Amoxicillin is a semi synthetic broad spectrum, acid stable, penicillinase-susceptible penicillin. It acts by inhibition of transpeptidase, the enzyme responsible for the final stage of bacterial cell wall mucopeptide synthesis. It thus exerts its effect on dividing bacteria.
It is active against certain Gram-positive and Gram-negative organisms such as Haemophilis influenzae, Escherichia coli, Proteus mirabilis, Neisseria gonorrhoea, Neisseria meningitis, Streptococcus spp. D. pneumoniae and non-penicillinase producing Staphylococci. Listeria monocytogenes, Salmonellae, Bordetella pertussis and Brucella spp, are also sensitive.
It is inactivated by penicillnase and therefore not active against Pseudomonas species, Klebsiella spp, Enterobacter spp, indole-positive Proteus spp, Serratia marcescens, Citrobacter spp, penicillinase-producing N.gonorrhoeae and penicillinase-producing H.influenzae.
Complete cross-resistance between ampicillin and amoxicillin has been reported. Resistance mechanisms reported are production of penicillinase, altered penicillin binding proteins.
The minimum inhibitory concentrations range from 0.01 to 5µg per ml.
Amoxicillin is stable in the presence of gastric acid and rapidly absorbed when given orally. Peak plasma concentrations of about 5µg per ml are observed in 2 hours after a dose of 250mg. Doubling the dose double the peak concentrations. The presence of food in the stomach does not diminish absorption significantly.
It diffuses rapidly into most body tissues and fluids except brain and spinal fluid unless when meninges are inflamed. Up to 20% is bound to plasma proteins in the circulation.
Plasma half-life of about one hour have been reported. It penetrates well into purulent and mucoid sputum and low concentrations have been found in ocular fluid. It diffuses across the placenta and a little appears in breast milk. About 60% of an oral dose is excreted unchanged in the urine in 6 hours by glomerular filtration and tubular secretion. A further 15% is excreted in urine as Penicilloic acid.
High concentrations have been reported in bile.
Concurrent administration of probenecid retards excretion thus prolonging its therapeutic effect.
Amoxicillin is indicated for the treatment of the following infections due to susceptible strains of sensitive organisms:
- Skin and skin structure: Non-penicillinase producing Staphylococcus, Streptococcus, E.coli
- Respiratory (acute and chronic): H.influenzae, Streptococcus, S.pneumoniae, Non-penicillinase producing Staphylococcus, E.coli.
- Genitourinary tract (complicated and uncomplicated, acute and chronic): E.coli, P. mirabilis and S.faecalis
- Gonorrhea: N.gonorrhoeae (non-penicillinase producing)
Upper respiratory tract infections, genito-urinary tract infections, skin and soft tissue infections:
Adults: 250mg every 8 hours
Children (under 20kg): 20mg/kg/day in equally divided doses every 8 hours.
In severe infections or those caused by less susceptible organisms, the dose may be doubled.
Lower respiratory tract infections:
Adults: 500mg every 8 hours
Children (under 20kg): 40mg/kg/day in equally divided doses every 8 hours.
Adults: 3g as a single dose
Acute, uncomplicated lower urinary tract infections in non-pregnant adult female:
Adults: 3g as a single dose.
Children weighing more than 20kg should be dosed according to adult recommendations. Note that two 5ml spoonfuls of the reconstituted suspension will give 250mg dose.
It may be necessary to reduce the total daily dosage in renal impairment. In patients receiving peritoneal dialysis it may be necessary to use a higher dosage regimen.
Treatment should be continued for a minimum of 48 to 72 hours beyond the time the patient becomes asymptomatic. In stubborn urinary infections therapy may be required for several weeks.
Amoxicillin should not be administered to patients with a history of allergic reaction to penicillins or cephalosporins.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins.
Before commencing therapy with any penicillin careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.
If an allergic reaction occurs, amoxicillin therapy should be discontinued and appropriate therapy instituted.
Serious anaphylactic reactions require immediate emergency treatment with Adrenalin Oxygen, intravenous steroids and airway management, including intubation should also be administered, as indicated.
As with any potent drug, periodic assessment of renal, hepatic and haematopoietic function should be made during prolonged therapy.
Amoxicillin should be given with caution to patients with infectious mononucleosis or lymphatic leukemia, since they are especially susceptible to erythematous rashes.
Possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur the drug should be discontinued and/or appropriate therapy instituted.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this in patients who develop diarrhoea or colitis in association with antibiotic use. This may occur up to several weeks after cessation of antibiotic therapy.
Mild cases usually respond to drug discontinuation and moderate to severe cases may require therapy with susceptible antibiotic agent effective against Clostridium difficile. Fluids, electrolytes and protein replacement should also be provided when indicated. Drugs which delay peristalsis e.g. opiates and diphenoxylate with atropine may prolong or worsen the condition and should not be used.
Adequate fluid intake and urinary outputs should be maintained in patients receiving high doses of amoxicillin.
Use in pregnancy and lactation
The limited number of reported cases of use in human pregnancy have shown no evidence of untoward effect. The use of amoxicillin in pregnancy should however be reserved for cases considered essential by the clinician. Amoxicillin is excreted in milk and should be used with caution when administering to a nursing woman.
Drug/ laboratory test interactions
Oral amoxicillin administration may interfere with urine glucose testing kits.
Administration of ampicillin to pregnant women has shown a transient decrease in plasma concentration of total conjugated oestriol-glucoronide, conjugated oestrone and oestradiol. The same may occur with amoxicillin.
Probenecid decreases renal tubular secretion of amoxicillin resulting in increased and prolonged blood levels of concurrently administered amoxicillin.
Concurrent administration with allopurinol increases the incidence of rashes in patients.
Amoxicillin may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
As with other penicillins, adverse reactions will mainly be due to penicillin hypersensitivity. These include erythematous maculopapular rash, pruritus, urticaria. Rarely skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and bullous exfoliative dermatitis and acute generalised exanthematous pustulosis have been reported. Severe allergic reactions including angioneurotic oedema, anaphylaxis, serum sickness, hypersensitivity vasculitis and interstitial nephritis have been reported rarely. When such reactions occur use should be discontinued.
Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water/electrolyte imbalance should be treated symptomatically. During administration of high doses adequate fluid intake and urinary output must be maintained to minimize possibility of amoxicillin crystalluria. Amoxicillin can be removed from the circulation by haemodialysis.