Amoxicillin bubble gum

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. 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 AMOXIL, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AMOXIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents

alters

difficile produces toxins A and B which contribute to the development of CDAD.

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. Appropriate fluid and electrolyte management, protein

supplementation

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. Amoxil chewable tablets contain aspartame which contains phenylalanine. Each 200 mg chewable

tablet

The oral suspensions of Amoxil do not contain phenylalanine and can be used by phenylketonurics.

Carcinogenesis, Mutagenesis, Impairment Of Fertility.

Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Studies to detect mutagenic potential of amoxicillin alone have not been conducted; however, the following information is available from tests on a 4:1 mixture of amoxicillin

and

AUGMENTIN was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay.

AUGMENTIN was weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at doses that were also associated with decreased cell survival. AUGMENTIN was negative in the mouse micronucleus test and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test, and was negative in each of these assays. In a multi-generation reproduction study in rats, no impairment of fertility or other adverse reproductive effects were seen at doses up to 500 mg/kg (approximately 2 times the 3 g human dose based on body surface area). 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

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 AMOXIL should be modified in pediatric patients 12 weeks or younger ( ? 3 months). An analysis of clinical studies of AMOXIL 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.

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. Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin 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. AMOXIL is contraindicated in patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to AMOXIL or to other ?-lactam antibiotics (e.g.,

penicillins

The effect of food on the absorption of amoxicillin from the tablets and suspension of AMOXIL has been partially investigated; 400-mg and 875-mg formulations have been studied only when administered at the

start

Orally administered doses of 250-mg and 500-mg amoxicillin capsules result in average peak blood levels 1 to 2 hours after administration in the range of 3.5 mcg/mL to 5.0 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.

Mean amoxicillin pharmacokinetic parameters from an open, two-part, single-dose crossover bioequivalence study in 27 adults comparing 875 mg of AMOXIL with 875 mg of AUGMENTIN® (amoxicillin/clavulanate potassium) showed that the 875-mg tablet of AMOXIL produces an AUC0-? of 35.4 ± 8.1 mcg•hr/mL and a Cmax of 13.8 ± 4.1 mcg/mL.

Dosing was at the start of a light meal following an overnight fast. Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3.0 mcg/mL and 3.5 mcg/mL to 5.0 mcg/mL, respectively. Oral administration of single doses of 400-mg chewable tablets and 400 mg/5 mL suspension of AMOXIL to 24 adult volunteers yielded comparable pharmacokinetic data: Table 3: Mean Pharmacokinetic Parameters of Amoxicillin (400 mg chewable tablets and 400 mg/5 mL suspension) in Healthy Adults Dose* AUC0-? (mcg•hr/mL) Cmax (mcg/mL)† Amoxicillin Amoxicillin (±S.D.) Amoxicillin (±S.D.) 400 mg (5 mL of suspension) 17.1 (3.1) 5.92 (1.62) 400 mg (1 chewable tablet) 17.9 (2.4) 5.18 (1.64) * Administered at the start of a light meal.

Peak concentrations occurred approximately 1 hour after the dose. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. In blood serum, amoxicillin is approximately 20% protein-bound.

Following a 1-gram dose and utilizing a special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid. Approximately 60% of an orally administered dose of amoxicillin is excreted in the urine within 6 to 8 hours.

Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxicillin. Since most of the amoxicillin is excreted unchanged in the urine, its excretion can be delayed by concurrent administration of probenecid [see DRUG INTERACTIONS ]. Amoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication.

It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.

Resistance to amoxicillin is mediated primarily through enzymes called beta-lactamases that

cleave

Amoxicillin has been shown to be active against most isolates of the bacteria listed below, both in vitro and in clinical

infections

Escherichia coli Haemophilus influenzae Helicobacter pylori

Proteus

When available, the clinical microbiology laboratory should provide cumulative in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial. Dilution Techniques : Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs).

These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method -(broth or agar) 2,4 .

The MIC values should be interpreted according to the criteria in Table 4. Diffusion Techniques : Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds 3,4 .

The zone size should be determined using a standardized test method 3 .

Susceptibility to amoxicillin of Enterococcus spp., Enterobacteriaceae , and H.

influenzae, may be inferred by testing ampicillin 4 .

Susceptibility to amoxicillin of Staphylococcus spp., and beta-hemolytic Streptococcus spp., may be inferred by testing penicillin 4 . that are resistant to ampicillin or amoxicillin produce a TEM-type beta-lactamase.

A beta-lactamase test can provide a rapid means of determining resistance to ampicillin and amoxicillin 4 .

Susceptibility to amoxicillin of Streptococcus pneumoniae (non-meningitis isolates) may be inferred by testing penicillin or oxacillin 4 .

pneumoniae to amoxicillin are provided in Table 4 4 .

Table 4: Susceptibility Interpretive Criteria for Amoxicillin Minimum Inhibitory Concentration (mcg/mL) Disk Diffusion (zone diameter in mm) Susceptible Intermediate Resistant Susceptible Intermediate Resistant Streptococcus pneumoniae (non-meningitis isolates)* ? 2 4 ? 8 - - - * S.

pneumoniae should be tested using a 1-mcg oxacillin disk.

Isolates with oxacillin zone sizes of ? 20 mm are susceptible to amoxicillin.

An amoxicillin MIC should be determined on isolates of S.

pneumoniae with oxacillin zone sizes of ? 19 mm 4 . A report of “Susceptible” indicates the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches a concentration at the infection site

necessary

This category implies possible clinical applicability in body sites where the drug is physiologically concentrated.

This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration usually achievable at the infection site; other therapy should be selected. Amoxicillin in vitro susceptibility testing methods for determining minimum inhibitory concentrations (MICs) and zone sizes have not been standardized, validated, or approved for testing H. pylori and clarithromycin susceptibility test results should be obtained on isolates from patients who fail triple therapy. If clarithromycin resistance is found, a non-clarithromycin-containing regimen should be used.

Standardized susceptibility test procedures 2,3,4 require use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test control.

Standard amoxicillin powder should provide the following range of MIC values provided in Table 5 4 .

For the diffusion technique the criteria provided in Table 5 should be achieved. Table 5: Acceptable Quality Control Ranges for Amoxicillin a Quality Control Microorganism Minimum Inhibitory Concentrations (mcg/mL) Disc Diffusion Zone Diameter (mm) Streptococcus pneumoniae ATCC b 49619 0.03 to 0.12 ---- Klebsiella pneumoniae ATCC 700603 > 128 — a QC limits for testing E.

coli 35218 when tested on Haemophilus Test Medium (HTM) are ? 256 mcg/mL for amoxicillin; testing amoxicillin may help to determine if the isolate has maintained its ability to produce betalactamase 4 . pylori Eradication To Reduce The Risk Of Duodenal Ulcer Recurrence. Randomized, double-blind clinical studies performed in the United States in patients with H.

pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within 1 year) evaluated the efficacy of lansoprazole in combination with amoxicillin capsules and clarithromycin tablets as triple 14-day therapy, or in combination with amoxicillin capsules as dual 14-day therapy, for the eradication of H.

Based on the results of these studies, the safety and efficacy of 2 different eradication regimens were established: Triple therapy: Amoxicillin 1 gram twice daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg twice daily (see Table 6).

Dual therapy: Amoxicillin 1 gram three times daily/lansoprazole 30 mg three times daily (see Table 7. pylori eradication was defined as 2 negative tests (culture and histology) at 4 to 6 weeks following the end of treatment.

Triple therapy was shown to be more effective than all possible dual therapy combinations.

Dual therapy was shown to be more effective than both monotherapies.

pylori has been shown to reduce the risk of duodenal ulcer recurrence. pylori Eradication Rates When Amoxicillin is Administered as Part of a Triple Therapy Regimen Study Triple Therapy Triple Therapy Evaluable Analysis a [95% Confidence Interval] (number of patients) Intent-to-Treat Analysis b [95% Confidence Interval] (number of patients) Study 1 92 86 [80.0 - 97.7] [73.3 -93.5] (n = 48) (n = 55) Study 2 86 83 [75.7 - 93.6] [72.0 - 90.8] (n = 66) (n = 70) a This analysis was based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H.

pylori infection at baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, histology, and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy. b Patients were included in the analysis if they had documented H.

pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within 1 year).

pylori Eradication Rates When Amoxicillin is Administered as Part of a Dual Therapy Regimen Study Dual Therapy Dual Therapy Evaluable Analysis a [95% Confidence Interval] (number of patients) Intent-to-Treat Analysis b [95% Confidence Interval] (number of patients) Study 1 77 70 [62.5 - 87.2] [56.8 -81.2] (n = 51) (n = 60) Study 2 66 61 [51.9 -77.5] [48.5 -72.9] (n = 58) (n = 67) a This analysis was based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H.