AMOXICILLIN AND CLAVULANATE POTASSIUM

Main information

  • Trade name:
  • AMOXICILLIN AND CLAVULANATE POTASSIUM- amoxicillin and clavulanate potassium powder, for suspension
  • Composition:
  • AMOXICILLIN ANHYDROUS 400 mg in 5 mL
  • Administration route:
  • ORAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMOXICILLIN AND CLAVULANATE POTASSIUM- amoxicillin and clavulanate potassium powder, for suspension
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  •        To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP (amoxicillin/ clavulanate potassium) and other antibacterial drugs, Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP 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 Powder for Oral Suspension, 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*: - caused by beta-lactamase-producing isolates of Haemophilus  
  • Product summary:
  • Product: 50090-0831 NDC: 50090-0831-0 100 mL in a BOTTLE Product: 50090-0832 NDC: 50090-0832-0 100 mL in a BOTTLE

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 50090-0831-0, 50090-0832-0
  • Last update:
  • 17-06-2019

Summary of Product characteristics: dosage, interactions, side effects

AMOXICILLIN AND CLAVULANATE POTASSIUM- amoxicillin and clavulanate

potassium powder, for suspension

A-S Medication Solutions

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use Amoxicillin and Clavulanate Potassium

Powder for Oral Suspension, USP safely and effectively. See full prescribing information for Amoxicillin and

Clavulanate Potassium Powder for Oral Suspension, USP.

Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP

Initial U.S. Approval: 1984

Rx Only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and Clavulanate

Potassium 200 and 400 and other antibacterial drugs, Amoxicillin and Clavulanate Potassium 200 and 400 should be used

only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (11.3)

INDICATIONS AND USAGE

Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP is a combination penicillin-class antibacterial and

beta-lactamase inhibitor indicated for treatment of the following:

Lower respiratory tract infections (1.1)

Acute bacterial otitis media (1.2)

Sinusitis (1.3)

Skin and skin structure infections (1.4)

Urinary tract infections (1.5)

DOSAGE AND ADMINISTRATION

Adults and Pediatric Patients > 40 kg: 500 or 875 mg every 12 hours or 250 or 500 mg every 8 hours. (2.1, 2.2)

Pediatric patients aged 12 weeks (3 months) and older: 25 to 45 mg/kg/day every 12 hours or 20 to 40 mg/kg/day every

8 hours, up to the adult dose. (2.2)

Neonates and infants < 12 weeks of age: 30 mg/kg/day divided every 12 hours, based on the amoxicillin component.

Use of the 125 mg/5 mL oral suspension is recommended. (2.2)

DOSAGE FORMS AND STRENGTHS

Formulation and amoxicillin/clavulanate content is:

Powder for Oral Suspension: 200 mg/28.5 mg per 5 mL, 400 mg/57 mg per 5 mL (3)

CONTRAINDICATIONS

History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin and

clavu lanate potassium or to other beta-lactams (e.g., penicillins or cephalosporins) (4)

History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium for oral

suspension. (4)

WARNINGS AND PRECAUTIONS

Serious (including fatal) hypersensitivity reactions: Discontinue amoxicillin and clavulanate potassium for oral

suspension if a reaction occurs. (5.1)

Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function

tests in patients with hepatic impairment. (5.2)

Clostridium difficile-associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. (5.3)

Patients with mononucleosis who receive amoxicillin and clavulanate potassium for oral suspension develop skin rash.

Avoid amoxicillin and clavulanate potassium use in these patients. (5.4)

Overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy.

(5.5)

ADVERSE REACTIONS

The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria

(3%), vomiting (1%) and vaginitis (1%) (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-233-2001,

or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

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

Concomitant use of amoxicillin and clavulanate potassium for oral suspension and oral anticoagulants may increase the

prolongation of prothrombin time. (7.2)

Coadministration with allopurinol increases the risk of rash. (7.3)

Amoxicillin and clavulanate potassium for oral suspension may reduce efficacy of oral contraceptives. (7.4)

USE IN SPECIFIC POPULATIONS

Pediatric Use: Modify dose in patients 12 weeks or younger. (8.4)

Renal impairment: Dosage adjustment is recommended for severe renal impairment (GFR< 30mL/min). (2.3, 8.6)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 1/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Lower Respiratory Tract Infections

1.2 Acute Bacterial Otitis Media

1.3 Sinusitis

1.4 Skin and Skin Structure Infections

1.5 Urinary Tract Infections

1.6 Limitations of Use

2 DOSAGE AND ADMINISTRATION

2.1 Adults

2.2 Pediatric Patients

2.3 Patients with Renal Impairment

2.4 Directions for Mixing Oral Suspension

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Serious Hypersensitivity Reactions

4.2 Cholestatic Jaundice/Hepatic Dysfunction

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

5.2 Hepatic Dysfunction

5.3 Clostridium difficile Associated Diarrhea (CDAD)

5.4 Skin Rash in Patients with Mononucleosis

5.5 Potential for Microbial Overgrowth

5.6 Phenylketonurics

5.7 Development of Drug-Resistant Bacteria

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Probenecid

7.2 Oral Anticoagulants

7.3 Allopurinol

7.4 Oral Contraceptives

7.5 Effects on Laboratory Tests

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Dosing in Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Lower Respiratory Tract and Complicated Urinary Tract Infections

14.2 Acute Bacterial Otitis Media and Diarrhea in Pediatric Patients

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17.1 Information for Patients

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin

and Clavulanate Potassium Powder for Oral Suspension, USP (amoxicillin/clavulanate potassium) and

other antibacterial drugs, Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP

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 Powder for Oral Suspension, 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*:

1.1 Lower Respiratory Tract Infections

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

1.2 Acute Bacterial Otitis Media

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

1.3 Sinusitis

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

1.4 Skin and Skin Structure Infections

- caused by beta-lactamase-producing isolates of Staphylococcus aureus, Escherichia coli, and

Klebsiella species.

1.5 Urinary Tract Infections

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

Sections or subsections omitted from the full prescribing information are not listed.

1.6 Limitations of Use

- When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase

production, Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP should not be

used.

2 DOSAGE AND ADMINISTRATION

Amoxicillin and clavulanate potassium suspension may be taken without regard to meals; however,

absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium

suspension is administered at the start of a meal. To minimize the potential for gastrointestinal

intolerance, amoxicillin and clavulanate potassium suspension should be taken at the start of a meal.

2.1 Adults

The usual adult dose is one 500-mg tablet of amoxicillin and clavulanate potassium every 12 hours or

one 250-mg tablet of amoxicillin and clavulanate potassium every 8 hours. For more severe infections

and infections of the respiratory tract, the dose should be one 875-mg tablet of amoxicillin and

clavulanate potassium every 12 hours or one 500-mg tablet of amoxicillin and clavulanate potassium

every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/5 mL or 250 mg/5 mL

suspension in place of the 500-mg tablet. The 200 mg/5 mL suspension or the 400 mg/5 mL suspension

may be used in place of the 875-mg tablet.

Two 250-mg tablets of amoxicillin and clavulanate potassium should not be substituted for one 500-mg

tablet of amoxicillin and clavulanate potassium. Since both the 250-mg and 500-mg tablets of

amoxicillin and clavulanate potassium contain the same amount of clavulanic acid (125 mg, as the

potassium salt), two 250-mg tablets are not equivalent to one 500-mg tablet of amoxicillin and

clavulanate potassium.

The 250-mg tablet of amoxicillin and clavulanate potassium and the 250-mg chewable tablet should not

be substituted for each other, as they are not interchangeable. The 250-mg tablet of amoxicillin and

clavulanate potassium and the 250-mg chewable tablet do not contain the same amount of clavulanic acid

(as the potassium salt). The 250-mg tablet of amoxicillin and clavulanate potassium contains 125 mg of

clavulanic acid, whereas the 250-mg chewable tablet contains 62.5 mg of clavulanic acid.

2.2 Pediatric Patients

Based on the amoxicillin component, amoxicillin and clavulanate potassium suspension should be dosed

as follows:

Neonates and Infants Aged <12 weeks (<3 months): The recommended dose of amoxicillin and

clavulanate potassium suspension 30 mg/kg/day divided every 12 hours, based on the amoxicillin

component. Experience with the 200 mg/5 mL formulation in this age group is limited, and thus, use of

the 125 mg/5 mL oral suspension is recommended.

Patients Aged 12 weeks (3 months) and Older: See dosing regimens provided in Table 1. The every

12 hours regimen is recommended as it is associated with significantly less diarrhea [see Clinical Studies

(14.2)]. However, the every 12 hours suspension (200 mg/5 mL and 400 mg/5 mL) and chewable tablets

(200 mg and 400 mg) contain aspartame and should not be used by phenylketonurics. [see Warnings and

Precautions (5.6)]

Table 1: Dosing in Patients Aged 12 weeks (3 months) and Older

INFECTION

DOSING REGIMEN

Every 12 hours

Every 8 hours

200 mg/5 mL or 400 mg/5 mL

oral suspension

125 mg/5 mL or 250 mg/5 mL

oral suspension

Otitis media , sinusitis,

lower respiratory tract

infections, and more

severe infections

45 mg/kg/day every 12 hours

40 mg/kg/day every 8 hours

Less severe infections

25 mg/kg/day every 12 hours

20 mg/kg/day every 8 hours

Each strength of suspension of amoxicillin and clavulanate potassium is available as a chewable tablet

for use by older children.

Duration of therapy studied and recommended for acute otitis media is 10 days.

Patients Weighing 40 kg or More: Pediatric patients weighing 40 kg or more should be dosed

according to adult recommendations.

The 250-mg tablet of amoxicillin and clavulanate potassium should not be used until the child weighs at

least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250-mg tablet of amoxicillin

and clavulanate potassium (250/125) versus the 250-mg chewable tablet of amoxicillin and clavulanate

potassium (250/62.5).

2.3 Patients with Renal Impairment

Patients with impaired renal function do not generally require a reduction in dose unless the

impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should

not receive the 875-mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should

receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a

glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours,

depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the

infection. They should receive an additional dose both during and at the end of dialysis.

2.4 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 2 below) and shake

vigorously to suspend powder. Add remainder of the water and again shake vigorously.

Table 2: Amount of Water for Mixing Oral Suspension

Strength

Bottle Size

Amount of Water

for Reconstitution

Contents of Each Teaspoonful (5

mL)

200 mg/5 mL

50 mL

75 mL

100 mL

48 mL

71 mL

95 mL

200 mg amoxicillin and 28.5 mg of

clavulanic acid as the potassium salt

400 mg/5 mL

50 mL

75 mL

100 mL

45 mL

68 mL

90 mL

400 mg amoxicillin and 57.0 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.

3 DOSAGE FORMS AND STRENGTHS

200 mg/28.5 mg per 5 mL: The dry powder is white to off white with fruity flavor. Each 5 mL of

reconstituted creamy suspension contains 200 mg amoxicillin and 28.5 mg clavulanic acid as the

potassium salt.

400 mg/57 mg per 5 mL: The dry powder is white to off white with fruity flavor. Each 5 ml of

reconstituted creamy suspension contains 400 mg amoxicillin and 57 mg clavulanic acid as the

potassium salt.

4 CONTRAINDICATIONS

4.1 Serious Hypersensitivity Reactions

Amoxicillin and clavulanate potassium suspension 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

Amoxicillin and clavulanate potassium suspension is contraindicated in patients with a previous

history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate

potassium suspension.

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in

patients receiving beta-lactam antibacterials, including amoxicillin and clavulanate potassium

suspension. 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 suspension, careful inquiry should be made regarding previous

hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction

occurs, amoxicillin and clavulanate potassium suspension should be discontinued and appropriate

therapy instituted.

5.2 Hepatic Dysfunction

Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of

amoxicillin and clavulanate potassium suspension. Hepatic toxicity is usually reversible; however,

deaths have been reported. Hepatic function should be monitored at regular intervals in patients with

hepatic impairment.

5.3 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 suspension, 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.

5.4 Skin Rash in Patients with Mononucleosis

5.4 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 suspension should not be

administered to patients with mononucleosis.

5.5 Potential for Microbial Overgrowth

The possibility of superinfections with fungal or bacterial pathogens should be considered during

therapy. If superinfection occurs, amoxicillin/clavulanate potassium suspension should be discontinued

and appropriate therapy instituted.

5.6 Phenylketonurics

Amoxicillin and clavulanate potassium for oral suspension contains aspartame which contains

phenylalanine. Each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL suspension contains 7 mg

phenylalanine.

5.7 Development of Drug-Resistant Bacteria

Prescribing amoxicillin and clavulanate potassium suspension 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.

6 ADVERSE REACTIONS

The following are discussed in more detail in other sections of the labeling:

Anaphylactic reactions [see Warnings and Precautions (5.1)]

Hepatic Dysfunction [see Warnings and Precautions (5.2)]

CDAD [see Warnings and Precautions (5.3)]

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 frequently reported adverse reactions were diarrhea/loose stools (9%), nausea (3%), skin

rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued

therapy because of drug-related adverse reactions. The overall incidence of adverse reactions, and in

particular diarrhea, increased with the higher recommended dose. Other less frequently reported

adverse reactions (<1%) include: Abdominal discomfort, flatulence, and headache.

In pediatric patients (aged 2 months to 12 years), 1 US/Canadian clinical trial was conducted which

compared 45/6.4 mg/kg/day (divided every 12 hours) of amoxicillin and clavulanate potassium for 10

days versus 40/10 mg/kg/day (divided every 8 hours) of amoxicillin and clavulanate potassium 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 reactions seen were comparable to that noted

above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area

rashes. [See Clinical Studies (14.2)]

6.2 Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following have been identified

during postmarketing use of amoxicillin and clavulanate potassium. 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 and clavulanate potassium.

Gastrointestinal: 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 and

Precautions (5.3)]

Hypersensitivity Reactions: Pruritus, angioedema, serum sickness-like reactions (urticaria or skin rash

accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens-

Johnson syndrome, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and cases of

exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. [see Warnings and

Precautions (5.1)]

Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum

transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with

amoxicillin and clavulanate potassium. 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. Deaths have been

reported. [see Contraindications (4.2), Warnings and Precautions (5.2)]

Renal: Interstitial nephritis, hematuria, and crystalluria have 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. Thrombocytosis was noted in less than 1% of the patients treated with amoxicillin and

clavulanate potassium. There have been reports of increased prothrombin time in patients receiving

amoxicillin and clavulanate potassium and anticoagulant therapy concomitantly. [see Drug Interactions

(7.2)]

Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness,

insomnia, and reversible hyperactivity 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 DRUG INTERACTIONS

7.1 Probenecid

Probenecid decreases the renal tubular secretion of amoxicillin but does not delay renal excretion

of clavulanic acid. Concurrent use with amoxicillin and clavulanate potassium may result in increased

and prolonged blood concentrations of amoxicillin. Coadministration 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 with amoxicillin and clavulanate

potassium. 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 and clavulanate potassium 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 amoxicillin and clavulanate potassium, 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.

8 USE IN SPECIFIC POPULATIONS

8.1 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 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 has 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 powder 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)]

8.5 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.

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 .

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 Powder for Oral Suspension, USP is an oral antibacterial

combination consisting of amoxicillin and the beta-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

H N O S3H 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 beta-lactam

structurally related to the penicillins and possesses the ability to inactivate some beta-lactamases by

blocking the active sites of these enzymes. The clavulanate potassium molecular formula is

C H KNO , 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:

Inactive Ingredients:

Aspartame, colloidal silicon dioxide, HPMC 2910/ hypromellose 5 cP, silicon dioxide, succinic

acid, xanthan gum, golden syrup flavor, orange flavor.

See PRECAUTIONS - Information for the Patient.

Each 5 mL of reconstituted amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL

suspension contains 0.268 mEq of potassium.

Each 5 mL of reconstituted amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL

suspension contains 0.143 mEq of potassium

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Amoxicillin and clavulanate potassium for oral suspension is an antibacterial drug. [see Microbiology

12.4]

12.3 Pharmacokinetics

Mean amoxicillin and clavulanate potassium pharmacokinetic parameters in normal adults following

administration of amoxicillin and clavulanate potassium tablets are shown in Table 3 and following

administration of amoxicillin and clavulanate potassium powder for oral suspension and chewable

tablets are shown in Table 4.

Table 3: Mean (±S.D.) Amoxicillin and Clavulanate Potassium Pharmacokinetic

Parameters

with Amoxicillin and Clavulanate Potassium Tablets

Dose and Regimen

(mcg/mL)

(mcg*h/mL)

a,b

0-24

Amoxicillin/Clavulanate

potassium

Amoxicillin

Clavulanate

potassium

Amoxicillin

Clavulanate

potassium

250/125 mg every 8 hours

3.3 ± 1.12

1.5 ± 0.70

26.7 ± 4.56

12.6 ± 3.25

500/125 mg every 12 hours

6.5 ± 1.41

1.8 ± 0.61

33.4 ± 6.76

8.6 ± 1.95

500 125 mg every 8 hours

7.2 ± 2.26

2.4 ± 0.83

53.4 ± 8.87

15.7 ± 3.86

875/125 mg every 12 hours

11.6 ± 2.78

2.2 ± 0.99

53.5 ± 12.31

10.2 ± 3.04

Mean (± standard deviation) values of 14 normal adults (N=15 for clavulanate potassium in the low-

dose regimens). Peak concentrations occurred approximately 1.5 hours after the dose.

Amoxicillin/clavulanate potassium administered at the start of a light meal.

Table 4: Mean (±S.D.) Amoxicillin and Clavulanate Potassium Pharmacokinetic

Parameters

with Amoxicillin and Clavulanate Potassium Powder for Oral

Suspension and Chewable Tablets

Dose

(mcg/mL)

(mcg*h/mL)

Amoxicillin/Clavulanate

potassium

Amoxicillin

Clavulanate

potassium

Amoxicillin

Clavulanate

potassium

400/57 mg (5 mL of

suspension)

6.94 ± 1.24

1.10 ± 0.42

17.29 ± 2.28

2.34 ± 0.94

400/57 mg (1 chewable

tablet)

6.67 ± 1.37

1.03 ± 0.33

17.24 ± 2.64

2.17 ± 0.73

Mean (± standard deviation) values of 28 normal adults. Peak concentrations occurred approximately 1

hour after the dose.

Amoxicillin/clavulanate potassium administered at the start of a light meal.

Oral administration of 5 mL of 250 mg/62.5 mg per 5 mL suspension of amoxicillin and clavulanate

potassium or the equivalent dose of 10 mL of 125 mg/31.25 mg per 5 mL suspension of amoxicillin and

clavulanate potassium provides average peak serum concentrations approximately 1 hour after dosing of

6.9 mcg/mL for amoxicillin and 1.6 mcg/mL for clavulanic acid. The areas under the serum

concentration curves obtained during the first 4 hours after dosing were 12.6 mcg*h/mL for amoxicillin

and 2.9 mcg*h/mL for clavulanic acid when 5 mL of 250 mg/62.5 mg per 5 mL suspension of

amoxicillin and clavulanate potassium or equivalent dose of 10 mL of 125 mg/31.25 mg per 5 mL

suspension of amoxicillin and clavulanate potassium were administered to normal adults. One 250

mg/62.5 mg chewable tablet of amoxicillin and clavulanate potassium or two 125 mg/31.25 mg chewable

tablets of amoxicillin and clavulanate potassium are equivalent to 5 mL of 250 mg/ 62.5 mg per 5 mL

suspension of amoxicillin and clavulanate potassium and provide similar serum concentrations of

amoxicillin and clavulanic acid.

Amoxicillin serum concentrations achieved with amoxicillin and clavulanate potassium suspension

are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. Time

above the minimum inhibitory concentration of 1 mcg/mL for amoxicillin has been shown to be similar

after corresponding every 12 hour and every 8 hour dosing regimens of amoxicillin and clavulanate

potassium suspension in adults and children.

Absorption: Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of

amoxicillin. While amoxicillin and clavulanate potassium suspension can be given without regard to

meals, absorption of clavulanate potassium when taken with food is greater relative to the fasted state. In

one study, the relative bioavailability of clavulanate was reduced when amoxicillin and clavulanate

potassium suspension was dosed at 30 and 150 minutes after the start of a high-fat breakfast.

Distribution: Neither component in amoxicillin and clavulanate potassium suspension is highly

protein-bound; clavulanic acid is approximately 25% bound to human serum and amoxicillin

a,b

0-24

approximately 18% bound.

Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and

spinal fluid.

Two hours after oral administration of a single 35 mg/kg dose of suspension of amoxicillin and

clavulanate potassium to fasting children, average concentrations of 3 mcg/mL of amoxicillin and 0.5

mcg/mL of clavulanic acid were detected in middle ear effusions.

Metabolism and Excretion: The half-life of amoxicillin after the oral administration of amoxicillin

and clavulanate potassium suspension is 1.3 hours and that of clavulanic acid is 1 hour.

Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic acid

are excreted unchanged in urine during the first 6 hours after administration of a single 250-mg or

500-mg tablet of amoxicillin and clavulanate potassium.

12.4 Microbiology

Amoxicillin is a semisynthetic antibiotic with in vitro bactericidal activity against Gram-positive and

Gram-negative bacteria. Amoxicillin is, however, susceptible to degradation by beta-lactamases, and

therefore, the spectrum of activity does not include organisms which produce these enzymes.

Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to

inactivate some beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and

cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated beta-

lactamases frequently responsible for transferred drug resistance.

The formulation of amoxicillin and clavulanic acid in amoxicillin and clavulanate potassium for oral

suspension protects amoxicillin from degradation by some beta-lactamase enzymes and extends the

antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin.

Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following bacteria,

both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive bacteria

Staphylococcus aureus

Gram-negative bacteria

Enterobacter species

Escherichia coli

Haemophilus influenzae

Klebsiella species

Moraxella catarrhalis

The following in vitro data are available, but their clinical significance is unknown. At least 90

percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or

equal to the susceptible breakpoint for amoxicillin/clavulanic acid. However, the efficacy

of amoxicillin/clavulanic acid in treating clinical infections due to these bacteria has not been

established in adequate and well-controlled clinical trials.

Gram-positive bacteria

Enterococcus faecalis Staphylococcus epidermidis Staphylococcus saprophyticus Streptococcus

pneumoniae Streptococcus pyogenes Viridans group Streptococcus

Gram-negative Bacteria

Eikenella corrodens

Proteus mirabilis

Anaerobic Bacteria

Bacteroides species including Bacteroides fragilis

Fusobacterium species

Peptostreptococcus species

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro

susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as

periodic reports that describe the susceptibility profile of nosocomial and community-acquired

pathogens. These reports should aid the physician in selecting an antibacterial drug product for

treatment.

Dilution techniques:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs).

These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs

should be determined using a standardized test method

(broth and/or agar). The MIC values should be

interpreted according to criteria provided in Table 5.

Diffusion techniques:

Quantitative methods that require measurement of zone diameters can also provide reproducible

estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an

estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be

determined using a standardized test method

. This procedure uses paper disks impregnated with 30

mcg amoxicillin/clavulanic acid (20 mcg amoxicillin plus 10 mcg clavulanic acid) to test the

susceptibility of bacteria to amoxicillin/clavulanic acid. The disc diffusion interpretive criteria are

provided in Table 5.

Table 5: Susceptibility Test Interpretive Criteria for Amoxicillin Clavulanic Acid

Minimum Inhibitory Concentrations

(mcg/mL)

Disk Diffusion (zone diameters in mm)

Pathogen

Enterobacteriaceae

16/8

32/16

≥18

14-17

≤13

Haemophilus influenzae and

Staphylococcus aureus

≥20

≤19

Quality Control:

Standardized susceptibility test procedures require the use of laboratory controls to monitor and

ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the

individuals performing the test

. Standard amoxicillin/clavulanic acid powder should provide the

following range of MIC values noted in Table 6 for the diffusion technique using the 30 mcg

amoxicillin/clavulanic acid (20 mcg amoxicillin plus 10 mcg clavulanic acid) disk, the criteria in Table

6 should be achieved.

Table 6: Acceptable Quality Control Ranges for Amoxicillin/Clavulanic Acid

QC Strain

Minimum Inhibitory

Concentration

(mcg/mL)

Disk Diffusion (zone

diameter in mm)

Escherichia coli ATCC 25922

2/1 to 8/4

18 to 24

2, 3

2,3,4

Escherichia coli ATCC 35218

4/2 to 16/8

17 to 22

Haemophilus influenzae ATCC 49247

2/1 to 16/8

15 to 23

Staphylococcus aureus ATCC 29213

0.12/0.06 to 0.5/0.25

Staphylococcus aureus ATCC 29523

28 to 36

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Amoxicillin and clavulanate potassium (4:1 ratio formulation of amoxicillin:clavulanate) was non-

mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and

clavulanate potassium was weakly positive in the mouse lymphoma assay, but the trend toward increased

mutation frequencies in this assay occurred at doses that were also associated with decreased cell

survival.

Amoxicillin and clavulanate potassium suspension was negative in the mouse micronucleus test, and in

the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation

assay and in the mouse micronucleus test, and was negative in each of these assays.

Amoxicillin and clavulanate potassium suspension (2:1 ratio formulation of amoxicillin:clavulanate)

at oral doses of up to 1,200 mg/kg/day was found to have no effect on fertility and reproductive

performance in rats. Based on body surface area, this dose of amoxicillin is approximately 4 times the

maximum recommended adult human oral dose (875 mg every 12 hours). For clavulanate, the dose

multiple is approximately 9 times higher than the maximum recommended adult human oral dose (125 mg

every 8 hours), also based on body surface area.

14 CLINICAL STUDIES

14.1 Lower Respiratory Tract and Complicated Urinary Tract Infections

Data from 2 pivotal trials in 1,191 patients treated for either lower respiratory tract infections or

complicated urinary tract infections compared a regimen of 875-mg tablets of amoxicillin and

clavulanate potassium every 12 hours to 500-mg tablets of amoxicillin and clavulanate potassium dosed

every 8 hours (584 and 607 patients, respectively). Comparable efficacy was demonstrated between the

every 12 hours and every 8 hours dosing regimens. There was no significant difference in the

percentage of adverse events in each group. The most frequently reported adverse event was diarrhea;

incidence rates were similar for the 875-mg every 12 hours and 500-mg every 8 hours dosing regimens

(15% and 14%, respectively); however, there was a statistically significant difference (p < 0.05) in rates

of severe diarrhea or withdrawals with diarrhea between the regimens: 1% for 875-mg every 12 hours

regimen versus 2% for the 500-mg every 8 hours regimen.

In one of these pivotal trials, patients with either pyelonephritis (n = 361) or a complicated urinary

tract infection (i.e., patients with abnormalities of the urinary tract that predispose to relapse of

bacteriuria following eradication, n = 268) were randomized (1:1) to receive either 875-mg tablets of

amoxicillin and clavulanate potassium every 12 hours (n=308) or 500-mg tablets of amoxicillin and

clavulanate potassium every 8 hours (n=321).

The number of bacteriologically evaluable patients was comparable between the two dosing

regimens. Amoxicillin and clavulanate potassium produced comparable bacteriological success rates in

patients assessed 2 to 4 days immediately following end of therapy. The bacteriologic efficacy rates

were comparable at one of the follow-up visits (5 to 9 days post-therapy) and at a late post-therapy visit

(in the majority of cases, this was 2 to 4 weeks post-therapy), as seen in Table 7.

Table 7: Bacteriologic efficacy rates for Amoxicillin and Clavulanate Potassium

Time Post Therapy

875 mg every 12 hours % (n)

500 mg every 8 hours % (n)

2 to 4 days

81% (58)

80% (54)

5 to 9 days

58% (41)

52% (52)

2 to 4 weeks

52% (101)

55% (104)

As noted before, though there was no significant difference in the percentage of adverse events in

each group, there was a statistically significant difference in rates of severe diarrhea or withdrawals

with diarrhea between the regimens.

14.2 Acute Bacterial Otitis Media and Diarrhea in Pediatric Patients

One US/Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12

hours) of amoxicillin and clavulanate potassium for 10 days versus 40/10 mg/kg/day (divided every 8

hours) of amoxicillin and clavulanate potassium for 10 days in the treatment of acute otitis media. Only

the suspension formulations were used in this trial. A total of 575 pediatric patients (aged 2 months to 12

years) were enrolled, with an even distribution among the 2 treatment groups and a comparable number

of patients were evaluable (i.e., ≥ 84%) per treatment group. Otitis media-specific criteria were

required for eligibility and a strong correlation was found at the end of therapy and follow-up between

these criteria and physician assessment of clinical response. The clinical efficacy rates at the end of

therapy visit (defined as 2-4 days after the completion of therapy) and at the follow-up visit (defined as

22-28 days post-completion of therapy) were comparable for the 2 treatment groups, with the following

cure rates obtained for the evaluable patients: At end of therapy, 87% (n = 265) and 82% (n = 260) for

45 mg/kg/day every 12 hours and 40 mg/kg/day every 8 hours, respectively. At follow-up, 67% (n =

249) and 69% (n = 243) for 45 mg/kg/day every 12 hours and 40 mg/kg/day every 8 hours, respectively.

Diarrhea was defined as either: (a) 3 or more watery or 4 or more loose/watery stools in 1 day; OR

(b) 2 watery stools per day or 3 loose/watery stools per day for 2 consecutive days. The incidence of

diarrhea was significantly lower in patients who received the every 12 hours regimen compared to

patients who received the every 8 hours regimen (14% and 34%, respectively). In addition, the number

of patients with either severe diarrhea or who were withdrawn with diarrhea was significantly lower in

the every 12 hours treatment group (3% and 8% for the every 12 hours/10 day and every 8 hours/10 day,

respectively). In the every 12 hours treatment group, 3 patients (1%) were withdrawn with an allergic

reaction, while 1 patient in the every 8 hours group was withdrawn for this reason. The number of

patients with a candidal infection of the diaper area was 4% and 6% for the every 12 hours and every 8

hours groups, respectively.

It is not known if the finding of a statistically significant reduction in diarrhea with the oral

suspensions dosed every 12 hours, versus suspensions dosed every 8 hours, can be extrapolated to the

chewable tablets. The presence of mannitol in the chewable tablets may contribute to a different

diarrhea profile. The every 12 hour oral suspensions (200 mg/5 mL and 400 mg/5 mL) are sweetened

with aspartame.

15 REFERENCES

1. Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and cephalosporin

ingestions in children less than six years of age. Vet Hum Toxicol. 1988; 30: 66-67.

2. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility

Tests for Bacteria that Grow Aerobically; Approved Standard – 8

ed. CLSI Document M7-A9. CLSI,

940 West Valley Road, Suite 1400, Wayne, PA, 19087, 2012.

3. Clinical and Laboratory Standards Institute (CLSI). Performance Standard for Antimicrobial Disk

Susceptibility Tests; Approved Standard – 11

ed. CLSI Document M2-A11. CLSI, 940 West Valley

Road, Suite 1400, Wayne, PA, 19087, 2012.

4. CLSI. Performance Standards for Antimicrobial Susceptibility Testing: 22

Informational

Supplement. CLSI document M100-S22. CLSI, Wayne, PA, 2012.

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 50090-0831

NDC: 50090-0831-0 100 mL in a BOTTLE

Product: 50090-0832

NDC: 50090-0832-0 100 mL in a BOTTLE

17 PATIENT COUNSELING INFORMATION

17.1 Information for Patients

Patients should be informed that amoxicillin and clavulanate potassium suspension 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

suspension, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the

common cold). When amoxicillin and clavulanate potassium suspension is 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

suspension 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 suspension, 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 suspension 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 suspension contains a penicillin

class drug product that can cause allergic reactions in some individuals.

CLINITEST is a registered trademark of Miles, Inc.

Distributed by:

West-Ward Pharmaceutical Corp.

Eatontown, NJ 07724 USA

Manufactured by:

HIKMA Pharmaceuticals

P.O. Box 182400

Amman 11118 - Jordan

Revised April 2013

Amoxicillin and Clavulanate Potassium

Amoxicillin and Clavulanate Potassium

AMOXICILLIN AND CLAVULANATE POTASSIUM

amoxicillin and clavulanate potassium powder, for suspension

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:50 0 9 0 -0 8 31(NDC:0 143-9 9 8 2)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

AMO XICILLIN (UNII: 8 0 48 26 J2HU) (AMOXICILLIN ANHYDROUS -

UNII:9 EM0 5410 Q9 )

AMOXICILLIN

ANHYDROUS

40 0 mg

in 5 mL

CLAVULANIC ACID (UNII: 23521W1S24) (CLAVULANIC ACID - UNII:23521W1S24)

CLAVULANIC ACID

57 mg in 5 mL

Inactive Ingredients

Ingredient Name

Stre ng th

ASPARTAME (UNII: Z0 H242BBR1)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

HYPRO MELLO SE 2 9 10 ( 5 MPA.S) (UNII: R75537T0 T4)

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

XANTHAN GUM (UNII: TTV12P4NEE)

Product Characteristics

Color

S core

S hap e

S iz e

Flavor

FRUIT (Fruity Flavo r)

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:50 0 9 0 -0 8 31-0

10 0 mL in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

11/28 /20 14

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 6 519 1

12/0 1/20 0 7

AMOXICILLIN AND CLAVULANATE POTASSIUM

amoxicillin and clavulanate potassium powder, for suspension

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:50 0 9 0 -0 8 32(NDC:0 143-9 9 8 1)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

AMO XICILLIN (UNII: 8 0 48 26 J2HU) (AMOXICILLIN ANHYDROUS -

UNII:9 EM0 5410 Q9 )

AMOXICILLIN

ANHYDROUS

20 0 mg in 5 mL

CLAVULANIC ACID (UNII: 23521W1S24) (CLAVULANIC ACID - UNII:23521W1S24)

CLAVULANIC ACID

28 .5 mg

in 5 mL

Inactive Ingredients

Ingredient Name

Stre ng th

ASPARTAME (UNII: Z0 H242BBR1)

A-S Medication Solutions

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

HYPRO MELLO SE 2 9 10 ( 5 MPA.S) (UNII: R75537T0 T4)

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

XANTHAN GUM (UNII: TTV12P4NEE)

Product Characteristics

Color

S core

S hap e

S iz e

Flavor

FRUIT (Fruity Flavo r)

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:50 0 9 0 -0 8 32-0

10 0 mL in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

11/28 /20 14

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 6 519 1

12/0 1/20 0 7

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

A-S Medicatio n So lutio ns

8 30 0 16 429

RELABEL(50 0 9 0 -0 8 31, 50 0 9 0 -0 8 32)

Revised: 1/2019