Augmentin® - (IR): composition and pharmaceutical form
Augmentin® - (IR) is a combination antibiotic in film-coated tablets. One tablet contains amoxicillin trihydrate in an amount corresponding to 500 mg or 875 mg of amoxicillin, and potassium clavulanate in an amount corresponding to 125 mg of clavulanic acid.
The medicine is intended for oral use. It should be taken at the start of a meal: this reduces the likelihood of gastrointestinal upset and improves absorption. If necessary, treatment begins with the parenteral form and then continues with tablets.
How Augmentin® - (IR) works
Amoxicillin is a semisynthetic penicillin, that is a β-lactam antibiotic. It inhibits one or more enzymes known as penicillin-binding proteins on the biosynthetic pathway of bacterial peptidoglycan, the main structural component of the cell wall. Wall synthesis is disrupted, the wall weakens, and the cell usually dies from lysis.
Amoxicillin's weak point is that resistant bacteria destroy it with β-lactamases, and on such organisms it has no effect. Clavulanic acid is a β-lactam structurally similar to the penicillins: it has no clinically significant antibacterial action of its own, but it inactivates some β-lactamases and thereby protects amoxicillin from destruction.
Indications
The medicine is used in adults and children with bacterial infections: correctly diagnosed acute bacterial sinusitis, acute otitis media, exacerbation of chronic bronchitis, community-acquired pneumonia, cystitis and pyelonephritis.
It is also prescribed for skin and soft tissue infections — above all cellulitis, animal bites and severe periodontal abscess with spreading cellulitis — and for bone and joint infections, in particular osteomyelitis. When choosing the antibiotic the doctor takes the official recommendations on antibacterial therapy into account.
Method of use and dosage
The dose is chosen with regard to the likely pathogens and their sensitivity, the severity and site of the infection, and also the patient's age, body weight and kidney function. Doses are stated by the content of amoxicillin and clavulanic acid. The length of treatment is determined by the response to therapy; in some infections, for example osteomyelitis, the course must be longer, while extending treatment beyond 14 days without a further examination is not allowed.
| Situation | Dosing scheme |
|---|---|
| Adults and children from 40 kg, the 500 mg + 125 mg form | 1 tablet 3 times a day |
| Adults and children from 40 kg, the 875 mg + 125 mg form | 1 tablet twice a day; in otitis media, sinusitis and lower respiratory and urinary tract infections, 3 times a day |
| Children under 40 kg, ratio 4:1 | From 20 mg + 5 mg to 60 mg + 15 mg per kg of body weight a day in three intakes |
| Children under 40 kg, ratio 7:1 | From 25 mg + 3.6 mg to 45 mg + 6.4 mg per kg a day in two intakes; up to 70 mg + 10 mg per kg in otitis, sinusitis and lower respiratory tract infections |
| Elderly patients | No dose adjustment is required |
Children, kidneys and liver
The tablets are not used in children weighing less than 25 kg, since they must not be split, and children under 6 are given the suspension. There are no data on the use of doses above 45 mg + 6.4 mg per kg a day in children under 2, and for the 7:1 ratio form there are no recommendations in children under 2 months. With a creatinine clearance above 30 ml/min no dose adjustment is needed. With a clearance of 10–30 ml/min, adults and children over 40 kg are given the 500 mg + 125 mg dose twice a day and, with a clearance below 10 ml/min, once a day; the 7:1 ratio forms are not used with a clearance below 30 ml/min. In impaired liver function the dose is chosen cautiously and liver parameters are monitored regularly.
Contraindications
The medicine is not prescribed in the following cases:
- hypersensitivity to amoxicillin, clavulanic acid, any of the penicillins or the excipients;
- a severe immediate hypersensitivity reaction, for example anaphylaxis, to another β-lactam medicine — cephalosporin, carbapenem or monobactam — in the past;
- previous jaundice or impaired liver function caused by amoxicillin or clavulanic acid.
Special warnings and precautions
Before treatment begins it is essential to establish whether there have been previous hypersensitivity reactions to penicillins, cephalosporins or other β-lactams. In those who have received penicillins, severe allergic reactions have been described, occasionally with a fatal outcome; their likelihood is higher in people with previous penicillin allergy and with atopic disease. If an allergic reaction occurs the medicine is withdrawn and another treatment is used. Generalised reddening of the skin with pustules and fever at the start of treatment may be a manifestation of acute generalised exanthematous pustulosis — in that case the medicine is withdrawn and further use of amoxicillin is contraindicated.
- if the pathogen is known to be sensitive to amoxicillin alone, the combination with clavulanic acid is replaced by amoxicillin in line with the official recommendations;
- the medicine is unsuitable when the pathogen's resistance to β-lactams is most likely not due to β-lactamases sensitive to clavulanic acid, and it is not used in infections caused by penicillin-resistant S. pneumoniae;
- where infectious mononucleosis is suspected the medicine is avoided: in such patients taking amoxicillin is linked to the appearance of a measles-like rash;
- allopurinol during treatment with amoxicillin raises the likelihood of allergic skin reactions;
- diarrhoea during or after a course of any antibiotic requires antibiotic-associated colitis to be ruled out: if it develops the medicine is withdrawn at once and agents that slow peristalsis are contraindicated;
- liver disturbances occur more often in men and elderly people and may be linked to prolonged treatment; they are usually transient, but in extremely rare cases they are severe;
- in patients with impaired kidney function and at high doses seizures are possible; with a high dose of amoxicillin sufficient fluid intake is needed so that crystals do not form in the urine;
- in long-term treatment kidney and liver function and blood parameters are checked periodically, and with concomitant anticoagulants clotting is monitored — prolongation of the prothrombin time has rarely been noted.
Prolonged use sometimes leads to the growth of non-susceptible organisms. The influence on laboratory tests is also worth noting: glucose in urine is measured by the enzymatic method with glucose oxidase, since non-enzymatic methods give false positive results; clavulanic acid may cause a false positive Coombs test, as well as a false positive result of the Platelia Aspergillus test, which should be confirmed by other methods. No specific studies of the influence on driving have been carried out, but allergic reactions, dizziness and seizures may affect the ability to drive.
Drug interactions
Oral anticoagulants and penicillins are used together widely without reports of interaction, yet the literature describes cases of a rise in INR in patients taking acenocoumarol or warfarin when amoxicillin was added. If concomitant use is necessary, the prothrombin time or INR is monitored carefully at the start and after the end of the course, and the anticoagulant dose changed if needed.
Penicillins may reduce the elimination of methotrexate and thereby increase its toxicity. Probenecid lowers the tubular secretion of amoxicillin, so its blood concentration rises and lasts longer (clavulanic acid is unaffected), and that combination is therefore not recommended. In patients on mycophenolate mofetil the concentration of the active metabolite — mycophenolic acid — before the next dose fell by about 50%; changing the dose is usually unnecessary, but the patient is watched closely during the combined treatment and shortly after it ends.
Pregnancy and breastfeeding
Animal studies have found no direct or indirect harmful effect on pregnancy, embryonic and foetal development, delivery or postnatal development. Limited data on the use of amoxicillin with clavulanic acid in pregnant women do not indicate an increased risk of congenital malformations. However, in one study in women with premature rupture of the membranes, prophylactic use of the combination was linked to an increased risk of necrotising enterocolitis in newborns, so during pregnancy the medicine is avoided unless the doctor considers its prescription necessary.
Both substances are excreted in breast milk, and the influence of clavulanic acid on the child is unknown. In the child diarrhoea and fungal involvement of the mucous membranes are possible, which sometimes makes it necessary to stop breastfeeding. Using the medicine while breastfeeding is possible only after the doctor has assessed the balance of benefit and risk.
Adverse effects
The most frequent are diarrhoea, nausea and vomiting. Nausea is usually linked to higher doses; gastrointestinal symptoms lessen if the medicine is taken at the start of a meal.
- very common — diarrhoea with the film-coated tablets;
- common — nausea, vomiting, candidiasis of the skin and mucous membranes;
- uncommon — dizziness, headache, dyspepsia, skin rash, itching, urticaria, increased AST and ALT activity;
- rare — transient leucopenia including neutropenia, thrombocytopenia, erythema multiforme;
- frequency not known — angioedema, anaphylaxis, serum sickness, allergic vasculitis;
- frequency not known — antibiotic-associated colitis, including pseudomembranous and haemorrhagic, black hairy tongue;
- frequency not known — hepatitis and cholestatic jaundice, interstitial nephritis, crystalluria;
- frequency not known — Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis and acute generalised exanthematous pustulosis; with any cutaneous hypersensitivity reaction treatment is stopped.
Transient agranulocytosis, haemolytic anaemia, prolongation of bleeding time and prothrombin time, transient motor hyperactivity, seizures and aseptic meningitis have also been recorded and, with prolonged use, overgrowth of non-susceptible bacteria.
Overdose
In an overdose gastrointestinal symptoms and disturbances of water and electrolyte balance are possible. The formation of amoxicillin crystals in the urine has been observed, in some cases leading to renal failure. In patients with impaired kidney function and when high doses are taken, seizures may develop.
Cases of amoxicillin precipitating in urinary catheters have also been recorded, mainly after intravenous administration of high doses, so catheter patency is checked regularly. Gastrointestinal symptoms are treated symptomatically with particular attention to water and electrolyte balance; if necessary, amoxicillin with clavulanic acid can be removed from the circulation by haemodialysis.
How to get a prescription for Augmentin® - (IR) online
Antibiotics are dispensed on prescription and should be prescribed only for a confirmed bacterial infection — in viral illnesses they are useless and merely promote the growth of resistance.
During the online consultation the doctor will assess the symptoms and the history of allergic reactions, choose the dose and the length of the course and, where indicated, issue an electronic prescription — the medicine can be collected at a pharmacy with its code.
