Amoxicillin and Clavulanate Tablets

Name: Amoxicillin and Clavulanate Tablets

Indications and Usage for Amoxicillin and Clavulanate Tablets

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium tablets USP, and other antibacterial drugs, amoxicillin and clavulanate potassium should be used only to treat 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.


Amoxicillin and clavulanate potassium tablets USP is a combination penicillin-class antibacterial and beta-lactamase inhibitor indicated in the treatment of infections due to susceptible isolates of the designated bacteria in the conditions listed below*:

Lower Respiratory Tract Infections


– caused by beta-lactamase–producing isolates of Haemophilus influenzae and Moraxella catarrhalis.

Acute Bacterial Otitis Media


– caused by beta-lactamase–producing isolates of H. influenzae and M. catarrhalis.

Sinusitis


– caused by beta-lactamase–producing isolates of H. influenzae and M. catarrhalis.

Skin and Skin Structure Infections


– caused by beta-lactamase–producing isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella species.

Urinary Tract Infections


– caused by beta-lactamase–producing isolates of E. coli, Klebsiella species, and Enterobacter species.

Limitations of Use


– When susceptibility test results show susceptibility to amoxicillin, USP, indicating no beta-lactamase production, amoxicillin and clavulanate potassium tablets USP should not be used.

Dosage Forms and Strengths


250 mg/125 mg Tablets: White to off-white colored, capsule shaped, biconvex, film-coated tablets, debossed with “I 05” on one side and plain on the other side. Each tablet contains 250 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.

500 mg/125 mg Tablets: White to off-white colored, capsule shaped, biconvex, film-coated tablets debossed with “I 06” on one side and plain on the other side. Each tablet contains 500 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.  

875 mg/125 mg Tablets: white to off-white colored, capsule shaped, biconvex, film-coated tablets debossed with “I 07” on one side score line on the other side. Each tablet contains 875 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.


The 250 mg/125 mg amoxicillin and clavulanate potassium tablet and the 250 mg/62.5 mg chewable tablet should NOT be substituted for each other, as they are not interchangeable and the 250 mg/125 mg tablet should not be used in children weighing less than 40 kg. The 250 mg/125 mg amoxicillin and clavulanate potassium tablet and the 250 mg/62.5 mg chewable tablet do not contain the same amount of clavulanic acid. The 250 mg/125 mg amoxicillin and clavulanate potassium tablet contains 125 mg of clavulanic acid whereas the 250 mg/62.5 mg chewable tablet contains 62.5 mg of clavulanic acid.


Two 250 mg/125 mg amoxicillin and clavulanate potassium tablets should NOT be substituted for one 500 mg/125 mg amoxicillin and clavulanate potassium tablet. Since both the 250 mg/125 mg and 500 mg/125 mg amoxicillin and clavulanate potassium tablets contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250 mg/125 mg amoxicillin and clavulanate potassium tablets are not equivalent to one 500 mg/125 mg amoxicillin and clavulanate potassium tablet.

Contraindications

Serious Hypersensitivity Reactions


Amoxicillin and clavulanate potassium 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).

Cholestatic Jaundice/Hepatic Dysfunction


Amoxicillin and clavulanate potassium is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium.

Warnings and Precautions

Hypersensitivity Reactions


Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including amoxicillin and clavulanate potassium. 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 amoxicillin and clavulanate potassium, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin and clavulanate potassium tablets should be discontinued and appropriate therapy instituted.

Hepatic Dysfunction


Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of amoxicillin and clavulanate potassium. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.

Clostridium difficile-Associated Diarrhea (CDAD)


Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium, 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 antibacterial 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.

Skin Rash in Patients with Mononucleosis


A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin and clavulanate potassium tablets should not be administered to patients with mononucleosis.

Potential for Microbial Overgrowth


The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin and clavulanate potassium should be discontinued and appropriate therapy instituted.

Development of Drug-Resistant Bacteria


Prescribing amoxicillin and clavulanate potassium tablets 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.

Use in specific populations

Pregnancy


Teratogenic Effects

Pregnancy Category B

Reproduction studies performed in pregnant rats and mice given amoxicillin and clavulanate potassium (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day revealed no evidence of harm to the fetus due to amoxicillin and clavulanate potassium. The amoxicillin doses in rats and mice (based on body surface area) were approximately 4 and 2 times the maximum recommended adult human oral dose (875 mg/125 mg every 12 hours). For clavulanate, these dose multiples were approximately 9 and 4 times the maximum recommended adult human oral dose (125 mg every 8 hours). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery


Oral ampicillin-class antibiotics are poorly absorbed during labor. It is not known whether use of amoxicillin and clavulanate potassium 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.

Nursing Mothers


Amoxicillin has been shown to be excreted in human milk. Amoxicillin and clavulanate potassium use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin and clavulanate potassium is administered to a nursing woman.

Pediatric Use


The safety and effectiveness of amoxicillin and clavulanate potassium for oral suspension and chewable tablets have been established in pediatric patients. Use of amoxicillin and clavulanate potassium in pediatric patients is supported by evidence from studies of amoxicillin and clavulanate potassium tablets in adults with additional data from a study of amoxicillin and clavulanate potassium for oral suspension in pediatric patients aged 2 months to 12 years with acute otitis media. [see Clinical Studies (14.2)]

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed; clavulanate elimination is unaltered in this age group. Dosing of amoxicillin and clavulanate potassium should be modified in pediatric patients aged <12 weeks (<3 months). [ see Dosage and Administration (2.2)]

Geriatric Use


Of the 3,119 patients in an analysis of clinical studies of amoxicillin and clavulanate potassium, 32% were ≥65 years old, and 14% were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but 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 adverse 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.

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 Patients with Renal Impairment (2.3) for specific recommendations in patients with renal impairment.

Patient Counseling Information

Information for Patients

Patients should be informed that amoxicillin and clavulanate potassium tablets may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset.


Patients should be counseled that antibacterial drugs, including amoxicillin and clavulanate potassium tablets, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin and clavulanate potassium tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin and clavulanate potassium tablets or other antibacterial drugs in the future.


Counsel patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician.


Patients should be advised to keep suspension refrigerated.  Shake well before using.  When dosing a child with the suspension (liquid) of amoxicillin and clavulanate potassium, use a dosing spoon or medicine dropper.  Be sure to rinse the spoon or dropper after each use.  Bottles of suspension of amoxicillin and clavulanate potassium may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires.  Discard any unused medicine.


Patients should be aware that amoxicillin and clavulanate potassium tablets contain a penicillin class drug product that can cause allergic reactions in some individuals.


All brand names listed are the registered trademarks of their respective owners and are not trademarks of Micro Labs Limited.


Manufactured by:

Micro Labs Limited

Banglore-560 100, India.


Manufactured for:

Micro Labs USA Inc.

Princeton, NJ 08540


Revised: August 2017

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