Amoxicillin (amoxicillin 250 mg) Dailymed

2 Dosage And Administration

Click or tap here to enter text.

• In Adults, 750 to1750 mg/day in divided doses every 8 to12 hours.
• In Pediatric Patients over 3 Months of Age, 20 to 45 mg/kg/day in divided doses every 8 to12 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)

2.1 Important Administration Instructions

To minimize the potential for gastrointestinal intolerance, amoxcillin 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 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

Infection	Severity	Recommended Dosage for Adult and Pediatrics Patients Aged 3 Months and Older and Weight Greater than 40 kg	Recommended Dosage for Pediatric Patient 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

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 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 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

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 125 mg/5 mL	80 mL	55 mL
	100 mL	68 mL
	150 mL	102 mL
For Oral Suspension 200 mg/5 mL	50 mL	34 mL
	75 mL	51 mL
	100 mL	68 mL
For Oral Suspension 250 mg/5 mL	80 mL	55 mL
	100 mL	68 mL
	150 mL	102 mL
For Oral Suspension 400 mg/5 mL	50 mL	34 mL
	75 mL	51 mL
	100 mL	68 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.

NOTE: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.

• 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)
• Clostridiodes 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 and institute appropriate therapy.

5.4 Associated Diarrhea (CDAD)

Clostridioides-difficileassociated 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. difficileproduces 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.

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.

6 Adverse Reactions

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 capsules, tablets or for oral suspension were diarrhea, rash, vomiting, and nausea. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 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 (greater than 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 :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.

6.2 Postmarketing Experience

In addition to adverse events reported from clinical trials, the following events have been identified during post-marketing 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.
• 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.