Amoxicillin Oral Susp

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and other antibacterial drugs, Amoxicillin for Oral Suspension 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 for Oral Suspension is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of the designated bacteria in the conditions listed below:

1.1 Infections of the ear, nose, and throat – due to Streptococcus species.(α- and β-hemolytic isolates only), Streptococcus pneumoniae, Staphylococcus spp., or Haemophilus influenzae.

1.2 Infections of the genitourinary tract – due to Escherichia coli, Proteus mirabilis, or Enterococcus faecalis.

1.3 Infections of the skin and skin structure – due to Streptococcus spp. (α- and β-hemolytic isolates only), Staphylococcus spp., or E. coli.

1.4 Infections of the lower respiratory tract – due to Streptococcus spp. (α- and β-hemolytic isolates only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

1.5 Gonorrhea, acute uncomplicated (ano-genital and urethral infections in males and females) – due to Neisseria gonorrhoeae. Because of high rates of Amoxicillin resistance, Amoxicillin for Oral Suspension is not recommended for empiric treatment of gonorrhea. Amoxicillin for Oral Suspension use should be limited to situations where N. gonorrhoeae isolates are known to be susceptible to Amoxicillin.

1.6 Triple therapy for Helicobacter pylori with clarithromycin and lansoprazole: Amoxicillin for Oral Suspension 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.

1.7 Dual therapy for H. pylori with lansoprazole Amoxicillin for Oral Suspension, 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.

Amoxicillin for Oral Suspension:125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL. Each 5 mL of reconstituted fruity flavored suspension contains 125 mg, 200 mg, 250 mg or 400 mg Amoxicillin as the trihydrate.

Amoxicillin is contraindicated in patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to Amoxicillin or to other β-lactam antibiotics (e.g., penicillins and cephalosporins).

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.

5.2 Clostridium difficile Associated Diarrhea Clostridium 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 antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.3 Potential for Microbial Overgrowth or Bacterial Resistance The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfections occur, Amoxicillin should be discontinued and appropriate therapy instituted. Prescribing Amoxicillin either 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.

5.4 Use 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.

5.5 Phenylketonurics The oral suspensions of Amoxicillin do not contain phenylalanine and can be used by phenylketonurics.

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)]

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 (> 1%) observed in clinical trials of Amoxicillin for 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 or Other Experience 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, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and urticaria have been reported. 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. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

7.1 Probenecid Probenecid decreases the renal tubular secretion of Amoxicillin. Concurrent use of Amoxicillin and probenecid may result in increased and prolonged blood levels of Amoxicillin.

7.2 Oral Anticoagulants 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.

7.3 Allopurinol 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.

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

7.5 Other Antibacterials 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.

7.6 Effects on Laboratory Tests High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST® (manufactured by Miles, Inc.), 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® (manufactured by Bayer Corporation)] 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.

8.1 Pregnancy Teratogenic Effects: Pregnancy Category B. 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.

8.2 Labor and Delivery Oral ampicillin is poorly absorbed during labor. 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.

8.3 Nursing Mothers 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.

8.4 Pediatric Use 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).]

8.5 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.

8.6 Dosing in Renal Impairment Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR <30 mL/min). See Dosing in Renal Impairment (2.4) for specific recommendations in patients with renal impairment.