Each film-coated tablet contains amoxicillin trihydrate equivalent to 500 mg amoxicillin and potassium clavulanate equivalent to 125 mg of clavulanic acid.
Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors; ATC code: J01CR02.
Amoxicillin 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.
Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes.
Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some betalactamase enzymes thereby preventing inactivation of amoxicillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.
Redmentin is indicated for the treatment of the following infections in adults and children:
- Acute bacterial sinusitis (adequately diagnosed)
- Acute otitis media
- Acute exacerbations of chronic bronchitis (adequately diagnosed)
- Community acquired pneumonia
- 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 and method of administration
Doses are expressed throughout in terms of amoxicillin/clavulanic acid content except when doses are stated in terms of an individual component.
The dose of Redmentin-625 that is selected to treat an individual infection should take into account:
- The expected pathogens and their likely susceptibility to antibacterial agents
- The severity and the site of the infection
- The age, weight and renal function of the patient as shown below.
The use of alternative presentations of Redmentin-625 (e.g. those that provide higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary.
For adults and children ≥ 40 kg, this formulation of Redmentin-625 provides a total daily dose of 1500 mg amoxicillin/375 mg clavulanic acid, when administered as recommended below. For children < 40 kg, this formulation of Redmentin-625 provides a maximum daily dose of 2400 mg amoxicillin/600 mg clavulanic acid, when administered as recommended below. If it is considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of Redmentin-625 is selected in order to avoid administration of unnecessarily highmdaily doses of clavulanic acid.
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.
Adults and children ≥ 40 kg: One 500 mg/125 mg dose taken three times a day.
Children < 40 kg: 20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day given in three divided doses.
Children may be treated with Redmentin-625 tablets, suspensions or paediatric sachets.
As the tablets cannot be divided, children weighing less than 25 kg must not be treated withmRedmentin-625 tablets.
Elderly: No dose adjustment is considered necessary.
Renal impairment: Dose adjustments are based on the maximum recommended level of amoxicillin. No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30ml/min.
Hepatic impairment: Dose with caution and monitor hepatic function at regular intervals.
Method of administration
Redmentin-625 is for oral use.
Redmentin-625 should be administered with a meal to minimize potential gastrointestinal intolerance. Therapy can be started parenterally according the SPC of the IV formulation and continued with an oral preparation.
Amoxicillin-clavulanate is contraindicated: in patients with a history of hypersensitivity to betalactams, e.g. penicillins and cephalosporins and to any of the excipients.
In patients with a previous history of amoxicillin-clavulanate associated jaundice/hepatic dysfunction.
Special Warnings and Special Precautions for Use
Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other betalactam agents.
Serious and occasionally fatal hypersensitivity 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, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.
In the case that an infection is proven to be due to an amoxicillin-susceptible organisms(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance.
This presentation of Redmentin-625 is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This presentation 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.
Amoxicillin/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 amoxicillin.
Concomitant use of allopurinol during treatment with amoxicillin 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 exanthemous pustulosis (AGEP). This reaction requires Redmentin-625 discontinuation and contraindicates any subsequent administration of amoxicillin.
Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment. 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.
Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin and may range in severity from mild to life threatening. 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, amoxicillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contraindicated 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 amoxicillin/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.
In patients with renal impairment, the dose should be adjusted according to the degree of impairment.
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. In patients with bladder catheters, a regular check of patency should be maintained.
During treatment with amoxicillin, 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 Redmentin-625 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 amoxicillin/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 amoxicillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.
Interaction with Other Medicinal Products and Other Forms of Interaction
Oral anticoagulants: Oral anticoagulants and penicillin antibiotics have been widely used in practice without reportsof interaction. However, in the literature there are cases of increased international normalizedratio in patients maintained on acenocoumarol or warfarin and prescribed a course ofamoxicillin. If co-administration is necessary, the prothrombin time or international normalizedratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover,adjustments in the dose of oral anticoagulants may be necessary.
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 amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin 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 amoxicillin 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.
Pregnancy and Lactation
This product should only be used in pregnancy or lactation if considered essential by the physician. Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered amoxicillinclavulanate 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 amoxicillin-clavulanate may be associated with an increased risk of necrotising enterocolitis in neonates.
Amoxicillin 500mg + Clavulanate 125mg Tablets 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 breast-fed infant.
Effects on Ability to Drive and Use Machines
Amoxicillin 500mg + Clavulanate 125 mg Tablets has no influence on the ability to drive and use machine
The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.
Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. GI symptoms may be treated symptomatically, with attention to the water/electrolyte balance. it can be removed from the circulation by haemodialysis. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.