Augmentin®: composition and pharmaceutical form
One film-coated tablet contains 250 mg, 500 mg or 875 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as potassium clavulanate. There is also a prolonged-release tablet: 1000 mg of amoxicillin as the trihydrate and sodium salt plus 62.5 mg of clavulanic acid.
Note the pattern: the dose of clavulanic acid stays almost unchanged and what varies is the amount of amoxicillin. Hence the rule — if a higher daily dose of amoxicillin is needed, another form of the medicine is chosen rather than the number of tablets increased, so as not to give excess clavulanic acid.
How Augmentin® works
Amoxicillin is a semisynthetic penicillin, a beta-lactam antibiotic. It inhibits one or more enzymes known as penicillin-binding proteins in the biosynthetic chain of bacterial peptidoglycan, the structural basis of the cell wall. Wall synthesis is disrupted, the wall weakens, and the cell usually lyses and dies.
The problem is that resistant bacteria produce beta-lactamases which destroy amoxicillin, so on its own it does not act on such organisms. Clavulanic acid is a beta-lactam structurally similar to the penicillins: it has no clinically useful antibacterial action of its own, but it inactivates some beta-lactamases and thereby protects amoxicillin from destruction.
Indications
Augmentin® is used in children and adults with bacterial infections. The 375 mg form is indicated in acute bacterial sinusitis with a confirmed diagnosis, cystitis, pyelonephritis, inflammation of the subcutaneous tissue, animal bites and severe periodontal abscess with spreading cellulitis.
The 625 mg and 1000 mg forms cover a wider range: to the above are added acute otitis media, exacerbation of chronic bronchitis with a confirmed diagnosis, community-acquired pneumonia, skin and soft tissue infections, and bone and joint infections, above all osteomyelitis. In every case the official recommendations on the rational use of antibacterials are taken into account.
Method of use and dosage
The medicine is taken by mouth at the start of a meal: this reduces the likelihood of gastrointestinal intolerance and optimises absorption. The dose is chosen with regard to the likely pathogens and their sensitivity, the severity and site of the infection, and also age, body weight and kidney function.
| Situation | Dose |
|---|---|
| Adults and children from 40 kg, the 375 mg form | one 250 mg + 125 mg tablet three times a day |
| Adults and children from 40 kg, the 625 mg form | one 500 mg + 125 mg tablet three times a day |
| Children under 40 kg | film-coated tablets are not used; the dose is calculated per kilogram of body weight in three intakes |
| Creatinine clearance of 10–30 ml/min | 250 mg + 125 mg twice a day |
| Creatinine clearance below 10 ml/min | 250 mg + 125 mg once a day |
| Haemodialysis | 250 mg + 125 mg every 24 hours, plus a dose during dialysis and another at its end |
With a creatinine clearance above 30 ml/min the dose is unchanged, and in the elderly no adjustment is needed. In impaired liver function the medicine is dosed cautiously and liver parameters are monitored regularly. A course longer than 14 days is not extended without reassessing the patient; in some infections, for example osteomyelitis, longer treatment is required.
Contraindications
All the contraindications relate to two things: allergy to beta-lactams and previous liver damage caused by this very medicine.
- hypersensitivity to the active substances, to any penicillin or to any excipient;
- a severe immediate hypersensitivity reaction, that is anaphylaxis, to another beta-lactam — 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 starts the patient must be questioned in detail about previous reactions to penicillins, cephalosporins and other beta-lactams. In those who have received penicillins, severe allergic reactions have been described, occasionally fatal; their likelihood is higher in people with penicillin hypersensitivity in the history and with atopic disease. If an allergic reaction occurs, treatment is stopped and another prescribed.
Liver and intestine
Liver disturbances were recorded mainly in men and elderly patients and may be linked to prolonged treatment; in children they are very rare. The symptoms usually appear during treatment or right afterwards, sometimes only after several weeks, and as a rule they are reversible. Liver damage can, however, be severe, and isolated fatal outcomes are known — almost always in patients with a serious underlying disease or taking other medicines that affect the liver. A separate topic is antibiotic-associated colitis: it develops with almost all antibacterial agents and ranges in severity from mild to life-threatening, so diarrhoea during treatment or after it should always be assessed from that angle and, if colitis is confirmed, the medicine is withdrawn at once.
Other warnings
- if the pathogen is known to be sensitive to amoxicillin, it is more sensible to switch to amoxicillin without clavulanic acid;
- this form is unsuitable when the pathogen's resistance is probably not due to beta-lactamases sensitive to clavulanic acid;
- in infections caused by penicillin-resistant S. pneumoniae the medicine is not used;
- in patients with impaired kidney function and at high doses seizures are possible;
- where infectious mononucleosis is suspected the medicine is avoided: in such patients a link has been noted between taking amoxicillin and a measles-like rash;
- allopurinol during treatment raises the likelihood of allergic skin reactions;
- prolonged use sometimes leads to the growth of non-susceptible organisms;
- widespread redness with pustules and fever at the start of treatment may be a sign of acute generalised exanthematous pustulosis — the medicine is then withdrawn and further use of amoxicillin is contraindicated.
Drug interactions
Penicillins and oral anticoagulants have been used together very widely without reports of interactions, but the literature describes cases of a rise in the international normalised ratio in patients on acenocoumarol or warfarin who were prescribed amoxicillin. If concomitant use is necessary, the prothrombin time or INR is monitored strictly after the start and after the end of the course, and the anticoagulant dose adjusted if needed.
Penicillins may reduce the elimination of methotrexate, which raises the risk of its toxicity. Probenecid decreases the tubular secretion of amoxicillin, so its blood concentration rises and lasts longer — this does not extend to clavulanic acid, and concomitant use is not recommended. In patients receiving mycophenolate mofetil, the concentration of the active metabolite before the next dose fell by about half; changing the dose is usually unnecessary in the absence of signs of graft dysfunction, but the patient is watched closely during the antibiotic course and shortly afterwards.
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 use in pregnant women do not indicate an increased risk of congenital malformations. At the same time, in one study in women with premature rupture of the membranes, prophylactic administration of amoxicillin with clavulanic acid was linked to an increased risk of necrotising enterocolitis in newborns. For that reason use during pregnancy is avoided unless the doctor considers it necessary.
Both substances pass into 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. Prescribing the medicine to a breastfeeding woman is possible only after the treating doctor has weighed benefit against risk.
Adverse effects
The most frequent are diarrhoea, nausea and vomiting. Nausea is usually linked to high oral doses, and the severity of gastrointestinal symptoms falls if the medicine is taken at the start of a meal.
- very common for film-coated tablets: diarrhoea;
- common: nausea, vomiting, candidiasis of the skin and mucous membranes;
- uncommon: dyspepsia, dizziness, headache, skin rash, itching, urticaria, moderate increase in AST and ALT activity;
- rare: transient leucopenia including neutropenia, thrombocytopenia, erythema multiforme;
- frequency not known, allergic: angioedema, anaphylaxis, serum sickness, allergic vasculitis;
- frequency not known, cutaneous: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis;
- frequency not known, digestive and hepatic: antibiotic-associated colitis, including pseudomembranous and haemorrhagic, hepatitis, cholestatic jaundice, black hairy tongue;
- frequency not known, other: transient agranulocytosis, haemolytic anaemia, prolongation of bleeding time and prothrombin time, seizures, aseptic meningitis, interstitial nephritis, crystalluria, overgrowth of non-susceptible bacteria.
Any cutaneous hypersensitivity reaction is grounds for stopping treatment, not for waiting it out. The same applies to diarrhoea that appears during the course or shortly afterwards: it must be assessed as possible antibiotic-associated colitis.
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 described, which in some cases led to renal failure. In patients with impaired kidney function and at high doses seizures may occur.
Precipitation of amoxicillin in urinary catheters has also been noted, mainly after intravenous administration of high doses, so catheter patency is checked regularly. The product information gives no specific measures for oral overdose — the condition is assessed by a doctor.
How to get a prescription for Augmentin® online
Augmentin® is a prescription-only medicine: the choice of antibiotic, of its form and of the length of the course depends on the likely pathogen, the severity of the infection and kidney function, and uncontrolled use promotes the growth of bacterial resistance. During the online consultation the doctor will go through the symptoms, clarify past allergic reactions to penicillins and cephalosporins and assess contraindications.
If the antibiotic is indicated, the doctor will issue an electronic prescription, choose the dose and explain how many days to take the medicine and with which symptoms — above all rash and diarrhoea — treatment must be stopped and a doctor contacted.
