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.

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