|Pharmacology: Amoxicillin, a semisynthetic penicillin of the aminopenicillin group, is bactericidal against sensitive organisms. It acts through the inhibition of mucopeptide synthesis in the bacterial cell wall.
The spectrum of activity of amoxicillin includes H. influenzae, E. coli, P. mirabilis, Salmonella and some Shigella species while also retaining activity against penicillin-sensitive gram-positive bacteria (see Penicillin G/Penicillin V, General Monograph). However, many Enterobacteriaceae, H. Influenzae, Salmonella and Shigella species are resistant to amoxicillin because these organisms produce beta-lactamase. Amoxicillin has the same invitro activity as ampicillin but has slightly better activity against E. faecalis, E. coli and Salmonella species. Combining amoxicillin with a B-lactamase inhibitor such as clavulanic acid effectively broadens its spectrum of activity to include many strains of B-lactamase-producing bacteria.
Pharmacokinetics: Amoxicillin is rapidly absorbed by the gastrointestinal tract after oral administration and is stable in the presence of gastric acid. Peak serum concentrations are usually attained within 1 to 2 hours following oral administration and are generally 2 to 2.5 times greater than those obtained with an equivalent dose of oral ampicillin. Amoxicillin diffuses readily into most body tissue and fluids, with the exception of the cerebrospinal fluid, although higher concentrations of the drug may be attained in patients with inflamed meninges. Amoxicillin is not highly protein bound. Its elimination half-life ranges from 0.7 to 1.4 hours in patients with normal renal function. Amoxicillin is partially metabolized to microbiologically inactive metabolites and both are then rapidly excreted in urine. Small amounts of the compounds are excreted in feces and bile.
Indications: Amoxicillin is indicated for the treatment of: bronchitis, acute otitis media, pharyngitis, pneumonia, sinusitis and urinary tract infections caused by susceptible organisms; chlamydial infections in pregnant women who cannot tolerate erythromycin; gastritis and peptic ulcer disease caused by H. pylori (in combination with metronidazole and bismuth subsalicylate); Lyme disease caused by B. burgdorferi; typhoid fever caused by S. typhi.
Amoxicillin is recommended for prophylaxis against endocarditis in patients undergoing certain dental, oral, upper respiratory tract or esophageal procedures, who have any of the following conditions: congenital cardiac malformations, rheumatic and other acquired valvular lesions, prosthetic heart valves, previous history of bacterial endocarditis, hypertrophic cardiomyopathy, surgically constructed systemic pulmonary shunts or conduits, mitral valve prolapse with valvular regurgitation or mitral valve prolapse without valvular regurgitation but associated with thickening and/or redundancy of the valve leaflets. Amoxicillin is also included in prophylactic regimens for certain genitourinary and non-esophageal gastrointestinal procedures.
tag_ContraindicationsContraindications: History of allergic reaction to penicillins.
Warnings: Serious and occasionally fatal hypersensitivity 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. These reactions are more apt to occur in individuals with a history of sensitivity to multiple allergens.
Careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, other b-lactam antibiotics or other allergens. The incidence of cross-sensitivity between penicillins and other B-lactam antibiotics such as cephalosporins or carbapenems is not precisely known. The possibility of cross-sensitivity must be considered in all patients reporting an allergic reaction to a B-lactam antibiotic.
If an allergic reaction occurs, discontinue amoxicillin and institute appropriate therapy. Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, i.v. corticosteroids and airway management, including intubation, as indicated.
Precautions: If suprainfections with fungal or bacterial pathogens occur (usually involving Enterobacter, Candida or Pseudomonas), amoxicillin should be discontinued and appropriate therapy instituted.
Because amoxicillin is excreted mostly by the kidney, dosage reduction is important in patients with a creatinine clearance less than 0.5 mL/s and it should be reduced in proportion to the degree of loss of renal function (see Dosage).
Amoxicillin should not be used if infectious mononucleosis is suspected due to an increased incidence of maculopapular rash (see Adverse Effects).
Drug Interactions : Concurrent use of probenecid or other inhibitors of the renal acid secretory system decrease renal secretion of amoxicillin and increase and prolong blood amoxicillin concentrations. Allopurinol may increase the possibility of skin rash. Tetracyclines, chloramphenicol and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin.
Whether amoxicillin decreases the effectiveness of oral contraceptives is controversial. Some clinicians recommend adding an alternative method of contraception for the duration of the cycle when amoxicillin is taken.
Pregnancy: Amoxicillin readily crosses the placenta. Amoxicillin's safety in the treatment of infections during pregnancy has not yet been established. However harmful effects have not been documented. The benefits of amoxicillin therapy must be weighed against its possible hazards to the mother and child.
Lactation: Amoxicillin appears in milk in low concentrations. See Drugs in Lactation in the Clin-Info Section for more information.
Adverse Effects: Gastrointestinal: nausea, vomiting, diarrhea, anorexia, epigastric distress and gastritis. Black hairy tongue, glossitis and stomatitis have also been noted. Diarrhea is generally less frequent than with ampicillin. Antibiotic-associated pseudomembranous colitis has been reported. Severe abdominal pain and bloody diarrhea associated with acute, transient enterocolitis, but without evidence of pseudomembranous colitis, has also been reported.
Renal: Acute interstitial nephritis has been reported rarely.
Hematologic: Anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, neutropenia and agranulocytosis have been reported during therapy with amoxicillin. These reactions are usually reversible on discontinuation of therapy.
Hypersensitivity: A morbilliform, erythematous, urticarial rash, similar to those reported with other penicillins, may occur. In addition, aminopenicillins may cause an erythematous, maculopapular rash which may or may not be immunologically mediated. The overall incidence of rash in patients taking amoxicillin is 1.4 to 10%, with greater than 65% being of the maculopapular type.
Hepatic: Moderate rise in serum aspartate transferase (AST), alkaline phosphatase and lactic dehydrogenase has been noted, but the significance of these findings is unknown.
tag_OverdoseOverdose: Symptoms: Serious toxicity is unlikely following large doses of amoxicillin. Acute ingestion of large doses of amoxicillin may cause nausea, vomiting, diarrhea and abdominal pain. Acute oliguric renal failure and hematuria may occur following large doses.
Treatment: Empty stomach only if a very large amount has been ingested and if the patient is conscious and not experiencing seizures. Activated charcoal may be administered to decrease further absorption. Monitor fluid and electrolyte status and renal function in patients with severe vomiting and/or diarrhea.
Dosage: Amoxicillin is stable in the presence of gastric acid and may be given without regard to meals. For upper respiratory tract infections, including otitis media, due to susceptible strains of streptococci, nonpenicillinase producing staphylococci or H. influenzae, genitourinary tract infections caused by susceptible strains of E. coli, P. mirabilis or E. faecalis, or skin and soft tissue infections involving susceptible streptococci, nonpenicillinase-producing staphylococci, or E. coli: Adults and children >20 kg: 250 mg every 8 hours. Children <20 kg: 20 mg/kg/day in divided doses every 8 hours, not to exceed the recommended adult dose.
For severe infections or those caused by less susceptible organisms: 500 mg every 8 hours for adults and children >20 kg; 40 mg/kg/day in divided doses every 8 hours for children <20 kg, not to exceed the recommended adult dosage.
For lower respiratory tract infections due to streptococci, nonpenicillinase-producing staphylococci or H. influenzae: Adults and children>20 kg: 500 mg every 8 hours. Children <20 kg: 40 mg/kg/day in divided doses every 8 hours, not to exceed the recommended adult dosage.
Amoxicillin is not included in the Canadian guidelines for treatment of N. gonorrhoeae (Can Commun Dis Rep 1995; 21 Suppl 4). However, some clinicians recommend it for acute, uncomplicated gonorrhea when the infecting strain has been tested and found to be susceptible: Adults and children >45 kg: 3 g as a single dose; 1 g of oral probenecid should be administered concomitantly, as well as appropriate therapy (doxycycline or tetracycline) for presumptive or proven infection with C. trachomatis. Children <45 kg: a single 50 mg/kg dose of amoxicillin (maximum 3 g) given with a single 25 mg/kg (up to 1 g) dose of probenecid. However, probenecid is not recommended in children under 2 years of age. Appropriate therapy of presumptive or proven infection with C. trachomatis should be included as well.
For prophylaxis of bacterial endocarditis in selected patients: Adults: 2 g 1 hour before the procedure. Children: 50 mg/kg 1 hour before the procedure, to a maximum of 2 g. For more information, see Endocarditis Prophylaxis in the Clin-Info section.
In chronic urinary tract infections, frequent bacteriologic and clinical appraisals are necessary. Do not use doses smaller than those recommended above for the treatment of genitourinary tract infections. In persistent infections, therapy may be required for several weeks, sometimes at higher doses than recommended above. Concurrent bacteriologic sensitivity monitoring is recommended. It may be necessary to continue clinical and/or bacteriologic follow up for several months after cessation of therapy.
For treatment of H. pylori infection in adults with associated peptic ulcer disease, amoxicillin 1 g twice daily is given for 7 days with a proton pump inhibitor plus clarithromycin.
For most infections, except gonorrhea, continue treatment for a minimum of 48 to 72 hours beyond the time the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Although natural penicillins are generally preferred, if amoxicillin is used in the treatment of infections caused by group A beta-hemolytic streptococci, at least 10 days of treatment is recommended to prevent acute rheumatic fever or glomerulonephritis.
Dosage in Renal Failure: ClCr 0.83 to 0.17 mL/s: increase dosing interval from 8 hours to 12 hours; ClCr <0.17 mL/s: increase dosing interval to 12 to 24 hours.
Hemodialysis: 250 to 500 mg orally every 16 to 24 hours. An additional 250 mg may be given after each dialysis period.