Amoxicillin 250 MG Chewable Tablet

INDICATIONS AND USAGE Adults and Pediatric Patients • Upper Respiratory Tract Infections of the Ear, Nose, and Throat: Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcus species. (α- and β-hemolytic isolates only), Streptococcus pneumoniae , Staphylococcus spp., or Haemophilus influenzae . • Infections of the Genitourinary Tract: Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Escherichia coli , Proteus mirabilis , or Enterococcus faecalis . • Infections of the Skin and Skin Structure: Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcus spp. (α- and β-hemolytic isolates only), Staphylococcus spp., or E. coli . • Infections of the Lower Respiratory Tract: Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcus spp. (α- and β-hemolytic isolates only), S. pneumoniae , Staphylococcus spp., or H. influenzae . Adult Patients only • Helicobacter pylori Infection and Duodenal Ulcer Disease: Triple therapy for Helicobacter pylori (H. pylori) with clarithromycin and lansoprazole: Amoxicillin, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori . Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Dual therapy for H. pylori with lansoprazole: Amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. (See the clarithromycin package insert, MICROBIOLOGY.) Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and other antibacterial drugs, amoxicillin should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Amoxicillin is a penicillin-class antibacterial indicated for treatment of infections due to susceptible strains of designated microorganisms. ( 1 ) Adults and Pediatric Patients ( 1 ) • Upper Respiratory Tract Infections of the Ear, Nose, and Throat • Infections of the Genitourinary Tract • Infections of the Skin and Skin Structure • Infections of the Lower Respiratory Tract Adult Patients only ( 1 ) • Helicobacter pylori Infection and Duodenal Ulcer Disease Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules and other antibacterial drugs, amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1 )

DOSAGE AND ADMINISTRATION • In Adults, 750 to 1750 mg/day in divided doses every 8 to 12 hours. • In Pediatric Patients over 3 Months of Age, 20 to 45 mg/kg/day in divided doses every 8 to 12 hours. Refer to full prescribing information for specific dosing regimens. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ) • The upper dose for neonates and infants aged 3 months or younger is 30 mg/kg/day divided every 12 hours. ( Error! Hyperlink reference not valid. ) • Dosing for H. pylori Infection (in Adults): Triple therapy: 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual therapy: 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days. ( Error! Hyperlink reference not valid. ) • Reduce the dose in patients with severe renal impairment (GFR greater than 30 mL/min). ( Error! Hyperlink reference not valid. ) 2.1 Important Administration Instructions To minimize the potential for gastrointestinal intolerance, amoxicillin should be taken at the start of a meal. 2.2 Dosage for Adults and Pediatric Patients Aged 3 Months (12 weeks) and Older • Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic, or evidence of bacterial eradication has been obtained. • It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. • In some infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy. Table 1. Dosage Recommendations for Adult and Pediatric Patients Aged 3 Months (12 weeks) and Older Infection Severity a Recommended Dosage for Adults and Pediatric Patients Aged 3 Months and Older and Weight Greater than 40 kg Recommended Dosage for Pediatric Patients Aged 3 Months and Older and Weight Less than 40 kg Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract Mild/Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/Moderate or Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours a Dosage for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections. 2.3 Dosage in Pediatric Patients Aged Less than 12 Weeks (3 months) • It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. • Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin is 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function. • Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic, or evidence of bacterial eradication has been obtained. 2.4 Dosage for H. pylori Infection in Adults Triple therapy: The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual therapy: The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days. Please refer to clarithromycin and lansoprazole full prescribing information. 2.5 Dosage in Renal Impairment for Adults and Pediatric Patients Aged 3 Months and Older and Weight Greater than 40 kg • 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 of less than 30 mL/min should NOT receive the 875 mg dose. See dosage regimens in patients with severe renal impairment provided in Table 2. Table 2. Dosing in Patients with Severe Renal Impairment Patients with Renal Impairment Dosage Regimen GFR 10 to 30 mL/min 500 mg or 250 mg every 12 hours, depending on the severity of the infection GFR less than 10 mL/min 500 mg or 250 mg every 24 hours, depending on severity of the infection Hemodialysis 500 mg or 250 mg every 24 hours, depending on severity of the infection Administer an additional dose both during and at the end of dialysis 2.6 Directions for Mixing Oral Suspension Prepare a suspension at time of dispensing as follows: Tap bottle until all powder flows freely. Measure the total amount of water (see Table 3). Add approximately 1/3 of the water to powder. Replace cap and shake vigorously to wet powder. Add remaining water. Replace cap and shake vigorously . Table 3. Amount of Water for Mixing For Oral Suspension Strength Bottle Size Total Amount of Water Required for Reconstitution For Oral Suspension 200 mg/5 mL 50 mL 39 mL 75 mL 57 mL 100 mL 75 mL For Oral Suspension 250 mg/5 mL 80 mL 47 mL 100 mL 60 mL 150 mL 90 mL For Oral Suspension 400 mg/5 mL 50 mL 35 mL 75 mL 51 mL 100 mL 67 mL After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing. Alternate means of administration are to add the required amount of suspension to formula, milk, fruit juice, water, ginger ale, or cold drinks. These preparations should then be taken immediately. SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable, but not required.

WARNINGS AND PRECAUTIONS • Anaphylactic reactions: Serious and occasionally fatal anaphylactic reactions have been reported in patients on penicillin therapy, including amoxicillin. Discontinue Amoxicillin for Oral Suspension, USP if a reaction occurs ( 5.1 ). • Severe cutaneous adverse reactions (SCAR): Monitor closely. Discontinue if rash progresses. ( 5.2 ) • Drug-induced enterocolitis syndrome (DIES) has been reported with amoxicillin use. If this occurs, discontinue Amoxicillin for Oral Suspension, USP and institute appropriate therapy. ( 5.3 ) • Clostridioides difficile -associated diarrhea (CDAD) (ranging from mild diarrhea to fatal colitis): Evaluate if diarrhea occurs. ( 5.4 ) 5.1 Anaphylactic Reactions 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 amoxicillin, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin should be discontinued, and appropriate therapy instituted. 5.2 Severe Cutaneous Adverse Reactions Amoxicillin may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop skin rash they should be monitored closely, and amoxicillin discontinued if lesions progress. 5.3 Drug-Induced Enterocolitis Syndrome (DIES) Drug-induced enterocolitis syndrome (DIES) has been reported with amoxicillin use [ see Adverse Reactions ( 6.2 ) ], with most cases occurring in pediatric patients ≤18 years of age. DIES is a non-IgE mediated hypersensitivity reaction characterized by protracted vomiting occurring 1 to 4 hours after drug ingestion in the absence of skin or respiratory symptoms. DIES may be associated with pallor, lethargy, hypotension, shock, diarrhea within 24 hours after ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue Amoxicillin for Oral Suspension, USP and institute appropriate therapy. 5.4 Clostridioides difficile -Associated Diarrhea (CDAD) Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. 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 antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.5 Development of Drug-Resistant Bacteria Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 5.6 Skin Rash in Patients with Mononucleosis 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. 5.7 Phenylketonurics Amoxicillin chewable tablets contain aspartame which contains phenylalanine. Each 200 mg chewable tablet contains 1.82 mg phenylalanine; each 400 mg chewable tablet contains 3.64 mg phenylalanine. The oral suspension formulations of amoxicillin do not contain phenylalanine and can be used by phenylketonurics.

CONTRAINDICATIONS Amoxicillin for oral suspension is contraindicated in patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin for oral suspension or to other β-lactam antibacterial drugs (e.g., penicillins and cephalosporins). History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin for oral suspension or to other beta-lactams (e.g., penicillins or cephalosporins). (4)

CLINICAL PHARMACOLOGY SECTION 12.1 Mechanism of Action Amoxicillin is an antibacterial drug [see Clinical Pharmacology (12.4) ].12.3 Pharmacokinetics 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. 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 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 amoxicillin with 875 mg of amoxicillin/clavulanate potassium showed that the 875 mg tablet of amoxicillin 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 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively. Oral administration of single doses of 400 mg chewable tablets and 400 mg/5 mL suspension of amoxicillin 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 * Administered at the start of a light meal. † Mean values of 24 normal volunteers. Peak concentrations occurred approximately 1 hour after the dose. 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) Distribution: 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. Metabolism and Excretion: The half-life of amoxicillin is 61.3 minutes. 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 (7.1) ].12.4 Microbiology Mechanism of Action 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. Method of Resistance Resistance to amoxicillin is mediated primarily through enzymes called beta-lactamases that cleave the beta-lactam ring of amoxicillin, rendering it inactive. Amoxicillin has been shown to be active against most isolates of the bacteria listed below, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Gram-Positive Bacteria Gram-Negative Bacteria Enterococcus faecalis Staphylococcusspp. Streptococcus pneumoniae Alpha and β-hemolytic streptococci. Escherichia coli Haemophilus influenzae Neisseria gonorrhoeae Proteus mirabilis Helicobacter pylori Susceptibility Test Methods: (susceptibility to amoxicillin can be determined using ampicillin powder and a 10 mcg ampicillin disk) When available, clinical microbiology should provide the results of in vitro susceptibility test results for antimicrobial drugs used in resident hospitals 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 an antimicrobial drug product for treatment. 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 procedure. Standardized procedures are based on dilution methods (broth or agar)2,3 or equivalent with standardized inoculum concentrations and standardized concentrations of ampicillin powder. The MIC values should be interpreted according to the criteria in Table 4. Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 10 mcg ampicillin to test the susceptibility of bacteria to ampicillin. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for amoxicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 10 mcg ampicillin disk should be interpreted according to the criteria listed in Table 4. Table 4. Susceptibility Test Interpretive Criteria for Amoxicillin Minimum Inhibitory Concentration (mcg/mL) Disk Diffusion (zone diameter in mm) Susceptible Intermediate Resistant Susceptible Intermediate Resistant * 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. ** A positive beta lactamase test indicates resistance to amoxicillin. Isolates that are resistant to penicillin by MIC testing are also expected to be resistant to amoxicillin. Enterococcus spp. ≤ 8 - ≥ 16 ≥ 17 - ≤ 16 Staphylococcus spp. ≤ 0.25 ≥ 0.5 ≥ 29 ≤ 28 Streptococci, viridians group (alpha-hemolytic streptococci) ≤ 0.25 0.5 to 4 ≥ 8 - - - β-hemolytic streptococci ≤ 0.25 - - ≥ 24 - - Streptococcus pneumoniae(non-meningitis isolates)* ≤ 2 4 ≥ 8 - - - Enterobacteriaceae ≤ 8 16 ≥ 32 ≥ 17 14 to 16 ≤ 13 Haemophilus influenzae ≤ 1 2 ≥ 4 ≥ 22 19 to 21 ≤ 18 Neisseria gonorrhoeae** - - - - - - A report of “Susceptible” indicates the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches concentrations that are usually achievable. A report of “Intermediate” indicates that result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. The intermediate category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. The intermediate category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches concentrations that are usually achievable and other therapy(ies) are likely to be preferred. Quality Control Susceptibility techniques require use of laboratory control microorganisms to control the technical aspects of the laboratory standardized procedures.2,3,4 Standard ampicillin powder should provide the MIC values described below. For the diffusion technique using the 10 mcg ampicillin disk, the criteria are provided in Table 5. Table 5. Acceptable QualityControlRanges for Amoxicillin Bacteria ATCC# MICRange (mcg/mL) DiskDiffusionZoneRange (mm) # ATCC = American Type Culture Collection Escherichia coli 25922 2