Amoclan

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Amoxicillin falls into category B. There are no well-done studies that have been done in humans with amoxicillin. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

Take Amoxicillin exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Amoxicillin dose your doctor recommends will be based on the following:

• the condition being treated

• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Neonates and Infants aged 12 weeks or younger (≤ 3 months): the recommended upper dose of amoxicillin is 30 mg/kg/day divided and given twice daily.

Adult Dosing (or children 40kg/88 lbs or greater):

• Ear/Nose/Throat infection, mild or moderate: 500 mg twice daily or 250 mg three times daily
• Ear/Nose/Throat, severe infection: 875 mg twice daily or 500 mg three times daily
• Lower respiratory tract (airway) infection, mild or moderate or severe: 875 mg twice daily or 500 mg three times daily
• Skin/Skin Structure infection, mild or moderate: 500 mg twice daily or 250 mg three times
• Skin/Skin Structure infection, severe: 875 mg twice daily or 500 mg three times daily
• Genitourinary tract infection, mild or moderate: 500 mg twice daily or 250 mg three times daily
• Genitourinary tract infection, severe: 875 mg twice daily or 500 mg three times daily
• Gonorrhea Acute, uncomplicated ano-genital and urethral infections in males and females: 3 grams as single oral dose

Dosing in Children (greater than 3 months old or less than 40 kg/88 lbs):

• Ear/Nose/Throat infection, mild or moderate: hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours
• Ear/Nose/Throat, severe infection: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
• Lower respiratory tract (airway) infection, mild or moderate or severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
• Skin/Skin Structure infection, mild or moderate: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours
• Skin/Skin Structure infection, severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
• Genitourinary tract infection, mild or moderate: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours
• Genitourinary tract infection, severe: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
• Gonorrhea Acute, uncomplicated ano-genital and urethral infections in males and females:
  • Prepubertal children: 50 mg/kg amoxicillin, combined with 25 mg/kg probenecid as a single dose. SINCE PROBENECID IS CONTRAINDICATED IN CHILDREN UNDER 2 YEARS, DO NOT USE THIS REGIMEN IN THESE CASES.

In the U.S.

• Amoclan
• Augmentin
• Augmentin ES-600
• Augmentin XR

In Canada

• Alti-Amoxi Clav
• Apo-Amoxi Clav
• Novo-Clavamoxin 125
• Novo-Clavamoxin 250
• Ratio-Amoxi Clav 250f

Available Dosage Forms:

• Tablet
• Tablet, Extended Release
• Powder for Suspension
• Tablet, Chewable

Therapeutic Class: Antibiotic

Pharmacologic Class: Penicillin, Aminopenicillin

Amoxicillin and clavulanate potassium for oral suspension is an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the "ß-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 C16H19N3O5S•3H2O, 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 ß-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of ß-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated ß-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C8H8KNO5 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: Powder for Oral Suspension Aspartame, colloidal silicon dioxide, hypromellose, orange powder flavor, silicon dioxide, succinic acid, xanthan gum.

• See PRECAUTIONS–Information for the Patient/Phenylketonurics.

Each 5 mL of reconstituted amoxicillin and clavulanate potassium for oral suspension 600 mg/42.9 mg per 5 mL contains 0.248 mEq potassium.

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is 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.

General: While amoxicillin/clavulanate possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable if therapy is for longer than the drug is approved for administration.

A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.

Prescribing amoxicillin and clavulanate potassium for oral suspension, in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for the Patient: amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL should be taken every 12 hours with a meal or snack to reduce the possibility of gastrointestinal upset. If diarrhea develops and is severe or lasts more than 2 or 3 days, call your doctor.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, 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 the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Keep suspension refrigerated. Shake well before using. When dosing a child with the suspension (liquid) of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, 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 for oral suspension, 600 mg/42.9 mg per 5 mL 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 counseled that antibacterial drugs, including amoxicillin and clavulanate potassium for oral 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 600 mg/42.9 mg per 5 mL 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 for oral suspension, or other antibacterial drugs in the future.

Phenylketonurics: Each 5 mL of Amoxicillin and Clavulanate Potassium for oral suspension 600 mg/42.9 mg per 5 mL contains 7 mg phenylalanine.

Drug Interactions: Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may result in increased and prolonged blood levels of amoxicillin. Co-administration of probenecid cannot be recommended.

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, 600 mg/42.9 mg per 5 mL and allopurinol administered concurrently.

In common with other broad-spectrum antibiotics, amoxicillin/clavulanate may reduce the efficacy of oral contraceptives.

Drug/Laboratory Test Interactions: Oral administration of amoxicillin and clavulanate potassium will result in high urine concentrations of amoxicillin. High urine concentrations of ampicillin 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 therefore amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX®) be used.

Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted. This effect may also occur with amoxicillin and therefore amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to evaluate carcinogenic potential. The mutagenic potential of amoxicillin and clavulanate potassium was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations. Amoxicillin and clavulanate potassium at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum adult human dose based on body surface area) was found to have no effect on fertility and reproductive performance in rats, dosed with a 2:1 ratio formulation of amoxicillin:clavulanate.

Teratogenic Effects: Pregnancy (Category B). Reproduction studies performed in pregnant rats and mice given amoxicillin and clavulanate potassium at oral dosages up to 1,200 mg/kg/day (4.9 and 2.8 times the maximum adult human oral dose based on body surface area, respectively), revealed no evidence of harm to the fetus due to amoxicillin and clavulanate potassium. 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 generally poorly absorbed during labor. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the 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 that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with amoxicillin and clavulanate potassium may be associated with an increased risk of necrotizing enterocolitis in neonates.

Nursing Mothers: Ampicillin-class antibiotics are excreted in human milk; therefore, caution should be exercised when amoxicillin and clavulanate potassium is administered to a nursing woman.

Pediatric Use: Safety and efficacy of amoxicillin and clavulanate potassium 600 mg/42.9 mg per 5 mL in infants younger than 3 months have not been established. Safety and efficacy of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL have been demonstrated for treatment of acute otitis media in infants and children 3 months to 12 years (see Description of Clinical Studies).

The safety and effectiveness of amoxicillin and cavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL have been established for the treatment of pediatric patients (3 months to 12 years) with acute bacterial sinusitis. This use is supported by evidence from adequate and well-controlled studies of amoxicillin and clavulanate potassium Extended Release Tablets in adults with acute bacterial sinusitis, studies of amoxicillin and clavulanate potassium 600 mg/42.9 mg per 5 mL in pediatric patients with acute otitis media, and by similar pharmacokinetics of amoxicillin and clavulanate in pediatric patients taking amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (see CLINICAL PHARMACOLOGY) and adults taking amoxicillin and clavulanate potassium.

Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients.

In the case of overdosage, discontinue amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. 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 and do not require gastric emptying.4

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin 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 both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis.

Amoclan (Amoxicillin and clavulanate potassium for Oral Suspension USP 600 mg/42.9 mg per 5 mL): Each 5 mL of reconstituted orange-flavored suspension contains 600 mg amoxicillin and 42.9 mg clavulanic acid as the potassium salt.

Two clinical studies were conducted in pediatric patients with acute otitis media.

A non-comparative, open-label study assessed the bacteriologic and clinical efficacy of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) for 10 days in 521 pediatric patients (3 to 50 months) with acute otitis media. The primary objective was to assess bacteriological response in children with acute otitis media due to S. pneumoniae with amoxicillin/clavulanic acid MICs of 4 mcg/mL. The study sought the enrollment of patients with the following risk factors: Failure of antibiotic therapy for acute otitis media in the previous 3 months, history of recurrent episodes of acute otitis media, ≤2 years, or daycare attendance. Prior to receiving amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, all patients had tympanocentesis to obtain middle ear fluid for bacteriological evaluation. Patients from whom S. pneumoniae (alone or in combination with other bacteria) was isolated had a second tympanocentesis 4 to 6 days after the start of therapy. Clinical assessments were planned for all patients during treatment (4-6 days after starting therapy), as well as 2-4 days post-treatment and 15-18 days post-treatment. Bacteriological success was defined as the absence of the pretreatment pathogen from the on-therapy tympanocentesis specimen. Clinical success was defined as improvement or resolution of signs and symptoms. Clinical failure was defined as lack of improvement or worsening of signs and/or symptoms at any time following at least 72 hours of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL; patients who received an additional systemic antibacterial drug for otitis media after 3 days of therapy were considered clinical failures. Bacteriological eradication on therapy (day 4-6 visit) in the per protocol population is summarized in the following table:

Clinical assessments were made in the per protocol population 2-4 days post-therapy and 15-18 days post-therapy. Patients who responded to therapy 2-4 days post-therapy were followed for 15-18 days post-therapy to assess them for acute otitis media. Nonresponders at 2-4 days post-therapy were considered failures at the latter timepoint.

In the intent-to-treat analysis, overall clinical outcomes at 2-4 days and 15-18 days post-treatment in patients with S. pneumoniae with penicillin MIC = 2 mcg/mL and 4 mcg/mL were 29/41 (71%) and 17/41 (41.5%), respectively.

In the intent-to-treat population of 521 patients, the most frequently reported adverse events were vomiting (6.9%), fever (6.1%), contact dermatitis (i.e., diaper rash) (6.1%), upper respiratory tract infection (4%), and diarrhea (3.8%). Protocol-defined diarrhea (i.e., 3 or more watery stools in one day or 2 watery stools per day for 2 consecutive days as recorded on diary cards) occurred in 12.9% of patients.

A double-blind, randomized, clinical study compared amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) to amoxicillin and clavulanate potassium(45/6.4 mg/kg/day, divided every 12 hours) for 10 days in 450 pediatric patients (3 months to 12 years) with acute otitis media. The primary objective of the study was to compare the safety of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL to amoxicillin and clavulanate potassium. There was no statistically significant difference between treatments in the proportion of patients with 1 or more adverse events. The most frequently reported adverse events for amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and the comparator of amoxicillin and clavulanate potassium were coughing (11.9% versus 6.8%), vomiting (6.5% versus 7.7%), contact dermatitis (i.e., diaper rash, 6% versus 4.8%), fever (5.5% versus 3.9%), and upper respiratory infection (3.0% versus 9.2%), respectively. The frequencies of protocol-defined diarrhea with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL (11.1%) and Amoxicillin and Clavulanate Potassium (9.4%) were similar (95% confidence interval on difference: −4.2% to 7.7%). Only 2 patients in the group treated with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and 1 patient in the group treated with amoxicillin and clavulanate potassium 600 mg/42.9 mg per 5 mL were withdrawn due to diarrhea.

1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically – Sixth Edition; Approved Standard, NCCLS Document M7-A6, Vol. 23, No. 2, NCCLS, Wayne, PA, January 2003.
2. National Committee for Clinical Laboratory Standards for Antimicrobial Susceptibility Testing: Fourteenth Informational Supplement; Approved Standard, NCCLS Document 100-S14, Vol. 24, No. 1, NCCLS, Wayne, PA, January 2004.
3. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests – Eighth Edition; Approved Standard, NCCLS Document M2-A8, Vol. 23, No. 1, NCCLS, Wayne, PA, January 2003.
4. 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.

CLINITEST is a registered trademark of Miles, Inc.

CLINISTIX is a registered trademark of Bayer Corporation.

West-ward Pharmaceutical Corp.
Eatontown, NJ 07724 – USA
Distributor

Manufactured by:
Hikma Pharmaceuticals
P.O. Box 182400
Amman 11118 - Jordan

Revised: June 2008