Augmentin (amoxicillin and clavulanic acid) Side Effects, Warnings and Drug Interactions

Augmentin (amoxicillin and clavulanic acid) contains a penicillin antibiotic and a beta-lactamase inhibitor used to treat infections of the middle ear (otitis media), tonsillitis, throat infections (pharyngitis), laryngitis, bronchitis, sinusitis, and pneumonia. It is also used in treating urinary tract infections, and skin infections.

Common side effects of Augmentin include abdominal discomfort, bloating, diarrhea, gas, headache, heartburn, nausea, vomiting, bloody or prolonged diarrhea, easy bruising or bleeding, reversible hepatitis, rash, and allergic reactions.

Serious side effects of Augmentin include seizures, severe allergic reactions (anaphylaxis), low platelet or red blood cell count, and pseudomembranous colitis.

Drug interactions of Augmentin include probenecid, birth control pills, and allopurinol.

Use of Augmentin in pregnant women has not been well studied. Penicillins are generally considered safe for use by pregnant women who are not allergic to penicillin. Augmentin is excreted in breast milk and may cause diarrhea in the infant.

Common side effects are:

• abdominal discomfort,
• bloating,
• diarrhea,
• gas,
• headache,
• heartburn,
• nausea, and
• vomiting.

Other important side effects include:

• bloody or prolonged diarrhea,
• easy bruising or bleeding,
• reversible hepatitis,
• rash, and
• allergic reactions.

Serious but rare reactions include seizures, severe allergic reactions (anaphylaxis), and low platelet or red blood cell count.

Antibiotics can alter the normal bacteria in the colon and encourage overgrowth of some bacteria such as Clostridium difficile which causes inflammation of the colon (pseudomembranous colitis). Patients who develop signs of pseudomembranous colitis after starting Augmentin (diarrhea, fever, abdominal pain, and possibly shock) should contact their physician immediately.

People who are allergic to the cephalosporin class of antibiotics, which are related to the penicillins, for example, cefaclor (Ceclor), cephalexin (Keflex), and cefprozil (Cefzil), may or may not be allergic to penicillins.

The following are discussed in more detail in other sections of the labeling:

• Anaphylactic reactions
• Hepatic Dysfunction
• CDAD

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most frequently reported adverse reactions were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy because of drug related adverse reactions. The overall incidence of adverse reactions, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported adverse reactions (<1%) include: Abdominal discomfort, flatulence, and headache.

In pediatric patients (aged 2 months to 12 years), 1 US/Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12 hours) of Augmentin for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of Augmentin for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse reactions seen were comparable to that noted above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following have been identified during postmarketing use of Augmentin. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Augmentin.

Gastrointestinal

Indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

Hypersensitivity Reactions

Pruritus, angioedema, serum sickness–like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens Johnson syndrome, acute generalized exanthematouspustulosis, hypersensitivity vasculitis, and cases of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported.

Liver

Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with Augmentin. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported.

Renal

Interstitial nephritis, hematuria, and crystalluria have been reported.

Hemic And Lymphatic Systems

Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosishave been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Thrombocytosis was noted in less than 1% of the patients treated with Augmentin. There have been reports of increased prothrombin time in patients receiving Augmentin and anticoagulant therapy concomitantly.

Central Nervous System

Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported.

Miscellaneous

Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Probenecid

Probenecid decreases the renal tubular secretion of amoxicillin but does not delay renal excretion of clavulanic acid. Concurrent use with Augmentin may result in increased and prolonged blood concentrations of amoxicillin. Coadministration of probenecid is not recommended.

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 with Augmentin. 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

Augmentin may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Effects On Laboratory Tests

High urine concentrations of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST^®, Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with Augmentin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

Following administration of amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.