SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Amoxicillin Sugar Free Suspension BP 250mg/5ml

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Amoxicillin Sugar Free Suspension 250mg/5ml contains Amoxicillin Trihydrate BP equivalent to Amoxicillin BP 250mg.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Pale yellow powder for reconstitution as suspension

4 CLINICAL PARTICULARS

4.1    Therapeutic indications

Amoxicillin is a broad spectrum antibiotic indicated for the treatment of commonly occurring bacterial infections including upper respiratory infections, acute and chronic bronchitis, chronic bronchial sepsis, pneumonia, ear, nose and throat infections, otitis media, urinary tract infection, cystitis, urethritis, pyelonephritis, gonorrhoea, invasive salmonellosis, bacteriuria in pregnancy, gynaecological infections including puerperal sepsis and septic abortion, peritonitis, intra-abdominal sepsis, septicaemia, osteomyelitis, meningitis, bacterial endocarditis, typhoid and paratyphoid fever, skin and soft tissue infections, dental abscess (as an adjunct to surgical management)

In children with urinary tract infection, the need for further clinical investigation should be considered.

Prophylaxis of endocarditis: Amoxicillin may be used for the 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

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

Up to a maximum of 6g 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 infections

Two 3 g doses with 10-12 hours between the doses.

Dental abscess

Two 3 g doses with 8 hours between the doses.

Gonorrhoea

3 g single dose in combination with 1 g Probenecid.

Children (up to ten years of age):

125mg every eight hours which may be doubled in severe infections.

In dental prophylaxis, the same precautions apply as with adults, the normal dosage in children, 5 - 10 years is half the adult dose and quarter the adult dose in children under 5 years.

Children weighing < 40 kg

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).

*PK/PD data indicate that dosing three times daily is associated with enhanced efficacy, thus twice daily dosing is only recommended when the dose is in the upper range.

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

Special dosage recommendation Tonsillitis: 50 mg/kg/day in two divided doses.

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.

Early Lyme disease (isolated erythema migrans): 50 mg/kg/day in three divided doses, over 14-21days.

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).

Glomerular filtration rate > 30 ml/min: No adjustment necessary.

Glomerular filtration rate 10-30 ml/min: Amoxicillin max. 500 mg b.d Glomerular filtration rate < 10 ml/min: Amoxicillin max. 500 mg/day 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)

Prophylaxis of endocarditis:

CONDITION		ADULTS’ DOSAGE (INCLUDING ELDERLY)	CHILDREN'S DOSAGE (< 40 kg)	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 Amoxicillin orally 1 hour before procedure. A second dose may be given 6 hours later, if considered necessary.	50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure.	Note 1. If prophylaxis with Amoxicillin is given twice within one 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 a penicillin during the previous month. Note 2. To minimise pain on injection, Amoxicillin may be given as two injections of 500 mg dissolved in sterile 1% lidocaine solution (see Administration).
	Patient having general anaesthetic: if oral antibiotics considered to be appropriate.	Initially 3 g Amoxicillin orally 4 hours prior to anaesthesia, followed by 3 g orally (or 1 g 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 Amoxicillin 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 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 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		Initially: 1 g		See Notes 2, 3 and 4

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.		Amoxicillin IV or IM with 120 mg gentamicin IV or IM immediately before induction. Followed by (6 hours later): 500 mg Amoxicillin orally or IV or IM according to clinical condition.		above.
Surgery or Instrumentation of the Upper Respiratory Tract	Patients other than those with prosthetic heart valves.	1 g Amoxicillin IV or IM immediately before induction; 500 mg Amoxicillin IV or IM 6 hours later.	50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure	See Note 2 above. Note 5. The second dose of Amoxicillin be administered orally as Amoxicillin Syrup SF/DF.
	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.

Method of administration:

Oral

Treatment should be continued for 2 to 3 days following the disappearance of symptoms. It is recommended that at least 10 days treatment be given for any infection caused by beta-haemolytic streptococci in order to achieve eradication of the organism.

4.3    Contraindications

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

4.4    Special warnings and precautions for use

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, 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 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).

In patients with renal impairment, the rate of excretion of amoxicillin will be reduced depending on the degree of impairment and it may be necessary to reduce the total daily unit amoxicillin dosage accordingly.

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.

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).

Penicillins reduce excretion of methotrexate (increased risk of toxicity).

Excretion of penicillins reduced by sulfinpyrazone.

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 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

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

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 (see section 4.5 - Interaction with other Medicaments and other Forms of Interaction)

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.

Gastro intestinal 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

Amoxicillin is a broad spectrum antibiotic. It is rapidly bactericidal and possesses the safety profile of penicillin.

The wide range of organisms sensitive to the bactericidal action of Amoxicillin include:

Aerobes:

Gram-positive

Streptococcus faecalis

Streptococcus pneumoniae

Streptococcus pyogenes

Streptococcus viridans

Staphylococcus aureus (penicillin-sensitive

strains only)

Corynebacterium species Bacillus anthracis Listeria monocytogenes

Anaerobes: Clostridium species

5.2 Pharmacokinetic properties

Amoxicillin is well absorbed by the oral and parenteral routes. Oral administration, usually at convenient t.d.s. 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 rapidly absorbed when given by mouth; it is not converted to ampicillin. It is widely distributed and is reported to produce peak antibiotic plasma concentrations that are up to twice as high as those from the same dose of ampicillin. Peak plasma-amoxicillin concentrations of about 5 g per ml have been observed 2 hours after a dose of 250 mg, with detectable amounts present for up to 8 hours. Doubling the dose can produce double the concentration. The presence of food in the stomach does not appear to diminish absorption significantly.

Up to 20% is bound to plasma proteins in the circulation and plasma half-lives of about one hour have been reported. Amoxicillin diffuses across the placenta; little appears to be excreted in breast milk. It penetrates will into purulent and mucoid sputum and low concentrations have been found in ocular fluid.

In preterm infants with gestational age 26-33 weeks, the total body clearance after intravenous dosing of amoxicillin, day 3 of life, ranged between 0.75 - 2 ml/min, very similar to the inuline clearance (GFR) in this population. Following oral administration, the absorption pattern and the bioavailability of amoxicillin in small children may be different to that of adults. Consequently, due to the decreased CL,

the exposure is expected to be elevated in this group of patients, although this increase in exposure may in part be diminished by decreased bioavailability when given orally.

5.3 Preclinical safety data

Not applicable.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium Benzoate BP Disodium Edetate BP Sodium Citrate BP Citric Acid BP

Colloidal Anhydrous Silica BP Sorbitol

Saccharin Sodium BP Banana Flavour Quinoline Yellow, E104 Xantham Gum USNF

6.2    Incompatibilities

None Known

6.3 Shelf life

3 years unopened. 7 days after reconstitution.

Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

High density polyethylene bottles with tamper-evident and child resistant cap of the appropriate size to accommodate 100ml.

And

High density polyethylene bottles with tamper-evident cap of the appropriate size to accommodate 100ml.

6.6 Special precautions for disposal

Quantities of potable water to be added are: 84ml to reconstitute 100ml of 125/5ml Amoxicillin Sugar Free Suspension.

7. Marketing Authorisation Holder

Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF

8    MARKETING AUTHORISATION NUMBER(S)

PL 21880/0124

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

17/11/2011

10    DATE OF REVISION OF THE TEXT

06/12/13