Amoxicillin and Clavulanate Potassium (Page 4 of 7)

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects

Pregnancy Category B

Reproduction studies performed in pregnant rats and mice given amoxicillin/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/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.

8.2 Labor and Delivery

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

The safety and effectiveness of amoxicillin and clavulanate potassium for oral suspension and amoxicillin and clavulanate potassium tablets (chewable) have been established in pediatric patients. Use of amoxicillin and clavulanate potassium for oral suspension and amoxicillin and clavulanate potassium tablets (chewable) 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 for oral suspension and amoxicillin and clavulanate potassium tablets (chewable) should be modified in pediatric patients aged < 12 weeks (< 3 months). [ see Dosage and Administration ( 2.2) ]

8.5 Geriatric Use

Of the 3,119 patients in an analysis of clinical studies of amoxicillin/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.

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

10 OVERDOSAGE

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms 1.

Interstitial nephritis resulting in oliguric renal failure has been reported in patients after overdosage with amoxicillin/clavulanate potassium.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin/clavulanate potassium overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin/clavulanate potassium crystalluria.

Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin/clavulanate potassium. Amoxicillin/clavulanate potassium may be removed from circulation by hemodialysis. [see Dosage and Administration ( 2.3) ]

11 DESCRIPTION

Amoxicillin and Clavulanate Potassium Tablets, Amoxicillin and Clavulanate Potassium for Oral Suspension, and Amoxicillin and Clavulanate Potassium Tablets (Chewable) are oral antibacterial combinations consisting of the semisynthetic antibiotic amoxicillin, USP and the beta-lactamase inhibitor, clavulanate potassium, USP (the potassium salt of clavulanic acid). Amoxicillin, USP is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. Chemically, amoxicillin, USP 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 has the following structural formula:

amoxicillin structural formula
(click image for full-size original)

C 16 H 19 N 3 O 5 S•3H 2 O M.W. 419.45

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a beta-lactam structurally related to the penicillins and possesses the ability to inactivate some beta-lactamases by blocking the active sites of these enzymes. Chemically, clavulanate potassium, USP is potassium ( Z)-(2 R ,5 R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate, and has the following structural formula:

clavulanic acid structural formula

C 8 H 8 KNO 5 M.W. 237.25

Amoxicillin and Clavulanate Potassium Tablets USP

Each tablet contains 500 mg or 875 mg amoxicillin, USP as the trihydrate and 125 mg clavulanic acid as the potassium salt. Each Amoxicillin and Clavulanate Potassium Tablet USP contains 0.63 mEq potassium.

Inactive Ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium starch glycolate, titanium dioxide, and triacetin.

Amoxicillin and Clavulanate Potassium for Oral Suspension USP

After reconstitution each teaspoonful (5 mL) of suspension will contain 200 mg amoxicillin, USP as the trihydrate and 28.5 mg clavulanic acid as the potassium salt or 400 mg amoxicillin, USP as the trihydrate and 57 mg clavulanic acid as the potassium salt. Each 5 mL of reconstituted Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 200 mg/28.5 mg per 5 mL contains 0.14 mEq potassium. Each 5 mL of reconstituted Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 400 mg/57 mg per 5 mL contains 0.29 mEq of potassium.

Inactive Ingredients: Powder for oral suspension: artificial raspberry powder, aspartame*, citric acid, colloidal silicon dioxide, mannitol, hypromellose, natural orange flavor, sodium citrate, sodium saccharin and xanthan gum.

* See Warnings and Precautions ( 5.6) .

Amoxicillin and Clavulanate Potassium Tablets USP (Chewable)

Each chewable tablet contains 200 mg amoxicillin, USP as the trihydrate and 28.5 mg clavulanic acid as the potassium salt or contains 400 mg amoxicillin, USP as the trihydrate and 57 mg clavulanic acid as the potassium salt. Each Amoxicillin and Clavulanate Potassium Tablet USP, (Chewable) 200 mg/28.5 mg contains 0.14 mEq potassium. Each Amoxicillin and Clavulanate Potassium Tablet USP, (Chewable) 400 mg/57 mg contains 0.29 mEq potassium.

Inactive Ingredients: aspartame*, colloidal silicon dioxide, FD&C Red #40 lake, magnesium stearate, mannitol, microcrystalline cellulose, SA84 artificial ripe banana flavor, and artificial cherry flavor powder.

* See Warnings and Precautions ( 5.6) .

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