Adults and Pediatric Patients

• Upper Respiratory Tract Infections of the Ear, Nose, and Throat:Amoxicillin tablets are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcusspecies. (α- and β-hemolytic isolates only), Streptococcus pneumoniae, Staphylococcusspp., or Haemophilus influenzae.

• Infections of the Genitourinary Tract:Amoxicillin tablets 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 are indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of Streptococcusspp. (α- and β-hemolytic isolates only), Staphylococcusspp., or E. coli.

• Infections of the Lower Respiratory Tract:Amoxicillin tablets are indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of Streptococcusspp. (α- and β-hemolytic isolates only), S. pneumoniae, Staphylococcusspp., 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 tablets, in combination with clarithromycin plus lansoprazole as triple therapy, are indicated for the treatment of patients with H. pyloriinfection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylorihas been shown to reduce the risk of duodenal ulcer recurrence.

Dual therapy for H. pyloriwith lansoprazole :  Amoxicillin tablets, in combination with lansoprazole delayed-release capsules as dual therapy, are indicated for the treatment of patients with H. pyloriinfection 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. pylorihas 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 tablets and other antibacterial drugs, amoxicillin tablets 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 tablets are 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 pyloriInfection and Duodenal Ulcer Disease

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin tablets and other antibacterial drugs, amoxicillin tablets should be used only to treat  or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1)

• 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. ( 2.2, 2.3)
• The upper dose for neonates and infants aged 3 months or younger is 30 mg/kg/day divided every 12 hours. ( 2.3)
• Dosing for H. pyloriInfection (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. ( 2.4)
•  Reduce the dose in patients with severe renal impairment (GFR greater than 30 mL/min). ( 2.5)

To minimize the potential for gastrointestinal intolerance, amoxicillin tablets should be taken at the start of a meal.

• 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 pyogenesto 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

^aDosage for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections.

• It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenesto 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 tablets 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.

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.

• 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 NOTreceive 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

Amoxicillin tablets are contraindicated in patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin tablets 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 tablets or to other beta-lactams (e.g., penicillins or cephalosporins). (4)

• Anaphylactic reactions: Serious and occasionally fatal anaphylactic reactions have been reported in patients on penicillin therapy, including amoxicillin. Discontinue amoxicillin 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 and institute appropriate therapy. (5.3)  
• Clostridioides difficile-associated diarrhea (CDAD) (ranging from mild diarrhea to fatal colitis): Evaluate if diarrhea occurs. (5.4)

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.

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.

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 afterdrug 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 and institute appropriate therapy.

Clostridioidesdifficile- 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. difficilecause 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. difficilemay 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.

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.

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)]
• Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)]
• Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and  Precautions (5.3)]
• Clostridioides difficile-Associated Diarrhea (CDAD) [see Warnings and Precautions (5.4)]  

The most common adverse reactions (greater than 1%) observed in clinical trials of amoxicillin tablets or for oral suspension were diarrhea, rash, vomiting, and nausea.  (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc.at 1-844-874-7464or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 (greater than 1%) observed in clinical trials of amoxicillin 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:The most frequently reported adverse events for patients who received double therapy amoxicillin/lansoprazole were diarrhea (8%) and headache (7%). 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:Drug-induced enterocolitis syndrome (DIES), black hairy tongue, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.4)].
• 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 [see Warnings and Precautions (5.1) ]. 
• Skin and Appendages:Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis.
• 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, aseptic meningitis, and/or dizziness 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.