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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Amoxicillin 1g, Powder for Solution for Injection or Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 20ml vial contains 1g Amoxicillin as Amoxicillin Sodium.

Each vial contains approximately 76 mg sodium.

3 PHARMACEUTICAL FORM

Powder for Solution for Injection or Infusion.

Glass vial containing white or almost white powder.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of Infection:

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

•    Upper respiratory tract infections

•    Otitis media

•    Acute and chronic bronchitis

•    Chronic bronchial sepsis

•    Lobar and bronchopneumonia

•    Cystitis, urethritis, pyelonephritis

•    Bacteriuria in pregnancy

•    Gynaecological infections including puerperal sepsis and septic abortion

•    Gonorrhoea

•    Peritonitis

•    Intra-abdominal sepsis

•    Septicaemia

•    Bacterial endocarditis

• Typhoid and paratyphoid fever

• Skin and soft tissue infections

In children with urinary tract infection the need for 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.

4.2 Posology and method of administration

Adult dosage (including elderly patients):

Treatment of infection:

Moderate infections: 500 mg via intramuscular injection every 8 hours (or more frequently if necessary). This dose may be given by slow intravenous injection if more convenient.

Severe infections: 1 g via intravenous injection every 6 hours.

Prophylaxis of endocarditis:

Condition		Dosage	Notes
Dental	Patient not	3 g Amoxicillin	Note 1.
procedures:	having	orally, 1 hour before	If prophylaxis with
prophylaxis	general	procedure. A second	Amoxicillin' is given
for patients	anaesthetic	dose may be given 6	twice within one month,
undergoing		hours later, if	emergence of resistant
extraction,		considered	streptococci is unlikely to
scaling or		necessary.	be a problem. Alternative
surgery	Patient having	Initially 3 g	antibiotics are
involving	general	Amoxicillin orally 4	recommended if more
gingival	anaesthetic: if	hours prior to	frequent prophylaxis is
tissues and	oral	anaesthesia,	required, or if the patient
who have	antibiotics	followed by 3 g	has received a course of
not	considered to	orally (or	treatment with a
received a	be appropriate	1 g IV or IM if oral	penicillin during the
penicillin in		dose not tolerated)	previous month.
the		as soon as possible
previous		after the operation.	Note 2

month.	Patient having	1 g Amoxicillin IV	To minimise pain on
	general	or IM immediately	injection, Amoxicillin
(N.B.	anaesthetic: if	before induction;	may be given as two
Patients	oral	with 500 mg orally,	injections of 500 mg
with	antibiotics not	6 hours later.	dissolved in sterile 1%
prosthetic heart valves should be referred to hospital -see below).	appropriate.		lidocaine solution (see Administration).

Condition		Dosage	Notes
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	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 orally or IV or IM according to clinical condition.	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 Amoxicillin IV or IM immediately before induction; 500 mg Amoxicillin IV or IM 6 hours later.	See Note 2 above. Note 5. The second dose of Amoxicillin 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.	See Notes 2, 3, 4 and 5 above.

Children:

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

*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.

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.

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

Prophylaxis for endocarditis: 50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure.

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)

Administration:

Intravenous injection, intravenous infusion, intramuscular injection: See Section 6.6, Instructions for use and handling.

4.3 Contraindications

Amoxicillin is a penicillin and should not be given to patients with a history of hypersensitivity to penicillins or 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). Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.

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

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

Amoxicillin injection contains approximately 3.3 mmol sodium per gram. This should be taken into consideration by patients on a sodium controlled diet.

4.5 Interaction with other medicinal products and other forms of interaction

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

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

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.

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

Pregnancy

Animal studies with amoxicillin have shown no teratogenic effects. It 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.

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) and very rare (<1/10,000).

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

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.

Gastrointestinal disorders Common: Diarrhoea and nausea.

Uncommon: Vomiting

Very rare: Mucocutaneous candidiasis and antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis).

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

Common: Skin rash

Uncommon: Urticaria and pruritus

Very rare: Skin reactions such bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP) (See also Immune system disorders). Not known: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Renal and urinary disorders

Very rare: Interstitial nephritis, crystalluria (See Section 4.9 Overdose).

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.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC code: J01CA04

Pharmacotherapeutic group: Penicillins with extended spectrum

Amoxicillin is a broad spectrum antibiotic. It is rapidly bactericidal and possesses the safety profile of a penicillin. The wide range of organisms sensitive to the bactericidal action of Amoxicillin include:

5.2    Pharmacokinetic properties

Amoxicillin is well absorbed by the oral and parenteral routes. Amoxicillin gives good penetration into bronchial secretions and high urinary concentrations of unchanged antibiotic.

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

No further information of relevance.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None

6.2    Incompatibilities

Amoxicillin should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates, or with intravenous lipid emulsions.

If Amoxicillin is prescribed concurrently with an aminoglycoside, the antibiotics should not be mixed in the syringe, intravenous fluid container or giving set because loss of activity of the aminoglycoside can occur under these conditions.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3    Shelf life

Unopened vial: 36 months.

After opening: To be used immediately.

6.4 Special precautions for storage

Store below 25°C

6.5 Nature and contents of container

Clear Type III glass vials with chlorobutyl rubber closure, in cartons of 1, 5, 10, 20 or 50 vials. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Intravenous Injection:

Dissolve 1g in 20ml Water for Injections BP (final volume 20.8 ml).

Amoxicillin injection, suitably diluted, may be injected directly into a vein or the infusion line over a period of three to four minutes.

Intravenous Infusion:

Solutions may be prepared as described for intravenous injections and then added to an intravenous solution in a minibag or in-line burette and administered over a period of half to one hour. Alternatively, using a suitable reconstitution device, the appropriate volume of intravenous fluid may be transferred from the infusion bag into the vial and then drawn back into the bag after dissolution.

Intramuscular injection:

Add 2.5 ml Water for Injections BP and shake vigorously (final volume 3.3 ml).

A transient pink colouration or slight opalescence may appear during reconstitution. Reconstituted solutions are normally a pale straw colour.

Amoxicillin injection may be added to the following intravenous fluids and used immediately.

•    Water for Injections BP

•    Sodium Chloride Intravenous Infusion (0.9%)

•    Potassium Chloride (0.3%) and Sodium Chloride (0.9%) Intravenous Infusion

•    Glucose Intravenous Infusion

•    Sodium Chloride (0.18%) and Glucose (4%) Intravenous Infusion

•    Dextran 40 Intravenous Infusion (10%) in Sodium Chloride Intravenous Infusion (0.9%)

•    Dextran 40 Intravenous Infusion (10%) in Glucose Intravenous Infusion (5%)

•    Sodium Lactate Intravenous Infusion (M/6)

Compound Sodium Lactate Intravenous Infusions (Ringer-Lactate: Hartmann’s Solution)

7 MARKETING AUTHORISATION HOLDER

Actavis Group PTC ehf.

Reykjavikurvegi 76-78 220 HafnarfjorQur Iceland

MARKETING AUTHORISATION NUMBER(S)

PL 30306/0609

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

26/03/2009

DATE OF REVISION OF THE TEXT

09/06/2015