Amoxil Amoxicillin Trihydrate Capsules and Suspension

AMOXIL™

Amoxicillin

 

QUALITATIVE AND QUANTITATIVE COMPOSITION

AMOXIL Capsules 250 mg: Each capsule contains amoxicillin 250 mg as Amoxicillin Trihydrate.

AMOXIL Capsules 500 mg: Each capsule contains amoxicillin 500 mg as Amoxicillin Trihydrate.

AMOXIL oral suspension 125 mg/5 ml: Each 5m1 after reconstitution contains amoxicillin 125 mg as Amoxicillin Trihydrate.

 

PHARMACEUTICAL FORM

AMOXIL Capsules 250 & 500 mg: Hard gelatin capsules filled with almost white granular powder.

AMOXIL oral suspension 125 mg/5 ml: Off white free flowing granular powder.

 

CLINICAL PARTICULARS

Indications

AMOXIL should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.

AMOXIL is a broad spectrum antibiotic indicated for the treatment of commonly occurring bacterial infections such as:

• Upper respiratory tract infections e.g. ear, nose and throat infections, otitis media

• Lower respiratory tract infections e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia

• Gastrointestinal tract infections e.g. typhoid and parathyroid fever

• Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis, bacteriuria in pregnancy, septic abortion, puerperal sepsis

• Other infections including Borreliosis (Borrelia burgdorferi) (Lyme disease)

• Skin and soft tissue infections

• Billiary tract infections

• Bone infections

• Pelvic infections

• Gonorrhoea (non-penicillinase producing strains)

• Septicaemia

• Endocarditis

• Meningitis

• Peritonitis

• Dental abscess (as an adjunct to surgical management)

• Helicobacterpylori eradication in peptic (duodenal and gastric) ulcer disease.

Infections such as septicaemia, endocarditis and meningitis due to susceptible organisms should be treated initially with high doses of a parenteral therapy and, where appropriate, in combination with another antibiotic.

Prophylaxis of endocarditis: AMOXIL may be used for the prevention of bacteraemia associated with procedures such as dental extraction, in patients at risk of developing endocarditis (see Table in Dosage and Administration).

Susceptibility to amoxicillin will vary with geography and time and local susceptibility data should be consulted where available and microbiological sampling and susceptibility testing performed where necessary (see Pharmacodynamics).

 

Dosage and Administration

Adults and children over 40 kg

Standard adult dosage: 250 mg 3 times daily, increasing to 500 mg 3 times daily for more severe infections.

High dosage therapy (maximum recommended oral dosage 6 g daily in divided doses): A dosage of 3 g twice daily is recommended in appropriate cases for the treatment of severe or recurrent purulent infection of the respiratory tract.

Short course therapy: Simple acute urinary tract infection: Two 3 g doses with 10 to 12 hours between the doses. Dental abscess: two 3 g doses with 8 hours between the doses. Gonorrhoea: single 3 g dose.

AMOXIL Eradication of H. Pylori: amoxicillin 750 mg to 1 g twice daily in combination with a proton pump inhibitor (e.g. omeprazole, lansoprazole) and another antibiotic (e.g. clarithromycin, metronidazole) for 7 days.

 

Children under 40 kg

Standard children’s dosage: 125 mg 3 times daily, increasing to 250 mg 3 times daily for more severe infections.

AMOXIL Paediatric Suspension is recommended for children under 6 months of age. Acute otitis media: 750 mg twice a day for 2 days may be used as an alternative course of treatment.

 

Patients with renal impairment

In renal impairment the excretion of the antibiotic will be delayed and, depending on the degree of impairment, it may be necessary to reduce the total daily dosage according to the following scheme:

 

Adults and Children over 40 kg

Mild impairment (creatinine clearance greater than 30 ml/min) – No change in dosage.

Moderate impairment (creatinine clearance 10 to 30 ml/min) – 500 mg twice a day maximum.

Severe impairment (creatinine clearance less than 10 ml/min) – 500 mg/day maximum.

 

Children under 40 kg

Mild impairment (creatinine clearance greater than 30 ml/min) – No change in dosage.

Moderate impairment (creatinine clearance 10 to 30 ml/min) – 15 mg/kg twice a day (maximum 500 mg/twice daily).

Severe impairment (creatinine clearance less than 10 ml/min) – 15 mg/kg once a day (maximum 500 mg).

 

Patients receiving peritoneal dialysis

Amoxicillin maximum 500 mg/day. Dosing as for patients with severe renal impairment (creatinine clearance less than 10 ml/min). Amoxicillin is not removed by peritoneal dialysis.

 

Patients receiving haemodialysis

Dosing as for patients with severe renal impairment (creatinine clearance less than 10 ml/min). Amoxicillin is removed from the circulation by haemodialysis. Therefore, 1 additional dose (500 mg for adults or 15 mg/kg for children under 40 kg) may be administered during dialysis and at the end of each dialysis.

Prophylaxis of endocarditis: see table below.

 

Prophylaxis of endocarditis

AMOXIL is given twice within 1 month, emergence of resistant streptococci is unlikely to be a problem.

Alternative antibiotics are recommended if more frequent prophylaxis is required, or if the patient has received a course of treatment with penicillin during the previous month.
Note 2.

To minimise pain on injection, AMOXIL may be given as 2 injections of 500mg dissolved in sterile 1% lignocaine solution.

Condition   Adults’ Dosage (Including Elderly) Children’s Dosage Notes
Dental procedures: Prophylaxis for patients undergoing extraction, scaling or surgery involving gingival tissues and who have not received a penicillin in the previous month (N.B. Patients with prosthetic heart valves should be referred to hospital- see below).

 

 

 

Patient not having general anaesthetic. 3 g AMOXIL orally, 1 hour before procedure. A second dose may be given 6 hours later, if considered necessary.

 

Under 10 years: half adult dose.

Under 5 years:
quarter adult dose.

The use of AMOXIL 500 mg Dispersible Tablets or 750 mg Sachets SF is recommended.

 

Note 1.

If prophylaxis with AMOXIL is given twice within 1 month, emergence of streptococci is unlikely to be a problem.

Alternative antibiotics are recommended if more frequent prophylaxis is required, or if the patient has received a course of treatment with penicillin during the previous month.

Note 2

To minimize pain on injection, AMOXIL may be given as 2 injections of 500 mg dissolved in sterile 1% lignocaine solution.

Patient having general anaesthetic: if oral antibiotics are considered to be appropriate. Initially 3 g AMOXIL orally 4 hours prior to anaesthesia, followed by 3 g orally (or 1g IV or IM if oral dose not tolerated) as soon as possible after the operation.
Patient having general anaesthetic: if oral antibiotics not appropriate 1 g AMOXIL IV or IM immediately before induction; with 500 mg orally, 6 hours later.
Dental procedures:
Patients for whom referral to hospital is recommended:
a) Patients to be given a general anaesthetic who have been given penicillin in the previous month.
b) Patients to be given a general anaesthetic who have a prosthetic heart valve.
c) Patients who have had one or more attacks of endocarditis.
Initially: 1g AMOXIL IV or IM with 120 mg gentamicin IV or IM immediately prior to anaesthesia (if given) or 15 minutes prior to dental procedure. Followed by (6 hours later): 500 mg
AMOXIL orally.
Under 10 years: the doses of AMOXIL should be half the adult dose; the dose of gentamicin should be 2 mg/kg. See Note 2. Note 3. AMOXIL and gentamicin should not be mixed in the same syringe.
Note 4. Please consult the appropriate data sheet for full prescribing information on gentamicin.
Genitourinary Surgery or Instrumentation:
Prophylaxis for patients who have no urinary tract infection and who are to have genito-urinary surgery or instrumentation under general anaesthesia.
Obstetric and Gynaecological Procedures and Gastrointestinal Procedures: Routine prophylaxis is recommended only for patients with prosthetic heart valves
Initially: 1 g AMOXIL IV or IM with 120 mg gentamicin IV or IM, immediately before induction, Followed by (6 hours later): 500 mg AMOXIL orally or IV or IM according to clinical condition Under 10 years: the doses of AMOXIL should be half the adult dose; the dose of gentamicin should be 2 mg/kg.
Under 5years: the doses of AMOXIL should be quarter the adult dose; the dose of gentamicin should be 2 mg/kg.
See Notes 2, 3 and 4 above.
Surgery or Instrumentation of the Upper Respiratory Tract Patients other than those with prosthetic heart valves. 1 g AMOXIL IV or IM immediately before induction; 500 mg AMOXIL IV or IM 6 hours later. Under 10 years: half adult dose.
Under 5 years: quarter adult dose.
See Note 2 above.
Note 5.
The second dose of AMOXIL may be administered orally as AMOXIL suspension sucrose free.
  Patients with prosthetic heart valves. Initially: 1 g AMOXIL IV or IM with 120mg gentamicin IV or IM, immediately before induction; followed by (6 hours later) 500 mg AMOXIL IV or IM. Under 10 years: the dose of AMOXIL should be half the adult dose; the gentamicin dose should be 2 mg/kg. Under 5 years: the dose of AMOXIL should be quarter the adult dose; the dose of gentamicin should be 2 mg/kg. See Notes 2, 3, 4 and 5 above.

Parenteral therapy is indicated if the oral route is considered impracticable or unsuitable, and particularly for the urgent treatment of severe infection.

 

Contraindications

Amoxicillin is a penicillin and should not be given to patients with a history of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins).

 

Warnings and Precautions

Before initiating therapy with AMOXIL, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins or cephalosporins. 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 hypersensitivity to beta lactam antibiotics (see Contraindications). If an allergic reaction occurs, amoxicillin should be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation, may also be required.

Amoxicillin 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.

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

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

Dosage should be adjusted in patients with renal impairment (see Dosage and Administration).

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 (see Overdose).

Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving AMOXIL and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

AMOXIL suspensions contain sodium benzoate which is a mild irritant to the skin, eyes and mucus membrane. It may increase the risk of jaundice in newborn babies.

AMOXIL suspensions may contain aspartame which is a source of phenylalanine and so should be used with caution in patients with phenylketonuria.

AMOXIL suspensions may contain sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

 

Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with AMOXIL may result in increased and prolonged blood levels of amoxicillin.

In common with other antibiotics, AMOXIL may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.

It is recommended that when testing for the presence of glucose in urine during AMOXIL treatment, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.

In the literature there are rare 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 AMOXIL.

 

Pregnancy and Lactation

Pregnancy: The safety of this medicinal product for use in human pregnancy has not been established by well controlled studies in pregnant women. Reproduction studies have been performed in mice and rats at doses of up to 10 times the human dose and these studies have revealed no evidence of impaired fertility or harm to the foetus due to amoxicillin. AMOXIL may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

Lactation: AMOXIL may be given during lactation. With the exception of the risk of sensitisation associated with the excretion of trace quantities of amoxicillin in breast milk, there are no known detrimental effects for the breast-fed infant.

 

Effects on Ability to Drive and Use Machines

Adverse effects on the ability to drive or operate machinery have not been observed.

Adverse Reactions

The following convention has been utilised for the classification of undesirable effects: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1,000); Very rare (≤1/10,000).

The majority of the side-effects listed below are not unique to AMOXIL and may occur when using other penicillins.

Unless otherwise stated, the frequency of adverse events (AEs) has been derived from more than 30 years of post-marketing reports.

 

Blood and lymphatic system disorders

Very rare: Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia.

Prolongation of bleeding time and prothrombin time.

 

Immune system disorders

Very rare: As with other antibiotics, severe allergic reactions, including angioneurotic oedema, anaphylaxis (see Warnings and Precautions), serum sickness and hypersensitivity vasculitis.

If a hypersensitivity reaction is reported, the treatment must be discontinued (see also Skin and subcutaneous tissue disorders).

 

Nervous system disorders

Very rare: Hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

 

Infections and Infestations

Very rare: Mucocutaneous candidiasis.

 

Gastrointestinal disorders

#Common: Diarrhoea and nausea.

#Uncommon: Vomiting.

Very rare: Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis see Warnings and Precautions).

Black hairy tongue.

Superficial tooth discolouration has been reported in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing (for suspension formulations only).

 

Hepatobiliary disorders

Very rare: Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT. The significance of a rise in AST and/or ALT is unclear.

 

Skin and subcutaneous tissue disorders

#Common: Skin rash.

#Uncommon: Urticaria and pruritus.

Very rare: Skin reactions such as erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP). (See also Immune system disorders).

 

Renal and urinary tract disorders

Very rare: Interstitial nephritis, crystalluria (see Overdose).

#The incidence of these AEs was derived from clinical studies involving a total of approximately 6,000 adult and paediatric patients taking amoxicillin.

Overdose: Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water/electrolyte balance should be treated symptomatically.

Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Warnings and Precautions).

AMOXIL can be removed from the circulation by hemodialysis.

 

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics: Amoxicillin is a semi-synthetic aminopenicillin of the beta-lactam group of antibiotics. It has a broad spectrum of antibacterial activity against many Gram-positive and Gram-negative micro-organisms, acting through the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin is, however, susceptible to degradation by beta-lactamases and therefore the spectrum of activity does not include organisms which produce these enzymes including resistant staphylococci, and all strains of Pseudomonas, Kiebsiella and Enterobacter. It is rapidly bactericidal and possesses the safety profile of penicillin.

The prevalence of acquired resistance is geographically and time dependent and for select species may be very high. Local information on resistance is desirable, particularly when treating severe infections.

 

In vitro susceptibility of micro-organisms to Amoxicillin

Where clinical efficacy of amoxicillin has been demonstrated in clinical trials this is indicated with an asterisk (*).

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

 

Commonly Susceptible Species

Gram-positive aerobes:

Bacillus anthracis

Beta -hemolytic streptococci*

Enterococcus faecalis*

Listeria monocytogenes

Gram-negative aerobes:

Bordetella pertussis

 

Other:

Leptospira icterohaemorrhagiae

Treponema pallidum

 

Species for which acquired resistance may be a problem

Gram-negative aerobes:

Escherichia coli*

Shigella spp.

Haemophilus intluenzae *

Neisseria gonorrhoeae *

Helicobacter pylori*

Pasteurella spp.

Proteus mirabilis *

Vibrio cholerae

Salmonella spp.

 

Gram-positive aerobes:

Coagulase negative staphylococcus *

Streptococcus pneumoniae *

Corynebacterium spp.

Viridans group streptococcus*

Staphylococcus aureus *

 

Gram-positive anaerobes:

Clostridium spp.

 

Gram-negative anaerobes:

Fusobacterium spp.

 

Other:

Borrelia burgdorferi

 

Inherently resistant organisms

Gram-positive aerobes:

Enterococcus faecium

 

Gram-negative aerobes:

Acinetobacter spp.

Klebsiella spp.

Enterobacter spp.

Pseudomonas spp.

 

Gram-negative anaerobes:

Bacteroides spp. (many strains of Bacteroides fragilis are resistant).

 

Others:
Chlamydia spp.

Legionella spp.

Mycoplasma spp.

 

Pharmacokinetics

Amoxicillin is well absorbed. Oral administration, usually at convenient three times a day dosage, produces high serum levels independent of the time at which food is taken.

Amoxicillin gives good penetration into bronchial secretions and high urinary concentrations of unchanged antibiotic.

Amoxicillin is not highly protein bound; approximately 18% of total plasma drug content is bound to protein. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of the brain and spinal fluid. Inflammation generally increases the permeability of the meninges to penicillins and this may apply to amoxicillin.

The major route of elimination for amoxicillin is via the kidney. Approximately 60 to 70% of amoxicillin is excreted unchanged in urine during the first six hours after administration of a standard dose. The elimination half-life is approximately one hour.

Amoxicillin is also partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to 10 to 25% of the initial dose.

Concurrent administration of probenecid delays amoxicillin excretion. Small amounts of the drug are also excreted in faeces and bile.

 

PHARMACEUTICAL PARTICULARS

List of excipients

AMOXIL Capsules 250 & 500 mg: Colloidal Anhydrous Silica, Magnesium Stearate, Hard Empty Gelatin Capsule.

AMOXIL oral suspension 125 mg/5 ml: Silicon Dioxide, Disodium Edetate, Sodium Benzoate, Xanthan gum, Colloidal Anhydrous Silica, Quinoline Yellow Supra, Peach Dry Flavour, Strawberry Dry Flavour, Lemon Dry Flavour, Sorbitol.

 

Special Precautions for Storage

AMOXIL Capsules 250 mg and 500 mg: Store in a dry place below 25°C

AMOXIL oral suspension 125 mg/5 ml: Store in a dry place below 25°C. Keep the bottle tightly closed and use within 7 days of reconstitution.

 

Shelf-Life

The expiry date is indicated on the packaging.

 

Nature and contents of container

AMOXIL Capsules 250 mg and 500 mg: Tropical blister and Alu/Alu

AMOXIL oral suspension 125 mg/5 ml: Bottles

 

Instructions for Use and Handling

Directions for making up the suspension:

• Check cap seal is intact before use.

• Invert and shake bottle to loosen powder.

• Fill the bottle with boiled and cooled water to just below the mark on the label. Invert and shake well, then top up with boiled and cooled water to the mark on the label. Invert and shake again.

• Shake well before taking each dose.

 

KEEP OUT OF REACH OF CHILDREN

 

Not all presentations are available in every country.

 

Version number: 04 GA

Version date: 19 NOVEMBER 2014

 

AMOXIL is a trademark of the GlaxoSmithKline group of companies.

© 2014 GlaxoSmithKline

 

Manufactured under licence by

MEDREICH LIMITED

Bangalore, INDIA.

Koact Co amoxiclav Tablets

KOACT

Co-amoxiclav Tablets BP 250-125 mg, 500-125 mg and 875-125 mg

Rx Only

 

NAME OF DRUG PRODUCT

Co-amoxiclav Tablets BP 250-125 mg

Co-amoxiclav Tablets BP 500-125 mg

Co-amoxiclav Tablets BP 875-125 mg

 

(TRADE) NAME OF PRODUCT

KOACT 375

KOACT 625

KOACT 1000

 

STRENGTH

375 mg, 625 mg and 1000 mg.

 

PHARMACEUTICAL DOSAGE FORM

Tablet

 

QUALITATIVE AND QUANTITATIVE COMPOSITIONS

Co-amoxiclav Tablets BP 375 mg

Each film-coated tablet contains:

Amoxicillin Trihydrate Ph.Eur. equivalent to Amoxicillin 250 mg and Potassium

Clavulanate Ph.Eur. equivalent to Clavulanic Acid 125 mg.

 

Co-amoxiclav Tablets BP 625 mg

Each film-coated tablet contains:

Amoxicillin Trihydrate Ph.Eur. equivalent to Amoxicillin 500 mg and Potassium

Clavulanate Ph.Eur. equivalent to Clavulanic Acid 125 mg.

 

Co-amoxiclav Tablets BP 1000 mg

Each film-coated tablet contains:

Amoxicillin Trihydrate Ph.Eur. equivalent to Amoxicillin 875 mg and Potassium

Clavulanate Ph.Eur. equivalent to Clavulanic Acid 125 mg.

 

PHARMACEUTICAL FORM

Co-amoxiclav Tablets BP 375 mg: White oval shaped film coated tablets, debossed with ‘A’ on one side and ‘63’ on the other side.

Co-amoxiclav Tablets BP 625 mg: White oval shaped film coated tablets, debossed with ‘A’ on one side and ‘64’ on the other side.

Co-amoxiclav Tablets BP 1000 mg: White colored capsule shaped film coated tablets, debossed with ‘A’ on one side and with a score line in between ‘6’ and ‘5’ on the other side.

 

CLINICAL PARTICULARS

Therapeutic indications

Co-amoxiclav is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The β-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other β-lactam antibiotics.

Co-amoxiclav oral preparations are indicated for short-term treatment of bacterial infections at the following sites when amoxicillin resistant β-lactamase-producing strains are suspected as the cause. In other situations, amoxicillin alone should be considered.

– Upper Respiratory Tract Infections (including ENT) in particular sinusitis, otitis media, recurrent tonsillitis. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis* and Streptococcus pyogenes.

– Lower Respiratory Tract Infections in particular acute exacerbations of chronic bronchitis (especially if considered severe), bronchopneumonia. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis*.

– Genito-urinary Tract and Abdominal Infections in particular cystitis (especially when recurrent or complicated – excluding prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis. These infections are often caused by Enterobacteriaceae* (mainly Escherichia coli*), Staphylococcus saprophyticus, Enterococcus species.*

– Skin and Soft Tissue Infections in particular cellulitis, animal bites and severe dental abscess with spreading cellulitis. These infections are often caused by Staphylococcus aureus*, Streptococcus pyogenes and Bacteroides species*.

* Some members of these species of bacteria produce b-lactamase, rendering them insensitive to amoxicillin alone.

Mixed infections caused by amoxicillin-susceptible organisms in conjunction with Co-amoxiclav-susceptible 3-lactamase-producing organisms may be treated with Co-amoxiclav. These infections should not require the addition of another antibiotic resistant to β-lactamases.

 

Posology and method of administration

Since both the 375 mg and 625 mg tablets of Co-amoxiclav contain the same amount of Clavulanic acid (125 mg, as the potassium salt), two 375mg tablets of Co-amoxiclav are not equivalent to one 625 mg tablet of Co-amoxiclav; therefore, two 375 mg tablets of Co-amoxiclav should not be substituted for one 625 mg tablet of Co-amoxiclav.

 

Adults

The usual adult dose is one 625 mg tablet of Co-amoxiclav every 12 hours or one 375 mg tablet of Co-amoxiclav every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 1000 mg tablet of Co-amoxiclav every 12 hours or one 625 mg tablet of Co-amoxiclav 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 100 mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 625 mg or 375 mg every 12 hours, depending on the severity of the infection.

Patients with a less than 10 mL/min glomerular filtration rate should receive 625 or 375 every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 625 mg or 375 mg 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.

Due to the different amoxicillin to Clavulanic acid ratios in the 375 mg tablet of Co-amoxiclav (250/125) versus the 250 mg chewable tablet of Co-amoxiclav (250/62.5), the 375 mg tablet of Co-amoxiclav should not be used until the pediatric patients weighs at least 40 kg or more.

 

Administration

Co-amoxiclav may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when Co-amoxiclav is administered at the start of a meal.

To minimize the potential for gastrointestinal intolerance, Co-amoxiclav should be taken at the start of a meal.

 

Contraindications

Penicillin hypersensitivity. Attention should be paid to possible cross-sensitivity with other β-lactam antibiotics, e.g. cephalosporins.

A previous history of Co-amoxiclav or penicillin-associated jaundice/hepatic dysfunction.

 

Special Warnings and Precautions for use

Changes in liver function may occur in some patients receiving Co-amoxiclav. The clinical significance of these changes is uncertain but Co-amoxiclav should be used with caution in patients with evidence of hepatic dysfunction.

Cholestatic jaundice, which may be severe, but is usually reversible, may occur rarely. Signs and symptoms may not become apparent for several weeks after treatment has ceased.

In patients with renal impairment, dosage should be adjusted according to the degree of impairment.

In patients with reduced urine output, crystalluria may occur very rarely, predominately 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 Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions may occur in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity.

Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.

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

 

Interaction with other drugs and other forms of interactions

Prolongation of bleeding time and prothrombin time may occur in some patients receiving Co-amoxiclav. Co-amoxiclav should be used with care in patients on anti-coagulation therapy.

In common with other broad-spectrum antibiotics, Co-amoxiclav may reduce the efficacy of oral contraceptives and patients should be warned accordingly.

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

 

Use in pregnancy and lactation

Treatment with Co-amoxiclav may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential bsç the physician. Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.

 

Effects on ability to drive and use machines

None Known.

 

Undesirable effects

Side effects are uncommon and mainly of a mild and transitory nature.

 

Gastrointestinal reactions

Diarrhoea, indigestion, nausea, vomiting, and mucocu-taneous candidiasis may occur. Antibiotic-associated colitis (including pseudomembranous. colitis and haemorrhagic colitis) may occur rarely. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal side effects occur with oral therapy they may be reduced by taking Co-amoxiclav at the start of meals.

Superficial tooth discolouration may occur rarely, mostly with the suspension. It can usually be removed by brushing.

 

Renal and urinary tract disorders

Crystalluria occurs very rarely.

 

Genito-urinary effects

Vaginal itching, soreness and discharge may occur.

 

Hepatic effects

Moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases occurs occasionally. Hepatitis and cholestatic jaundice occurs rarely. These hepatic reactions occurs more commonly with Co-amoxiclav than with other penicillins.

After Co-amoxiclav hepatic reactions occurs more frequently in males and elderly patients, particularly those over 65 years. The risk increases with duration of treatment longer than 14 days. These reactions may occur very rarely in children.

Signs and symptoms usually occur during or shortly after treatment but in some cases may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and very rarely, deaths occurs.

 

Hypersensitivity reactions

Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis occurs. Treatment should be discontinued if one of these disorders occurs. In common with other β-lactam antibiotics angioedema and anaphylaxis occurs. Interstitial nephritis can occur rarely.

 

Haematological effects

As with other β-lactams transient leucopenia (including neutropenia and agranulocytosis), thrombocytopenia and haemolytic anaemia occurs rarely.

Prolongation of bleeding time and prothrombin time also occurs rarely.

 

CNS effects

CNS effects occurs very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.

 

Overdosage

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. They may be treated symptomatically with attention to the water electrolyte balance. Co-amoxiclav may be removed from the circulation by haemodialysis.

Amoxicillin crystalluria, in some cases leading to renal failure, may occur.

 

PHARMACOLOGICAL PROPERTIES

Pharmacokinetic properties

The pharmacokinetics of the two components of Co-amoxiclav is closely matched. Peak serum levels of both occur about one hour after oral administration. Absorption of Co-amoxiclav is optimized at the start of a meal. Both clavulanate and amoxicillin have low levels of serum binding: about 70% remains free in the serum.

Doubling the dosage of Co-amoxiclav approximately doubles the serum levels achieved.

 

Pharmacodynamic properties

Bacterial enzymes that destroy the antibiotic before it can act on the pathogen cause resistance to many antibiotics. The clavulanate in Co-amoxiclav anticipates this defence mechanism by blocking the β-lactamase enzymes, thus rendering the organisms sensitive to amoxicillin’s rapid bactericidal effect at concentrations readily attainable in the body.

Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as Co-amoxiclav, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.

 

Gram-positive

Aerobes: Enterococcus faecalis*, Enterococcus faecium*, Streptococcus pneumonia, Streptococcus pyogenes, Streptococcus varidans, Staphylococcus aureus*, Coagulase negative staphylococci* (including Staphylococcus epidermis*), Coryne-bacterium species, Bacillus anthracis*, Listeria monocytogenes.

Anaerobes: Clostridium species, Peptococcus species, Peptostrptococcus.

 

Gram-negative

Aerobes: Haemophilus influenza*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella species*, Salmonella species*, Shigella species*, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae*, Neisseria meningitides*, Vibrio cholerae, Pasteurella multocida.

Anaerobes: Bacteroides species* including B. fragilis.
Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.

 

PHARMACEUTICAL PARTICULARS

List of Excipients

Cellulose, Microcrystalline, Purified Water, Sodium Starch Glycolate, Silica, Colloidal anhydrous, Magnesium Stearate, Opadry white, lsopropyl alcohol and Methylene chloride.

 

Incompatibilities

None.

 

Shelf-life

24 months.

 

Special precautions for storage

Store in a dry place at or below 30°C. Protect from moisture.

Keep out of the reach of children.

 

Authorisation Numbers

KOACT 375

TFDA. Reg. No: TAN 07,138 J01C AUR

NAFDAC. Reg. No: A4-3715

Zambia. Reg. No: 127/068

 

KOACT 625

TFDA. Reg. No: TAN 07, 266 J01C AUR

NAFDAC Reg. No: A4-4185

Zambia Reg. No: 127/069

 

KOACT 1000

TFDA. Reg. No: TZ 15 H 0245

Zambia Reg. No: 127/070

 

Nature and contents of container

KOACT 375, KOACT 625 and KOACT 1000: Blister of 5 tablets.

HDPE Container Pack:

KOACT 375 and KOACT 625: 100 and 500 tablets.

KOACT 1000: 60 Tablets.

 

MARKETING AUTHORIZATION HOLDER

Aurobindo Pharma Ltd.,

Plot No.: 2, Maitrivihar,

Ameerpet, Hyderabad-500 038,

Telangana State, India.

 

DATE OF PREPARATION OF THIS LEAFLET

April 2016.

Amclavin Amoxicillin and Clavulanate Potassium Oral Suspension and Tablets

Amclavin®

Amoxicillin and Clavulanate Potassium for Oral Suspension and Tablets.

For the use only of a Registered Medical Practitioner or a hospital or a Laboratory.
 

AMCLAVIN 156.25 Oral Suspension

COMPOSITION

Each 5mI of reconstituted suspension contains:

Amoxicillin Trihydrate BP

equivalent to Amoxicillin 125 mg

Diluted Potassium Clavulanate BP

equivalent to Clavulanic Acid 31.25 mg

Excipients q.s.

In a flavoured syrupy base.

 

AMCLAVIN – 375 Tablets

COMPOSITION

Each film coated tablet contains:

Amoxicillin Trihydrate USP equivalent to Amoxicillin 250mg

Diluted Potassium Clavulanate BP

equivalent to Clavulanic Acid 125mg

Excipients q.s.

Colour: Titanium Dioxide BP

 

AMCLAVIN – 312.5 Oral suspension

COMPOSITION

Each 5ml of reconstituted suspension contains:

Amoxicillin Trihydrate BP equivalent to Amoxicillin 250 mg Diluted Potassium Clavulanate BP

equivalent to Clavulanic Acid 62.5 mg

Excipients q.s.

In a flavoured syrupy base.

 

AMCLAVIN 625 Tablets

COMPOSITION

Each film coated tablet contains:

Amoxicillin Trihydrate USP equivalent to Amoxicillin 500 mg Diluted Potassium

Clavulanate BP equivalent to Clavulanic Acid 125 mg

Excipients q.s.

Colour: Titanium Dioxide BP

 

DESCRIPTION

Amclavin is an oral antibacterial combination consisting of the semisynthetic antibiotic Amoxicillin and the beta-lactamase inhibitor potassium Clavulanate providing a broad spectrum of antibacterial activity against beta-lactamase producing bacteria. Amoxicillin is chemically designated as (6R)-6-(ᾳ-4- hydroxypheny-D-glycylamino) penicillanic acid trihydrate. Its molecular formula is C16H19N3O5S.3H2O and its molecular weight is 419.45.

Clavulanate Potassium is chemically designated as Potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1azabicyclo[3.20] heptane-2-carboxylate. Its molecular formula is C8H8KNO5 and its molecular weight is 237.25.

 

PHARMACOLOGY

Mechanism of Action

Amoxicillin acts through inhibition of biosynthesis of the bacterial cell wall mucopeptide. Antibacterial Spectrum Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative micro-oganisms.

Amoxicillin is, however, susceptible to degradation by β-lactamase and, therefore the spectrum of activity does not include organisms, which produce these enzymes.

Clavulanic acid is a β-lactam, structurally related to the Penicillins, which possesses the ability to inactivate a wide range of (β-lactamase enzymes commonly found in a micro-organisms resistant to Penicillins and cephas.

In particular, it has good activity against the clinically important plasmid mediated β-lactamases frequently responsible for transferred drug resistance.

The formulation of Amoxicillin and Clavulanic acid in Amclavin protects Amoxicillin from degradation by B-lactamase enzymes and effectively extends the antibiotic spectrum of Amoxicillin to include many bacteria normally resistant to Amoxicillin and other β-lactam antibiotics. Thus, co-amoxiclav possesses the properties of a broad-spectrum antibiotic and a β-lactamase inhibitor. Amoxicillin/Clavulanic acid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections (see INDICATIONS).

 

GRAM-POSITIVE AEROBES

Staphylococcus aureus (β-lactamase and non β-lactamase producing).

Staphylococci, which are resistant to Methicillln/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 Amclavin in urinary tract infections caused by these organisms.) Escherichia coli (β-lactamase and non-a β lactamase producing) Haemophilus influenzae (β -lactamase and non- β -lactamase producing).

Klebsiella species (All known strains are β -Iactamase producing).

Moraxella catarrhalis (β -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 2µg/ml or less against most (≥90%) strains of Streptococcus pneumoniae, MICs of 0.06 mg/ml or less against most (≥90%) strains of Neisseria gonorrhoeae; MICs of 4µg/ml or less against most (≥90%) strains of staphylococci and anaerobic bacteria; and MIC’s of 8µg/ml 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 micro-organisms 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, Staphylococcus 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 Bacteroidos 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 organism and, therefore, are susceptible to Amoxicillin alone.

 

PHARMACOKINETICS

Amoxicillin and Clavulanate potassium are well absorbed from the gastrointestinal tract after oral administration of Amclavin. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of Amoxicillin. While Amclavin 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 Amclavin was dosed at 30 and 150 minutes after the start of a high fat breakfast.

The safety and efficacy of Amclavin have been established in clinical trials where Amclavin was taken without regard to meals. Amoxicillin serum concentrations achieved with Amclavin 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 Amclavin is 1.3 hours and that of clavulanic acid is 1.0 hour.

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. Neither component in Amclavin is highly protein-bound; clavulanic acid has been found to be approximately 25% found to human serum and Amoxicillin approximately 18% found. 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 Amclavin 625 or Amclavin 375 tablet.

 

INDICATIONS

Amclavin is indicated for the treatment of following Infections caused by susceptible pathogens:

Lower respiratory tract infections (e.g., Pneumonia, bronchitis)

Acute otitis media

Sinusitis

Urinary tract Infections

Skin and soft tissue infections

Bone and joint infections

 

DOSAGE AND ADMINISTRATION: (As directed by the physician)

While Amclavin Is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to Amclavin treatment due to its Amoxicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and β-lactamase-producing organisms susceptible to Amclavin 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 Amclavin (see Antibacterial Spectrum).

Bacteriological studies, to determine the causative organisms and their susceptibility to Amclavin, should be performed together with any indicated surgical procedures. Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies to determine the causative organisms and their susceptibility to Amclavin when there is reason to believe the infection may involve any of the β-lactamase-producing organisms listed above. Once the results are known, therapy should be adjusted, if appropriate.

 

Pediatric Patients: Based on the Amoxicillin component, Amclavin should be dosed as follows:

Neonates and Infants aged < 12weeks (3 months):

Due to incompletely developed renal function affecting elimination of Amoxicillin in this age group, the recommended dose of Amclavin is 30mg/kg/day divided q 12th based on the Amoxicillin component. Clavulanate elimination is unaltered in this age group.

 

Premature: No dosage recommendations can be made for this category.

Children 3-9 months: 1.25mL of AMCLAVIN 156.25 Oral Suspension three times a day.

Children 9 months – 2 years: 2.5mL of AMCLAVIN 156.25 Oral Suspension three times a day.

Children 2-6 years: 5mL of AMCLAVIN 156.25 Oral Suspension three times a day. In severe infections this may be increased to 10mI AMCLAVIN 156.25 Oral Suspension three times a day.

Children 7-12 years: 5mL of AMCLAVIN 312.5 Oral Suspension three times daily. In severe infections this may be increased to 10mL of AMCLAVIN 312.5 Suspension three times a day.

 

Adults: Adult who have difficulty in swallowing may be given the Amclavin 156.25 or Amclavin 312.5 Oral Suspension in place of the Amclavin 625 tablet.

Since both AMCLAVIN 375 & AMCLAVIN 625 tablets contain the same amount of Clavulanic acid (125 mg, as the potassium salt), two tablets of AMCLAVIN 375 are not equivalent to one tablet of AMCLAVIN 625; therefore, two tablets of AMCLAVIN 375 should not be substituted for one tablet of AMCLAVIN 625.

Adults: The usual adult dose is one tablet of AMCLAVIN 625 every 12 hours or one tablet of AMCLAVIN 375 every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one tablet of AMCLAVIN 625 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 875 mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive AMCLAVIN 625 or AMCLAVIN 375 every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/min glomerular filtration rate should receive AMCLAVIN 625 or AMCLAVIN 375 every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive AMCLAVIN 625 or AMCLAVIN 375 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. (See WARNINGS).

 

Pediatric Patients: Pediatric patients weighing 40 kg or more should be dosed according to the adult recommendations, due to the different Amoxicillin to clavulanic acid ratios in the 375 mg tablet of AMCLAVIN (250/125), it should not be used until the pediatric patient weighs at least 40 kg or more.

 

Administration: AMCLAVIN may be taken without regard to meals; however, absorption of Clavulanate potassium is enhanced when AMCLAVIN is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, AMCLAVIN should be taken at the start of a meal.

 

DIRECTIONS FOR USE

Do not chew, swallow with Water.

 

PRECAUTIONS

General

While Amclavin 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 infectious mononucleosis.

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

 

Warnings

Serious and occasionally fatal hypersensitivity (Anaphylactic) reactions have been reported in patients Penicillin therapy. These reactions are more likely to occur in individuals with a history of Penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of Penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with Amclavin, careful inquiry should be made concerning previous hypersensitivity reactions to Penicillins, Cephalosporins or other allergens. If an allergic reaction occurs, Amclavin should be discontinued and appropriate therapy instituted.

Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, Intravenous steroids and airway management, including intubation, should also be administered as indicated.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Amclavin, 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.

Amclavin should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of Amclavin is usually reversible. On rare occasions, deaths have been reported (less than 4 death reported per estimated 4 million prescriptions worldwide). These have been generally cases associated with serious underlying diseases or concomitant medications (see contraindications and Adverse Reactions).

 

Contraindications

Amclavin is contraindicated in patients with a history of allergic reactions to any Penicillin. It is also contraindicated in patients with a previous history of Amclavin -associated cholestatic jaundice/hepatic dysfunction.

 

Carcinogenicity/Mutagenicity//Impairment of Fertility

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

The mutagenic potential of Amoxicillin and Clavulanate potassium combination was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.

Amclavin at oral doses of up to 1200mg/kg/day (5.7 times the maximum human dose. 1480 mg/m2/day, based on body surface area) was found to have no effect on fertility and reproductive performance in rates, dosed with a 2:1 ration formulation of Amoxicillin: Clavulanate.

 

Pregnancy

There are not adequate and well-controlled studies in pregnant women. Reproduction studies performed in pregnant rats and mice given Amclavin at oral dosages up to 1200mg/kg/day, equivalent to 7200 and 4080 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 Amclavin. 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

The use of Amclavin in humans during labor or delivery has immediate or delayed adverse effects on the foetus, 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 fatal membranes, it was reported that prophylactic treatment with Amclavin may be associated with an increased risk of necrotizing enterocolitis in neonates.

 

Lactation

Amclavin are excreted in the milk; therefore, caution should be exercised when Amclavin is administered to a nursing woman.

 

Pediatrics

Pediatric patients above 12 years of age should be dosed according to adult recommendation (see DOSAGE & ADMINISTRATION).

 

Geriatrics

Amclavin have been used in geriatric patients and no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have an age-related decrease in renal function, which may require an adjustment in dosage in patients receiving Amclavin.

 

Drug Interactions

Probenecid decreases the renal tubular secretion of Amoxicillin. Concurrent use with Amclavin may result in increased and prolonged blood levels of Amoxicillin. Co-administration of Probenecid cannot be recommended. There are no data with Amclavin and Allopurinol administered concurrently.

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

 

Drug/Laboratory Test interactions

Oral administration of Amclavin will result in high urine concentrations of Amoxicillin. High urine concentrations of Amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using a standardized self-heating method for quantitative determination of urine sugar by copper reduction, or Benedict’s Solution or Fehlirig’s Solution. Since this effect occurs with Amoxicillin and therefore Amclavin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

Following administration of Amoxicillin to pregnant women may cause transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol . This effect may occurs with Amoxicillin and therefore Amclavin.

 

Adverse Effects

Amclavin 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 Amoxicillin 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 (see Warnings).

 

Hypersensitivity Reactions

Skin rashes, pruritius, urticaria, angioedema, serum sickness- like reactions (urticaria or skin rash accompanied by arthritis, arthraigia, 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 (see Warnings).

 

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 Amclavin. It has been reported more commonly in the elderly, in males, or in patients or prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes.

The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. 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.

 

Hemic and Lymphatic Systems

Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopania and agranulocytosis have been reported during therapy with Penicillins. These reactions are usually reversible on discontinuations of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in less than 1% of the patients treated with Amclavin. There have been reports of increased prothrombin time in patients receiving and anticoagulant therapy concomitantly.

 

Central Nervous System

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

 

Miscellaneous

Tooth discoloration has been reported very rarely in children. Good hygiene may help to prevent tooth discoloration as it can usually be removed by brushing.

 

OVERDOSAGE

Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients. In the case of overdosage, discontinue Amclavin, 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 less than 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. 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 (see DOSAGE AND ADMINISTRATION).

 

STORAGE

AMCLAVIN ORAL SUSPENSION: Store in a cool and dry place, below 25°C. Protect from light.

AMCLAVIN TABLETS: Store in a cool and dry place, below 25°C. Protect from light.

 

Keep all medicines away from Children.

 

SUPPLIED

AMCLAVIN 312.5 Oral Suspension

AMCLAVIN 156.25 Oral Suspension

AMCLAVIN 625 Tablets

AMCLAVIN 375 Tablets

 

Manufactured by

Medicef Pharma Pvt Ltd,

28, Phase-1, EPIP, Jharmajri,

Baddi, Distt. solan(HP) -173205

 

Marketed by

SEAGREEN PHARMACEUTICALS LTD.

3, Okunfolami Street, Anthony Village,

Lagos, Nigeria.