Amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP

Amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets. USP are an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin molecular formula is C 16 H 19 N 3 O 5 S•3H 2 O and the molecular weight is 419.46. Chemically, amoxicillin is ( 2S ,5R,6R )- 6-(( R )-(-)-2-Amino-2-( p -hydroxyphenyl) acetamido]-3,3-dimethyl- 7-oxo-4-thia-1-azabicyclo(3.2.0) heptane-2-carboxylic acid trihydrate and may be represented structurally as: Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus . It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C 8 H 8 KNO 5 and the molecular weight is 237.25. Chemically clavulanate potassium is potassium ( Z )-( 2R,5R )-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate and may be represented structurally as: Each chewable tablet and each teaspoon (5 mL) of reconstituted oral suspension contains 200 mg or 400 mg amoxicillin as the trihydrate and 28.5 or 57 mg clavulanic acid as the potassium salt. Each 200 mg/28.5 mg chewable tablet and each 5 mL of reconstituted amoxicillin and clavulanate potassium 200 mg/28.5 mg oral suspension contains 0.14 mEq potassium. Each 400 mg/57 mg chewable tablet and each 5 mL of reconstituted 400 mg/57 mg oral suspension contains 0.29 mEq of potassium. Inactive Ingredients Powder for Oral Suspension - Aspartame*, colloidal silicon dioxide, hydroxypropyl methylcellulose, mannitol, orange flavoring, precipitated silicon dioxide, succinic acid, xanthan gum, and golden syrup flavoring (carmel). Chewable Tablets - Aspartame*, banana flavoring (See HOW SUPPLIED ), cherry flavoring (See HOW SUPPLIED ), colloidal silicon dioxide, FD&C Red No. 40, magnesium stearate, mannitol, and sodium starch glycolate. *See PRECAUTIONS-Information for Patients . Amoxicillin Chemical Structure Clavulanate Potassium Chemical Structure

Amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP are indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower Respiratory Tract Infections - caused by β-lactamase-producing strains of H. influenzae and M. catarrhalis . Otitis Media - caused by β-lactamase-producing strains of H. influenzae and M. catarrhalis . Sinusitis - caused by β-lactamase-producing strains of H. influenzae and M. catarrhalis . Skin and Skin Structure Infections - caused by β-lactamase-producing strains of S. aureus , E. coli and Klebsiella spp. Urinary Tract Infections - caused by β-lactamase-producing strains of E. coli , Klebsiella spp. and Enterobacter spp. While amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP are indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP treatment due to its amoxicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and β-lactamase-producing organisms susceptible to amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP should not require the addition of another antibiotic. Because amoxicillin has greater in-vitro activity against S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin and amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP. (See Microbiology .) To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP and other antibacterial drugs, amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP 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. Bacteriological studies, to determine the causative organisms and their susceptibility to amoxicillin and clavulanate potassium for oral suspension, USP and chewable tablets, USP, should be performed together with any indicated surgical procedures.

All recommended dosages for Amoxicillin and Clavulanate Potassium for Oral Suspension and Chewable Tablets are included in this section for informational purposes only. Some of the dosages may not be obtainable with the 400 mg/57 mg per 5 mL and 200 mg/28.5 mg per 5 mL strengths of oral suspension or the 400 mg/57 mg and 200 mg/28.5 mg strengths of chewable tablets. Dosage Pediatric Patients Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension and chewable tablets should be dosed as follows: Neonates and Infants Aged < 12 Weeks (3 Months) Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended dose of amoxicillin and clavulanate potassium for oral suspension and chewable tablets is 30 mg/kg/day divided q12h, based on the amoxicillin component. Clavulanate elimination is unaltered in this age group. Experience with the 200 mg/28.5 mg per 5 mL formulation in this age group is limited and, thus, use of the 125 mg/31.25 mg per 5 mL oral suspension is recommended. Patients Aged 12 Weeks (3 Months) and Older INFECTIONS DOSING REGIMEN q12h The q12h regimen is recommended as it is associated with significantly less diarrhea. (See CLINICAL STUDIES .) However, the q12h formulations (200 mg/28.5 mg and 400 mg/57 mg) contain aspartame and should not be used by phenylketonurics. q8h 200 mg/28.5 mg per 5 mL or 400 mg/57 mg per 5 mL oral suspension Each strength of amoxicillin and clavulanate potassium suspension is available as a chewable tablet for use by older children. 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL oral suspension Otitis media Duration of therapy studied and recommended for acute otitis media is 10 days. , sinusitis, lower respiratory tract infections, and more severe infections 45 mg/kg/day q12h 40 mg/kg/day q8h Less severe infections 25 mg/kg/day q12h 20 mg/kg/day q8h Pediatric Patients Weighing 40 kg and More Should be dosed according to the following adult recommendations: The usual adult dose is one amoxicillin and clavulanate potassium 500 mg/125 mg tablet every 12 hours or one amoxicillin and clavulanate potassium 250 mg/125 mg tablet every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one amoxicillin and clavulanate potassium 875 mg/125 mg tablet every 12 hours or one amoxicillin and clavulanate potassium 500 mg/125 mg tablet every 8 hours. Among adults treated with 875 mg/125 mg every 12 hours, significantly fewer experienced severe diarrhea or withdrawals with diarrhea versus adults treated with 500 mg/125 mg every 8 hours. For detailed adult dosage recommendations, please see complete prescribing information for amoxicillin/clavulanate potassium tablets. Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS .) Adults Adults who have difficulty swallowing may be given the 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. The 200 mg/28.5 mg per 5 mL suspension or the 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet. See dosage recommendations above for children weighing 40 kg or more. The amoxicillin and clavulanate potassium, USP 250 mg/125 mg tablet and the 250 mg/62.5 mg chewable tablet do not contain the same amount of clavulanic acid (as the potassium salt). Amoxicillin and clavulanate potassium, USP 250 mg/125 mg tablet contains 125 mg of clavulanic acid, whereas the 250 mg/62.5 mg chewable tablet contains 62.5 mg of clavulanic acid. Therefore, the amoxicillin and clavulanate potassium, USP 250 mg/125 mg tablet and the 250 mg/62.5 mg chewable tablet should not be substituted for each other, as they are not interchangeable. Due to the different amoxicillin to clavulanic acid ratios in the amoxicillin and clavulanate potassium, USP 250 mg/125 mg tablet versus the amoxicillin and clavulanate potassium, USP 250 mg/62.5 mg chewable tablet, the amoxicillin and clavulanate 250 mg/125 mg tablet should not be used until the child weighs at least 40 kg and more. DIRECTIONS FOR MIXING ORAL SUSPENSION Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously. AMOXICILLIN AND CLAVULANATE POTASSIUM 200 mg/28.5 mg per 5 mL SUSPENSION Bottle Size Amount of Water Required for Suspension 100 mL 88 mL Each teaspoonful (5 mL) will contain 200 mg amoxicillin and 28.5 mg of clavulanic acid as the potassium salt. AMOXICILLIN AND CLAVULANATE POTASSIUM 400 mg/57 mg per 5 mL SUSPENSION Bottle Size Amount of Water Required for Reconstitution 100 mL 84 mL Each teaspoonful (5 mL) will contain 400 mg amoxicillin and 57 mg of clavulanic acid as the potassium salt. NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING. Reconstituted suspension must be stored under refrigeration and discarded after 10 days. Administration Amoxicillin and clavulanate potassium for oral suspension and chewable tablets may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium for oral suspension and chewable tablets are administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium for oral suspension and chewable tablets should be taken at the start of a meal. Tablets may be chewed before being swallowed or may be swallowed whole.

Amoxicillin and clavulanate potassium for oral suspension and chewable tablets are contraindicated in patients with a history of allergic reactions to any penicillin. It is also contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium.

Amoxicillin and clavulanate potassium for oral suspension and chewable tablets are generally well tolerated. The majority of side effects observed in clinical trials were of a mild and transient nature and less than 3% of patients discontinued therapy because of drug-related side effects. From the original premarketing studies, where both pediatric and adult patients were enrolled, the most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The overall incidence of side effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include: abdominal discomfort, flatulence and headache. In pediatric patients (aged 2 months to 12 years), one U.S./Canadian clinical trial was conducted which compared amoxicillin and clavulanate potassium for oral suspension and chewable tablets 45/6.4 mg/kg/day (divided q12h) for 10 days versus amoxicillin and clavulanate potassium for oral suspension and chewable tablets 40/10 mg/kg/day (divided q8h) for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse event profile seen was comparable to that noted above. However, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes. (See CLINICAL STUDIES .) The following adverse reactions have been reported for ampicillin class antibiotics: Gastrointestinal Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS .) Hypersensitivity Reactions Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia and frequently fever), erythema multiforme (rarely Stevens-Johnson Syndrome), acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corti-costeroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with oral penicillin. (See WARNINGS .) Liver A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin class antibiotics but the significance of these findings is unknown. Hepatic dysfunction, including hepatitis and cholestatic jaundice, (see CONTRAINDICATIONS ), increases in serum transaminases (AST and/or ALT), serum bilirubin and/or alkaline phosphatase, has been infrequently reported with amoxicillin and clavulanate potassium for oral suspension and chewable tablets. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications. Renal Interstitial nephritis and hematuria have been reported rarely. Crystalluria has also been reported (see OVERDOSAGE ). Hemic And Lymphatic Systems Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in less than 1% of the patients treated with amoxicillin and clavulanate potassium for oral suspension and chewable tablets. There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium for oral suspension and chewable tablets and anticoagulant therapy concomitantly. Central Nervous System Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia and reversible hyperactivity have been reported rarely. Miscellaneous Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin and clavulanate potassium for oral suspension and chewable tablets may result in increased and prolonged blood levels of amoxicillin. Co-administration of probenecid cannot be recommended. Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported rarely 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. The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with amoxicillin and clavulanate potassium for oral suspension and chewable tablets and allopurinol administered concurrently. In common with other broad-spectrum antibiotics, amoxicillin and clavulanate potassium for oral suspension and chewable tablets may reduce the efficacy of oral contraceptives.

Store tablets and dry powder at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Dispense in tightly closed, moisture-proof containers. Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days.