Augmentin Sachet

Amoxicillin, clavulanic acid.

Each 250-mg and 500-mg sachet contains amoxicillin 250 mg and 500 mg, and clavulanic acid 31.25 and 62.50 mg, respectively.
Excipients/Inactive Ingredients: Crospovidone, hydrated precipitated silica, peach-lemon-strawberry flavour [orange, bergamot and lemon oils, vanillin, butylated hydroxyanisole(E320), maltodextrin], aspartame (E951).
Augmentin (β-lactam antibacterial penicillin co-formulated with a β-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 β-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other β-lactam antibiotics.

ATC code: J01CR02.
Pharmacology: Pharmacodynamics: Mechanism of Action: Amoxicillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by β-lactamases and therefore, the spectrum of activity of amoxicillin alone 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. It is generally less effective against chromosomally-mediated type 1 β-lactamases.
The presence of clavulanic acid in Augmentin formulations protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other penicillins and cephalosporins. Thus, Augmentin possesses the distinctive properties of a broad spectrum antibiotic and a β-lactamase inhibitor.
Pharmacodynamic Effects: In the list as follows, organisms are categorised according to their in vitro susceptibility to Augmentin (see Table 1).


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Pharmacokinetics: Absorption: The 2 components of Augmentin, 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 Augmentin is optimised when taken at the start of a meal.
Amoxicillin serum concentrations achieved with Augmentin 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 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 breastfed 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 10-25% 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 60-70% of the amoxicillin and approximately 40-65% of the clavulanic acid are excreted unchanged in urine during the first 6 hrs 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).

Augmentin should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.
Short-term treatment of bacterial infections at the following sites when caused by amoxicillin-clavulanate-susceptible organisms:
Upper respiratory tract infections (including ENT) eg, recurrent tonsillitis, sinusitis, otitis media, typically caused by Streptococcus pneumoniae, Haemophilus influenzae^#, Moraxella catarrhalis^# and Streptococcus pyogenes.
Lower respiratory tract infections eg, acute exacerbations of chronic bronchitis, lobar and bronchopneumonia, typically caused by Streptococcus pneumoniae, Haemophilus influenzae^# and Moraxella catarrhalis^#.
Genitourinary tract infections eg, cystitis, urethritis, pyelonephritis, female genital infections typically caused by Enterobacteriaceae^* (mainly Escherichia coli^#), Staphylococcus saprophyticus and Enterococcus spp and gonorrohoea caused by Neisseria gonorrhoeae^#.
Skin and soft tissue infections typically caused by Staphylococcus aureus^#, Streptococcus pyogenes and Bacteroides spp^#.
Bone and joint infections eg, osteomyelitis typically caused by Staphylococcus aureus^#, where more prolonged therapy may be appropriate.
Other Infections eg, septic abortion, puerperal sepsis, intra-abdominal sepsis.
^#Some members of these species of bacteria produce β-lactamase, rendering them insensitive to amoxicillin alone (see Pharmacology: Pharmacodynamic under action).
Susceptibility to Augmentin will vary with geography and time. Local susceptibility data should be consulted where available and microbiological sampling and susceptibility testing performed where necessary.
Infections caused by amoxicillin-susceptible organisms are amenable to Augmentin treatment due to its amoxicillin content. Mixed infections caused by amoxicillin-susceptible organisms in conjunction with amoxicillin-clavulanate-susceptible β-lactamase-producing organisms may therefore be treated by Augmentin.

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 amoxicillin-clavulanate content except when doses are stated in terms of an individual component.
Adults: See Table 2.


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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). Weighing ≥40 kg: Dose should be according to the adult recommendations.
Children up to 12 years: Recommended Dose: 40 mg/5 mg/kg/day to 80 mg/10 mg/kg/day (not exceeding 3000 mg/375 mg/day) given in 3 divided doses, depending on the severity of infection.
The duration of therapy should be determined by the response of the patient. Some infections (eg, osteomyelitis) require longer periods of treatment.
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.
Renal Impairment: No dose adjustment is required in patients with creatinine clearance (CrCl) >30 mL/min. In patients with CrCl <30 mL/min, the use of Augmentin presentations with an amoxicillin to clavulanic acid ratio of 8:1 is not recommended, as no recommendations for dose adjustments are available.
Haemodialysis: Augmentin 500 mg/62.5 mg powder for oral suspension in sachets should only be used in patients with a creatinine clearance of >30 mL/min.
Hepatic Impairment: Dose with caution; monitor hepatic function at regular intervals. There are insufficient data on which to base a dosage recommendation.
Administration: To minimise potential gastrointestinal intolerance, administer at the start of the meal.
The absorption of 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.

Symptoms: 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. Augmentin can be removed from the circulation by haemodialysis.
Drug Abuse and Dependence: Drug dependency, addiction and recreational abuse have not been reported as a problem with Augmentin sachet.

Hypersensitivity to β-lactams eg, penicillin and cephalosporin. History of amoxicillin-clavulanate-associated jaundice/hepatic dysfunction.

Before initiating therapy with 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, 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.
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.
In general, Augmentin 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 Augmentin 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.
Augmentin should be used with caution in patients with evidence of hepatic dysfunction.
In patients with renal impairment, dosage should be adjusted according to the degree of impairment (see Renal Impairment under 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 amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (see Overdosage).
Augmentin sachets, contain aspartame, which is a source of phenylalanine and so should be used with caution in patients with phenylketonuria.
Effects on Ability to Drive and Operate Machinery: Adverse effects on the ability to drive or operate machinery have not been observed.
Use in pregnancy: Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered Augmentin have shown no teratogenic effects. In a single study in women with pre-term, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with 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: Augmentin may be administered during the period of lactation. With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breastfed infant.

Use in pregnancy: Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered Augmentin have shown no teratogenic effects. In a single study in women with pre-term, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with 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: Augmentin may be administered during the period of lactation. With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breastfed infant.

Data from large clinical trials were used to determine the frequency of very common to rare adverse effects. The frequencies assigned to all other adverse effects (ie, 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: Genital moniliasis, mucocutaneous candidiasis.
Blood and Lymphatic System Disorders: Rare: Reversible leucopenia (including neutropenia) and thrombocytopenia. Very Rare: Reversible agranulocytosis and haemolytic anaemia. 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, convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Gastrointestinal Disorders: 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 Augmentin at the start of a meal. Uncommon: Indigestion. Very Rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis), 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.
Hepatobiliary Disorders: Uncommon: A moderate rise in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) has been noted in patients treated with β-lactam class antibiotics, but the significance of these findings is unknown. Very Rare: Hepatitis, 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.
Children: These events have been very rarely reported in children.
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).

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with Augmentin 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 Augmentin and allopurinol.
In common with other antibiotics, 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 amoxicillin.

Instructions for Use and Handling: Sachet contents should be stirred into water before taking.
Children: For administration to children up to 2 years, amoxicillin-clavulanate suspensions may be diluted to ½-strength using water.

Stored below 30°C.
Shelf-Life: 24 months.

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.