Enhancin Amoxicillin and Clavulanate Potassium Tablets


(Amoxicillin and Clavulanate Potassium Tablets USP)

For the use only of a Registered Medical Practitioner.




Each Film coated tablet contains:

Amoxicillin USP equivalent to anhydrous Amoxicillin 250mg

Clavulanate potassium equivalent to Clavulanic acid 125mg


Each Film coated tablet contains:

Amoxicillin USP equivalent to anhydrous Amoxicillin 500mg

Clavulanate potassium equivalent to Clavulanic acid 125mg


Each Film coated tablet contains:

Amoxicillin USP equivalent to anhydrous Amoxicillin 875mg

Clavulanate potassium equivalent to Clavulanic acid 125mg



ENHANCIN TABLET (amoxicillin/clavulanate potassium) is an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the beta-lactamase inhibitor clavulanate potassium. Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. Amoxicillin is chemically designated as (2S,5R, 6R)-6-[(R)-(-)-2-Amino-2- (p-hydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptanes-2-carboxylic acid trihydrate. Its molecular formula is C16H19N3O5S•3H20. Its molecular weight is 419.45.

Clavulanate potassium is chemically designated as potassium (Z)-(2R, 5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1 -azabicyclo [3.2.0]heptane-2-carboxylate. Its molecular formula is C8H8KNO5 and its molecular weight is 237.25.



Mechanism of action

Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by β-lactamases and, therefore, the spectrum of activity does not include organisms, which produce these enzymes. Clavulanic acid is β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated β-Iactamases frequently responsible for transferred drug resistance.

The formulation of amoxicillin and clavulanic acid protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics. Thus, amoxicillin/clavulanate potassium combination possesses the distinctive properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.


Antibacterial Spectrum

Amoxicillin/clavulanic acid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections.


Gram-Positive Aerobes

Staphylococcus aureus (β-lactamase and non-β-lactamase producing)§
§Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic acid.


Gram-Negative Aerobes

Enterobacter species (Although most strains of Enterobacter species are resistant in vitro, clinical efficacy has been demonstrated with amoxicillin/clavulanate potassium combination in urinary tract infections caused by these organisms)

Escherichia coli (β-lactamase and non β-lactamase producing)

Haemophilus influenzae (β-lactamase and non-β-lactamase producing)

Klebsiella species (All known strains are β-lactamase producing.) Moraxella catarrhalis (B-lactamase and non β-lactamase producing).

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

Amoxicillin/clavulanic acid exhibits in vitro minimal inhibitory concentrations (MICs) of 2 µg/mL or less against most (≥90%) strains of Streptococcus pneumoniaeII; MICs of 0.06 µg/mL or less against most (≥90%) strains of Neisseria gonorrhoeae; MICs of 4 µg/mL or less against most (≥90%) strains of staphylococci and anaerobic bacteria; and MICs of 8 µglmL or less against most (≥90%) strains of other listed organisms. However, with the exception of organisms shown to respond to amoxicillin alone, the safety and effectiveness of amoxicillin/clavulanic acid in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Because amoxicillin has greater in vitro activity against Streptococcus pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin.


Gram-Positive Aerobes

Enterococcus faecalis

Staph ylococcus epidermidis (β-lactamase and non-β-lactamase producing)

Staphylococcus saprophyticus (β-lactamase and non-β-lactamase producing)

Streptococcus pneumoniae¶**

Streptococcus pyogenes¶**

viridans group Streptococcus¶**


Gram-Negative Aerobes

Eikenella corrodens (β-lactamase and non-β-lactamase producing)

Neisseria gonorrhoeae (β-lactamase and non-β-lactamase producing)

Proteus mirabilis (β-lactamase and non-β-lactamase producing)


Anaerobic Bacteria

Bacteroides species, including Bacteroides fragilis (β-lactamase and non-β-lactamase producing)

Fusobacterium species (β-lactamase and non-β-lactamase producing)

Peptostreptococcus species**

Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in treating certain clinical infections due to these organisms.

**These are non-β-lactamase-producing organisms and, therefore, are susceptible to amoxicillin alone.



Amoxicillin and clavulanate potassium are well absorbed from the gastrointestinal tract after oral administration of amoxicillin/clavulanate potassium combination. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While amoxicillin/clavulanate potassium combination 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/clavulanate potassium was dosed at 30 and 150 minutes after the start of a high fat breakfast. The safety and efficacy of amoxicillin/clavulanate potassium combination have been established in clinical trials where amoxicillin/clavulanate potassium was taken without regard to meals.

Mean* amoxicillin and clavulanate potassium pharmacokinetic parameters are shown in the table below:

Dose and regimen AUC0∞ (µg.hr/mL) Cmax (µg/mL)
Amoxicillin Clavulanate potassium Amoxicillin
Clavulanate potassium (±SD) Amoxicillin (±SD) Clavulanate potassium (±SD)
250/125mg tablet q 8 h 267±4.56 126 ± 3.25 3.3 ± 1.12 1.5±0.70
500/125 mgtablet q 12 h 33.4 ± 6.76 8.6 ± 1.95 6.5 ± 1.41 1.8±0.61
500/125mg tablet q 8 h 53.4 ± 8.87 15.7 ± 3.86 7.2 ± 2.26 2.4 ± 0.83
875/125mg tablet q 12 h 53.5 ± 12.31 10.2 ± 3.04 11.6 ±2.78 2.2±0.99

Mean values of 14 normal volunteers (n=15 for clavulanate potasaium in the low dose regimens), Peak concentrations occurred approximately 1.5 hours after the dose.

Administered at the start of a light meal.

Amoxicillin serum concentrations achieved with amoxicillin/clavulanate potassium combination are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. The half life of amoxicillin after the oral administration of amoxicillin/clavulanate potassium is 1.3 hours and that of clavulanic acid is 1.0 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/clavulanate potassium combination.

Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.

Neither component in amoxicillin/clavulanate potassium is highly protein-bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound.

Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.



ENHANCIN TABLET (amoxicillin/clavulanate potassium) is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below:

Lower Respiratory Tract Infections-caused by β-lactamase- producing strains of Haemophilus influenzae and Moraxella catarrhalis.

Otitis Media-caused by β-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis.

Sinusitis-caused by β-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis.

Skin and Skin Structure Infections-caused by β-lactamase- producing strains of Staphylococcus aureus, Escherichia coli and Klebsiella spp.

Urinary Tract Infections-caused by β-lactamase-producing strains of Escherichia coli, Klebsiella spp. and Enterobacter spp.

While amoxicillin/clavulanate potassium is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with amoxicillin/clavulanate potassium due to its amoxicillin content.

Therefore, mixed infections caused by ampicillin-susceptible organisms and β-lactamase-producing organisms susceptible to amoxicillin/clavulanate potassium should not require the addition of another antibiotic. Because amoxicillin has greater in vitro activity against Streptococcus pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin and amoxicillin/clavulanate potassium.

To reduce the development of drug resistant bacteria and maintain the effectiveness of amoxicillin and amoxicillin/clavulanate potassium and other antibacterial drugs, amoxicillin and amoxicillin/clavulanate potassium should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Bacteriological studies, to determine the causative organisms and their susceptibility to amoxicillin/clavulanate potassium, should be performed together with any indicated surgical procedures.



Adults: The usual adult dose is one ENHANCIN 625 (amoxicillin/clavulanate potassium) every 12 hours or one ENHANCIN 375 (amoxicillin/clavulanate potassium) every 8 hours. For more severe infections and infections of respiratory tract, the dose should be one ENHANCIN 1000 (amoxicillin/clavulanate potassium) every 12 hourly or one ENHANCIN 625 (amoxicillin/clavulanate potassium) every 8 hours.

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min should not receive the ENHANCIN 1000 (amoxicillin/clavulanate potassium). Patients with a glomerular filtration rate of 10 to 30 mL/min should receive ENHANCIN 625 (amoxicillin/clavulanate potassium) or ENHANCIN 375 (amoxicillin/clavulanate potassium) every 12 hours, depending on the severity of the infection. Patients with a less than 10-mL/min glomerular filtration rate should receive ENHANCIN 625 (amoxicillin/clavulanate potassium) or ENHANCIN 375 (amoxicillin/clavulanate potassium) every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive ENHANCIN 625 (amoxicillin/clavulanate potassium) or ENHANCIN 375 (amoxicillin/clavulanate potassium) every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

Pediatric Patients: Pediatric patients weighing 40 kg or more should be dosed according to the adult recommendations.

Administration: ENHANCIN TABLETS (amoxicillin/clavulanate potassium) may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanic acid are administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, ENHANCIN TABLET (amoxicillin/clavulanate potassium) should be taken at the start of a meal.




While amoxicillin/clavulanate potassium 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 during prolonged therapy.

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.






Pseudomembranous colitis has been reported with nearly all antibacterial agents, including amoxicillin/clavulanate potassium, and has ranged in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic associated colitis.’

After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

Amoxicillin/clavulanate potassium should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of amoxicillin/ clavulanate potassium is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide).

These have generally been cases associated with serious underlying diseases or concomitant medications.



ENHANCIN TABLETS (amoxicillin/clavulanate potassium) are contraindicated in patients with a history of allergic reactions to any penicillin. It is also contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin/clavulanate potassium.



Teratogenic effects: Pregnancy (Category B). Reproduction studies performed in pregnant rats and mice given amoxicillin/clavulanate potassium at oral dosages up to 1,200 mg/kg/day, equivalent to 7,200 and 4,080 mg/m2/day, respectively (4.9 and 2.8 times the maximum human oral dose based on body surface area), revealed no evidence of harm to the fetus due to amoxicillin/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/ 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/clavulanate potassium might be associated with an increased risk of necrotizing enterocolitis in neonates.



Ampicillin class antibiotics are excreted in the milk; therefore, caution should be exercised when amoxicillin/clavulanate potassium is administered to a nursing woman.


Drug Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin/clavulanate potassium 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/clavulanate potassium and allopurinol administered concurrently.

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

Drug/Laboratory Test Interactions: Oral administration of amoxicillin/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 CIinitest® (copper sulfate), Benedict’s Solution or Fehling’s Solution. Since this effect may also occur with amoxicillin and therefore amoxicillin/clavulanate potassium, 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, estriolglucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with amoxicillin and therefore amoxicillin/clavulanate potassium.


Carcinogenicity/Mutagenicity/Impairment of Fertility

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

The mutagenic potential of amoxicillin/clavulanate potassium was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test and a mouse Iymphoma 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/clavulanate potassium at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum human dose, 1,480 mg/m2/day, 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.


Adverse Reactions

Amoxicillin/clavulanate potassium is generally well tolerated. The majority of side effects observed in clinical trials were of a mild and transient nature and <3% of patients discontinued therapy because of drug-related side effects. The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The overall incidence of side effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include: abdominal discomfort, flatulence and headache.

The following adverse reactions have been reported for ampicillin class antibiotics:

Gastrointestinal: Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/ pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

Hypersensitivity Reactions: Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia and frequently fever), erythema multiforme (rarely Stevens-Johnson syndrome), acute generalized exanthematous pustulosis and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids.

Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with oral penicillin.

Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin class antibiotics but the significance of these findings is unknown. Hepatic dysfunction, including increases in serum transaminases (AST and/or ALT), serum bilirubin and/or alkaline phosphatase, has been infrequently reported with amoxicillin/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 cholestatichepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy have been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications.

Renal: Interstitial nephritis and hematuria have been reported rarely. Crystalluria has also been reported.

Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and agranulocytosis has been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity
phenomena. A slight thrombocytosis was noted in < 1% of the patients treated with amoxicillin/clavulanate potassium. There have been reports of increased prothrombin time in patients receiving amoxicillin/clavulanate potassium and anticoagulant therapy concomitantly.

Central Neivous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely.

Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.



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

In the case of overdosage, discontinue amoxicillin/clavulanate potassium, 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 center suggested that overdosages of < 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.

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.



Store below 25°C, protected from moisture.

Keep all medicines out of reach of children.



ENHANCIN 375: Strip of 4’s/10’s and box of 5 x 4’s/10’s/10 x 10’s/20’s/5 x 20’s

ENHANCIN 625: Strip of 4’s/10’s and box of 5 x 4’s/10’s/10 x 10’s/20’s/5 x 20’s

ENHANCIN 1000: Strip of 2’s/4’s/6’s and box of 6 x 2’s/3 x 4’s/5 x 4’s/2 x 6’s



1. Prescribing information of AUGMENTIN Tablets, GlaxoSmithKline, August 2005.

2. ABPI Compendium of Data Sheets and Summaries of Product Characteristics; AUGMENTIN Tablets and Suspension, GlaxoSmithKline UK, November 2005.


Information compiled in February 2006.


Manufactured in India by

Sun Pharmaceutical Ind. Ltd.

Industrial Area – 3, Dewas – 455 001


Marketed by

Ranbaxy Nigeria Ltd.

a SUN PHARMA company

1st Floor, Abimbola House, 24, Abimbola Street,

Ilasamaja, Isolo, Lagos, Nigeria.

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