CONFIDENTIAL

Clamoxyl 500 mg Capsule

Amoxicillin trihydrate

QUALITATIVE AND QUANTITATIVE COMPOSITION

CLAMOXYL Capsules 500 mg contain 500 mg amoxicillin per capsule.

The amoxicillin is present as the trihydrate in CLAMOXYL oral presentations.

PHARMACEUTICAL FORM
CLAMOXYL Capsules: maroon and gold capsules (may be referred to as ‘red and yellow’
in some markets) over-printed with ‘GS LEX’ on the 250 mg and ‘GS JVL’ on the
500 mg.

CLINICAL PARTICULARS

Indications

CLAMOXYL should be used in accordance with local official antibiotic-prescribing

guidelines and local susceptibility data.
CLAMOXYL 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 paratyphoid 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.
• Biliary tract infections.
• Bone infections.
• Pelvic infections.
• Gonorrhoea (non-penicillinase producing strains).
• Septicaemia.
• Endocarditis.
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• Meningitis.
• Peritonitis.
• Dental abscess (as an adjunct to surgical management).
• Helicobacter pylori 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: CLAMOXYL 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.
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.

• 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
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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) may be administered during dialysis and at the end of each
dialysis.
Prophylaxis of endocarditis: see table below.

Prophylaxis of endocarditis:

Consideration should be given to official guidelines and/or hospital and dental

formularies.

Condition Adults and children over

40 kg

Dental procedures: Patients 2 g as a single oral dose

not having 30 to 60 minutes before
In patients with the highest risk of general procedure.
infective endocarditis that require anaestheti
manipulation of the gingival or periapical c.
region of the teeth, or perforation of the
oral mucosa.
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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 CLAMOXYL, careful enquiry should be made concerning
previous hypersensitivity reactions to penicillins or cephalosporins.
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 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 CLAMOXYL 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.
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Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with
CLAMOXYL may result in increased and prolonged blood levels of amoxicillin.
In common with other antibiotics, CLAMOXYL 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
CLAMOXYL 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 CLAMOXYL.

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.
CLAMOXYL may be used in pregnancy when the potential benefits outweigh the potential
risks associated with treatment.
Lactation
CLAMOXYL 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 (≥1/1,000 to <1/100); rare
(≥1/10,000 to <1/1,000); very rare (<1/10,000).
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The majority of the side-effects listed below are not unique to CLAMOXYL 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, aseptic meningitis 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).
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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, acute generalised exanthematous pustulosis (AGEP), and
drug reaction with eosinophilia and systemic symptoms (DRESS).
(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 imbalance should be treated symptomatically.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see
Warnings and Precautions).
CLAMOXYL can be removed from the circulation by haemodialysis.

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, Klebsiella and
Enterobacter.
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It is rapidly bactericidal and possesses the safety profile of a 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
Enterococcus faecalis*
Beta-hemolytic streptococci*
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*
Haemophilus influenzae*
Helicobacter pylori*
Proteus mirabilis*
Salmonella spp.
Shigella spp.
Neisseria gonorrhoeae*
Pasteurella spp.
Vibrio cholerae
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Gram-positive aerobes:
Coagulase negative staphylococcus*
Corynebacterium spp.
Staphylococcus aureus *
Streptococcus pneumoniae*
Viridans group streptococcus*
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.
Enterobacter spp.
Klebsiella spp.
Pseudomonas spp.
Gram-negative anaerobes:
Bacteroides spp. (many strains of Bacteroides fragilis are resistant).
Others:
Chlamydia spp.
Mycoplasma spp.
Legionella 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
 CONFIDENTIAL

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

Shelf-Life

The expiry date is indicated on the packaging.

Special Precautions for Storage

Keep out of reach of children.

should be stored in a dry place, below30 °C (refer to the pack for information).

Manufactured by:

Glaxo Wellcome Production

Z.I. de la Peyenniere 53100 Mayenne, France

Version number: GDS31/IPI13

Date of issue: 13 June 2019

Trade marks are owned by or licensed to the GSK group of companies