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Amoxicillin Sodium for Injection

SPC Table of Contents
1. Name of the medicinal product

Amoxicillin Sodium 250mg Powder for Solution for Injection

Amoxicillin Sodium 500mg Powder for Solution for Injection

Amoxicillin Sodium 1g Powder for Solution for Injection

2. Qualitative and quantitative composition

Sodium Amoxicillin equivalent to Amoxicillin Ph Eur 250mg

Sodium Amoxicillin equivalent to Amoxicillin Ph Eur 500mg

Sodium Amoxicillin equivalent to Amoxicillin Ph Eur 1g

3. Pharmaceutical form

Powder for solution for injection.

4. Clinical particulars
4.1 Therapeutic indications

Amoxicillin is a broad-spectrum aminopenicillin and is indicated in the treatment of bacterial infections such as actinomycosis, biliary-tract infections, bone and joint infections, acute exacerbations of chronic bronchitis, gastroenteritis, (including Escherichia coli enteritis and Salmonella enteritis, but not shigellosis), gonorrhoea, mouth infections, sinusitis, otitis media, pneumonia (except where Mycoplasma suspected), typhoid and paratyphoid fever, urinary-tract infections, bacterial meningitis and the prophylaxis of endocarditis.

It is also used in the treatment of Lyme disease.

4.2 Posology and method of administration

Posology

Treatment of Infections in Adults and the Elderly

By intramuscular injection:

500mg every eight hours.

By intravenous injection or infusion:

500mg every eight hours (or in severe infection 1g every six hours) may be given by slow iv injection over three to four minutes or by infusion over 30 to 60 minutes.

Treatment of Infection in Children up to 10 years

By intramuscular or intravenous injection or infusion:

50-100mg per kg bodyweight daily in divided doses.

Renal impairment

It may be necessary to reduce the total daily dosage depending on the degree of renal impairment.

As amoxicillin is removed by haemodialysis, patients receiving haemodialysis may require another dose of amoxicillin at the end of their dialysis.

Endocarditis prophylaxis

Dental procedures under general anaesthesia

Upper respiratory tract procedures under general anaesthesia:

No special risk (ie, no prosthetic heart valves, no history of endocarditis, not more than a single dose of a penicillin in the previous month)

Adults and the elderly:

1g amoxicillin iv at induction, followed by 500mg oral, iv or im amoxicillin six hours later

Children under 5 years:

Quarter adult dose

Children 5-10 years:

Half adult dose

Special risk (with prosthetic heart valves, history of endocarditis, or receipt of more than a single dose of a penicillin in the previous month)

Adults and the elderly:

1g amoxicillin iv with im or iv gentamicin at induction, followed by 500mg oral, iv or im amoxicillin six hours later

Children under 5 years:

Quarter adult dose plus gentamicin

Children 5-10 years:

Half adult dose plus gentamicin

NB Amoxicillin and gentamicin should not be mixed in the same syringe

Genito-urinary procedures under general anaesthesia in patients with no urinary tract infection:

Gastrointestinal, obstetric and gynaecological procedures under general anaesthesia for patients with prosthetic heart valves or history of endocarditis:

Adults and the elderly:

1g amoxicillin iv with im or iv gentamicin at induction, followed by 500mg oral, iv or im amoxicillin six hours later

Children under 5 years:

Quarter adult dose plus gentamicin

Children 5-10 years:

Half adult dose plus gentamicin

NB Amoxicillin and gentamicin should not be mixed in the same syringe

Method of Administration

Intravenous Injection:

Dissolve 250mg in 5mL Water for Injections Ph Eur (final volume 5.2mL).

Dissolve 500mg in 10mL Water for Injections Ph Eur (final volume 10.4mL).

Dissolve 1g in 20mL Water for Injections Ph Eur (final volume 20.8mL).

Amoxicillin Sodium for Injection BP, when diluted may be injected slowly into a vein or infusion line over three to four minutes.

Intravenous Infusion:

Prepare as above and add to an iv solution in a minibag or in-line burette. Administer over 30 to 60 minutes. Alternatively the appropriate volume of iv fluid may be transferred from the infusion bag into the vial, using a suitable reconstitution device, and drawn back into the bag after dissolution.

Intramuscular Injection:

Add 1.5mL Water for Injections Ph Eur to 250mg and shake vigorously (final volume 1.7mL).

Add 2.5mL Water for Injections Ph Eur to 500mg and shake vigorously (final volume 2.9mL).

4.3 Contraindications

Amoxicillin should not be given to patients with a history of hypersensitivity to the beta-lactam antibiotics (e.g. penicillins, cephalosporins).

Bacterial resistance to amoxicillin or ampicillin.

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).

If a hypersensitivity reaction is reported, treatment with amoxicillin must be discontinued.

Discontinue treatment if skin rash appears.

Amoxicillin-induced flare of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) has been reported.

Amoxicillin should be given with caution to patients with a history of allergy, especially to drugs. Desensitisation may be necessary if treatment is essential.

Amoxicillin should not be used for long-term treatment of recurrent urinary tract infection, as resistance may develop in the enteric flora.

Erythematous (morbilliform) rashes have been associated with glandular fever in patients receiving amoxicillin. Amoxicillin should not be used in patients with glandular fever.

Care is necessary if very high doses of amoxicillin are given, especially if renal function is poor, because of the risk of nephrotoxicity and/or neurotoxicity. Dosage should be adjusted in patients with renal impairment (see Section 4.2). Adequate fluid intake and urinary output must be maintained during high dose parenteral administration of amoxicillin in order to minimise the occurrence of crystalluria (see Section 4.9). The intrathecal route should be avoided. Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.

Care is also necessary if large doses of sodium (as amoxicillin sodium) are given to patients with impaired renal function or heart failure. Renal and haematological status should be monitored during prolonged and high-dose therapy.

Care is required when treating some patients with spirochaete infections such as syphilis or leptospirosis because the Jarisch-Herxheimer reaction may occur shortly after treatment with a penicillin is started.

Contact with amoxicillin should be avoided since skin sensitisation may occur.

Amoxicillin should preferably not be given to patients with undiagnosed pharyngitis (who may have mononucleosis) or patients with lymphatic leukaemia or possibly HIV infection who may also be at increased risk of developing skin rashes with amoxicillin.

In case of severe and persistent diarrhoea, the possibility of pseudomembranous colitis should be considered; amoxicillin therapy should be discontinued.

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

There is a potential for increased serum levels of amoxicillin in the newborn or in young infants due to reduced renal excretion.

Abnormal prolongation of prothrombin time (increased International Normalised Ratio (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).

Amoxicillin sodium 250mg, 500mg and 1g powder for solution for injection contains 0.65mmol (14.9mg), 1.3mmol (29.7mg) and 2.6mmol (59.4mg) of sodium per dose, respectively. To be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interaction

Broad spectrum antibiotics including amoxicillin may increase the effects of oral anticoagulants or they may reduce the effects of oral anticoagulants. In the literature there are rare cases of increased INR in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or INR should be carefully monitored with the addition or withdrawal of amoxicillin (see Sections 4.4 and 4.8).

In common with other antibiotics, amoxicillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

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

There is reduced excretion of methotrexate (increased risk of toxicity).

There may be antagonism between amoxicillin and bacteriostatic agents such as chloramphenicol. An increased frequency of skin rashes has been reported in patients receiving amoxicillin together with allopurinol, compared to those receiving amoxicillin alone.

Tetracyclines may reduce the effectiveness of penicillins particularly in the treatment of infections such as pneumococcal meningitis and scarlet fever.

Penicillins may produce false-positive results with the direct antiglobulin (Coombs') test.

Penicillins may produce falsely high urinary glucose results with the copper sulphate test.

Glucose enzymatic tests such as the glucose oxidase test are not affected by penicillins.

Penicillins may produce falsely high urinary protein results.

Bromophenol blue reagent test strips are not affected by penicillins.

4.6 Fertility, pregnancy and lactation

Pregnancy:

Amoxicillin crosses the placenta, however, there has been no evidence of a teratogenic effect in animals or untoward effect in humans. Amoxicillin 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.

Breast-feeding:

Amoxicillin may be given during breast-feeding.

With the exception of the risk of sensitisation associated with the excretion of trace quantities of amoxicillin in breast milk and modification of bowel flora resulting in diarrhoea, there are no known detrimental effects for the breast-fed infant.

Fertility:

Reproduction studies in mice and rats, at doses up to ten times the human dose of amoxicillin, have shown no evidence of impaired fertility.

4.7 Effects on ability to drive and use machines

None.

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 (>1/1,000, <1/100), rare (>1/10,000, <1/1,000), very rare (<1/10,000), unknown (cannot be estimated from the available data).

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 (common after oral administration but may also occur following parenteral administration).

Blood and lymphatic system disorders

Generally associated with large intravenous doses of amoxicillin or impaired renal function.

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).

Unknown: purpura non-thrombocytopenic. Defective platelet function, eosinophilia.

Immune system disorders

Very rare: as with other antibiotics, severe allergic reactions including angioedema, anaphylaxis (see Section 4.4), serum sickness and hypersensitivity vasculitis. Anaphylaxis has sometimes been fatal. Late sensitivity reactions may include serum sickness-like reactions (featuring symptoms such as arthralgia, rash, urticaria, fever, angioedema, lymphadenopathy).

Unknown: some patients with spirochaete infections such as syphilis or leptospirosis may experience a Jarisch-Herxheimer reaction shortly after treatment with a penicillin is started. Symptoms include fever, chills, headache and reaction at the site of lesions. The reaction can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy.

If a hypersensitivity reaction is reported, the treatment must be discontinued (see also skin and subcutaneous tissue disorders).

Metabolism and nutrition disorders

Unknown: electrolyte disturbances such as hypokalaemia (due to administration of large amounts of sodium).

Psychiatric disorders

Unknown: hallucinations

Nervous system disorders

Very rare: hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Unknown: signs of central nervous system toxicity; generally associated with large intravenous doses of amoxicillin or impaired renal function.

Encephalopathy has been reported following intrathecal administration and can be fatal.

A coma may develop with high doses of amoxicillin.

Vascular disorders

Unknown: vasculitis.

Respiratory, thoracic and mediastinal disorders

Unknown: bronchospasm, acute severe dyspnoea and allergic pneumonitis; generally associated with large intravenous doses of amoxicillin or impaired renal function.

Gastrointestinal disorders

Clinical Trial Data

Common: diarrhoea and nausea.

Uncommon: vomiting

Post-marketing Data

Very rare: antibiotic associated colitis (including pseudomembranous colitis and haemorrhagic colitis).

Unknown: sore mouth or tongue, commonly occur after oral administration but may also occur following parenteral administration.

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

Clinical Trial Data

Common: skin rash

Uncommon: urticaria and pruritis

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 (APEG). (see also immune system disorders).

Unknown: other skin reactions include maculopapular rashes (often occurring more than seven days after commencing treatment), morbilliform rash, drug eruption (including baboon syndrome), erythema nodosum, and pemphigoid reactions.

Most patients with infectious mononucleosis develop a maculopapular rash when treated with amoxicillin, and patients with other lymphoid disorders such as lymphatic leukaemia or HIV infection also appear to be at higher risk.

Musculoskeletal and connective tissue disorders

Unknown: joint pain.

Renal and urinary disorders

Very rare: interstitial nephritis, crystalluria.

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy (see Section 4.9).

Unknown: Nephropathy.

General disorders and administration site conditions

Unknown: fever.

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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms: gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically with attention to the water/electrolyte balance. Gross overdosage will produce very high urinary concentrations, particularly after parenteral administration. Problems are unlikely if adequate fluid intake and urinary output are maintained but crystalluria, in some cases leading to renal failure, has been observed (see Section 4.4).

Treatment: is symptomatic. More specific measures may be necessary in patients with impaired renal function. Amoxicillin is removed by haemodialysis.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Beta-lactam antibacterials, Penicillins with extended spectrum, ATC code: J01CA04

Amoxicillin is a member of the penicillin family. The penicillin nucleus consists of a thiazolidine ring connected to a β-lactam ring to which is attached a side-chain. The side-chain determines most of the pharmacological and antibacterial properties of the penicillin in question. In the case of amoxicillin the benzyl ring in the side chain extends the range of antimicrobial activity into the Gram-negative bacteria. Amoxicillin kills bacteria by interfering with the synthesis of the bacterial cell wall. As a result the bacterial cell wall is weakened, the cell swells and then ruptures. Amoxicillin is readily hydrolysed by the staphylococcal penicillinase. Its spectrum of activity is extended by administration with the beta-lactamase inhibitor clavulanic acid.

5.2 Pharmacokinetic properties

Absorption

After the equivalent of 500mg intramuscular amoxicillin, given as amoxicillin sodium, the serum level peaks at one hour at approximately 14mg L-1

Distribution

Amoxicillin is rapidly distributed throughout the body but penetrates the uninflamed meninges poorly. Its distribution into the cerebrospinal fluid is known to be less efficient than that of ampicillin. Amoxicillin concentrations in interstitial fluid peak around one hour after the serum peak, according to skin window tests. Concentrations in umbilical cord blood have been found to be a fraction of those in maternal blood. Concentrations in amniotic fluid are variable but less than 50% of maternal blood levels. The volume of blood distribution is 0.3 Lkg-1 bodyweight. Plasma protein binding is around 20%. Only small amounts of the drug are excreted in breast-milk.

Biotransformation

A small amount (10-20%) of the drug is metabolised by hydrolysis of the β-lactam ring to penicilloic acid, which is excreted in the urine. There is limited enterohepatic circulation of the antibiotic.

Elimination

Elimination of amoxicillin occurs via the kidneys by glomerular filtration and tubular secretion. After parenteral administration, 75% of the dose is excreted via the kidneys within the following six hours. High concentrations have been recorded in the bile, but in the presence of biliary tract obstruction amoxicillin may be undetectable.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections.

6. Pharmaceutical particulars
6.1 List of excipients

None

6.2 Incompatibilities

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

Amoxicillin should not be mixed with blood products or other proteinaceous fluids (eg protein hydrolysates) or with intravenous lipid emulsions.

Amoxicillin should not be mixed with ciprofloxacin.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store below 25°C

Reconstituted solutions should be administered immediately after preparation.

6.5 Nature and contents of container

Vials containing 250mg or 500mg of amoxicillin sodium for injection in packs of 10 vials. Vials containing 1g of amoxicillin sodium for injection in single packs.

6.6 Special precautions for disposal and other handling

The vials are not suitable for multidose use.

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

7. Marketing authorisation holder

Wockhardt UK Ltd

Ash Road North

Wrexham

LL13 9UF

UK

8. Marketing authorisation number(s)

Amoxicillin Sodium 250mg Powder for Solution for Injection - PL 29831/0010

Amoxicillin Sodium 500mg Powder for Solution for Injection - PL 29831/0012

Amoxicillin Sodium 1g Powder for Solution for Injection - PL 29831/0011

9. Date of first authorisation/renewal of the authorisation

22/02/2008

10. Date of revision of the text

10/02/2016

Company Information

Wockhardt UK Ltd

Address : Ash Road North, Wrexham Industrial Estate, Wrexham, LL13 9UF

Telephone : +44 (0)1978 661 261

Fax : +44 (0)1978 660 130

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