SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Amoxicillin Sugar Free 3g Powder for Oral Suspension Sachets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Amoxicillin Sugar Free 3g Powder for Oral Suspension Sachets contains 3g amoxicillin per sachet.

Amoxicillin is present as the trihydrate.

Excipients with known effect: Sorbitol

For the full list of excipients see section 6

3 PHARMACEUTICAL FORM

Powder for oral suspension White to slightly yellowish powder

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Amoxicillin is indicated for the treatment of commonly occurring bacterial infections such as:

Acute sinusitis and bacterial pharyngitis Otitis media

Acute and chronic bronchitis Lobar and bronchopneumonia Cystitis, urethritis, pyelonephritis Bacteriuria in pregnancy

Gynaecological infections including puerperal sepsis and septic abortion

Gonorrhoea

Peritonitis

Intra-abdominal sepsis Bacterial endocarditis Typhoid and paratyphoid fever Skin and soft tissue infections Osteomyelitis

Dental abscess (as an adjunct to surgical management)

Prophylaxis of endocarditis: Prevention of bacteraemia, associated with procedures such as dental extraction, in patients at risk of developing bacterial endocarditis.

Consideration should be given to official local guidance (e.g. national requirements) on the appropriate use of antibacterial agents. Susceptibility of the causative organism to the treatment should be tested (if possible), although the therapy may be initiated before the results are available.

4.2 Posology and method of administration

The reconstituted product is a white to slightly yellowish suspension

For instruction on reconstitution of the medicinal product before administration, see section 6.6.

Administration:

Oral:

Treatment of Infection:

Adult dosage (including elderly patients):

Standard adult dosage: 250 mg three times daily, increasing to 500 mg three 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 10-12 hours between the doses. Dental abscess: two 3 g doses with 8 hours between the doses. Gonorrhoea: single 3 g dose.

Children weighing <40kg:

The daily dosage for children is 40 - 90 mg/kg/day in two to three divided doses (not exceeding 3 g/day) depending on the indication, severity of the disease and the susceptibility of the pathogen (see special dosage recommendations below and sections 4.4, 5.1 and 5.2).

Children weighing more than 40 kg should be given the usual adult dosage.

Special dosage recommendation:

Acute otitis media: In areas with high prevalence of pneumococci with reduced susceptibility to penicillins, dosage regimens should be guided by national/local recommendations. In severe or recurrent acute otitis media, especially where compliance may be a problem, 750 mg twice a day for two days may be used as an alternative course of treatment in children aged 3 to 10 years.

Amoxicillin Paediatric Suspension is recommended for children under six months of age.

Prophylaxis of endocarditis:

CONDITION		ADULT’S	CHILDREN'S	NOTES
		DOSAGE	DOSAGE
		(INCLUDING ELDERLY)	( < 40 kg)
Dental	Patient not	3 g 'Amoxicillin	50 mg	Note 1. If
procedures:	having	Sugar Free 3g	amoxicillin/kg	prophylaxis
prophylaxis for	general	powder for oral	body weight	with 'Amoxicillin
patients	anaesthetic.	Suspension	given as a	Sugar Free 3g
undergoing		Sachets' orally, 1	single dose	powder for oral
extraction,		hour before	one hour	Suspension
scaling or		procedure.	preceding the	Sachets' is given
surgery		A second dose	surgical	twice within one
involving		may be given 6	procedure	month, emergence
gingival		hours later, if		of resistant
tissues and who		considered		streptococci is
have		necessary.		unlikely to be a
not received a	Patient	Initially 3 g		problem.
penicillin in the	having	'Amoxicillin		Alternative
previous month.	general	Sugar Free 3g		antibiotics are
(N.B. Patients	anaesthetic:	powder for oral		recommended if
with	if oral	Suspension		more frequent
prosthetic heart	antibiotics	Sachets' orally 4		prophylaxis is
valves	considered to	hours prior to		required, or if the
should be	be	anaesthesia,		patient has
referred to	appropriate.	followed by 3 g		received a course
hospital - see		orally (or 1 g IV		of treatment with a
below).		or IM if oral dose		penicillin during
		not tolerated) as		the previous
		soon as possible		month.
		after the		Note 2
		operation.		To minimise pain
	Patient	1 g 'Amoxicillin'		on
	having	IV or IM		injection,
	general	immediately		'Amoxicillin' may
	anaesthetic:	before		be given as two
	if oral	induction; with		injections of 500
	antibiotics	500 mg orally, 6		mg dissolved in
	not	hours later.		sterile 1%

CONDITION		ADULT’S DOSAGE (INCLUDING ELDERLY)	CHILDREN'S DOSAGE ( < 40 kg)	NOTES
	appropriate.			lidocaine solution (see Administration).
Dental procedures: patients for whom referral to hospital is recommended: a)    Patients to be given a general anaesthetic who have been given a 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: 1 g 'Amoxicillin' 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 'Amoxicillin Sugar Free 3g powder for oral Suspension Sachets' orally.	50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure	See Note 2. Note 3. 'Amoxicillin' 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. In the case of Obstetric and Gynaecological Procedures and Gastrointestinal Procedures -routine prophylaxis is recommended only for patients with prosthetic heart valves.		Initially: 1 g 'Amoxicillin' IV or IM with 120 mg gentamicin IV or IM, immediately before induction. Followed by (6 hours later): 500 mg 'Amoxicillin Sugar Free 3g powder for oral Suspension Sachets' orally or IV or IM according to clinical condition.		See Notes 2, 3 and 4 above.
Surgery or Instrumentation of the	Patients other than those with	1 g 'Amoxicillin' IV or IM immediately	50 mg amoxicillin/kg body weight	See Note 2 above. Note 5. The second dose of

CONDITION		ADULT’S DOSAGE (INCLUDING ELDERLY)	CHILDREN'S DOSAGE ( < 40 kg)	NOTES
Upper Respiratory Tract	prosthetic heart valves.	before induction; 500 mg 'Amoxicillin' IV or IM 6 hours later.	given as a single dose one hour preceding the surgical procedure	'Amoxicillin Sugar Free 3g powder for oral Suspension Sachets' may be administered orally
	Patients with prosthetic heart valves.	Initially: 1 g 'Amoxicillin' IV or IM with 120 mg gentamicin IV or IM, immediately before induction; followed by (6 hours later) 500 mg 'Amoxicillin' IV or IM.	50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure	See Notes 2, 3, 4 and 5 above.

Dosage in impaired renal function:

The dose should be reduced in patients with severe renal function impairment. In patients with a creatinine clearance of less than 30 ml/min an increase in the dosage interval and a reduction in the total daily dose is recommended (see section 4.4 and 5.2).

Renal impairment in children under 40 kg:

Creatinine clearance ml/min	Dose	Interval between administration
> 30	Usual dose	No adjustment necessary
10 - 30	Usual dose	12 h(corresponding to 2/3 of the dose)
< 10	Usual dose	24 h (corresponding to 1/3 of the dose)

4.3 Contraindications

Amoxicillin is penicillin and should not be given to penicillin-hypersensitive patients. Attention should be paid to possible cross-sensitivity with other beta-lactam antibiotics e.g. cephalosporins.

4.4 Special warnings and precautions for use

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 section 4.3).

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

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

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 section 4.9 Overdose).

Dosage should be adjusted in patients with renal impairment (see section 4.2).

Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections 4.5 and 4.8).

Precaution should be taken in premature children and during the neonatal period: renal, hepatic and haematological functions should be monitored.

Amoxicillin 3g Sachets contains 4.2 g of sorbitol (E420). Patients with intolerance to some sugar should not take this medicine.

Each sachet contains 11.9 mg of sodium. To be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interaction

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

In common with other antibiotics, amoxicillin 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.

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 amoxicillin (see sections 4.4 and 4.8).

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

4.6 Fertility, pregnancy and lactation

Use in pregnancy:

Animal studies with Amoxicillin have shown no teratogenic effects. The product has been in extensive clinical use since 1972 and its suitability in human pregnancy has been well documented in clinical studies. When antibiotic therapy is required during pregnancy, Amoxicillin may be considered appropriate when the potential benefits outweigh the potential risks associated with treatment.

Use in lactation:

Amoxicillin 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.

4.7 Effects on ability to drive and use machines

Amoxicillin Sugar Free 3g Powder for Oral Suspension has no effect on the ability to drive and use machines.

4.8 Undesirable effects

The following convention has been utilised for the classification of undesirable effects:-

Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000,< 1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000)

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

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

Infections and infestations

Very Rare: Mucocutaneous candidiasis

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 (see section 4.4 - Special Warnings and Precautions for Use.

Immune system disorders

Very rare: As with other antibiotics, severe allergic reactions, including angioneurotic oedema, anaphylaxis (see section 4.4 - Special Warnings and Precautions for Use), 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.

Gastrointestinal disorders

Clinical Trial Data *Common: Diarrhoea and nausea.

*Uncommon: Vomiting.

Post-marketing Data

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

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.

Hepato-biliary 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

Clinical Trial Data *Common: Skin rash ♦Uncommon: Urticaria and pruritus Post-marketing Data

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.

Very rare: Crystalluria (see section 4.9 Overdose)

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov .uk/yellowcard

4.9 Overdose

Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically with attention to the water/electrolyte balance. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see section 4.4 Special warnings and special precautions for use).

Amoxicillin may be removed from the circulation by haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Beta-lactam antibiotic, Penicillins.

ATC-Code: J01CA04

Mode of action:

Amoxicillin is an aminobenzyl penicillin that has a bactericidal action due to its inhibition of the synthesis of the bacterial cell wall..

It is rapidly bactericidal and possesses the safety profile of penicillin.

PK/PD relationship:

For amoxicillin, time above MIC (T>MIC) is the key pharmacodynamic parameter in predicting a successful clinical and bacteriological outcome.

Mechanism of resistance:

Bacteria may be resistant to amoxicillin due to production of beta-lactamases which hydrolyse aminopenicillins, due to alteration in penicillin-binding proteins, due to impermeability to the drug, or due to drug efflux pumps. One or more of these mechanisms may co-exist in the same organism, leading to a variable and unpredictable cross-resistance to other beta-lactams and to antibacterial drugs of other classes.

Breakpoints (EUCAST): Organism	Susceptibility Breakpoints (pg/ml)
	Susceptible	Intermediate	Resistant
Haemophilus influenzae	< 1	-	> 1
Moraxella catharrhalis	< 1	-	> 1
Enterococcus	< 4	8	> 8
Streptococcus A, B, C, G1	< 0.25	-	> 0.25
Streptococcus pneumoniae2	< 0.5	1-2	> 2
Enterobacteriaceae3	-	-	>8
Gram-negative anaerobes	< 0.5	-	> 2
Gram-positive Anaerobes	< 4	8	> 8
Non-species related breakpoints	< 2	4-8	> 8
1 Breakpoint values in the table are based on Benzylpenicillin brea			kpoints.
2 Breakpoint values in the table are based on ampicillin breakpoints.
3 The resistant breakpoint of R>8 mg/L ensures that all isolates with resistance mechanisms are reported resistant.

Susceptibility:

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

Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications

⁺pathogens resistance prevalence is > 50%

$ Naturally intermediate species

5.2 Pharmacokinetic properties

Absorption:

The absolute bioavailability of amoxicillin depends on the dose and ranges between 75 and 90%. In the dose range between 250 mg and 1000 mg the bioavailability (parameters: AUC and Cmax) is linearly proportional to the dose. At higher doses the extent of absorption decreases. The absorption is not affected by concomitant food intake. Oral administration of a single dose of 500 mg amoxicillin results in plasma concentrations of 6 - 11 mg/l. After administration of a single dose of 3 g amoxicillin, the plasma concentrations reach 27 mg/l. Peak plasma concentrations are present about 1-2 hours after administration.

Distribution:

Protein binding for amoxicillin is approximately 17%. Therapeutic drug levels are rapidly achieved in serum, lung tissue, bronchial secretions, middle ear fluid, bile and urine. In healthy meninges amoxicillin diffuses badly in liquor cerebrospinalisis. Amoxicillin crosses the placenta and a small percentage is excreted into the breast milk.

Biotransformation and elimination:

The main route of excretion of amoxicillin is the kidney. About 60-80% of an oral dose of amoxicillin are excreted in unchanged active form in the urine within 6 hours of administration, and a small fraction is excreted in the bile. Approximately 7 - 25% of the administered dose is metabolised to inactive penicilloic acid. The serum halflife in patients with normal renal function is approximately 1 - 1.5 hour. In patients with end-stage renal failure the half-life ranges between 5 to 20 hours. The substance is haemodialysable.

5.3 Preclinical safety data

Not applicable.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sorbitol (E 420), saccharine sodium (E 954), xanthan gum (E 415), colloidal anhydrous silica (E 551), raspberry flavour, orange flavour & golden caramel flavour.

6.2 Incompatibilities

None stated.

6.3 Shelf life

18 months

In use shelf-life following reconstitution: To be used immediately.

6.4 Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

Amoxicillin Sugar Free 3g Powder for Oral Suspension Sachets is packed in Paper laminated aluminium foil sachet. 2 or 14 sachets are packed in a carton. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

The reconstituted product is a white to slightly yellowish suspension.

Instructions for reconstitution:

Check that the sachet is intact before use

1.    Cut sachet along dotted line.

2.    Empty contents into a glass

3.    Half-fill sachet with water

4.    Pour into the glass, stir well and drink immediately

7    MARKETING AUTHORISATION HOLDER

Brown &Burk UK Ltd 5 Marryat Close Hounslow West Middlesex TW4 5DQ United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 25298/0032

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/06/2014

10    DATE OF REVISION OF THE TEXT

19/06/2014