Amoxicillin

Therapeutic Class

Semisynthetic ampicillin derivative

Indications

Treatment of infections of the ear, nose, throat, genitourinary tract (GU), skin and skin structure (SSSI), lower respiratory tract (LRTI); and acute, uncomplicated gonorrhea (anogenital and urethral infections) due to susceptible (β-lactamase negative) strains of microorganisms. Combination therapy for Helicobacter pylori eradication to reduce the risk of duodenal ulcer recurrence.

Oral
Biliary tract infections
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Endocarditis
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Gonorrhoea
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Otitis media
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Pneumonia
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Actinomycosis
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Bronchitis
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Typhoid and paratyphoid fever
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Gastroenteritis
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Lyme disease
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Mouth infections
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Spleen disorders
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Urinary tract infections
Adult: 250-500 mg every 8 hr or 500-875 mg every 12 hr.
Child: ≤10 yr: 125-250 mg every 8 hr; <40 kg: 20-40 mg/kg daily in divided doses every 8 hr. Max dose: Infant <3 mth: 30 mg/kg daily in divided doses every 12 hr.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 every 12 hr.
<10	250-500 every 24 hr.

Oral
Uncomplicated gonorrhoea
Adult: 3 g as a single dose with probenecid 1 g.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 mg every 12 hr.
<10	250-500 mg every 24 hr.

Oral
Dental abscesses
Adult: Initially, 3 g, repeat once after 8 hr.
Renal impairment: Dose reduction may be required.
Oral
Uncomplicated acute urinary tract infections
Adult: Initially, 3 g, repeat once after 10-12 hr.
Renal impairment: Dose reduction may be required.
Oral
Prophylaxis of endocarditis
Adult: 2 or 3 g as a single dose, 1 hr before dental procedure.
Child: Single dose of 50 mg/kg. To be taken 1 hr prior to dental procedure. Max: 2 g/dose.
Renal impairment: Dose reduction may be required.
Oral
Severe or recurrent respiratory tract infections
Adult: 3 g bid.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 mg every 12 hr.
<10	250-500 mg every 24 hr.

Oral
Otitis media
Child: 3-10 yr: 750 mg bid for 2 days.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 mg every 12 hr.
<10	250-500 mg every 24 hr.

Oral
H.pylori infection
Adult: 0.75 or 1 g bid or 500 mg tid in combination with either metronidazole or clarithromycin and a bismuth compound or an antisecretory drug.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 mg every 12 hr.
<10	250-500 mg every 24 hr.

Parenteral
Susceptible infections
Adult: 500 mg every 8 hr via IM or slow IV inj. Severe infections: May increase to 1 g every 6 hr via slow IV inj over 3-4 minutes or infuse over 30-60 minutes.
Child: ≤10 yr: 50-100 mg/kg daily in divided doses.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 mg every 12 hr.
<10	250-500 mg every 24 hr.

Intravenous
Listerial meningitis
Adult: 2 g every 4 hr for 10-14 days via IV infusion, to be used with other antibiotics.
Renal impairment: Patients on haemodialysis should receive 250-500 mg every 24 hr and an additional dose during and after each dialysis session.

CrCl (ml/min)	Dosage Recommendation
10-30	250-500 mg every 12 hr.
<10	250-500 mg every 24 hr.

Contraindications

Hypersensitivity

Warnings / Precautions

Serious, occasionally fatal, hypersensitivity (anaphylactic) reactions reported with penicillin (PCN) therapy. Clostridium difficile-associated diarrhea (CDAD) reported. Avoid use with mononucleosis; erythematous skin rash may develop in these patients. May result in bacterial resistance with prolonged use or use in the absence of a proven/suspected bacterial infection or a prophylactic indication; d/c and institute appropriate measures if superinfection develops. May result in false-positive urinary glucose tests; glucose tests based on enzymatic glucose oxidase reactions may be used. May cause a transient decrease in plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol in pregnancy. Monitor renal function in elderly. Caution in elderly.

Adverse Reactions

Hyperactivity, agitation, insomnia, dizziness; maculopapular rash, exfoliative dermatitis, urticaria, hypersensitivity vasculitis; diarrhoea, nausea, vomiting; anaemia, thrombocytopenia, leucopenia, agranulocytosis, black hairy tongue,pseudomembranous colitis,tooth discoloration.
Potentially Fatal: Neuromuscular hypersensitivity; pseudomembranous colitis.

Drug Interactions

Increased levels with disulfiram and probenecid. Decreased effects with tetracyclines and chloramphenicol.
Potentially Fatal: Increase effects of oral Anticoagulants.

Amoxicillin may also interact with the following groups of drugs:
Allopurinol (gout treatment)
Birth control pills
Cancer treatment (methotrexate)
Typhoid vaccine

Mechanism of Actions

This drug acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell walls of both Gram-positive and Gram-negative bacteria, thus inhibiting cell wall biosynthesis resulting in bacterial lysis.

Absorption: Rapidly and completely absorbed from the GI tract with peak plasma concentrations after 1-2 hr (oral). Not inactivated by gastric acid and presence of food does not impair absorption.

Distribution: Widely distributed, CSF (small concentrations except when the meninges are inflamed), bile (high concentrations); crosses the placenta and enters the breast milk (small amounts). Protein-binding: 20%.
Metabolism: Converted to a limited extent to penicilloic acid.
Excretion: Via the urine within 6 hr by glomerular filtration and tubular secretion (as penicilloic acid and 60% unchanged drug); via the faeces. May be removed by haemodialysis; 1-1.5 hr (elimination half-life).

Assesment

Assess for history of allergic reaction to PCNs, cephalosporins, or other allergens, mononucleosis, renal/hepatic function, pregnancy/nursing status, and possible drug interactio

Monitoring

Monitor for serious anaphylactic reactions, erythematous skin rash, development of drug-resistant bacteria or superinfection with fungal or bacterial pathogens, signs/symptoms of CDAD (may range from mild diarrhea to fatal colitis). Periodically monitor renal (especially in elderly) and hepatic function.

Patient Counselling

Inform drug treats bacterial, not viral, infections. Instruct to take exactly ud; skipping doses or not completing full course may decrease effectiveness and increase likelihood that bacteria will develop resistance. Inform about potential benefits/risks; notify physician if watery/bloody stool (with/without stomach cramps and fever) develops (may occur as late as 2 months after treatment). Advise patients that drug may cause allergic reactions.

Administration

May be taken with or without food. (May be taken w/ meals for better absorption & to reduce GI discomfort.)

Intravenous: Store at 20-25°C.

Parenteral: Store at 20-25°C

Pregnancy Category

B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.