GENERIC NAME OF THE MEDICINAL PRODUCT:

a) Amoxycillin and Potassium Clavulanate Tablets IP 250mg/125mg
b) Amoxycillin and Potassium Clavulanate Tablets IP 500mg/125mg
c) Amoxycillin and Potassium Clavulanate Tablets IP 875mg/125mg

QUALITATIVE AND QUANTITATIVE COMPOSITION:

Each tablet contains:
a) Amoxycillin Trihydrate IP equivalent to
Amoxycillin 250 mg
Potassium clavulanate IP
(as Potassium Clavulanate Diluted IP) equivalent to
Clavulanic Acid 125mg
b) Amoxycillin Trihydrate IP equivalent to
Amoxycillin 500 mg
Potassium clavulanate IP
(as Potassium Clavulanate Diluted IP)
equivalent to
Clavulanic Acid 125mg
b) Amoxycillin Trihydrate IP equivalent to
Amoxycillin 875mg
potassium clavulanate IP
(as Potassium Clavulanate Diluted IP)
equivalent to
Clavulanic Acid 125mg

THERAPEUTIC INDICATIONS:

Treatment of the following infections in adults and children. Acute bacterial sinusitis (adequately diagnosed) Cystitis Pyelonephritis Cellulitis Animal bites Severe dental abscess with spreading cellulitis.

Amoxycillin & Potassium Clavulanate Tablets IP (Clavuxan) 250mg/125mg Taj Pharma

1. Name of the medicinal product
a) Amoxycillin and Potassium Clavulanate Tablets IP 500mg/125mg
b) Amoxycillin and Potassium Clavulanate Tablets IP 875mg/125mg
2. Qualitative and quantitative composition

a) Each tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin 250 mg
Potassium clavulanate IP
(as Potassium Clavulanate Diluted IP) equivalent to
Clavulanic Acid 125mg
Excipients              q.s.

b) Each tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin 500 mg
Potassium clavulanate IP
(as Potassium Clavulanate Diluted IP)
equivalent to
Clavulanic Acid 125mg
Excipients              q.s.

c) Each tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin 875mg
potassium clavulanate IP
(as Potassium Clavulanate Diluted IP)
equivalent to
Clavulanic Acid 125mg
Excipients              q.s.

For a full list of excipients, see section 6.1.

  1. Pharmaceutical form

Film-coated tablet.

  1. Clinical particulars

4.1 Therapeutic indications

Treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1).

  • Acute bacterial sinusitis (adequately diagnosed)
  • Cystitis
  • Pyelonephritis
  • Cellulitis
  • Animal bites
  • Severe dental abscess with spreading cellulitis.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Doses are expressed throughout in terms of Amoxycillin/clavulanic acid content except when doses are stated in terms of an individual component.

The dose that is selected to treat an individual infection should take into account:

  • The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4)
  • The severity and the site of the infection
  • The age, weight and renal function of the patient as shown below.

The use of alternative presentations (e.g. those that provide higher doses of Amoxycillin and/or different ratios of Amoxycillin to clavulanic acid) should be considered as necessary (see sections 4.4 and 5.1).

250 mg/125 mg film-coated tablets

For adults and children ≥ 40 kg, this formulation provides a total daily dose of 750 mg Amoxycillin/375 mg clavulanic acid, when administered as recommended below. If it is considered that a higher daily dose of Amoxycillin is required, it is recommended that another preparation is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid (see sections 4.4 and 5.1).

Treatment should not be extended beyond 14 days without review.

Adults and children ≥ 40 kg

One 250 mg/125 mg tablet taken three times a day.

Children < 40 kg

Co-Amoxiclav 250mg/125mg film-coated tablets are not recommended in children < 40 kg.

Elderly

No dose adjustment is considered necessary.

Renal impairment

Dose adjustments are based on the maximum recommended level of Amoxycillin.

No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 ml/min.

Adults and children 40 kg

CrCl: 10-30 ml/min250 mg/125 mg twice daily
CrCl < 10 ml /min250 mg/125 mg once daily
HaemodialysisTwo doses of 250 mg/125 mg every 24 hours, plus two doses of 250 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both Amoxycillin and clavulanic acid are decreased)

Children < 40 kg

In children < 40 kg with creatinine clearance less than 30 ml/min, the use of Co-Amoxiclav presentations with an Amoxycillin to clavulanic acid ratio of 2:1 is not recommended, as no dose adjustments are available. In such patients, the formulations with an Amoxycillin to clavulanic acid ratio of 4:1 are recommended.

Hepatic impairment

Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4).

Method of administration

For oral use

Administer at the start of a meal to minimise potential gastrointestinal intolerance and optimise absorption of Amoxycillin/clavulanic acid.

4.3 Contraindications

Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients.

History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).

History of jaundice/hepatic impairment due to Amoxycillin/clavulanic acid (see section 4.8).

4.4 Special warnings and precautions for use

Before initiating therapy with Amoxycillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents.

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, Amoxycillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.

In the case that an infection is proven to be due to an Amoxycillin-susceptible organisms(s) then consideration should be given to switching from Amoxycillin/clavulanic acid to Amoxycillin in accordance with official guidance.

This presentation is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid (e.g. penicillin-insusceptible S. pneumoniae).

This medicinal product contains 0.63mmol (24.5mg) of potassium per tablet. To be taken into consideration in patients with reduced kidney function or patients on a controlled potassium diet.

Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8).

Amoxycillin/clavulanic acid should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of Amoxycillin.

Concomitant use of allopurinol during treatment with Amoxycillin can increase the likelihood of allergic skin reactions.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP) (see Section 4.8). This reaction requires discontinuation and contra-indicates any subsequent administration of Amoxycillin.

Amoxycillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment (see sections 4.2, 4.3 and 4.8).

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. In all populations, signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and, in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects (see section 4.8).

Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, Amoxycillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.

Prolongation of prothrombin time has been reported rarely in patients receiving Amoxycillin/clavulanic acid. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see section 4.5 and 4.8).

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of Amoxycillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of Amoxycillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.9).

During treatment with Amoxycillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.

The presence of clavulanic acid may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving Amoxycillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving Amoxycillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.

4.5 Interaction with other medicinal products and other forms of interaction

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of Amoxycillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of Amoxycillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see section 4.4 and 4.8).

Methotrexate

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

Probenecid

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of Amoxycillin. Concomitant use of probenecid may result in increased and prolonged blood levels of Amoxycillin but not of clavulanic acid.

4.6 Pregnancy and lactation

Pregnancy

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Limited data on the use of Amoxycillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with Amoxycillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.

Lactation

Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. The possibility of sensitisation should be taken into account. Amoxycillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).

4.8 Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

The ADRs derived from clinical studies and post-marketing surveillance, sorted by MedDRA System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Infections and infestations
Mucocutaneous candidosisCommon
Overgrowth of non-susceptible organismsNot known
Blood and lymphatic system disorders
Reversible leucopenia (including neutropenia)Rare
ThrombocytopeniaRare
Reversible agranulocytosisNot known
Haemolytic anaemiaNot known
Prolongation of bleeding time and prothrombin time1Not known
Immune system disorders10
Angioneurotic oedemaNot known
AnaphylaxisNot known
Serum sickness-like syndromeNot known
Hypersensitivity vasculitisNot known
Nervous system disorders
DizzinessUncommon
HeadacheUncommon
Reversible hyperactivityNot known
Convulsions2 Not known
Gastrointestinal disorders
DiarrhoeaVery common
Nausea3 Common
VomitingCommon
IndigestionUncommon
Antibiotic-associated colitis4 Not known
Black hairy tongueNot known
Hepatobiliary disorders
Rises in AST and/or ALT5 Uncommon
Hepatitis6 Not known
Cholestatic jaundice6Not known
Skin and subcutaneous tissue disorders 7
Skin rashUncommon
PruritusUncommon
UrticariaUncommon
Erythema multiformeRare
Stevens-Johnson syndromeNot known
Toxic epidermal necrolysisNot known
Bullous exfoliative-dermatitisNot known
Acute generalised exanthemous pustulosis (AGEP)9 Not known
Renal and urinary disorders
Interstitial nephritisNot known
Crystalluria8Not known
1 See section 4.4

2 See section 4.4.

3 Nausea is more often associated with higher oral doses. If gastrointestinal reactions are evident, they may be reduced by taking Amoxycillin/clavulanic acid at the start of a meal.

4 Including pseudomembranous colitis and haemorrhagic colitis (see section 4.4)

5 A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.

6 These events have been noted with other penicillins and cephalosporins (see section 4.4).

7 If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see section 4.4).

8 See section 4.9

9 See section 4.4

10 See sections 4.3 and 4.4

4.9 Overdose

Symptoms and signs of overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxycillin crystalluria, in some cases leading to renal failure, has been observed (see section 4.4).

Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Amoxycillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see section 4.4)

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.

Amoxycillin/clavulanic acid can be removed from the circulation by haemodialysis.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors.

Mode of action

Amoxycillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.

Amoxycillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of Amoxycillin alone does not include organisms which produce these enzymes.

Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby preventing inactivation of Amoxycillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.

PK/PD relationship

The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for Amoxycillin.

Mechanisms of resistance

The two main mechanisms of resistance to Amoxycillin/clavulanic acid are:

  • Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D.
  • Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

Breakpoints

MIC breakpoints for Amoxycillin/clavulanic acid are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST).

OrganismSusceptibility Breakpoints (µg/ml)
SusceptibleIntermediateResistant
Haemophilus influenzae1 ≤ 1> 1
Moraxella catarrhalis1 ≤ 1> 1
Staphylococcus aureus 2≤ 2> 2
Coagulase-negative staphylococci 2 ≤ 0.25> 0.25
Enterococcus1≤ 48> 8
Streptococcus A, B, C, G5 ≤ 0.25> 0.25
Streptococcus pneumoniae3 ≤ 0.51-2> 2
Enterobacteriaceae1,4 > 8
Gram-negative Anaerobes1 ≤ 48> 8
Gram-positive Anaerobes1 ≤ 48> 8
Non-species related breakpoints1 ≤ 24-8> 8
1 The reported values are for Amoxycillin concentrations. For susceptibility testing purposes, the concentration of Clavulanic acid is fixed at 2 mg/l.

2 The reported values are Oxacillin concentrations.

3 Breakpoint values in the table are based on Ampicillin breakpoints.

4 The resistant breakpoint of R>8 mg/l ensures that all isolates with resistance mechanisms are reported resistant.

5 Breakpoint values in the table are based on Benzylpenicillin breakpoints.

The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Commonly susceptible species
Aerobic Gram-positive micro-organisms

Enterococcus faecalis

Staphylococcus aureus (methicillin-susceptible)£

Streptococcus agalactiae

Streptococcus pneumoniae1

Streptococcus pyogenes and other beta-hemolytic streptococci

Streptococcus viridans group

Aerobic Gram-negative micro-organisms

Capnocytophaga spp.

Eikenella corrodens

Haemophilus influenzae2

Moraxella catarrhalis

Pasteurella multocida

Anaerobic micro-organisms

Bacteroides fragilis

Fusobacterium nucleatum

Prevotella spp.

Species for which acquired resistance may be a problem
Aerobic Gram-positive micro-organisms

Enterococcus faecium $

Aerobic Gram-negative micro-organisms

Escherichia coli

Klebsiella oxytoca

Klebsiella pneumoniae

Proteus mirabilis

Proteus vulgaris

Inherently resistant organisms
Aerobic Gram-negative micro-organisms

Acinetobacter sp.

Citrobacter freundii

Enterobacter sp.

Morganella morganii

Providencia spp.

Pseudomonas sp.

Serratia sp.

Stenotrophomonas maltophilia

$ Natural intermediate susceptibility in the absence of acquired mechanism of resistance.

£All methicillin-resistant staphylococci are resistant to Amoxycillin/clavulanic acid

1Streptococcus pneumoniae that is fully susceptible to penicillin may be treated with this presentation of Amoxycillin/clavulanic acid. Organisms that show any degree of reduced susceptibility to penicillin should not be treated with this presentation (see sections 4.2 and 4.4).

2 Strains with decreased susceptibility have been reported in some countries in the EU with a frequency higher than 10%.

5.2 Pharmacokinetic properties

Absorption

Amoxycillin and clavulanic acid, are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of Amoxycillin/clavulanic acid is optimised when taken at the start of a meal. Following oral administration, Amoxycillin and clavulanic acid are approximately 70% bioavailable. The plasma profiles of both components are similar and the time to peak plasma concentration (Tmax) in each case is approximately one hour.

The pharmacokinetic results for a study, in which Amoxycillin/clavulanic acid (250 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthy volunteers are presented below.

Mean (± SD) pharmacokinetic parameters
Active substance(s) administeredDoseCmaxTmax *AUC (0-24h)T 1/2
(mg)(µg/ml)(h)((µg.h/ml)(h)
Amoxycillin
AMX/CA

250 mg/125 mg

2503.3

± 1.12

1.5

(1.0-2.0)

26.7

±4.56

1.36

± 0.56

Clavulanic acid
AMX/CA

250 mg/125 mg

1251.5

± 0.70

1.2

(1.0-2.0)

12.6

± 3.25

1.01

± 0.11

AMX – Amoxycillin, CA – clavulanic acid

* Median (range)

Amoxycillin and clavulanic acid serum concentrations achieved with Amoxycillin/clavulanic acid are similar to those produced by the oral administration of equivalent doses of Amoxycillin or clavulanic acid alone.

Distribution

About 25% of total plasma clavulanic acid and 18% of total plasma Amoxycillin is bound to protein. The apparent volume of distribution is around 0.3-0.4 l/kg for Amoxycillin and around 0.2 l/kg for clavulanic acid.

Following intravenous administration, both Amoxycillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxycillin does not adequately distribute into the cerebrospinal fluid.

From animal studies there is no evidence for significant tissue retention of drug-derived material for either component. Amoxycillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk (see section 4.6).

Both Amoxycillin and clavulanic acid have been shown to cross the placental barrier (see section 4.6).

Biotransformation

Amoxycillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized in man and eliminated in urine and faeces and as carbon dioxide in expired air.

Elimination

The major route of elimination for Amoxycillin is via the kidney, whereas for clavulanic acid it is by both renal and non-renal mechanisms.

Amoxycillin/clavulanic acid has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the Amoxycillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 h after administration of single Co-Amoxiclav 250mg/125mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for Amoxycillin and between 27-60% for clavulanic acid over a 24 hour period. In the case of clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration.

Concomitant use of probenecid delays Amoxycillin excretion but does not delay renal excretion of clavulanic acid (see section 4.5).

Age

The elimination half-life of Amoxycillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. 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.

Gender

Following oral administration of Amoxycillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either Amoxycillin or clavulanic acid.

Renal impairment

The total serum clearance of Amoxycillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for Amoxycillin than for clavulanic acid, as a higher proportion of Amoxycillin is excreted via the renal route. Doses in renal impairment must therefore prevent undue accumulation of Amoxycillin while maintaining adequate levels of clavulanic acid (see section 4.2).

Hepatic impairment

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

5.3 Preclinical safety data

Nonclinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction.

Repeat dose toxicity studies performed in dogs with Amoxycillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.

Carcinogenicity studies have not been conducted with Amoxycillin/clavulanic acid or its components.

  1. Pharmaceutical particulars

a) Each tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin 250 mg
Potassium clavulanate IP
(as Potassium Clavulanate Diluted IP) equivalent to
Clavulanic Acid 125mg
b) Each tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin 500 mg
Potassium clavulanate IP
(as Potassium Clavulanate Diluted IP)
equivalent to
Clavulanic Acid 125mg
c) Each tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin 875mg
potassium clavulanate IP
(as Potassium Clavulanate Diluted IP)
equivalent to
Clavulanic Acid 125mg

6.1 List of excipients

Microcrystalline Cellulose, Sodium Starch Glycollate, Magnesium Stearate, Colloidal silica

Film Coat

Hypromellose, Titanium dioxide, Propylene glycol, Ethylcellulose

6.2 Incompatibilities

No incompatibilities are known to date.

6.3 Shelf life

24 months

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

A white high-density polyethylene bottle with a white pilfer proof polypropylene cap with a desiccant capsule, containing 21 or 100 tablets.

6.6 Special precautions for disposal and other handling

None

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
Plot No.220, Mahagujarat Industrial Estate,
At & Post: Moraiya, TAL- Sanand,
Dist. Ahmedabad, Gujarat(India)

Amoxycillin & Potassium Clavulanate Tablets IP (Clavuxan) 250mg/125mg Taj Pharma

Package leaflet: Information for the user

a) Amoxycillin and Potassium Clavulanate Tablets IP 250mg/125mg
b) Amoxycillin and Potassium Clavulanate Tablets IP 500mg/125mg
c) Amoxycillin and Potassium Clavulanate Tablets IP 875mg/125mg

 (Amoxicillin/clavulanic acid)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you

  • Keep this leaflet. You may need to read it
  • If you have any further questions, ask your doctor or
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section

What is in this leaflet:

  1. What Co-amoxiclav Tablet is and what it is used for
  2. What you need to know before you take Co-amoxiclav Tablets
  3. How to take Co-amoxiclav Tablets
  4. Possible side effects
  5. How to store Co-amoxiclav tablets
  6. Contents of the pack and other information

1.           What Co-amoxiclav Tablets is and what it is used for

 Co-amoxiclav is an antibiotic and works by killing bacteria that cause infections. It contains two different medicines called amoxicillin and clavulanic acid. Amoxicillin belongs to a group of medicines called “penicillins” that can sometimes be stopped from working (made inactive). The other active component (clavulanic acid) stops this from happening.

Co-amoxiclav is used in adults and children to treat the following infections:

  • middle ear and sinus infections
  • respiratory tract infections
  • urinary tract infections
  • skin and soft tissue infections including dental infections
  • bone and joint
What you need to know before you take Co-amoxiclav Tablets Do not take Co-amoxiclav:
  • if you are allergic to amoxicillin, clavulanic acid, penicillins or any of the other ingredients of this medicine (listed in section 6)
  • if you have ever had a severe allergic reaction to any other antibiotic. This can include a skin rash or swelling of the face or .
  • if you have ever had liver problems or jaundice (yellowing of the skin) when taking an antibiotic.

Do not take Co-amoxiclav if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Co-amoxiclav Tablets.

Warnings and precautions

Talk to your doctor or pharmacist before taking Co-amoxiclav Tablets if you:

  • have glandular fever
  • are being treated for liver or kidney problems
  • are not passing water

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking these tablets.

In some cases, your doctor may investigate the type of bacteria that is causing your infection. Depending on the results, you may be given a different strength of Co-amoxiclav or a different medicine.

Conditions you need to look out for:

Co-amoxiclav can make some existing conditions worse, or cause serious side effects. These include allergic reactions, convulsions (fits) and inflammation of the large intestine. You must look out for certain symptoms while you are taking Co-amoxiclav, to reduce the risk of any problems. See ‘Conditions you need to look out for’ in Section 4.

Blood and urine tests:

If you are having blood tests (such as red blood cell status tests or liver function tests) or urine tests (for glucose), let the doctor or nurse know that you are taking Co-amoxiclav. This is because Co- amoxiclav can affect the results of these types of tests.

Other medicines and Co-amoxiclav Tablets

 Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. This includes medicines that can be bought without a prescription and herbal medicines.

If you are taking allopurinol (used for gout) with Co-amoxiclav, it may be more likely that you will have an allergic skin reaction.

If you are taking probenecid (used for gout), your doctor may decide to adjust your dose of Co- amoxiclav.

If medicines to help stop blood clots (such as warfarin) are taken with Co-amoxiclav Tablets then extra blood tests may be needed.

Co-amoxiclav can affect how methotrexate (a medicine used to treat cancer or rheumatic diseases) works.

Co-amoxiclav can affect how mycophenolate mofetil (a medicine used to prevent the rejection of transplanted organ) works.

This medicine contains 0.63 mmol (or 24.632 mg) potassium per tablet. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

Pregnancy and breast-feeding

 If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

 Co-amoxiclav can have side effects and the symptoms may make you unfit to drive. Don’t drive or operate machinery unless you are feeling well.

2.           How to take Co-amoxiclav Tablets

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Adults and children weighing 40 kg and over

 Usual dose – 1 tablet two times a day Higher dose – 1 tablet three times a day

Children weighing less than 40 kg

Children aged 6 years or less should preferably be treated with Co-Amoxiclav oral suspension or sachets.

Ask your doctor or pharmacist for advice when giving Co-amoxiclav tablets to children weighing less than 40 kg. The tablets are not suitable for children weighing less than 25 kg.

Patients with kidney and liver problems

 If you have kidney problems the dose might be changed. A different strength or a different medicine may be chosen by your

  • If you have liver problems you may have more frequent blood tests to check how your liver is working.

How to take Co-amoxiclav Tablets

  • Take with a meal
  • Swallow the tablets whole with a glass of
  • Space the doses evenly during the day, at least 4 hours apart. Do not take 2 doses in 1
  • Do not take Co-amoxiclav for more than 2 weeks. If you still feel unwell you should go back to see the

If you take more Co-amoxiclav Tablets than you should

 If you take too much Co-amoxiclav, signs might include an upset stomach (feeling sick, being sick or diarrhoea) or convulsions. Talk to your doctor as soon as possible. Take the medicine carton or bottle to show the doctor.

If you forget to take Co-amoxiclav Tablets

 If you forget to take a dose, take it as soon as you remember. You should not take the next dose too soon, but wait about 4 hours before taking the next dose.

Do not take a double dose to make up for a forgotten dose.

If you stop taking Co-amoxiclav Tablets

 Keep taking Co-amoxiclav until the treatment is finished, even if you feel better. You need every dose to help fight the infection. If some bacteria survive they can cause the infection to come back.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

3.           Possible side effects

 Like all medicines, this medicine can cause side effects, although not everybody gets them.

Conditions you need to look out for

 Allergic reactions:

 skin rash

  • inflammation of blood vessels (vasculitis) which may be visible as red or purple raised spots on the skin, but can affect other parts of the body
  • fever, joint pain, swollen glands in the neck, armpit or groin
  • swelling, sometimes of the face or throat (angioedema), causing difficulty in breathing

Warning: Allergic reactions can sometimes occur delayed.

Contact a doctor immediately if you get any of these symptoms. Stop taking Co-amoxiclav Tablets.

 Inflammation of large intestine

Inflammation of the large intestine, causing watery diarrhoea usually with blood and mucus, stomach pain and/or fever.

Contact your doctor as soon as possible for advice if you get these symptoms.

Very common side effects

These may affect more than 1 in 10 people

  • diarrhoea (in adults).

Common side effects

These may affect up to 1 in 10 people

  • thrush (candida – a yeast infection of the vagina, mouth or skin folds)
  • feeling sick (nausea), especially when taking high doses

If affected take Co-amoxiclav with a meal

  • Diarrhoea (in children)

Uncommon side effects

 These may affect up to 1 in 100 people

  • skin rash, itching
  • raised itchy rash (hives)
  • indigestion
  • dizziness

Uncommon side effects that may show up in your blood tests:

  • increase in some substances (enzymes) produced by the liver

Rare side effects

 These may affect up to 1 in 1000 people

  • skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge-erythema multiforme)

If you notice any of these symptoms contact a doctor urgently.

Rare side effects that may show up in your blood tests:

  • low number of cells involved in blood clotting
  • low number of white blood

Frequency not known

Frequency cannot be estimated from the available data.

  • Allergic reactions (see above)
  • Inflammation of the large intestine (see above)
  • Serious skin reactions:
  • a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome), and a more severe form causing extensive peeling of the skin (more than 30% of the body surface – toxic epidermal necrolysis)
    • widespread red skin rash with small pus-containing blisters (bulloous exfoliative dermatitis)
    • a red, scaly rash with bumps under the skin and blisters (exanthemous pustulosis).
    • flu-like symptoms with a rash, fever, swollen glands, and abnormal blood test results (including increased white blood cells (eosinophilia) and liver enzymes) (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS))
  • Inflammation of the protective membrane sorrunding the brain (aseptic meningitis)

Contact a doctor immediately if you get any of these symptoms:

  • inflammation of the liver (hepatitis)
  • jaundice, caused by increases in the blood of bilirubin (a substance produced in the liver) which may make your skin and whites of eyes appear yellow
  • inflammation of tubes in the kidney
  • blood takes longer to clot
  • hyperactivity
  • convulsions (in people taking high doses of Co-amoxiclav or who have kidney problems)
  • black tongue which looks hairy

Side effects that may show up in your blood or urine tests:

  • severe reduction in the number of white blood cells
  • low number of red blood cells (haemolytic anaemia)
  • crystals in

4.           How to store Co-amoxiclav Tablets

 Keep this medicine out of the sight and reach of children. Do not store above 25°C.

Do not take this medicine after the expiry date which is stated on the carton and blister strip after EXP. The expiry date refers to the last day of that month.

Do not take this medicine if you notice any visible signs of deterioration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

Contents of the pack and other information

  1. What Co-amoxiclav Tablets contains:
  • The active substances are Amoxicillin Trihydrate and Potassium Clavulanate., Diluted

Each film-coated tablet contains 875mg amoxicillin as amoxicillin trihydrate and 125mg of clavulanic acid as potassium clavulanate, diluted.

  • The other ingredients are:

Cellulose, microcrystalline (E460),  Sodium starch glycolate, Type A Silica, Colloidal anhydrous (E551) Magnesium Stearate (E470b)

Film coat

Titanium dioxide (E171) Hypromellose (E464) Propylene glycol (E1520) Talc (E553b)

Ethyl cellulose

6. What Co-amoxiclav looks like and contents of the pack

White, capsule-shaped film-coated tablet.

The tablets are packaged in aluminium blisters consisting of: 4, 5, 6, 7, 8, 10, 12, 14, 15, 16, 20, 21,

25, 30, 35, 40, 50, 100 & 500 tablets

Not all pack sizes may be marketed

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
Plot No.220, Mahagujarat Industrial Estate,
At & Post: Moraiya, TAL- Sanand,
Dist. Ahmedabad, Gujarat(India)