Amoxicillin

Amoxicillin belongs to the Penicillin Derivative acts as an Antibiotic.

Amoxicillin is a penicillin derivative used for the treatment of infections caused by gram-positive bacteria, in particular streptococcal bacteria causing upper respiratory tract infections.

Amoxicillin rapidly and well absorbed from the gastrointestinal tract. The Bioavailability is approximately 70% (oral). The time to peak plasma concentration is about 1-2 hours (oral). Amoxicillin readily distributed in gall bladder, abdominal tissue, lungs, liver, prostate, middle ear effusions, maxillary sinus secretions, skin, fat, bone, muscle tissues, peritoneal and synovial fluids, bile, pus; poor penetration into the brain and CSF (except when meninges are inflamed). Crosses the placenta and enters breast milk (small amounts). The volume of distribution is approximately 0.3-0.4 L/kg. The Plasma protein binding is approximately 20%. Amoxicillin metabolized via hydrolysis (small amount) to inactive penicilloic acid. It is excreted via urine (60% as unchanged drug). The elimination half-life is approximately 1 hour.

Amoxicillin shows side effects like Stomach discomfort, Nausea and vomiting, Skin rash, Loose stools, Change in taste, Headache.

Amoxicillin is available in the form of Oral Tablet, Oral Capsule, Oral powder for reconstitution.

Amoxicillin is available in India, US, Canada, Malaysia, Japan, Switzerland, Germany, France, Russia, China, Italy, Spain, and Australia.

Amoxicillin belongs to the Antibiotic acts as a Penicillin Derivative.

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bactericidal action.

The Data of Onset and Duration of action of Amoxicillin is not clinically established.

The Tmax of Amoxicillin is about 1-2 hours (oral).

Amoxicillin is available in the form of Oral Tablet, Oral Capsule, Oral powder for reconstitution.

Amoxicillin Tablet, powder for reconstitution, Capsule is taken orally.

Amoxycillin is an antibiotic. It is used to treat different types of bacterial infections of the throat, lungs, ears, nose, urinary tract, and skin. Amoxycillin is also used with other medications to stop the growth of Helicobacter pylori bacteria that cause stomach ulcers.

Amoxicillin belongs to the Penicillin Derivative acts as an Antibiotic.

Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Amoxicillin is approved for use in the following clinical indications

• Actinomycosis
• Anthrax
• Asplenia, prophylaxis against bacterial infection in select high-risk patients
• Bronchiectasis
• Cervical infection in pregnancy due to Chlamydia trachomatis
• Endocarditis, prophylaxis
• Lyme disease
• Otitis media, acute
• Periodontitis, severe, plaque-associated
• Pneumonia, community acquired
• Prosthetic joint infection, chronic suppression
• Rhinosinusitis, acute bacterial
• Skin and soft tissue infection
• Streptococcal pharyngitis
• Urinary tract infection

• Actinomycosis

Oral: 500 mg 3 to 4 times daily or 1 g 3 times daily; higher doses of 4 to 6 g/day in divided doses have been utilized in case reports. Optimal duration is uncertain; some experts suggest total durations of 2 to 6 months for mild infection and 6 to 12 months for severe or extensive infection.

• Anthrax

Adult Dose

Inhalational exposure postexposure prophylaxis (PEP)

Oral: 1 g every 8 hours; duration depends on anthrax vaccine status and series completion, age, immune status, and pregnancy/breastfeeding status. For those who have not previously received anthrax vaccine, duration ranges from 42 to 60 days.

Cutaneous, without systemic involvement, treatment

Oral: 1 g every 8 hours; duration is 7 to 10 days after naturally acquired infection and 60 days following biological weapon-related event.

Infants, Children, and Adolescents

Postexposure prophylaxis, exposure to aerosolized spores

Oral: 75 mg/kg/day in divided doses every 8 hours for 60 days after exposure; maximum dose: 1,000 mg/dose.

Cutaneous, without systemic involvement

Oral: 75 mg/kg/day in divided doses every 8 hours; maximum dose: 1,000 mg/dose. Duration of therapy: 7 to 10 days for naturally acquired infection, up to 60 days for biological weapon-related exposure.

Systemic, oral step-down therapy

Oral: 75 mg/kg/day in divided doses every 8 hours as part of appropriate combination therapy to complete 60-day course; maximum dose: 1,000 mg/dose.

• Asplenia, prophylaxis against bacterial infection in select high-risk patients (off-label)

Oral: Based on expert opinion: 500 mg twice daily. Duration varies based on patient-specific factors.

• Bronchiectasis (off-label)

Treatment of pulmonary exacerbations in patients without beta-lactamase-positive H. influenzae or Pseudomonas aeruginosa

Oral: 500 mg 3 times daily or 1 g 3 times daily for up to 14 days.

Prevention of pulmonary exacerbations

Oral: 500 mg twice daily.

• Cervical infection in pregnancy due to Chlamydia trachomatis (off-label)

Oral: 500 mg 3 times daily for 7 days with test of cure ≥4 weeks after treatment.

• Endocarditis, prophylaxis (off-label)

Adult Dose

Oral: 2 g 30 to 60 minutes before procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure.

Infants, Children, and Adolescents

Oral: 50 mg/kg administered 30 to 60 minutes prior to procedure; maximum dose: 2,000 mg/dose

• Lyme disease (off-label)

Adult Dose

Erythema migrans

Oral: 500 mg 3 times daily for 14 days.

Carditis

Oral: 500 mg 3 times daily for 14 to 21 days.

Arthritis without neurologic involvement

Oral: 500 mg 3 times daily for 28 days

Infants, Children, and Adolescents

Oral: 50 mg/kg/day in divided doses every 8 hours; maximum dose: 500 mg/dose. Duration of therapy depends on clinical syndrome; treat erythema migrans and borrelial lymphocytoma for 14 days, carditis for 14 to 21 days, arthritis (initial, recurrent, or refractory) for 28 days, and acrodermatitis chronica atrophicans for 21 to 28 days.

• Otitis media, acute

Adult Dose

Oral: 500 mg every 8 hours or 875 mg every 12 hours.

Infants ≥3 months and Children

Oral: 40 to 50 mg/kg/day in divided doses every 8 to 12 hours. Maximum daily dose: 1,500 mg/day.

• Periodontitis, severe, plaque-associated (off-label)

Adult Dose

Oral: 500 mg every 8 hours in combination with metronidazole for 14 days or until clinical resolution, whichever is longer; use in addition to periodontal debridement.

Infants, Children, and Adolescents

Oral: 50 mg/kg as a single dose administered 30 to 60 minutes before dental procedure; maximum dose: 2,000 mg/dose.

• Pneumonia, community acquired

Empiric therapy, outpatient (patients without comorbidities or risk factors for antibiotic-resistant pathogens)

Oral: 1 g 3 times daily.

Oral step-down therapy following initial parenteral therapy, inpatient

Oral: 1 g 3 times daily; some experts use lower doses (500 mg 3 times daily or 875 mg twice daily) for patients without risk factors for drug-resistant S. pneumoniae (eg, age <65 years without comorbidities).

• Prosthetic joint infection, chronic suppression (off-label)

Oral: 500 mg 3 times daily; duration depends on patient-specific factors.

• Rhinosinusitis, acute bacterial

Adult Dose

Oral: 500 mg every 8 hours or 875 mg every 12 hours for 5 to 7 days.

Pediatric Dose

Standard-dose regimen

Children ≥2 years and Adolescents: Oral: 45 mg/kg/day in divided doses every 12 hours.

High-dose regimen

Children ≥2 years and Adolescents: Oral: 80 to 90 mg/kg/day in divided doses every 12 hours; maximum dose: 2,000 mg/dose.

• Skin and soft tissue infection

Erysipelas, treatment of mild infection or step-down therapy after initial parenteral therapy

Oral: 500 mg 3 times daily or 875 mg twice daily; total duration is 5 days, with extension to 14 days for slow response, severe infection, or immunosuppression.

Erysipeloid (localized cutaneous Erysipelothrix rhusiopathiae infection)

Oral: 500 mg 3 times daily for 5 to 10 days.

• Streptococcal pharyngitis

Adult Dose

Oral: 500 mg and 775 mg (extended release) twice daily or 1 g once daily for 10 days.

Children and Adolescents

Oral: 50 mg/kg/day once daily or in divided doses every 12 hours for 10 days; maximum daily dose: 1,000 mg/day.

• Urinary tract infection

Adult Dose

Asymptomatic bacteriuria (≥10⁵ CFU per mL) in pregnancy (eg, group B Streptococcus)

Oral: 500 mg every 8 hours or 875 mg every 12 hours for 4 to 7 days.

Cystitis, acute uncomplicated or acute simple cystitis due to Enterococcus spp.

Oral: 500 mg every 8 hours or 875 mg every 12 hours for 5 days.

Pediatric Dose

Prophylaxis

Infants ≤2 months:

Oral: 10 to 15 mg/kg once daily; some suggest administration in the evening.

Treatment

Infants

Oral: 50 to 100 mg/kg/day in divided doses every 12 hours.

Children and Adolescents

Oral: 50 to 100 mg/kg/day in divided doses every 8 hours; maximum dose: 500 mg/dose; for uncomplicated cystitis, may consider 30 mg/kg/day in divided doses every 8 hours.

Amoxicillin is available in various strengths as 250 mg; 500 mg; 125 mg/5 mL; 50 mg/mL; 250 mg/5 mL; 125 mg; 200 mg; 400 mg; 875 mg; 200 mg/5 mL; 400 mg/5 mL; 600 mg; 775 mg.

Amoxicillin is available in the form of Oral Tablet, Oral Capsule, Oral powder for reconstitution.

• Dosage Adjustment in Kidney Patient

CrCl ≥30 mL/minute: There are no dosage adjustments provided.

CrCl <30 mL/minute: Not recommended.

Hemodialysis, intermittent (thrice weekly): Not recommended.

Amoxicillin is contraindicated in patients with

• In patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to Amoxicillin or to other β-lactam antibiotics (e.g., penicillins and cephalosporins).

• Anaphylactic Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including amoxicillin. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with Amoxicillin, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.

• Clostridium Difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Amoxicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

• Development Of Drug-Resistant Bacteria

Prescribing Amoxicillin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

• Use In Patients with Mononucleosis

A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin should not be administered to patients with mononucleosis.

• Phenylketonurics

Amoxicillin chewable tablets contain aspartame which contains phenylalanine. Each 200 mg chewable tablet contains 1.82 mg phenylalanine; each 400 mg chewable tablet contains 3.64 mg phenylalanine. The oral suspensions of Amoxicillin do not contain phenylalanine and can be used by phenylketonurics.

Penicillin have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to a nursing woman.

Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (3 and 6 times the 3 g human dose, based on body surface area). There was no evidence of harm to the fetus due to amoxicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed.

Common

• Diarrhea, Nausea, Vulvovaginal infection, Headache, Abdominal pain, Vomiting.

Rare

• Hypersensitivity angiitis, Anaphylaxis, Angioedema.

• Probenecid

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.

• Oral Anticoagulants

Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

• Allopurinol

The concurrent administration of allopurinol and amoxicillin increases the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients.

• Oral Contraceptives

Amoxicillin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

• Other Antibacterial

Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.

The common side effects of Amoxicillin include the following

Common side effects

• Stomach discomfort, Nausea and vomiting, Skin rash, Loose stools, Change in taste, Headache.

Rare side effects

• Dizziness, Fever, Tooth discoloration.

• Pregnancy

Pregnancy Category B

Teratogenic Effects: Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (3 and 6 times the 3 g human dose, based on body surface area). There was no evidence of harm to the fetus due to amoxicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed.

• Nursing Mothers

Penicillin have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to a nursing woman.

• Pediatric Use

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of Amoxicillin should be modified in pediatric patients 12 weeks or younger (≤ 3 months).

• Geriatric Use

An analysis of clinical studies of Amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. These analyses have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

Symptoms: Nausea, vomiting, diarrhea, disturbance of fluid and electrolyte balances; crystalluria leading to renal failure (in some cases) and convulsions.

Management: Symptomatic and supportive treatment. Monitor water or electrolyte balance. Maintain adequate fluid intake and diuresis. May consider hemodialysis for removal from the circulation.

Pharmacodynamic

Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis. Amoxicillin has a long duration of action as it is usually given twice daily. Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity. Patients should be counselled regarding the risk of anaphylaxis, Clostridium difficile infections, and bacterial resistance.

Pharmacokinetics

• Absorption

Amoxicillin rapidly and well absorbed from the gastrointestinal tract. The Bioavailability is approximately 70% (oral). The time to peak plasma concentration is about 1-2 hours (oral).

• Distribution

Amoxicillin readily distributed in gall bladder, abdominal tissue, lungs, liver, prostate, middle ear effusions, maxillary sinus secretions, skin, fat, bone, muscle tissues, peritoneal and synovial fluids, bile, pus; poor penetration into the brain and CSF (except when meninges are inflamed). Crosses the placenta and enters breast milk (small amounts). The volume of distribution is approximately 0.3-0.4 L/kg. The Plasma protein binding is approximately 20%.

• Metabolism and Excretion

Amoxicillin metabolized via hydrolysis (small amount) to inactive penicilloic acid. It is excreted via urine (60% as unchanged drug). The elimination half-life is approximately 1 hour.

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• https://www.rxlist.com/amoxicillin-drug.htm#clinpharm
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