Amoxil Vials for Injection 500mg

1. Name Of The Medicinal Product

Amoxil® Vials for Injection 500 Mg

2. Qualitative And Quantitative Composition

Amoxil Vials for Injection 500 mg contain 500 mg amoxicillin

The amoxicillin is present as the sodium salt in Amoxil injections (each 1 g vial contains approximately 3.3 mmol of sodium).

3. Pharmaceutical Form

Amoxil Vials: vials containing sterile powder for reconstitution.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of Infection: Amoxil 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: Amoxil may be used for the prevention of bacteraemia, associated with procedures such as dental extraction, in patients at risk of developing bacterial endocarditis.

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

Gram-positive	Gram-negative
Streptococcus faecalis	Haemophilus influenzae
Streptococcus pneumoniae	Escherichia coli
Streptococcus pyogenes	Proteus mirabilis
Streptococcus viridans	Salmonella species
Staphylococcus aureus	Shigella species
(penicillin-sensitive)	Bordetella pertussis
Clostridium species	Brucella species
Corynebacterium species	Neisseria gonorrhoeae
Bacillus anthracis	Neisseria meningitidis
Listeria monocytogenes	Vibrio cholerae
	Pasteurella septica

4.2 Posology And Method Of Administration

Treatment of infection:

Adult dosage (including elderly patients):

Injectable:

500 mg IM eight hourly (or more frequently if necessary) in moderate infections. (This dose may be given by slow IV injection if more convenient.)

1 g IV six hourly in severe infections.

Children's dosage (up to 10 years of age):

Injectable:

50-100 mg/kg body weight a day, in divided doses.

Parenteral therapy is indicated if the oral route is considered impracticable or unsuitable, and particularly for the urgent treatment of severe infection.

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.

Prophylaxis of endocarditis: see table on next page.

Prophylaxis of endocarditis:

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: half adult dose. Under 5: quarter adult dose.	Note 1. If prophylaxis with 'Amoxil' 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, 'Amoxil' 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 'Amoxil' 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 '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 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 '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: the doses of 'Amoxil' should be half the adult dose; the dose of gentamicin should be 2 mg/kg.   Under 5: the doses of 'Amoxil' should be quarter 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.   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 '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.	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: half adult dose.   Under 5: quarter adult dose.	See Note 2 above. Note 5. The second dose of 'Amoxil' may be administered orally as 'Amoxil' Syrup SF/DF.
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' IV or IM.	Under 10: the dose of 'Amoxil' should be half the adult dose; the gentamicin dose should be 2 mg/kg.   Under 5: 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.

Administration:

Intravenous Injection, Intravenous Infusion, Intramuscular:

Using vials for injection (See Section 6.6)

4.3 Contraindications

Amoxil is a 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). 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).

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).

When prepared for intramuscular or direct intravenous injection, Amoxil should be administered immediately after reconstitution. The stability of Amoxil in various infusion fluids is given in the Package Enclosure Leaflet.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with Amoxil 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 Pregnancy And Lactation

Use in pregnancy

Animal studies with Amoxil 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, Amoxil 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 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).

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, 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.

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

Amoxil is a broad spectrum antibiotic.

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

5.2 Pharmacokinetic Properties

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

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Amoxil Injection:

None

6.2 Incompatibilities

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

If Amoxil 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.

6.3 Shelf Life

Injection Vials

24 months

6.4 Special Precautions For Storage

Amoxil Vials for Injection should be stored in a cool, dry place.

When prepared for intramuscular or direct intravenous injection, Amoxil should be administered immediately after reconstitution. The stability of Amoxil in various infusion fluids is dependent upon the concentration and temperature: stability times are given in the Package Enclosure Leaflet.

6.5 Nature And Contents Of Container

Amoxil Vials for Injection: Clear Type I glass vials fitted with a chlorobutyl rubber bung and an aluminium overseal. 500 mg: packs of 5 or 10. Each pack carries instructions for use.

6.6 Special Precautions For Disposal And Other Handling

Intravenous Injection:

Dissolve 500 mg in 10 ml Water for Injections BP (Final volume=10.4 ml).

Amoxil 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:

500 mg: Add 2.5 ml Water for Injections BP ^† and shake vigorously (Final volume=2.9 ml).

If pain is experienced on intramuscular injection, a sterile 1% solution of lidocaine hydrochloride or 0.5% solution of procaine hydrochloride may be used in place of Water for Injections.

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

ADMINISTRATIVE DATA

7. Marketing Authorisation Holder

Beecham Group plc

Great West Road, Brentford, Middlesex TW8 9GS

Trading as GlaxoSmithKline UK Stockley Park West, Uxbridge, Middlesex UB11 1BT

And/or

Bencard or SmithKline Beecham Pharmaceuticals at Mundells Welwyn Garden City, Hertfordshire AL7 1 EY

8. Marketing Authorisation Number(S)

Amoxil Vials for Injection 500 mg

0038/0222

9. Date Of First Authorisation/Renewal Of The Authorisation

Amoxil Vials for Injection 500 mg

13.10.98

10. Date Of Revision Of The Text

1^st March 2010

11. Legal Status

POM