Augmentin Suspension

Augmentin Suspension

amoxicillin + clavulanic acid

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Co-amoxiclav: Amoxicillin and potassium clavulanic acid.
Description
Augmentin suspension 228 mg/5 ml contains 200 mg amoxicillin (as amoxicillin trihydrate) and 28.5 mg clavulanic acid (as potassium clavulanate) per 5 ml.
Augmentin suspension 457 mg/5 ml contains 400 mg amoxicillin (as amoxicillin trihydrate) and 57 mg clavulanic acid (as potassium clavulanate) per 5 ml.
Excipients/Inactive Ingredients: Xanthan gum, hydroxypropylmethylcellulose, colloidal silica, succinic acid, silicon dioxide, raspberry, orange "1", orange "2", golden syrup dry flavours, aspartame.
Action
Pharmacology: Pharmacodynamics: Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in Augmentin suspension anticipates this defence mechanism by blocking the ß-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 Augmentin, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.
In the list as follows, organisms are categorised according to their in vitro susceptibility to Augmentin. (See Table 1.)

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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 Augmentin-susceptible β-lactamase producing organisms are therefore considered to be treated with Augmentin.
Pharmacokinetics: Absorption: The two components of Augmentin suspension 228 mg/5 ml and 457 mg/5 ml, amoxicillin and clavulanate, are each 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.
The mean AUC values for amoxicillin are essentially the same following twice a day dosing with the Augmentin 1g tablets ( 875/125 mg) or three times a day dosing with the Augmentin 625 mg tablets (500/125 mg), in adults. No differences between the 875 mg twice daily and 500 mg three times daily dosing regimes are seen when comparing the amoxicillin T½, or Cmax after normalisation for the different doses of amoxicillin administered. Similarly, no differences are seen for the clavulanate T½, Cmax or AUC values after appropriate dose normalisation.
The time of dosing of Augmentin relative to the start of a meal has no marked effects on the pharmacokinetics of amoxicillin in adults. In a study of the Augmentin 1g tablets (875/125 mg), the time of dosing relative to ingestion of a meal had a marked effect on the pharmacokinetics of clavulanate. For clavulanate AUC and Cmax, the highest mean values and smallest inter-subject variabilities were achieved by administering Augmentin at the start of a meal, compared to the fasting state or 30 or 150 minutes after the start of a meal.
The mean Cmax, Tmax, T½ and AUC values for amoxicillin and clavulanate are given below for Augmentin 1g tablets (an 875 mg/125 mg dose of amoxicillin/clavulanate) administered at the start of a meal. (See Table 2.)

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Amoxicillin serum concentrations achieved with Augmentin are similar to those produced by the oral administration of equivalent doses of amoxicillin alone.
Distribution: The pharmacokinetics of the two components of Augmentin are closely matched. Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Doubling the dosage of Augmentin approximately doubles the serum levels achieved.
Toxicology: Preclinical safety data: No further information of relevance.
Indications/Uses
Augmentin should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.
Augmentin suspension (228 mg/5 ml and 457 mg/5 ml), for twice daily oral dosing, is indicated for short term treatment of bacterial infections at the following sites when amoxicillin resistant beta-lactamase producing strains are suspected as the cause. In other situations, amoxicillin alone should be considered.
Upper respiratory tract infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media.
Lower respiratory tract infections e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia.
Urinary tract infections e.g. cystitis, urethritis, pyelonephritis.
Skin and soft tissue infections e.g. cellulitis, animal bites.
Dental infections e.g. severe dental abscess with spreading cellulitis.
Susceptibility to Augmentin will vary with geography and time (see Pharmacology: Pharmacodynamics under Actions for further information). Local susceptibility data should be consulted where available, and microbiological sampling and susceptibility testing performed where necessary.
Mixed infections caused by amoxicillin-susceptible organisms in conjunction with Augmentin susceptible beta-lactamase-producing organisms may be treated with Augmentin suspension 228 mg/5 ml and 457 mg/5 ml. These infections should not require the addition of another antibiotic resistant to beta-lactamases.
Dosage/Direction for Use
The usual recommended daily dosage is: 25/3.6 mg/kg/day in mild to moderate infections (upper respiratory tract infections e.g.recurrent tonsillitis, lower respiratory infections and skin and soft tissue infections).
45/6.4 mg/kg/day for the treatment of more serious infections (upper respiratory tract infections e.g. otitis media and sinusitis, lower respiratory tract infections e.g. bronchopneumonia and urinary tract infections).
The tables as follows give guidance for children. (See Tables 3 and 4.)

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Click on icon to see table/diagram/image

There is insufficient experience with Augmentin suspension 228 mg/5 ml and 457 mg/5 ml to make dosage recommendations for children under 2 months old.
Renal impairment: For children with a GFR of >30 ml/min no adjustment in dosage is required. For children with a GFR of <30 ml/min Augmentin suspension 228 mg/5 ml and 457 mg/5 ml are not recommended.
Infants with immature kidney function: For infants with immature renal function Augmentin suspension 228 mg/5 ml and 457 mg/5 ml are not recommended.
Hepatic impairment: Dose with caution; monitor hepatic function at regular intervals. There is, as yet, insufficient evidence on which to base a dosage recommendation.
Administration: To minimise potential gastrointestinal intolerance, administer at the start of a meal. The absorption of Augmentin is optimised when taken at the start of a meal. Duration of therapy should be appropriate to the indication and should not exceed 14 days without review.
Therapy can be started parenterally and continued with an oral preparation.
Overdosage
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).
Augmentin can be removed from the circulation by haemodialysis.
Contraindications
Augmentin is contraindicated in patients with a history of hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins.
Augmentin is contraindicated in patients with a previous history of Augmentin-associated jaundice/hepatic dysfunction.
Warnings
Do not use in patients with known hypersensitivity to this medicine.
This medicine may cause a serious hypersensitivity reaction which can be fatal.
In case of erythema rash, irritation or edema occur, discontinue this medicine and consult a physician.
In case of rash or flu-like symptoms, discontinue this medicine and promptly consult a physician.
In case of the following symptoms occur eg. fever, rash, vesicles, exfoliation of skin and other mucous membrane such as in the mouth, throat, nose, reproductive organ and conjunctivitis, discontinue this medicine and consult a physician since this may be Stevens-Johnson syndrome.
Special Precautions
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 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 (see Contraindications). If an allergic reaction occurs, Augmentin therapy must be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous (i.v.) steroids and airway management (including intubation) may also be required.
Augmentin should be avoided if infectious mononucleosis is suspected since the occurrence of a mobilliform 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.
Abnormal prolongation of prothrombin time (increase 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.
Changes in liver function tests have been observed in some patients receiving Augmentin. The clinical significance of these changes is uncertain but 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 Augmentin suspension 228 mg/5 ml and 457 mg/5 ml are not recommended.
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 228 mg/5 ml and 457 mg/5 ml suspensions contain 12.5 mg aspartame per 5 ml dose and therefore care should be taken 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) with orally and parenterally administered 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 Augmentin may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, 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 sensitisation, associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the 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: ≥ 1/1,000 and <1/100; Rare: ≥ 1/10,000 and <1/1,000; 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. 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: 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 haemorrhatgic 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.
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. These events have been very rarely reported in children.
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) and drug reaction with eosinophilia and systemic symptoms (DRESS)
If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
Renal and urinary disorders: Very rare: Interstitial nephritis, crystalluria (see Overdosage).
Drug Interactions
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 clavulanate.
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 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.
Caution For Usage
Incompatibilities: None known.
Instructions for Use and Handling: GLASS BOTTLES: 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.
Add volume of water (indicated in Tables 5 and 6). 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 to the mark. Invert and shake again.
Allow to stand for 5 minutes to ensure full dispersion.
Shake well before taking each dose. (See Tables 5 and 6.)

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The Augmentin suspension 457 mg/5 ml 30, 35 and 70 ml presentation may be provided with a dosing device.
Storage
The dry powder should be stored in unopened containers in a dry place at below 25°C.
Reconstituted suspensions should be stored in a refrigerator (2-8°C) and used within seven days.
MIMS Class
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
Powd for oral susp (dry powder for reconstitution in water, at time of dispensing, to form an oral sugar free suspension) 228 mg/5 mL x 70 mL. 457 mg/5 mL x 35 mL, 70 mL.
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