1. NAME OF THE MEDICINAL PRODUCT

Amoxicillin and Clavulanic Acid 500mg /125mg Tablets USP Taj Pharma
Amoxicillin and Clavulanic Acid 875mg /125mg Tablets USP Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

a) Each film-coated tablet contains:
Amoxicillin USP          500mg
Clavulanic acids            125mg
Excipients                        q.s

b) Each film-coated tablet contains:
Amoxicillin USP              875mg
Clavulanic acids             125mg
Excipients                          q.s

For the full list of excipients see section 6.1.

  1. PHARMACEUTICAL FORM

Film-coated tablet.

White to off-white film-coated oval shaped tablets.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Amoxicillin and Clavulanic Acid is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):

  • Acute bacterial sinusitis (adequately diagnosed)
  • Acute otitis media
  • Acute exacerbations of chronic bronchitis (adequately diagnosed)
  • Community-acquired pneumonia
  • Cystitis
  • Pyelonephritis
  • Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis.
  • Bone and joint infections, in particular osteomyelitis.

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 amoxicillin/clavulanic acid content except when doses are stated in terms of an individual component.

The dose of Amoxicillin and Clavulanic Acid 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 of Amoxicillin and Clavulanic Acid (e.g. those that provide higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary (see sections 4.4 and 5.1).

For adults and children ≥ 40 kg, this formulation of Amoxicillin and Clavulanic Acid provides a total daily dose of 1500 mg amoxicillin/375 mg clavulanic acid, when administered as recommended below. For children < 40 kg, this formulation of Amoxicillin and Clavulanic Acid provides a maximum daily dose of 2400 mg amoxicillin/600 mg clavulanic acid, when administered as recommended below. If it is considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of Amoxicillin and Clavulanic Acid is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid (see sections 4.4 and 5.1).

The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review (see section 4.4 regarding prolonged therapy).

Adults and children ≥40 kg

One 500 mg/125 mg dose taken three times a day.

Children < 40 kg

20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day given in three divided doses.

Children may be treated with Amoxicillin and Clavulanic Acid film-coated tablets, suspensions or paediatric sachets. Children aged 6 years and below should preferably be treated with suspension or paediatric sachets.

No clinical data are available on doses of Amoxicillin and Clavulanic Acid 4:1 formulations higher than 40 mg/10 mg/kg per day in children under 2 years.

Older people

No dose adjustment is considered necessary.

Renal impairment

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

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/min500 mg/125 mg twice daily
CrCl < 10 ml /min500 mg/125 mg once daily
Haemodialysis500 mg/125 mg every 24 hours, plus 500 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased)

Children < 40 kg

CrCl: 10-30 ml/min15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice daily).
CrCl < 10 ml /min15 mg/3.75 mg/kg as a single daily dose (maximum 500 mg/125 mg).
Haemodialysis15 mg/3.75 mg/kg per day once daily.

Prior to haemodialysis 15 mg/3.75 mg/kg. In order to restore circulating drug levels, 15 mg/3.75 mg per kg should be administered after haemodialysis.

Hepatic impairment

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

Method of administration

Amoxicillin and Clavulanic Acid is for oral use.

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

Therapy can be started parenterally according the SPC of the IV-formulation and continued with an oral preparation.

4.3 Contraindications

Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients listed in section 6.1.

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 amoxicillin/clavulanic acid (see section 4.8).

4.4 Special warnings and precautions for use

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see sections 4.3 and 4.8).

Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse 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, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.

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

This presentation of Amoxicillin and Clavulanic Acid 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. This presentation should not be used to treat penicillin-resistant S. pneumoniae.

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

Amoxicillin/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 amoxicillin.

Concomitant use of allopurinol during treatment with amoxicillin 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 Amoxicillin and Clavulanic Acid discontinuation and contra-indicates any subsequent administration of amoxicillin.

Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment (see section 4.2). Hepatic events have been reported predominantly in males and older 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, amoxicillin/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 amoxicillin/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 amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.9).

During treatment with amoxicillin, 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 in Amoxicillin and 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 amoxicillin/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 amoxicillin/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 amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 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 amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.

Mycophenolate mofetil

In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

4.6 Fertility, 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 amoxicillin/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 amoxicillin/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.

Breastfeeding

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. Amoxicillin/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 with Amoxicillin and Clavulanic Acid, 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)

System Organ ClassVery common

(≥1/10)

Common

(≥ 1/100 to < 1/10)

Uncommon

(≥1/1,000 to < 1/100)

Rare

(≥1/10,000 to <1/1,000)

Not Known

(cannot be estimated from the available data)

Infections and infestationsMucocutaneous candidosisOvergrowth of non-susceptible organisms
Blood and lymphatic systemReversible leucopenia (including neutropenia),

Thrombocytopenia

Reversible agranulocytosis,

Haemolytic anaemia,

Prolongation of bleeding time and prothrombin time1

Immune system disorders10Angioneurotic oedema,

Anaphylaxis,

Serum sickness-like syndrome,

Hypersensitivity vasculitis

Nervous system disordersDizziness,

Headache

Reversible hyperactivity,

Convulsions2,

Aseptic meningitis

Gastrointestinal disordersDiarrhoeaNausea3,

Vomiting

IndigestionAntibiotic-associated colitis4,

Black hairy tongue

Hepatobiliary disordersRises in AST and/or ALT5Hepatitis6,

Cholestatic jaundice6

Skin and subcutaneous tissue disorders7Skin rash,

Pruritus,

Urticaria

Erythema multiformeStevens-Johnson syndrome,

Toxic epidermal necrolysis,

Bullous exfoliative-dermatitis,

Acute generalised exanthemous pustulosis (AGEP)9 Drug reaction with eosinophilia and systemic symptoms (DRESS)

Renal and urinary disordersInterstitial nephritis,

Crystalluria8

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 amoxicillin/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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms and signs of overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin 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.

Amoxicillin 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.

Amoxicillin/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.

Mechanism of action

Amoxicillin 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.

Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin 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 amoxicillin. 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 amoxicillin.

Mechanisms of resistance

The two main mechanisms of resistance to amoxicillin/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 amoxicillin/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 Amoxicillin 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

Gardnerella vaginalis

Staphylococcus aureus (methicillin-susceptible)£

Coagulase-negative staphylococci (methicillin-susceptible)

Streptococcus agalactiae

Streptococcus pneumoniae1

Streptococcus pyogenes and other beta-haemolytic 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.

Legionella pneumophila

Morganella morganii

Providencia spp.

Pseudomonas sp.

Serratia sp.

Stenotrophomonas maltophilia

Other micro-organisms

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetti

Mycoplasma pneumoniae

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

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

1Streptococcus pneumoniae that are resistant to penicillin should not be treated with this presentation of amoxicillin/clavulanic acid (see sections 4.2 and 4.4).

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

5.2 Pharmacokinetic properties

Absorption

Amoxicillin 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 amoxicillin/clavulanic acid is optimised when taken at the start of a meal. Following oral administration, amoxicillin 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 amoxicillin/clavulanic acid (500 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)
Amoxicillin
AMX/CA

500/125 mg

5007.19 ± 2.261.5 (1.0-2.5)53.5 ± 8.871.15 ± 0.20
Clavulanic acid
AMX/CA

500 mg/125 mg

1252.40 ± 0.831.5 (1.0-2.0)15.72 ± 3.860.98 ± 0.12
AMX – amoxicillin, CA – clavulanic acid

* Median (range)

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

Distribution

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

Following intravenous administration, both amoxicillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin 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. Amoxicillin, 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 amoxicillin and clavulanic acid have been shown to cross the placental barrier (see section 4.6).

Biotransformation

Amoxicillin 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 amoxicillin is via the kidney, whereas for clavulanic acid it is by both renal and non-renal mechanisms.

Amoxicillin/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 amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 h after administration of single Amoxicillin and Clavulanic Acid 250 mg/125 mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for amoxicillin 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 amoxicillin excretion but does not delay renal excretion of clavulanic acid (see section 4.5).

Age

The elimination half-life of amoxicillin 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 older 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 amoxicillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either amoxicillin or clavulanic acid.

Renal impairment

The total serum clearance of amoxicillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for amoxicillin than for clavulanic acid, as a higher proportion of amoxicillin is excreted via the renal route. Doses in renal impairment must therefore prevent undue accumulation of amoxicillin 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 amoxicillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.

Carcinogenicity studies have not been conducted with Amoxicillin and Clavulanic Acid or its components.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core: Cellulose microcrystalline, Sodium starch glycolate, Silica colloidal anhydrous, Povidone, Eudragit & Magnesium stearate.

Tablet coating: Hypromellose, Titanium dioxide, Macrogol & Talc.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

Tablets should be used within 30 days of opening of the pouch

6.4 Special precautions for storage

Store in the original package in order to protect from light.

Do not store above 25°C.

6.5 Nature and contents of container

PVC/Aluminium blister pack.

In packs of 10, 12, 14, 15, 16, 20, 21, 24, 30, 40, 50, 100 or 250 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Amoxicillin and Clavulanic Acid Tablets USP 500mg /125mg, 875mg/125mg Taj Pharma
(Amoxicillin and Clavulanic acid)

Package Leaflet: Information for the patient

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 again.
  • If you have any further questions, ask your doctor or your pharmacist.
  • This medicine has been prescribed for you (or for your child) only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • 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 4.

What is in this leaflet

  1. What Amoxicillin and Clavulanic Acid tablets are and what are they used for
    2. What you need to know before you take Amoxicillin and Clavulanic Acid tablets
    3. How to take Amoxicillin and Clavulanic Acid tablets
    4. Possible side effects
    5. How to store Amoxicillin and Clavulanic Acid tablets
    6. Contents of the pack and other information

 

  1. WHAT AMOXICILLIN AND CLAVULANIC ACID TABLETS ARE AND WHAT ARE THEY USED FOR

Amoxicillin and Clavulanic Acid  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.

Amoxicillin and Clavulanic Acid tablets are 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 infections.
  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE AMOXICILLIN AND CLAVULANIC ACID TABLETS

Do not take Amoxicillin and Clavulanic Acid tablets

  • if you are allergic (hypersensitive) to amoxicillin, clavulanic acid, penicillin or any of the other ingredients of Amoxicillin and Clavulanic Acid tablets (listed in section 6).
  • if you have ever had a severe allergic (hypersensitive) reaction to any other antibiotic. This can include a skin rash or swelling of the face or neck
  • if you have ever had liver problems or jaundice (yellowing of the skin) when taking an antibiotic.

Do not take Amoxicillin and Clavulanic Acid tablets if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Amoxicillin and Clavulanic Acid tablets.

Warnings and precautions

Talk to your doctor or pharmacist before taking this medicine if you:

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

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Amoxicillin and Clavulanic Acid 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 Amoxicillin and Clavulanic Acid tablets or a different medicine.

Conditions you need to look out for

Amoxicillin and Clavulanic Acid tablets 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 Amoxicillin and Clavulanic Acid tablets, to reduce the risk of any problems. See 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 Amoxicillin and Clavulanic Acid tablets. This is because Amoxicillin and Clavulanic Acid tablets can affect the results of these types of tests.

Other medicines and Amoxicillin and Clavulanic Acid tablets

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines taken without a prescription.

If you are taking allopurinol (used for gout) with Amoxicillin and Clavulanic Acid tablets, it may be more likely that you’ll have an allergic skin reaction.

If you are taking probenecid (used for gout), your doctor may decide to adjust your dose of Amoxicillin and Clavulanic Acid tablets.

If medicines to help stop blood clots (such as warfarin) are taken with Amoxicillin and Clavulanic Acid tablets then extra blood tests may be needed.

Amoxicillin and Clavulanic Acid tablets can affect how methotrexate (a medicine used to treat cancer or rheumatic diseases) works.

Amoxicillin and Clavulanic Acid tablets may affect how mycophenolate mofetil (a medicine used to prevent the rejection of transplanted organs) works.

Pregnancy and breast-feeding

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

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Amoxicillin and Clavulanic Acid tablets can have side effects and the symptoms may make you unfit to drive. Don’t drive or operate machinery unless you are feeling well.

  1. HOW TO TAKE AMOXICILLIN AND CLAVULANIC ACID TABLETS

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

Adults and children weighing 40 kg and over

The usual dose is

  • 1 tablet three times a day

Children weighing less than 40 kg

Children aged 6 years or less should preferably be treated with amoxicillin/clavulanic acid oral suspension or sachets.

Ask your doctor or pharmacist for advice when giving Amoxicillin and Clavulanic Acid 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 doctor.
  • If you have liver problems you may have more frequent blood tests to check how your liver is working.

How to take Amoxicillin and Clavulanic Acid tablets

  • Swallow the tablets whole with a glass of water at the start of a meal or slightly before.
  • Space the doses evenly during the day, at least 4 hours apart. Do not take 2 doses in 1 hour.
  • Do not take Amoxicillin and Clavulanic Acid tablets for more than two weeks. If you still feel unwell you should go back to see your doctor.

If you take more Amoxicillin and Clavulanic Acid tablets than you should,

If you take too much Amoxicillin and Clavulanic Acid tablets, 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 to show the doctor.

If you forget to take Amoxicillin and Clavulanic Acid 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 Amoxicillin and Clavulanic Acid tablets

Keep taking Amoxicillin and Clavulanic Acid tablets 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.

  1. POSSIBLE SIDE EFFECTS

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

Serious side effects

If any of these serious side effects happen, stop taking the medicine and tell your doctor immediately or go to the emergency room at your nearest hospital.

Allergic reactions:

  • 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 mouth (angioedema), causing difficulty in breathing
  • collapse
  • 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)
  • 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)
  • widespread red skin rash with small pus-containing blisters (bullous 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))

The following serious side effects have also been reported:

  • inflammation of the large intestine, causing watery diarrhoea usually with blood and mucus, stomach pain and/or fever
  • 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 the eyes appear yellow
  • convulsions (in people taking high doses of Amoxicillin and Clavulanic Acid tablets or who have kidney problems)
  • blood takes longer to clot

Other side effects

If you get any of these side effects, talk to your doctor as soon as possible.

Very common: may affect more than 1 in 10 people

  • diarrhoea (in adults)

Common: 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 Amoxicillin and Clavulanic Acid tablets before food

  • vomiting
  • diarrhoea (in children)

Uncommon: may affect up to 1 in 100 people

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

Side effects that may show up in your blood tests:

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

Rare: may affect up to 1 in 1,000 people

Side effects that may show up in your blood tests:

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

Not known: frequency cannot be estimated from the available data

  • inflammation of tubes in the kidney
  • hyperactivity
  • black tongue which looks hairy
  • inflammation of the protective membrane surrounding the brain (aseptic meningitis)

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 urine

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE AMOXICILLIN AND CLAVULANIC ACID TABLETS

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and foil after ‘EXP’. The expiry date refers to the last day of that month.

Store in the original package in order to protect from light.

Do not store above 25°C.

The tablets should be used within 30 days of opening of the pouch.

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.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Amoxicillin and Clavulanic Acid tablets contain

The active substances are amoxicillin and clavulanic acid.

a) Each film-coated tablet contains:
Amoxicillin USP          500mg
Clavulanic acids            125mg
Excipients                        q.s

b) Each film-coated tablet contains:
Amoxicillin USP              875mg
Clavulanic acids             125mg
Excipients                          q.s

The other ingredients are:

Tablet core: Cellulose microcrystalline, Sodium starch glycolate, Silica colloidal anhydrous, Povidone, Eudragit & Magnesium stearate.

Tablet coating: Hypromellose, Titanium dioxide, Macrogol & Talc.

What Amoxicillin and Clavulanic Acid tablets look like and contents of the pack

Amoxicillin and Clavulanic Acid tablets are white to off-white film-coated oval shaped tablets.

PVC/Aluminium blister pack.

In packs of 10, 12, 14, 15, 16, 20, 21, 24, 30, 40, 50, 100 or 250 film-coated tablets.

Not all pack sizes may be marketed.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com