Augmentin Drug Information

Important Administration Instructions AUGMENTIN may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when AUGMENTIN is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, AUGMENTIN should be taken at the start of a meal.

Adult Patients

See dosing regimens of AUGMENTIN (based on the amoxicillin component) provided in Table 1 below. The every 12 hour regimen is recommended as it is associated with significantly less diarrhea. The Amoxicillin and Clavulanate Potassium 200 mg/28.5 mg per 5 mL and Amoxicillin and Clavulanate Potassium 400 mg/57 mg per 5 mL for oral suspension and Amoxicillin and Clavulanate Potassium 200 mg/28.5 mg and Amoxicillin and Clavulanate Potassium 400 mg/57 mg chewable tablets contain aspartame and should not be used by phenylketonurics.

The 250 mg/125 mg tablet of AUGMENTIN should NOT be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250 mg/125 mg tablet of AUGMENTIN versus the 250 mg/62.5 mg chewable tablet of AUGMENTIN.

Patients with Renal Impairment Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate (GFR) of less than 30 mL/min should NOT receive the 875 mg dose (based on the amoxicillin component) of AUGMENTIN. See dosing regimens in patients with severe renal impairment provided in Table 4.

Table 4. Dosing Regimens of AUGMENTIN in Patients with Severe Renal Impairment

Directions for Mixing Amoxicillin and Clavulanate Potassium for Oral Suspension Prepare AUGMENTIN for oral suspension at time of dispensing as follows: Tap bottle until all powder flows freely. Measure a total (see Table 5 below for total amount of water for reconstitution) OF WATER. Add approximately 2/3 of the water to the powder.

Replace cap and shake VIGOROUSLY. Add remaining water. Table 5: Amount of Water for Mixing AUGMENTIN for Oral Suspension Shake oral suspension well before using.

Reconstituted suspension must be stored under refrigeration and discarded after 10 days. Some color change is normal during dosing period.

Switching between Dosage Forms and between Strengths AUGMENTIN 250 mg/125 mg Tablet is NOT Substitutable with AUGMENTIN 250 mg/62.5 mg Chewable Tablet The 250 mg/125 mg tablet of AUGMENTIN and the 250 mg/62.5 mg chewable tablet of AUGMENTIN should NOT be substituted for each other and the 250 mg/125 mg tablet of AUGMENTIN should NOT be used in pediatric patients weighing less than 40 kg. The 250 mg tablet of AUGMENTIN and the 250 mg chewable tablet of AUGMENTIN do not contain the same amount of clavulanic acid. Two AUGMENTIN 250 mg/125 mg Tablets are NOT Substitutable with One 500 mg/125 mg AUGMENTIN Tablet Two 250 mg/125 mg tablets of AUGMENTIN should NOT be substituted for one 500 mg/125 mg tablet of AUGMENTIN.

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. 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 (less than 1%) include: Abdominal discomfort, flatulence, and headache. 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 Amoxicillin and Clavulanate Potassium.

Gastrointestinal: Drug-induced enterocolitis syndrome (DIES), indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. Immune: Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis.

Skin and Appendages: Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA dermatosis. 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 Amoxicillin and Clavulanate Potassium. 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, 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 agranulocytosis have 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, aseptic meningitis, 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. Co-administration of probenecid is not recommended.

Oral Anticoagulants

Abnormal prolongation of prothrombin time (increased international normalized ratio ) 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.

Pregnancy Teratogenic Effects: Pregnancy Category B. Reproduction studies performed in pregnant rats and mice given AUGMENTIN (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day revealed no evidence of harm to the fetus due to AUGMENTIN. There are, however, no adequate and well-controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Pediatric Use The safety and effectiveness of AUGMENTIN for Oral Suspension and Chewable Tablets have been established in pediatric patients. Use of AUGMENTIN in pediatric patients is supported by evidence from studies of AUGMENTIN Tablets in adults with additional data from a study of AUGMENTIN for Oral Suspension in pediatric patients aged 2 months to 12 years with acute otitis media. Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed; clavulanate elimination is unaltered in this age group.

Dosing of Amoxicillin and Clavulanate Potassium should be modified in pediatric patients aged less than 12 weeks (less than 3 months).

Serious Hypersensitivity Reactions AUGMENTIN is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta‑lactam antibacterial drugs (e.g., penicillins and cephalosporins).

Cholestatic Jaundice/Hepatic Dysfunction AUGMENTIN is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with AUGMENTIN.

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms 1. Interstitial nephritis resulting in oliguric renal failure has been reported in patients after overdosage with amoxicillin and clavulanate potassium.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin and clavulanate potassium overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin and clavulanate potassium crystalluria. Renal impairment appears to be reversible with cessation of drug administration.

High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin and clavulanate potassium. Amoxicillin and clavulanate potassium may be removed from circulation by hemodialysis.