Amoxicillin plus clavulanate

difficile , and surgical evaluation should be instituted as clinically indicated.

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. 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.

The following are discussed in more detail in other sections of the labeling: Anaphylactic reactions [see Warnings and Precautions ( 5.1)] CDAD [see Warnings and Precautions ( 5.2)] Clinical Trials 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 common adverse reactions (> 1%) observed in clinical trials of Amoxicillin capsules, tablets or oral suspension were diarrhea, rash, vomiting, and nausea. Triple therapy : The most frequently reported adverse events for patients who received triple therapy (Amoxicillin/clarithromycin/ lansoprazole) were diarrhea (7%), headache (6%), and taste perversion (5%). Dual

therapy

For more information on adverse reactions with clarithromycin or lansoprazole, refer to the Adverse Reactions section of their package inserts. In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of penicillins.

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.

Infections and Infestations: Mucocutaneous candidiasis.

Gastrointestinal: Black hairy tongue, and hemorrhagic/pseudomembranous colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions ( 5.2)] . Hypersensitivity Reactions: Anaphylaxis [see Warnings and Precautions ( 5.1)] .

Serum sickness–like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative

dermatitis

Liver: A moderate rise in AST and/or ALT has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported.

Renal: Crystalluria has been reported [see Overdosage ( 10)] . 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.

Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported. Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported.

Discoloration was reduced or eliminated with brushing or dental cleaning in most cases. Probenecid decreases the renal tubular secretion of Amoxicillin. Concurrent use of Amoxicillin and probenecid may result in increased and prolonged blood levels of Amoxicillin. 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.

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.

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

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.

High urine concentrations of ampicillin 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 Amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX®) be used.

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

It is not known whether use of Amoxicillin in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood of the necessity for an obstetrical intervention.

Penicillins 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. 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).

[See Dosage and Administration ( 2.2).] 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. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR 1 .

Crystalluria, in some cases leading to renal failure, has also been reported after Amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of Amoxicillin 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. Amoxicillin may be removed from circulation by hemodialysis. Formulations of Amoxicillin contain Amoxicillin, a semisynthetic antibiotic, an analog of ampicillin, with a broad spectrum of bactericidal activity against many Gram-positive and Gram-negative microorganisms. Chemically, it is (2 S ,5 R ,6 R )-6-[(R)-(-)-2-amino-2-( p -hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4- thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate.

It may be represented structurally as: The Amoxicillin molecular formula is C 16 H 19 N 3 O 5 S • 3H 2 O, and the molecular weight is 419.45.

Amoxicillin Capsules, USP: Each Amoxicillin capsule, with yellow opaque cap and body, contains 250 mg or 500 mg Amoxicillin as the

trihydrate

The 250 mg capsule is imprinted AMOX 250 on one side and GG 848 on the other side; the 500 mg capsule is imprinted AMOX 500 on one side and GG 849 on the other side. Inactive ingredients: Capsule shells - yellow ferric oxide, titanium dioxide, gelatin, black ferric oxide, shellac, propylene glycol, potassium hydroxide and ammonium hydroxide; Capsule contents - cellulose microcrystalline and magnesium stearate. Amoxicillin Tablets, USP: Each film coated tablet contains 500 mg or 875 mg Amoxicillin as the trihydrate. The tablets are oval-shaped and white to yellowish.

The 500 mg tablet is unscored, embossed GG-961 on one side and 500 on the other side. The 875 mg tablet is scored and embossed GG-962 on one side and 875 on the other side. In addition each Amoxicillin tablet contains these inactive ingredients: colloidal silicon dioxide, crospovidone, ethylcellulose aqueous dispersion, hypromellose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, talc, triethyl citrate, and titanium dioxide. Amoxicillin for Oral Suspension, USP: Each 5 mL of reconstituted suspension contains 125 mg, 200 mg, 250 mg or 400 mg Amoxicillin as the trihydrate.

Each 5 mL of the 125 mg, 200 mg, 250 mg, and 400 mg reconstituted suspension contains 0.30 mEq (6.95 mg) of sodium. Amoxicillin trihydrate for oral suspension 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL and 400 mg/5 mL are fruity flavored pink suspensions.

Inactive ingredients: anhydrous citric acid, colloidal silicon dioxide, flavorings: raspberry, strawberry, refrachessement, FD&C Red 40, sodium benzoate, sodium citrate, sucrose, and xantham gum. Absorption: Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration.

The effect of food on the absorption of Amoxicillin from the tablets and suspension of Amoxicillin has been partially investigated; 400-mg and 875-mg formulations have been studied only when administered at the start of a light meal.