Amoxicillin trihydrate – Potassium clavulanate
QUALITATIVE AND QUANTITATIVE COMPOSITION :
AUGMENTlN 1 g tablets: Each tablet contains 875 mg amoxicillln (as amoxicillin trihydrate) and 125 mg clavulanic acid (as potassium clavulanate).
PHARMACEUTICAL FORM :
AUGMENTIN 1 9 tablets: A white to off-white oval-shaped film-coated debossed tablet, with a score line on one side and plain on the other side.
CLINICAL PARTICULARS :
AUGMENTIN is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The B lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other Iactam antibiotics.
AUGMENTlN should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.
AUGMENTIN oral presentations for twice daily dosing, are indicated for short-term treatment of bacterial infections at the following sites: Upper respiratory tract infections (including ENT) e.g. tonsillitis, sinusitis, otitis media. Lower respiratory tract infections e.g. acute exacerbation of chronic bronchitis, lobar and
bronchopneumonia. Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis. Skin and soft tissue infections, e.g. boils, abscesses, cellulitis, wound infections. Bone and joint infections e.g. osteomyelitis.
Dental infections e.g. dentoalveolar abscess Susceptibility to AUGMENTIN will vary with geography and time (see Pharmacological Properties, Pharmacodynamics for further information). Local susceptibitity data should be consulted where available, and microbiological sampling and susceptibility testing
performed where necessary. Infections caused by amoxicitlin -susceptible organisms are amenable to Augmentin-treatment due to its amoxiclllin content. Mixed infections caused by amoxicillin
susceptible organisms in conjunction with augmentin -susceptible j3-lactamase producing organisms may therefore be treated with Augmentin.
Dosage and Administration :
Usual dosages for the treatment of infection
Adults and children over 12 years·
– Severe infections -One AUGMENTIN 1 g tablet twice daily
– Therapy can be started parenterally and continued with an oral preparation .
– AUGMENTIN 1 g tablets are not recommended in children of 12 years and under
Dosage in renal impairment :
The AUGMENTIN 1 g tablet should only be used in patients with a glomerular filtration rate of >30 ml/min.
Mild impairment (Creatinine clearance >30 mVmin) No change in dosage 1 g tablet twice daily
Moderate impairment (Creatinine clearance 10-30 mVmin) The 1 g tablet should not be administered.
Severe impairment (Creatinine clearance <10 mVmin)
Not more than one 625 mg tablet every 24 hours.
Dosage in hepatic impairment
Dose with caution; monitor hepatic function at regular intervals.
:Tablets should be swallowed whole without chewing. If required, tablets may be broken in half and swallowed without chewing.
To minimise potential gastrointestinal intolerance, administer at the start of a meal. The absorption of AUGMENTlN is optimised when taken at the start of a meal. Treatment should not be extended beyond 14 days without review. AUGMENTlN is also available as AUGMENTlN intravenous for the short-term treatment of
bacterial infections and for prophylaxis against infection which may be associated with major surgical procedures. AUGMENTlN intravenous is described in a separate Pack Insert.
AUGMENTIN is also available as a suspension for three times daily dosing for administration to children under the age of 12 years for the treatment of bacterial infections. AUGMENTlN
suspension three times daily is described in a separate Pack Insert.
AUGMENTlN is contra-indicated in patients with a history of hypersensitivity to beta-Iactams, e.g. penicillins and cephalosporins.
AUGMENTlN is contra-indicated in patients with a previous history of AUGMENTIN-associated jaundicelhepatic dysfunction.
Warnings and Precautions :
Before initiating therapy with AUGMENTlN 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 (see Contra-indications).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.
– Abnormal prolongation of prothrombin time ~ncreased INR) has been reported rarely in patients receiving AUGMENTlN 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. AUGMENTlN 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 AUGMENTlN dosage should be adjusted as recommended in the Dosage and Administration section. In patients with reduced urine output. crystalluria has beenobserved very rarety, 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 Overdose).
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with AUGMENTlN 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 AUGMENTlN and allopurinol.
In common with other antibiotics, AUGMENTlN 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 AUGMENT/N.
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.
Pregnancy and lactation :
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 pre-term. premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with AUGMENTlN 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.
AUGMENTlN 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 mitk, there are no detrimental effects for the infant.
Effects on Ability to Drive and Use Machines :
Adverse effects on the ability to drive or operate machinery have not been observed.
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 (l.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. Prolongation of bleeding
time and prothrombin time.
Immune system disorders
Very rare : Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome,
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.
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 AUGMENTlN at the start of a meal.
Very rare : Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis – see Warnings and Precautions).
Black hairy tongue
Uncommon A moderate rise in AST and/or ALT has been noted in patients treated with beta-Iactam 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
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 Overdose)
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 Wamings and Precautions).
AUGMENTIN can be removed from the circulation by haemodialysis.
PHARMACOLOGICAL PROPERTIES :
Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate in AUGMENTlN anticipates this defence mechanism by blocking the Iactamase enzymes, thus rendering the organisms susceptible 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.
-Augmentin is a bactericidal to a wide range of organisms.
Phannacokinetics The pharmacokinetics of the two components of AUGMENTlN are closely matched. Peak serum levels of both occur about 1 hour after oral administration. Absorption of AUGMENTlN is optimised at the start of a meal Doubling the dosage of AUGMENTIN approximately doubles the serum levels achieved.
Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Pre-clinical Safety Data
No further information of relevance.
PHARMACEUTICAL PARTICULARS :
list of Excipients
AUGMENTlN 1 g tablets contain the following inactive ingredients: colloidal silicon dioxide, sodium starch glycolate, magnesium stearate, microcrystalline cellulose, titanium dioxide, hydroxypropyl methylcellulose 5 CPS, hydroxypropyl melhylcellulose 15 CPS, polyethylene glycol 4000, 6000, silicone oil.
Special Precautions for Storage
AUGMENTlN tablets should be stored in un-opened, original packs in a dry place at temperature not exceeding 30°C.
Keep out of the reach of children.
Nature and Contents of Container
Carton box containinq 2 strips each of 7 film coated tablets and inner leaflet.
Manufactured by :
Medical Union Pharmaceuticals “Penicillin Plant” – Abu Sultan – Ismailia – Egypt For GlaxoSmithKline – EI-Salam City – Cairo – S.A.E.