Augmentin

Amoxycillin (as trihydrate), clavulanic acid (as clavulanate K).

375 mg & 625 mg tablet: Each 375- and 625-mg tablet contains amoxycillin 250 mg and 500 mg, respectively, and clavulanic acid 125 mg.
1 g tablet: Each film-coated tablet contains amoxycillin trihydrate equivalent to 875 mg amoxycillin and potassium clavulanate equivalent to 125 mg of clavulanic acid.
The score line is only to facilitate breaking and ease of swallowing and not to divide into equal doses.
Syrup: Each 5 mL of 156-mg syrup contains amoxycillin 125 mg, clavulanic acid 31.25 mg. It also contains aspartame. Augmentin presentations do not contain sucrose, tartrazine or any other azo dyes. Augmentin syrups do not contain preservatives.
Suspension: AUGMENTIN Suspension 457 mg/5 ml contains 400 mg amoxycillin and 57 mg clavulanic acid per 5 ml.
Dry powder for reconstitution in water, at time of dispensing, to form a suspension.
Excipients/Inactive Ingredients: 375 mg & 625 mg tablet: Each 375-mg and 625-mg tablet also contains the following excipients: Colloidal silicon dioxide, sodium starch glycolate, magnesium stearate, microcrystalline cellulose, titanium dioxide, hydroxypropyl methylcellulose, polyethylene glycol, dimethicone (silicon oil).
1 g tablet: Colloidal anhydrous silica, sodium starch glycolate Type A, magnesium stearate, microcrystalline cellulose, titanium dioxide, hypromellose, macrogol, dimeticone.
Suspension: Xanthan Gum, Aspartame, Succinic Acid, Colloidal Anhydrous Silica, Hypromellose, Orange Dry Flavour 1, Orange Dry Flavour 2, Raspberry Dry Flavour, Golden Syrup Dry Flavour, Silicon Dioxide (anhydrous).

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors. ATC code: J01CR02.
Pharmacology: Pharmacodynamics: Mechanism of action: Amoxycillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.
Amoxycillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxycillin alone does not include organisms which produce these enzymes.
Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby preventing inactivation of amoxycillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.
Pharmacokinetic/pharmacodynamic relationship: The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxycillin.
Mechanisms of resistance: The two main mechanisms of resistance to amoxycillin/clavulanic acid are: Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D; Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.
Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.
Breakpoints: MIC breakpoints for amoxycillin/clavulanic acid are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). (See Table 1.)

Click on icon to see table/diagram/image

The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. (See Table 2.)

Click on icon to see table/diagram/image

Pharmacokinetics: Absorption: Amoxycillin 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. Following oral administration, amoxycillin and clavulanic acid are approximately 70% bioavailable. The plasma profiles of both components are similar and the time-to-peak plasma concentration (T_max) in each case is approximately one hour.
The pharmacokinetic results for a study, in which amoxycillin/clavulanic acid (500 mg/125 mg tablets 3 times daily) was administered in the fasting state to groups of healthy volunteers are presented as follows. (See Table 3.)

Click on icon to see table/diagram/image

The pharmacokinetic results for a study, in which amoxycillin/clavulanic acid (875 mg/125 mg tablets given twice daily) was administered in the fasting state to groups of healthy volunteers are presented as follows. (See Table 4.)

Click on icon to see table/diagram/image

Amoxycillin and clavulanic acid serum concentrations achieved with amoxycillin/clavulanic acid are similar to those produced by the oral administration of equivalent doses of amoxycillin or clavulanic acid alone.
Distribution: About 25% of total plasma clavulanic acid and 18% of total plasma amoxycillin is bound to protein. The apparent volume of distribution is around 0.3-0.4 l/kg for amoxycillin and around 0.2 l/kg for clavulanic acid.
Following intravenous administration, both amoxycillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxycillin does not adequately distribute into the cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived material for either component. Amoxycillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk (see Use in Pregnancy & Lactation).
Both amoxycillin and clavulanic acid have been shown to cross the placental barrier (see Use in Pregnancy & Lactation).
Biotransformation: Amoxycillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolised in man, and eliminated in urine and faeces and as carbon dioxide in expired air.
Elimination: The major route of elimination for amoxycillin is via the kidney, whereas for clavulanic acid it is by both renal and non-renal mechanisms.
Amoxycillin/clavulanic acid has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the amoxycillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of single Augmentin 250 mg/125 mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for amoxycillin and between 27-60% for clavulanic acid over a 24 hour period. In the case of clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration.
Concomitant use of probenecid delays amoxycillin excretion but does not delay renal excretion of clavulanic acid (see Interactions).
Age: The elimination half-life of amoxycillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Gender: Following oral administration of amoxycillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either amoxycillin or clavulanic acid.
Renal impairment: The total serum clearance of amoxycillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for amoxycillin than for clavulanic acid, as a higher proportion of amoxycillin is excreted via the renal route. Doses in renal impairment must therefore prevent undue accumulation of amoxycillin while maintaining adequate levels of clavulanic acid (see Dosage & Administration).
Hepatic impairment: Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.
Toxicology: Preclinical safety data: Nonclinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction.
Repeat dose toxicity studies performed in dogs with amoxycillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.
Carcinogenicity studies have not been conducted with Augmentin or its components.

Augmentin is indicated for the treatment of the following infections in adults and children (see Dosage & Administration, Precautions, and Pharmacology: Pharmacodynamics under Actions): Acute bacterial sinusitis (adequately diagnosed); Acute otitis media; Acute exacerbations of chronic bronchitis (adequately diagnosed); Community acquired pneumonia; 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.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Posology: Doses are expressed throughout in terms of amoxycillin/clavulanic acid content except when doses are stated in terms of an individual component.
The dose of Augmentin that is selected to treat an individual infection should take into account: The expected pathogens and their likely susceptibility to antibacterial agents (see Precautions); The severity and the site of the infection; The age, weight and renal function of the patient as shown as follows.
The use of alternative presentations of Augmentin (e.g. those that provide higher doses of amoxycillin and/or different ratios of amoxycillin to clavulanic acid) should be considered as necessary (see Precautions and Pharmacology: Pharmacodynamics under Actions).
If it is considered that a higher daily dose of amoxycillin is required, it is recommended that another preparation of Augmentin is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid (see Precautions and Pharmacology: Pharmacodynamics under Actions).
The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review (see Precautions regarding prolonged therapy).
Elderly: No dose adjustment is considered necessary.
Renal impairment: Dose adjustments are based on the maximum recommended level of amoxycillin.
No dose adjustment is required in patients with creatinine clearance (CrCl) greater than 30 ml/min.
In patients with creatinine clearance less than 30 ml/min, the use of Augmentin presentations with an amoxycillin to clavulanic acid ratio of 7:1 is not recommended, as no recommendations for dose adjustments are available.
Hepatic impairment: Dose with caution and monitor hepatic function at regular intervals (see Contraindications and Precautions).
375 mg tablet: For adults and children ≥40 kg, this formulation of Augmentin provides a total daily dose of 750 mg amoxycillin/375 mg clavulanic acid, when administered as recommended as follows.
Adults and Children ≥40 kg: One 250 mg/125 mg tablet taken 3 times a day.
CrCl 10-30 mL/min: 250 mg/125 mg twice daily.
CrCl <10 mL/min: 250 mg/125 mg once daily.
Haemodialysis: Two doses of 250 mg/125 mg every 24 hrs, plus 2 doses of 250 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxycillin and clavulanic acid are decreased).
Children <40 kg: Augmentin 250 mg/125 mg film-coated tablets are not recommended in children <40 kg.
CrCl <30 mL/min: The use of Augmentin presentations with an amoxycillin to clavulanic acid ratio of 2:1 is not recommended, as no dose adjustments are available. In such patients, Augmentin formulations with an amoxycillin to clavulanic acid ratio of 4:1 are recommended.
625 mg tablet: Usual Dosages for the Treatment of Infection: Adults and Children >12 years: Mild to Moderate Infections: One 625-mg tablet twice daily.
Dental Infections (eg, dentoalveolar abscess): One 625-mg tablet 2 times a day for 5 days.
Mild Impairment (CrCl >30 mL/min): No change in dosage (ie, one 625-mg tablet twice daily).
Moderate Impairment (CrCl 10-30 mL/min): One 625-mg tablet twice daily. The 1-g tablet should not be administered.
Severe Impairment (CrCl <10 mL/min): One 625-mg tablet every 24 hrs.
1 g tablet: For adults and children ≥40 kg, this formulation of Augmentin provides a total daily dose of 1750 mg amoxycillin/250 mg clavulanic acid with twice daily dosing and 2625 mg amoxycillin/375 mg clavulanic acid with three times daily dosing, when administered as recommended as follows. For children <40 kg, this formulation of Augmentin provides a maximum daily dose of 1000-2800 mg amoxycillin/143-400 mg clavulanic acid, when administered as recommended as follows.
Adults and children ≥40 kg: Recommended doses: Standard dose (for all indications): 875 mg/125 mg two times a day.
Higher dose (particularly for infections such as otitis media, sinusitis, lower respiratory tract infections and urinary tract infections): 875 mg/125 mg three times a day.
Children <40 kg: Children may be treated with Augmentin tablets or suspensions.
Recommended doses: 25 mg/3.6 mg/kg/day to 45 mg/6.4 mg/kg/day given as two divided doses; up to 70 mg/10 mg/kg/day given as two divided doses may be considered for some infections (such as otitis media, sinusitis and lower respiratory tract infections).
As the tablets cannot be divided, children weighing less than 25 kg must not be treated with Augmentin tablets.
The following table presents the received dose (mg/kg body weight) in children weighing 25 kg to 40 kg upon administering a single 875/125 mg tablet. (See Table 5.)

Click on icon to see table/diagram/image

Children weighing less than 25 kg should preferably be treated with Augmentin suspension.
No clinical data are available for Augmentin 7:1 formulations regarding doses higher than 45 mg/6.4 mg per kg per day in children under 2 years.
There are no clinical data for Augmentin 7:1 formulations for patients under 2 months of age. Dosing recommendations in this population therefore cannot be made.
Syrup: For adults and children ≥40 kg, this formulation of Augmentin provides a total daily dose of 1,500 mg amoxycillin/375 mg clavulanic acid, when administered as recommended. For children <40 kg, this formulation of Augmentin provides a maximum daily dose of 2,400 mg amoxycillin/600 mg clavulanic acid, when administered as recommended.
Adults and Children ≥40 kg: One 500 mg/125 mg dose taken 3 times a day.
CrCl 10-30 mL/min: 500 mg/125 mg twice daily.
CrCl <10 mL/min: 500 mg/125 mg once daily.
Haemodialysis: 500 mg/125 mg every 24 hrs, plus 500 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxycillin and clavulanic acid are decreased).
Children <40 kg: 20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day given in 3 divided doses.
Children may be treated with Augmentin tablets, suspensions or paediatric sachets. Children ≤6 years should preferably be treated with Augmentin suspension or paediatric sachets.
No clinical data are available on doses of Augmentin 4:1 formulations higher than 40 mg/10 mg/kg per day in children <2 years.
CrCl 10-30 mL/min: 15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice daily).
CrCl <10 mL/min: 15 mg/3.75 mg/kg as a single daily dose (maximum 500 mg/125 mg).
Haemodialysis: 15 mg/3.75 mg/kg per day once daily. Prior to haemodialysis, 15 mg/3.75 mg/kg. In order to restore circulating drug levels, 15 mg/3.75 mg per kg should be administered after haemodialysis.
Suspension: For children <40 kg, this formulation of Augmentin provides a maximum daily dose of 1000-2800 mg amoxycillin/143-400 mg clavulanic acid, when administered as recommended as follows.
Children ≥40 kg: Should be treated with the adult formulations of Augmentin.
Children <40 kg: Children may be treated with Augmentin tablets or suspensions.
Recommended doses: 25 mg/3.6 mg/kg/day to 45 mg/6.4 mg/kg/day given as two divided doses; up to 70 mg/10 mg/kg/day given as two divided doses may be considered for some infections (such as otitis media, sinusitis and lower respiratory tract infections).
No clinical data are available for Augmentin 7:1 formulations regarding doses higher than 45 mg/6.4 mg per kg per day in children under 2 years.
There are no clinical data for Augmentin 7:1 formulations for patients under 2 months of age. Dosing recommendations in this population therefore cannot be made.
Method of administration: Augmentin is for oral use.
Augmentin should be administered with a meal to minimise potential gastrointestinal intolerance and optimise absorption of amoxycillin/clavulanic acid.
Therapy can be started parenterally according to the package insert of the IV-formulation and continued with an oral preparation.
Syrup/Suspension: Shake to loosen powder, add water as directed, invert and shake.
Shake the bottle before each dose (see Special precautions for disposal and other handling under Cautions for Usage).
For instructions on reconstitution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.

Symptoms and signs of overdose: Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxycillin crystalluria, in some cases leading to renal failure, has been observed (see Precautions).
Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Amoxycillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see Precautions).
Treatment of intoxication: Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.
Amoxycillin/clavulanic acid can be removed from the circulation by haemodialysis.
375 mg tablet & 156 mg syrup: Children: A prospective study of 51 paediatric patients at a poison control centre suggested that overdosages of <250 mg/kg of amoxycillin are not associated with significant clinical symptoms and do not require gastric emptying.

Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients listed in Description.
History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).
History of jaundice/hepatic impairment due to amoxycillin/clavulanic acid (see Adverse Reactions).

Before initiating therapy with amoxycillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam agents (see Contraindications and Adverse Reactions).
Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxycillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.
In the case that an infection is proven to be due to an amoxycillin-susceptible organisms(s) then consideration should be given to switching from amoxycillin/clavulanic acid to amoxycillin in accordance with official guidance.
These presentations of Augmentin are not suitable for use when there is a high risk that the presumptive pathogens have resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. These presentations should not be used to treat penicillin-resistant S. pneumoniae.
Convulsions may occur in patients with impaired renal function or in those receiving high doses (see Adverse Reactions).
Amoxycillin/clavulanic acid 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 amoxycillin.
Concomitant use of allopurinol during treatment with amoxycillin can increase the likelihood of allergic skin reactions.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthematous pustulosis (AGEP) (see Adverse Reactions). This reaction requires Augmentin discontinuation and contra-indicates any subsequent administration of amoxycillin.
Amoxycillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment (see Dosage & Administration, Contraindications, and Adverse Reactions).
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. In 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 (see Adverse Reactions).
Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxycillin and may range in severity from mild to life threatening (see Adverse Reactions). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxycillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic drugs are contra-indicated in this situation.
Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Prolongation of prothrombin time has been reported rarely in patients receiving amoxycillin/clavulanic acid. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see Interactions and Adverse Reactions).
In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see Dosage & Administration).
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxycillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxycillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see Overdosage).
During treatment with amoxycillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
The presence of clavulanic acid in Augmentin 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 amoxycillin/clavulanic acid 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 amoxycillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see Adverse Reactions).
Syrup: Augmentin 125 mg/31.25 mg/5 mL contains 2.5 mg of aspartame per mL, a source of phenylalanine. This medicine should be used with caution in patients with phenylketonuria.
Suspension: Augmentin 457 mg/5 ml powder for oral suspension contains 2.5 mg of aspartame (E951) per ml, a source of phenylalanine. This medicine should be used with caution in patients with phenylketonuria.
This medicinal product contains maltodextrin (glucose). Patients with rare glucose-galactose malabsorption should not take this medicine.

Pregnancy: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see Pharmacology: Toxicology: Preclinical safety data under Actions). Limited data on the use of amoxycillin/clavulanic acid during pregnancy in humans 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 amoxycillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.
Breastfeeding: Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. The possibility of sensitisation should be taken into account. Amoxycillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.
The ADRs derived from clinical studies and post-marketing surveillance with Augmentin, sorted by MedDRA System Organ Class are listed as follows.
The following terminologies have been used in order to classify the occurrence of undesirable effects: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data). (See Table 6.)

Click on icon to see table/diagram/image

Oral anticoagulants: Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxycillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxycillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see Precautions and Adverse Reactions).
Methotrexate: Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.
Probenecid: Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxycillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxycillin but not of clavulanic acid.
Mycophenolate mofetil: In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxycillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

Special precautions for disposal and other handling: 1 g tablet: No special requirements.
Syrup: Vigorous shaking is required for suspension preparation. Finding of lumps smaller than 3 mm is normal. A waiting time of 15 mins after mixing is needed to obtain an unclot suspension. It is important to shake the powder well before adding water.
Reconstitution Method: Invert bottle to loosen powder. Add water up to ⅔ of level indicated by the mark on label. Invert and shake well during 30 sec and let stand 30 sec. Add water up to the mark on label. Invert and shake well for 1 min. Shake well before taking each dose.
Suspension: Check cap seal is intact before using. Shake bottle to loosen powder. Add volume of water (as indicated in Table 7). Invert and shake well. Alternatively fill the bottle with water to just below the mark on bottle label, invert and shake well, then top up with water exactly to the mark, invert and again shake well. (See Table 7.)

Click on icon to see table/diagram/image

Shake the bottle well before each dose.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: Tablet/Suspension: Not applicable.

375 mg & 625 mg tablet: Store in dry place at 25°C or below. Tablets foil packing should only be opened before use. Use within 30 days of opening.
1 g tablet: Store in the original package in order to protect from moisture.
Shelf life: Tablets in desiccated pouch packs should be used within 14 days of opening.
Syrup: Store in a dry place at 25°C or below.
Once reconstituted, syrup must be stored in a refrigerator (but not frozen) and used within 7 days.
Suspension: Reconstituted suspensions should be stored in a refrigerator (2-8°C) and used within seven days.

Penicillins

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

A