Augmentin es-600 for For Suspension

AUGMENTIN ES-600 is indicated for the treatment of pediatric patients aged 3 months to 12 years weighing less than or equal to 40 kg with:

1. Recurrent or persistent acute otitis media due to S. pneumoniae(penicillin MICs less than or equal to 2 mcg/mL), H. influenzae(including beta-lactamase-producing strains), or M. catarrhalis(including beta-lactamase-producing strains) characterized by the following risk factors: 
   - Antibacterial drug exposure for acute otitis media within the preceding 3 months, and either of the following: 1) age 2 years, or younger or 2) day care attendance [see Microbiology (12.4)].

Limitations of Use

AUGMENTIN ES-600 is not indicated for the treatment of acute otitis media due to S. pneumoniaewith penicillin MIC greater than or equal to 4 mcg/mL. Acute otitis media due to S. pneumoniaealone can be treated with amoxicillin. Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S. pneumoniae(penicillin MIC less than or equal to 2 mcg/mL) and the beta-lactamase-producing organisms listed above.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AUGMENTIN ES-600 and other antibacterial drugs, AUGMENTIN ES-600 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible 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.

• History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to AUGMENTIN ES-600 or any other beta-lactams (e.g., penicillins or cephalosporins). (4.1)

• History of cholestatic jaundice/hepatic dysfunction associated with AUGMENTIN ES-600. (4.2) 4.1 Serious Hypersensitivity Reactions

AUGMENTIN ES-600 is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate, or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). 4.2 Cholestatic Jaundice/Hepatic Dysfunction

AUGMENTIN ES-600 is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin and clavulanate potassium.

AUGMENTIN ES-600 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 a skin rash, they should be monitored closely, and AUGMENTIN ES-600 discontinued if lesions progress.

The following clinically significant adverse reactions are described elsewhere in labeling:

1. Anaphylactic reactions [see Warnings and Precautions (5.1)]
2. Severe Cutaneous Adverse Reactions (SCAR) [see Warnings and Precautions (5.2)]
3. Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and Precautions (5.3)]
4. Hepatic Dysfunction [see Warnings and Precautions (5.4)]
5. Clostridioides difficile-Associated Diarrhea (CDAD) [see Warnings and Precautions (5.5)]
6. Skin Rash in Patients with Mononucleosis [see Warnings and Precautions (5.6)]

• Serious (including fatal) hypersensitivity reactions: Discontinue AUGMENTIN ES-600 if a reaction occurs and institute appropriate therapy. (5.1)

• Severe cutaneous adverse reactions (SCAR): Monitor closely. Discontinue if rash progresses. (5.2)

• Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of AUGMENTIN ES-600. If this occurs, discontinue AUGMENTIN ES-600 and institute appropriate therapy. (5.3)

• Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. (5.4)

• Clostridioides difficile-associated diarrhea (CDAD) (ranging from mild diarrhea to fatal colitis): Evaluate patients if diarrhea occurs. (5.5)

• Patients with mononucleosis who receive AUGMENTIN ES-600 develop skin rash. Avoid AUGMENTIN ES-600 use in these patients. (5.6) 5.1 Serious Allergic Reactions, including Anaphylaxis

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including AUGMENTIN ES-600. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with AUGMENTIN ES-600, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue AUGMENTIN ES-600 and institute appropriate therapy. 5.2 Severe Cutaneous Adverse Reactions

AUGMENTIN ES-600 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 a skin rash, they should be monitored closely, and AUGMENTIN ES-600 discontinued if lesions progress. 5.3 Drug-Induced Enterocolitis Syndrome (DIES)

Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of AUGMENTIN ES-600 [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 AUGMENTIN ES-600 and institute appropriate therapy. 5.4 Hepatic Dysfunction

Use AUGMENTIN ES-600 with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of AUGMENTIN ES-600 is usually reversible. Deaths have been reported (fewer than one death reported per estimated four million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications [

see Contraindications (4.2) and Adverse Reactions (6.2)

]. 5.5

Clostridioides difficile

-Associated Diarrhea (CDAD)

Clostridioides difficile-

associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AUGMENTIN ES-600, 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 drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug 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. 5.6 Skin Rash in Patients with Mononucleosis

A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Avoid AUGMENTIN ES-600 use in patients with mononucleosis. 5.7 Potential for Microbial Overgrowth

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving

Pseudomonas

spp. or

Candida

spp.), the drug should be discontinued, and appropriate therapy instituted. 5.8 Phenylketonurics

AUGMENTIN ES-600 contains aspartame which contains phenylalanine. Each 5 mL of suspension of AUGMENTIN ES-600 contains 7 mg phenylalanine. 5.9 Development of Drug-Resistant Bacteria

Prescribing AUGMENTIN ES-600 in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Pediatric patients aged 3 months to 12 years weighing less than or equal to 40 kg: Based on the amoxicillin component (600 mg/5 mL), the recommended dose of AUGMENTIN ES-600 is 90 mg/kg/day divided every 12 hours, administered for 10 days (see Table 1 as a general example guideline for attainment of this dosage). This dose provides 6.4 mg/kg/day of the clavulanic acid component.

Table 1: General Dosage Guidelines for AUGMENTIN ES-600 in Pediatric Patients

Experience with AUGMENTIN ES-600 in adults is not available and adults who have difficulty swallowing should not be given AUGMENTIN ES-600 in place of the 500 mg or 875 mg tablet of AUGMENTIN.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals [see Warnings and Precautions ( 5.4)] .

AUGMENTIN ES-600 does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of AUGMENTIN. AUGMENTIN ES-600 contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/28.5 mg per 5 mL suspension of AUGMENTIN contains 28.5 mg clavulanic acid per 5 mL and the 400 mg/57 mg per 5 mL suspension of AUGMENTIN contains 57 mg clavulanic acid per 5 mL. Therefore, the 200 mg/28.5 mg per 5 mL and 400 mg/57 mg per 5 mL suspensions of AUGMENTIN should not be substituted for AUGMENTIN ES-600 as they are not interchangeable.

Augmentin ES 600 for Oral Suspension: 600 mg/42.9 mg per 5 mL: Strawberry cream-flavored for oral suspension (each 5 mL of reconstituted suspension contains 600 mg of amoxicillin as the trihydrate, and 42.9 mg of clavulanic acid as the potassium salt).

• Co-administration with probenecid is not recommended. (7.1)

• Concomitant use of AUGMENTIN ES-600 with oral anticoagulants may increase the prolongation of prothrombin time. (7.2)

• Co-administration with allopurinol increases the risk of rash. (7.3)

• AUGMENTIN ES-600 may reduce efficacy of oral contraceptives. (7.4) 7.1 Probenecid

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with AUGMENTIN ES-600 may result in increased and prolonged blood levels of amoxicillin. Co-administration of probenecid is not recommended. 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 substantially 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. There are no data with AUGMENTIN ES-600 and allopurinol administered concurrently. 7.4 Oral Contraceptives

AUGMENTIN ES-600 may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. 7.5 Effects on Laboratory Tests

High urine concentrations of amoxicillin 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 AUGMENTIN ES-600, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

Following administration of amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.