourly intervals for 10 days (see Table 9). There is no experience in paediatric patients weighing > 40 kg, or in adults. There are no clinical data on Co-amoxiclav (Augmentin ES) in children under 3 months of age. (See Table 9.)

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Co-amoxiclav (Augmentin ES) does not contain the same amount of clavulanate (as the potassium salt) as any of the other Co-amoxiclav (Augmentin) suspensions. Co-amoxiclav (Augmentin ES) contains 42.9 mg of clavulanic acid per 5 mL whereas Co-amoxiclav (Augmentin) 200 mg/5 mL suspension contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/5 mL suspension contains 57 mg of clavulanic acid per 5 mL. Therefore, Co-amoxiclav (Augmentin) 200 mg/5 mL and 400 mg/5 mL suspensions should not be substituted for Co-amoxiclav (Augmentin ES), as they are not interchangeable.
Hepatic Impairment: Dose with caution; monitor hepatic function at regular intervals.
There are insufficient data on which to base a dosage recommendation.
Renal Impairment: There are no dosing recommendations for Co-amoxiclav (Augmentin ES) in patients with renal impairment.
Method of Administration: To minimise the potential for gastrointestinal intolerance, Co-amoxiclav (Augmentin ES) should be taken at the start of a meal. The absorption of Co-amoxiclav (Augmentin) is optimised when taken at the start of a meal.
Treatment should not be extended beyond 14 days without review.
Therapy can be started parenterally and continued with an oral preparation.
SHAKE ORAL SUSPENSION WELL BEFORE USING.
Overdosage
Augmentin: Symptoms and Signs: Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Precautions).
Treatment: Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.
Co-amoxiclav can be removed from the circulation by haemodialysis.
Children (Additional Statement): A prospective study of 51 paediatric patients at a poison control centre suggested that overdosages of less than 250 mg/kg amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.
Drug Abuse and Dependence: Drug dependency, addiction and recreational abuse have not been reported as a problem with this compound.
In injection: Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.
Augmentin ES: Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Precautions).
Co-amoxiclav (Augmentin ES) can be removed from the circulation by haemodialysis.
A prospective study of 51 paediatric patients at a poison control centre suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.
Contraindications
Co-amoxiclav (Augmentin) is contraindicated in patients with a history of hypersensitivity to beta-lactams e.g. penicillins and cephalosporins; in patients with a previous history of amoxicillin-clavulanate-associated jaundice/hepatic dysfunction.
Special Precautions
Before initiating therapy with Co-amoxiclav (Augmentin), careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity. If an allergic reaction occurs, Co-amoxiclav (Augmentin) therapy should be discontinued and appropriate alternative therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, IV steroids and airway management, including intubation may also be required.
Co-amoxiclav (Augmentin) should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.
In general, co-amoxiclav is well tolerated and possesses the characteristic low toxicity of the penicillin group of antibiotics. Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin-clavulanate and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (see Overdosage).
Augmentin: Changes in liver function tests have been observed in some patients receiving Co-amoxiclav (Augmentin). The clinical significance of these changes is uncertain but Co-amoxiclav (Augmentin) should be used with caution in patients with evidence of hepatic dysfunction.
Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased.
In patients with renal impairment, dosage should be adjusted according to the degree of impairment (see Renal Impairment under Dosage & Administration).
Co-amoxiclav Suspensions/Sachets/Chewable tablets (where applicable), contains aspartame, which is a source of phenylalanine and should be used with caution in patients with phenylketonuria.
Augmentin ES: Co-amoxiclav (Augmentin ES) should be used with caution in patients with evidence of hepatic dysfunction.
In patients with renal impairment, dosage of Co-amoxiclav (Augmentin) should be adjusted according to the degree of impairment. No dosing recommendations can be made for Co-amoxiclav (Augmentin ES) in renally impaired patients (see Dosage & Administration).
Co-amoxiclav (Augmentin ES) contains aspartame (each 5 mL of suspension contains 7 mg of phenylalanine) and so should be used with caution in patients with phenylketonuria.
Effects on Ability to Drive and Use Machines: Adverse effects on the ability to drive or operate machinery have not been observed.
Use In Pregnancy & Lactation
Use in Pregnancy: Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered Co-amoxiclav (Augmentin) have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with Co-amoxiclav (Augmentin) may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, unless considered essential by the physician.
Use in Lactation: Co-amoxiclav (Augmentin) may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.
Adverse Reactions
Data from large clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e. those occurring at <1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.
The following convention has been used for the classification of frequency: Very common >1/10; common >1/100 and <1/10; uncommon >1/1000 and <1/100; rare >1/10,000 and <1/1000; very rare <1/10,000.
Infections and Infestations: Common: Mucocutaneous candidiasis.
Blood and Lymphatic System Disorders: Rare: Reversible leucopenia (including neutropenia) and thrombocytopenia. Very Rare: Reversible agranulocytosis and haemolytic anaemia (see Precautions). Prolongation of bleeding time and prothrombin time.
Immune System Disorders: Very Rare: Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis.
Nervous System Disorders: Uncommon: Dizziness, headache. Very Rare: Reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Gastrointestinal Disorders: Tablet/Powder for Suspension: Adults: Very Common: Diarrhoea. Common: Nausea, vomiting.
Children: Common: Diarrhoea, nausea, vomiting.
All Populations: Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking Co-amoxiclav (Augmentin) at the start of a meal.
Uncommon: Indigestion. Very Rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see Precautions), black hairy tongue, superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing+.
+This statement is core safety for the syrup, suspension and chewable tablet formulations.
Infant Drops: Common: Diarrhoea, nausea, vomiting.
Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking Co-amoxiclav (Augmentin) at the start of a meal.
Uncommon: Indigestion. Very Rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis). Superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.
Injection: Common: Diarrhoea. Uncommon: Nausea, vomiting, indigestion. Very Rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis, see Precautions) are less likely to occur after parenteral administration.
Hepatobiliary Disorders: Uncommon: A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown. Very Rare: Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins.
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment.
All Populations: Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances, 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.
Skin and Subcutaneous Tissue Disorders: Uncommon: Skin rash, pruritus, urticaria. Rare: Erythema multiforme. Very Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP).
If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
Renal and Urinary Disorders: Very Rare: Interstitial nephritis, crystalluria (see Overdosage).
Augmentin: Children (Additional Statement): These events have been very rarely reported in children.
Drug Interactions
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with amoxicillin-clavulanate may result in increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of Co-amoxiclav (Augmentin) and allopurinol.
In common with other antibiotics, Co-amoxiclav (Augmentin) may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
In the literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of Co-amoxiclav (Augmentin).
In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure.
Augmentin: The presence of clavulanic acid in Co-amoxiclav (Augmentin) may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
Caution For Usage
Augmentin: Incompatibilities: Injection: Co-amoxiclav (Augmentin) intravenous should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates or with intravenous lipid emulsions.
If Co-amoxiclav (Augmentin) is prescribed concurrently with an aminoglycoside, the antibiotics should not be mixed in the syringe, intravenous fluid container or giving set because loss of activity of the aminoglycoside can occur under these conditions.
Instructions for Use and Handling: For sachet, contents should be stirred into water before taking.
Tablet/Powder for Suspension: For administration of suspensions to children below 3 months, a syringe graduated to permit accurate and reproducible volumes to be dispensed, should be used.
For administration to children up to 2 years, co-amoxiclav suspensions may be diluted to half-strength using water.
Injection: 600-mg Vial: To reconstitute dissolve in 10 mL Water for Injections BP. (Final volume 10.5 mL)
1.2-g Vial: To reconstitute dissolve in 20 mL Water for Injections BP. (Final volume 20.9 mL)
A transient pink coloration may or may not appear during reconstitution. Reconstituted solutions are normally colourless or a pale, straw colour.
Intravenous Injection: The stability of Co-amoxiclav (Augmentin) intravenous solution is concentration dependent, thus Co-amoxiclav (Augmentin) intravenous should be used immediately upon reconstitution and given by slow intravenous injection over a period of 3-4 minutes. Co-amoxiclav (Augmentin) intravenous solutions should be used within 20 minutes of reconstitution. Co-amoxiclav (Augmentin) may be injected directly into a vein or via a drip tube.
Intravenous Infusion: Alternatively, Co-amoxiclav (Augmentin) intravenous may be infused in Water for Injections BP or Sodium Chloride Intravenous injection BP (0.9% w/v). Add, without delay*, 600 mg reconstituted solution to 50 mL infusion fluid or 1.2 g reconstituted solution to 100 mL infusion fluid (e.g. using a minibag or in-line burette). Infuse over 30-40 minutes and complete within four hours of reconstitution. For other appropriate infusion fluids, see Stability and Compatibility as follows.
*Solutions should be made up to full infusion volume immediately after reconstitution.
Any residual antibiotic solutions should be discarded.
Therapy can be started parenterally and continued with an oral preparation. Treatment should not be extended beyond 14 days without review.
Infant Drops: First shake the bottle to loosen the powder. Water should be added until the fill line on the bottle label, and then shake the bottle well. Then top up with water until the level of the fill line is reached and shake again. When first reconstituted, allow to stand for 5 minutes to ensure full dispersion.
The device is used to dose patient under 2 years according to the schedule (see Dosage & Administration).
Shake bottle before use.
Insert pipette into adaptor, ensure firmly located.
Invert bottle and withdraw required dose.
Place bottle upright and remove pipette from adaptor.
Rinse pipette in clean water.
Replace bottle cap.
Stability and Compatibility: Intravenous infusions of Co-amoxiclav (Augmentin) may be given in a range of different intravenous fluids. Satisfactory antibiotic concentrations are retained at 5°C and at room temperature (25°C) in the recommended volume of the following infusion fluids. If reconstituted and maintained at room temperature, infusions should be completed within the times stated. (See Table 10.)

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Reconstituted solutions should not be frozen.
Co-amoxiclav (Augmentin) is less stable in infusions containing glucose, dextran or bicarbonate. Reconstituted solutions of Co-amoxiclav (Augmentin) should therefore not be added to such infusions but may be injected into the drip tubing over a period of 3-4 minutes.
For storage at 5°C, the reconstituted solution should be added to pre-refrigerated infusion bags which can be stored for up to 8 hours. Thereafter, the infusion should be administered immediately after reaching room temperature. (See Table 11.)

Click on icon to see table/diagram/image

Augmentin ES: At time of dispensing, the dry powder should be reconstituted to form an oral suspension, as detailed as follows: Check cap seal is intact before use.
Invert and shake bottle to loosen powder.
Fill the bottle with water to just below the mark on bottle label. Invert and shake well, then top up with water to the mark. Invert and shake again.
Shake well before taking each dose.
Each teaspoonful (5 mL) will contain 600 mg amoxicillin as the trihydrate and 42.9 mg of clavulanate as the potassium salt.
Storage
Augmentin: Tablet/Powder for Suspension: Co-amoxiclav 375 mg and 1 g tablet should be stored at temperatures not exceeding 25°C. Keep dry.
Co-amoxiclav 625 mg tablet should be stored at temperatures not exceeding 30°C. Protect from moisture. Tablets should be used within 14 days after opening of foil pouch.
Co-amoxiclav powder for suspension should be stored at temperatures not exceeding 25°C.
The reconstituted suspension should be stored and kept in a refrigerator (2-8°C) and used within 7 to 10 (maximum days). Do not freeze.
Injection: Co-Amoxiclav (Augmentin) vials should be stored between 2°C and 8°C.
Augmentin ES: The powder for oral suspension should be stored in a well sealed container, at temperatures not exceeding 30°C. Keep dry. Reconstituted suspensions should be stored in a refrigerator (2-8°C) and used within 10 days.
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.
Presentation/Packing
Augmentin: Tab 375 mg (white, oval film-coated with "AUGMENTIN" engraved on one side) x 30's. 625 mg (white to off-white oval-shaped film-coated, debossed, with a score line on one side and plain on the other side) x 14's, 21's, 30's. 1 g (white to off-white oval-shaped film-coated, debossed, with a score line on one side and plain on the other side) x 14's. Oral susp (fruit flavoured) 156.25 mg/5 mL x 60 mL. 228.5 mg/5 mL x 70 mL. 312.5 mg/5 mL x 60 mL. 457 mg/5 mL (strawberry flavoured) x 35 mL, 70 mL. Powd for inj (vial) 600 mg x 10's. 1.2 g x 10's.
Augmentin ES: Powd for oral susp (off-white powder with a characteristic strawberry odour) 50 mL, 100 mL.
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