Amoxicillin

Adverse effects

Adverse effects are similar to those for other β-lactam antibiotics, including nausea, vomiting, rashes, and antibiotic-associated colitis. Diarrhea (loose bowel movements) may also occur.

Rarer adverse effects include mental and behavioral changes, lightheadedness, insomnia, hyperactivity, agitation, confusion, anxiety, sensitivity to lights and sounds, and unclear thinking. Immediate medical care is required upon the first signs of these adverse effects. Similarly to other penicillins, amoxicillin has been associated with an increased risk of seizures. Amoxicillin-induced neurotoxicity has been especially associated with plasma concentrations of greater than 110 mg/L.

The onset of an allergic reaction to amoxicillin can be very sudden and intense; emergency medical attention must be sought as quickly as possible. The initial phase of such a reaction often starts with a change in mental state; a skin rash with intense itching (often beginning in the fingertips and around the groin area and rapidly spreading); and sensations of fever, nausea, and vomiting. Any other symptoms that seem even remotely suspicious must be taken very seriously. However, more mild allergy symptoms, such as a rash, can occur at any time during treatment, even up to a week after treatment has ceased. For some people allergic to amoxicillin, the adverse effects can be fatal due to anaphylaxis.

Use of the amoxicillin/clavulanic acid combination for more than one week has caused a drug-induced immunoallergic-type hepatitis in some patients. Young children having ingested acute overdoses of amoxicillin manifested lethargy, vomiting, and renal dysfunction.

There is poor reporting of adverse effects of amoxicillin from clinical trials. For this reason, the severity and frequency of adverse effects from amoxicillin are probably higher than reported in clinical trials.

Nonallergic rash

Between 3 and 10% of children taking amoxicillin (or ampicillin) show a late-developing (>72 hours after beginning medication and having never taken penicillin-like medication previously) rash, which is sometimes referred to as the "amoxicillin rash". The rash can also occur in adults and may rarely be a component of the DRESS syndrome.

The rash is described as maculopapular or morbilliform (measles-like; therefore, in medical literature, it is called "amoxicillin-induced morbilliform rash".). It starts on the trunk and can spread from there. This rash is unlikely to be a true allergic reaction and is not a contraindication for future amoxicillin usage, nor should the current regimen necessarily be stopped. However, this common amoxicillin rash and a dangerous allergic reaction cannot easily be distinguished by inexperienced persons, so a healthcare professional is often required to distinguish between the two.

A nonallergic amoxicillin rash may also be an indicator of infectious mononucleosis. Some studies indicate about 80–90% of patients with acute Epstein–Barr virus infection treated with amoxicillin or ampicillin develop such a rash.

Interactions

Amoxicillin may interact with these drugs:

• Anticoagulants (dabigatran, warfarin).
• Methotrexate (chemotherapy and immunosuppressant).
• Typhoid, Cholera and BCG vaccines.
• Probenecid reduces renal excretion and increases blood levels of amoxicillin.
• Oral contraceptives potentially become less effective.
• Allopurinol (gout treatment).
• Mycophenolate (immunosuppressant)

When given intravenously or intramuscularly:

• It should not be mixed with blood products, or proteinaceous fluids (including protein hydrolysates) or with intravenous lipid emulsions
• aminoglycoside should be injected at a separate site from amoxicillin if the patient is prescribed both medications at the same time. Neither drug should be mixed in a syringe. Neither should they be mixed in an intravenous fluid container or giving set because of loss of activity of the aminoglycoside under these conditions.
• ciprofloxacin should not be mixed with amoxicillin.
• Infusions containing dextran or bicarbonate should not be mixed with amoxicillin solutions.

Pharmacology

Amoxicillin (α-amino-p-hydroxybenzyl penicillin) is a semisynthetic derivative of penicillin with a structure similar to ampicillin but with better absorption when taken by mouth, thus yielding higher concentrations in blood and in urine. Amoxicillin diffuses easily into tissues and body fluids. It will cross the placenta and is excreted into breastmilk in small quantities. It is metabolized by the liver and excreted into the urine. It has an onset of 30 minutes and a half-life of 3.7 hours in newborns and 1.4 hours in adults.

Amoxicillin attaches to the cell wall of susceptible bacteria and results in their death. It is effective against streptococci, pneumococci, enterococci, Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Neisseria meningitidis, Neisseria gonorrhoeae, Shigella, Chlamydia trachomatis, Salmonella, Borrelia burgdorferi, and Helicobacter pylori. As a derivative of ampicillin, amoxicillin is a member of the penicillin family and, like penicillins, is a β-lactam antibiotic. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the bacterial cell wall. It has two ionizable groups in the physiological range (the amino group in alpha-position to the amide carbonyl group and the carboxyl group).

Chemistry

Amoxicillin is a β-lactam and aminopenicillin antibiotic in terms of chemical structure. It is structurally related to ampicillin.

The experimental log P of amoxicillin is 0.87. It is described as an "ambiphilic"—between hydrophilic and lipophilic—antibiotic.

History

Amoxicillin was one of several semisynthetic derivatives of 6-aminopenicillanic acid (6-APA) developed by the Beecham Group in the 1960s. It was invented by Anthony Alfred Walter Long and John Herbert Charles Nayler, two British scientists. It became available in 1972 and was the second aminopenicillin to reach the market (after ampicillin in 1961). Co-amoxiclav became available in 1981.

Society and culture

Economics

Amoxicillin is relatively inexpensive. In 2022, a survey of eight generic antibiotics commonly prescribed in the United States found their average cost to be about $42.67, while amoxicillin was sold for $12.14 on average.

Modes of delivery

Pharmaceutical manufacturers make amoxicillin in trihydrate form, for oral use available as capsules, regular, chewable and dispersible tablets, syrup and pediatric suspension for oral use, and as the sodium salt for intravenous administration.

An extended-release is available. The intravenous form of amoxicillin is not sold in the United States. When an intravenous aminopenicillin is required in the United States, ampicillin is typically used. When there is an adequate response to ampicillin, the course of antibiotic therapy may often be completed with oral amoxicillin.

Research with mice indicated successful delivery using intraperitoneally injected amoxicillin-bearing microparticles.

Names

Amoxicillin is the international nonproprietary name (INN), British Approved Name (BAN), Australian Approved Name (AAN), and United States Adopted Name (USAN), while amoxycillin is the former AAN.

Amoxicillin is one of the semisynthetic penicillins discovered by the former pharmaceutical company Beecham Group. The patent for amoxicillin has expired, thus amoxicillin and co-amoxiclav preparations are marketed under various brand names across the world.

Veterinary uses

Amoxicillin is also sometimes used as an antibiotic for animals. The use of amoxicillin for animals intended for human consumption (chickens, cattle, and swine for example) has been approved.