Geramox 250mg & 500mg Capsules

  • Name:

    Geramox 250mg & 500mg Capsules

  • Company:
    info
  • Active Ingredients:

    Amoxicillin trihydrate

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 27/07/18

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Summary of Product Characteristics last updated on medicines.ie: 27/7/2018

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Gerard Laboratories

Gerard Laboratories

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1 - 0 of 117 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 27 July 2018 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 3 - how to take/use

Updated on 27 July 2018 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 28 November 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 28 November 2017 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

1. NAME OF THE MEDICINAL PRODUCT

Geramox 250 mg Capsules, Hard
Geramox 500 mg Capsules, Hhard

4.2 Posology and method of administration

Indication*

Dose*

Acute bacterial sinusitis

250 mg to 500 mg every 8 hours or 750 mg to 1 g every 12 hours

 

For severe infections 750 mg to 1 g every 8 hours

 

Acute cystitis may be treated with 3 g twice daily for one day

Asymptomatic bacteriuria in pregnancy

Acute pyelonephritis

Dental abscess with spreading cellulitis

Acute cystitis

Acute otitis media

500 mg every 8 hours, 750 mg to 1 g every 12 hours

For severe infections 750 mg to 1 g every 8 hours for 10 days

Acute streptococcal tonsillitis and pharyngitis

Acute exacerbations of chronic bronchitis

Community acquired pneumonia

500 mg to 1 g every 8 hours

Typhoid and paratyphoid fever

500 mg to 2 g every 8 hours

Prosthetic joint infections

500 mg to 1 g every 8 hours

Prophylaxis of endocarditis

2 g orally, single dose 30 to 60 minutes before procedure

Helicobacter pylori eradication

750 mg to 1 g twice daily in combination with a proton pump inhibitor (e.g. omeprazole, lansoprazole) and another antibiotic (e.g. clarithromycin, metronidazole) for 7 days

Lyme disease (see section 4.4)

Early stage: 500 mg to 1 g every 8 hours up to a maximum of 4 g/day in divided doses for 14 days (10 to 21 days)

Late stage (systemic involvement): 500 mg to 2 g every 8 hours up to a maximum of 6 g/day in divided doses for 10 to 30 days

* Consideration should be given to the official treatment guidelines for each indication

 

* Consideration should be given to the official treatment guidelines for each indication

 

Children weighing < 40 kg

 

Children may be treated with amoxicillin capsules, dispersible tablets, suspensions or sachets.

 

Children weighing 40 kg or more should be prescribed the adult dosage.

 

Appropriate paediatric formulation, e.g. Geramox Powder for Oral suspension is recommended for children under six months of age.

 

Recommended doses:

Indication+

Dose+

Acute bacterial sinusitis

20 to 90 mg/kg/day in divided doses*

Acute otitis media

Community acquired pneumonia

Acute cystitis

Acute pyelonephritis

Dental abscess with spreading cellulitis

Acute streptococcal tonsillitis and pharyngitis

40 to 90 mg/kg/day in divided doses*

Typhoid and paratyphoid fever

100 mg/kg/day in three divided doses

Prophylaxis of endocarditis

50 mg/kg orally, single dose 30 to 60 minutes before procedure

Lyme disease (see section 4.4)

Early stage: 25 to 50 mg/kg/day in three divided doses for 10 to 21 days

Late stage (systemic involvement): 100 mg/kg/day in three divided doses for 10 to 30 days

* Twice daily dosing regimens should only be considered when the dose is in the upper range

+Consideration should be given to the official treatment guidelines for each indication.

 

 

                    +Consideration should be given to the official treatment guidelines for each indication.

 


Renal impairment

 

GFR (ml/min)

Adults and children ≥ 40 kg

Children < 40 kg *

Greater than > 30

nNo adjustment necessary

nNo adjustment necessary

10 to- 30

mMaximum 500 mg twice daily

15 mg/kg given twice daily (maximum 500 mg twice daily)

less than < 10

mMaximum 500 mg/day

15 mg/kg given as a single dose (maximum 500 mg)

*In the majority of cases, parenteral therapy is preferred.

 

*In the majority of cases, parenteral therapy is preferred.


Amoxicillin may be removed from the circulation by haemodialysis.

 

 

Haemodialysis

Adults and children over  >40 kg

500 mg every 24 h

 

Prior to haemodialysis one additional dose of 500 mg should be administered. In order to restore circulating drug levels, another dose of 500 mg should be administered after haemodialysis.

 

 Adults and cChildren under 40 kg

 

15 mg/kg/day given as a single daily dose (maximum 500 mg).

Prior to haemodialysis one additional dose of 15 mg/kg should be administered. In order to restore circulating drug levels, another dose of 15 mg/kg should be administered after haemodialysis.


4.8 Undesirable effects

System Organ Class (SOC)

Frequency

 

Very common

Common

Uncommon

Rare

Very rare

Not known

Renal and urinary tract disorders

 

 

 

 

Interstitial nephritis, Crystalluria (see sections 4.4 and 4.9 Overdose)

 

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

 

# Superficial tooth discolouration has been reported in children. Good oral hygiene may help to prevent tooth discolouration as it usually be removed by brushing.


4.9     Overdose

 

Treatment of intoxication

             Gastrointestinal symptoms should be treated symptomatically, with attention to the water/electrolyte balance. More specific measures may be necessary in patients with impaired renal function: the antibiotic is removed by haemodialysis.

 

Amoxicillin can be removed from the circulation by haemodialysis.

 

10.     DATE OF REVISION OF THE TEXT

 

SeptemberOctober 2017











Updated on 27 November 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 27 November 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - use in children/adolescents
  • Change to section 4 - possible side effects
  • Change to section 5 - how to store or dispose
  • Change to section 6 - date of revision

Updated on 3 October 2017 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4. CLINICAL PARTICULARS

4.4 Special warnings and precautions for use

Hypersensitivity reactions

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see section 4.3 and 4.8).

Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactionsanaphylaxis) haves been reported in patients onreceiving penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin therapy must be discontinued and appropriate alternative therapy instituted.

4.8 Undesirable effects

Skin and subcutaneous tissue disorders

 

*Clinical Trial Data: Skin rash

*Clinical Trial Data: Urticaria and pruritus

 

Post-marketing Data:

Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP) (see section 4.4) and drug reaction with eosinophilia and systemic symptoms (DRESS).

 


10. DATE OF REVISION OF THE TEXT

September November 20176

Updated on 3 October 2017 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 16 December 2016 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2 Posology and method of administration

Posology

The dose of Geramox that is selected to treat an individual infection should take into account:

The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4)
The severity and the site of the infection
The age, weight and renal function of the patient; as shown below

The duration of therapy should be determined by the type of infection and the response of the patient, and should generally be as short as possible. Some infections require longer period of treatment (see section 4.4 regarding prolonged therapy).

Adults and children ≥ 40 kg

Indication*

Dose*

Acute bacterial sinusitis

250 mg to 500 mg every 8 hours or 750 mg to 1 g every 12 hours

 

For severe infections 750 mg to 1 g every 8 hours

 

Acute cystitis may be treated with 3 g twice daily for one day

Asymptomatic bacteriuria in pregnancy

Acute pyelonephritis

Dental abscess with spreading cellulitis

Acute cystitis

Acute otitis media

500 mg every 8 hours, 750 mg to 1 g every 12 hours

For severe infections 750 mg to 1 g every 8 hours for 10 days

Acute streptococcal tonsillitis and pharyngitis

Acute exacerbations of chronic bronchitis

Community acquired pneumonia

500 mg to 1 g every 8 hours

Typhoid and paratyphoid fever

500 mg to 2 g every 8 hours

Prosthetic joint infections

500 mg to 1 g every 8 hours

Prophylaxis of endocarditis

2 g orally, single dose 30 to 60 minutes before procedure

Helicobacter pylori eradication

750 mg to 1 g twice daily in combination with a proton pump inhibitor (e.g. omeprazole, lansoprazole) and another antibiotic (e.g. clarithromycin, metronidazole) for 7 days

Lyme disease (see section 4.4)

Early stage: 500 mg to 1 g every 8 hours up to a maximum of 4 g/day in divided doses for 14 days (10 to 21 days)

Late stage (systemic involvement): 500 mg to 2 g every 8 hours up to a maximum of 6 g/day in divided doses for 10 to 30 days

* Consideration should be given to the official treatment guidelines for each indication

Paediatric population

Children weighing < 40 kg

Children may be treated with amoxicillin capsules, dispersible tablets or, suspensions or sachets.

Children weighing 40 kg or more should be prescribed the adult dosage.

Appropriate paediatric formulation, e.g. Geramox Powder for Oral suspension is recommended for children under six months of age.

Recommended doses

Indication+

Dose+

Acute bacterial sinusitis

20 to 90 mg/kg/day in divided doses*

Acute otitis media

Community acquired pneumonia

Acute cystitis

Acute pyelonephritis

Dental abscess with spreading cellulitis

Acute streptococcal tonsillitis and pharyngitis

40 to 90 mg/kg/day in divided doses*

Typhoid and paratyphoid fever

100 mg/kg/day in three divided doses

Prophylaxis of endocarditis

50 mg/kg orally, single dose 30 to 60 minutes before procedure

Lyme disease (see section 4.4)

Early stage: 25 to 50 mg/kg/day in three divided doses for 10 to 21 days

Late stage (systemic involvement): 100 mg/kg/day in three divided doses for 10 to 30 days

* Twice daily dosing regimens should only be considered when the dose is in the upper range

+Consideration should be given to the official treatment guidelines for each indication.

4.4 Special warnings and precautions for use

Hypersensitivity reactions

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see section 4.3 and 4.8).

Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) has been reported in patients receiving penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin should therapy must be discontinued and appropriate alternative therapy instituted.

4.5 Interaction with other medicinal products and other forms of interaction

Probenecid

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent Concomitant use of probenecid with amoxicillin may result in increased and prolonged blood levels of amoxicillin.

Allopurinol

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

Tetracyclines

Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, tn 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. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).

Methotrexate

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

4.8 Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.

The ADRs derived from clinical studies and post-marketing surveillance with amoxicillin, presented by MedDRA System Organ Class are listed below.

The following convention terminologies has have been utilised used for the classification of undesirable side effects: in order to classify the occurrence of undesirable effects.

System Organ Class (SOC)

Frequency

 

Very common

Common

Uncommon

Rare

Very rare

Not known

Infections and infestations

 

 

 

 

Mucocutaneous candidiasis

 

Blood and lymphatic system disorders

 

 

 

 

Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia.

 

Prolongation of bleeding time and prothrombin time (see section 4.45)

 

Immune System disorders

 

 

 

 

Severe allergic reactions, including angioneurotic oedema, anaphylaxis, serum sickness and hypersensitivity vasculitis (see section 4.4).

Jarisch-Herxheimer reaction (see section 4.4).

Nervous system disorders

 

 

 

 

Hyperkinesia, dizziness and convulsions (see section 4.4).

 

Gastrointestinal disorders

 

*Clinical Trial Data: Diarrhoea and nausea

*Clinical Trial Data: Vomiting

 

Post-marketing Data: Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis) (see section 4.4).

 

Black hairy tongue

 

Superficial tooth discolouration#

 

Hepatobiliary disorders

 

 

 

 

Hepatitis and cholestatic jaundice. A moderate rise in AST and/ or ALT.

 

Skin and subcutaneous tissue disorders

 

*Clinical Trial Data: Skin rash

*Clinical Trial Data: Urticaria and pruritus

 

Post-marketing Data:

Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP) (see section 4.4).

 

Renal and urinary tract disorders

 

 

 

 

Interstitial nephritis, Ccrystalluria (see section 4.4 and  4.9)

 

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

 

# Superficial tooth discolouration has been reported in children. Good oral hygiene may help to prevent tooth discolouration as it usually be removed by brushing.

Updated on 13 December 2016 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - dose and frequency
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 26 February 2016 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains amoxicillin trihydrate equivalent to 250 mg amoxicillin (anhydrous).
Each capsule contains amoxicillin trihydrate equivalent to 500 mg amoxicillin
(anhydrous).

For the full list of excipients, see section 6.1.

 

 

 

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

 

 

Geramox is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):

 

:

 

 

 

 

 

  •  Acute bacterial sinusitis

  • Upper respiratory tract infections
  • Acute otitis media
  • Acute streptococcal tonsillitis and pharyngitis
  •  Acute exacerbations of chronic bronchitis
  •  Community acquired pneumonia
  •  Acute cystitis
  • Lobar and bronchopneumonia
  • Cystitis, urethritis, pyelonephritis
  • Asymptomatic bacteriuria in pregnancy
  •  Acute pyelonephritis
  • 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
  • Dental abscess (as adjunct to surgical management) with spreading cellulitis
  • Prosthetic joint infections
  • Helicobacter pylori eradication
  • Lyme disease

    Geramox is also indicated of the prophylaxis of endocarditis.
    Consideration should be given to official guidance on the appropriate use of antibacterial agents.

     

     

     

    In children with urinary tract infection, the need for investigation should be considered.
    Parenteral therapy is indicated if the oral route is considered impracticable or unsuitable and particularly for the urgent treatment of severe episodes of the above conditions.
    Oral prophylaxis of endocarditis: Geramox may be used for the prevention of bacteraemia associated

     

     

     

    4.2 Posology and method of administration

     

     

    Posology

     

     

     

    The dose of Geramox that is selected to treat an individual infection should take into account:
    The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4)
    The severity and the site of the infection
    The age, weight and renal function of the patient; as shown below

    The duration of therapy should be determined by the type of infection and the response of the patient, and should generally be as short as possible. Some infections require longer period of treatment (see section 4.4 regarding prolonged therapy).

     

     

     

    Adults

     

    and children ≥ 40 kg Indication

    Dose

     

     

    Acute bacterial sinusitis

     

     

     

    250 mg to 500 mg every 8 hours or 750 mg to 1 g every 12 hours

    For severe infections 750 mg to 1 g every 8 hours

    Acute cystitis may be treated with 3 g twice daily for one day

     

     

     

    Asymptomatic bacteriuria in pregnancy

     

     

     

    Acute pyelonephritis

     

     

     

    Dental abscess with spreading cellulitis

     

     

     

    Acute cystitis

     

     

     

    Acute otitis media

     

     

     

    500 mg every 8 hours, 750 mg to 1 g every 12 hours

    For severe infections 750 mg to 1 g every 8 hours for 10 days

     

     

     

    Acute streptococcal tonsillitis and pharyngitis

     

     

     

    Acute exacerbations of chronic bronchitis

     

     

     

    Community acquired pneumonia

     

     

     

    500 mg to 1 g every 8 hours

     

     

     

    Typhoid and paratyphoid fever

     

     

     

    500 mg to 2 g every 8 hours

     

     

     

    Prosthetic joint infections

     

     

     

    500 mg to 1 g every 8 hours

     

     

     

    Prophylaxis of endocarditis

     

     

     

    2 g orally, single dose 30 to 60 minutes before procedure

     

     

     

    Helicobacter pylori

     

     

    eradication

    750 mg to 1 g twice daily in combination with a proton pump inhibitor (e.g. omeprazole, lansoprazole) and another antibiotic (e.g. clarithromycin, metronidazole) for 7 days

     

     

     

    Lyme disease (see section 4.4)

     

     

     

    Early stage: 500 mg to 1 g every 8 hours up to a maximum of 4 g/day in divided doses for 14 days (10 to 21 days)

    Late stage (systemic involvement): 500 mg to 2 g every 8 hours up to a maximum of 6 g/day in

     

     

     


     

    Consideration should be given to the official treatment guidelines for each indication

     

     

     

    Standard adult dosage: The usual daily dosage is 750 mg in divided doses (i.e. 250 mg three times daily by the oral route).
    In cases of severe infection the dosage may be doubled, or amoxicillin given by injection.
    High dosage therapy: (maximum recommended oral dosage of 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.
    Gonorrhoea: 3 g as a single dose.
    Dental Abscess: two 3 g doses with 8 hours between the doses.

     

     

    Prophylaxis of endocarditis

     

     

    For dental procedures where an oral dose is appropriate:
    Adults
    3 g dose followed by (6 hours later) a further 3 g dose (or a 1 g IM if oral dose not tolerated) if necessary.
    Patients with renal impairment: 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.

     

     

     

    Adults

     

     

    Glomerular filtration rate

    Oral treatment

     

     

     

    > 30 ml/min

     

     

    No adjustment necessary

     

     

    10-30 ml/min

     

     

    Amox. Max 500 mg b.d.

     

     

    < 10 ml/min

     

     

    Amox. Max 500 mg/day

     

     

     

    Paediatric population

     

     

    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 may be treated with amoxicillin capsules, dispersible tablets or suspensions.

     

    Children weighing 40 kg or more should be prescribed the adult dosage.

     

     

     

    Appropriate paediatric formulation, e.g. Geramox Powder for Oral suspension is recommended for children under six months of age.

     

     

     

    Recommended doses:

     

     

    Indication

    Dose

     

     

     

    Acute bacterial sinusitis

     

     

     

    20 to 90 mg/kg/day in divided doses*

     

     

     

    Acute otitis media

     

     

     

    Community acquired pneumonia

     

     

     



    * Twice daily dosing regimens should only be considered when the dose is in the upper range

     

     


     

    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.

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

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

     

     

     

    Special population

     

     

     

     

    Elderly

     

     

     

     

    No dose adjustment is considered necessary.

     

     

     

    Renal impairment

     

     

     

     

    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

    GFR (ml/min)

    Adults and children ≥ 40 kg

     

    Dose

    Interval between administration

     

    Children < 40 kg *

    > 30

     

     

    Usual dose

     

     

    No adjustment necessary

    No adjustment necessary

     

     

    10 – 30

     

     

    Usual dose

     

     

    Maximum 500 mg twice daily

    15 mg/kg given twice daily (maximum 500 mg twice daily)

     

     

    12 h

     

    (corresponding to 2/3 of the dose)

     

     

     

    < 10

     

     

    Usual dose

     

     

    Maximum 500 mg a day

    15 mg/kg given as a singly dose (maximum 500 mg)

     

     

    24 h

     

    (corresponding to 1/3 of the dose)

     

     

     

    *In the majority of cases, parenteral therapy is preferred.

     

     

     

     

    For small children (younger than 6 years of age) appropriate paediatric formulation should be used.

     

     

     

    In patients receiving haemodialysis:
    Amoxicillin may be removed from the circulation by haemodialysis.

     

     

    Haemodialysis

     

     

    Adults and children ≥ 40 kg

     

     

    15 mg/kg/day given as a single daily dose.

    Prior to haemodialysis one additional dose of 15 mg/kg should be administered. In order to restore circulating drug levels, another dose of 15 mg/kg should be administered after haemodialysis.

     

     

     


     

    In patients receiving peritoneal dialysis:

    Amoxicillin maximum 500 mg/day.

     

     

     

    Hepatic impairment

     

     

     

     

    Dose with caution and monitor hepatic function at regular intervals (see sections 4.4 and 4.8).

     

     

     

    Method of administration

    Geramox is for oral use.

     

     

    The absorption of Geramox is virtually unimpaired by the presence of food

     

    Swallow with water without opening capsule

     

     

     

     

    Absorption of Geramox is unimpaired by food.

    Therapy can be started parenterally according to the dosing recommendation of the intravenous formulation and continued with an oral preparation.

     

     

     

    4.3 Contraindications

     

     

    Hypersensitivity to the active substance,

     

    beta-lactam antibiotics including to any of the penicillins, cephalosporins or to any of the excipients listed in section 6.1.

     

     

     

     

    History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).

     

     

     

     

    4.4 Special warnings and precautions for use

     

     

    Hypersensitivity reactions

     

     

     

     

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

     

    , or cephalosporins or other beta-lactam agents (see section 4.3 and 4.8). Cross-sensitivity between penicillins and cephalosporins is well documented.

     

     

     

     

     

    Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) has been reported in patients receiving

     

    beta-lactam antibioticspenicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate alternative therapy instituted.

     

     

     

     

    Non-susceptible microorganisms

    Amoxicillin is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with amoxicillin (see section 5.1). This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.

    Convulsions

    Convulsions may occur in patients with impaired renal function or in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders (see section 4.8).

    Renal impairment

    In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

    Skin reactions

    The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AEGP, see section 4.8). This reaction requires amoxicillin discontinuation and contra-indicates any subsequent administration.

    Amoxicillin should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.

    Jarisch-Herxheimer reaction

    The Jarisch-Herxheimer reaction has been seen following amoxicillin treatment of Lyme disease (see section 4.8). It results directly from the bactericidal activity of amoxicillin on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

    Overgrowth of non-susceptible microorganisms

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

    Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during, or subsequent to, the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxicillin should immediately be discontinued, a physician consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

    Prolonged therapy

    Periodic assessment of organ system functions; including renal, hepatic and haematopoietic function is advisable during prolonged therapy. Elevated liver enzymes and changes in blood counts have been reported (see section 4.8).

    Anticoagulants

    Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. 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 section 4.5 and 4.8).

    Crystalluria

    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. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.8 and 4.9).

    Interference with diagnostic tests

    Elevated serum and urinary levels of amoxicillin are likely to affect certain laboratory tests. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.

    It is recommended that when testing for the presence of glucose in urine during amoxicillin treatment, enzymatic glucose oxidase methods should be used.

    The presence of amoxicillin may distort assay results for oestriol in pregnant women.

     

     

     

     

    Amoxicillin should be avoided if infectious mononucleosis (glandular fever) is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.

    Prolonged use of an anti-infective agent may occasionally result in overgrowth of non-susceptible organisms.

    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 concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

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

    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.

    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

    Concomitant use of probenecid is not recommended.

     

     

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

     

     

     

     

    Allopurinol

     

     

     

     

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

     

     

     

    Tetracyclines

    Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects 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.

     

     

     

     

    Oral anticoagulants

    Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However,

     

     

    Itn 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. Moreover, adjustments in the dose of oral

     

    anticoagulants may be necessary (see sections 4.4 and 4.8).

     

     

     

     

    Methotrexate

     

     

     

    Interaction between amoxicillin and methotrexate leading to methotrexate toxicity has been reported. Serum methotrexate levels should be closely monitored in patients who receive amoxicillin and methotrexate simultaneously. Amoxicillin decreases the renal clearance of methotrexate, probably by competition at the common tubular secretion system

     

     

     

     

    Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity

     

     

    .

     

     

     

     

    4.6 Fertility, pregnancy and lactation

     

     

    Pregnancy

    Animal studies with amoxicillin

     

    do not indicate direct or indirect harmful effects with respect to reproductive toxicityhave shown no teratogenic effects. Limited data on the use of amoxicillin during pregnancy in humans do not indicate an increased risk of congenital malformationsThe product has been in extensive clinical use since 1972 and its suitability in human pregnancy has been well documented in clinical studies. Amoxicillin may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

     

    Breast

     

    -feeding

     

     

     

     

    Amoxicillin may be administered during the period of 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 infant

     

     

     

     

    Amoxicillin is excreted into breast milk in small quantities with the possible risk of sensitisation. Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. Amoxicillin should only be used during breast-feeding after benefit/risk assessment by the physician in charge

     

     

    .

     

     

     

     

    Fertility

    There are no data on the effects of amoxicillin on fertility in humans. Reproductive studies in animals have shown no effects on fertility

     

     

     

     

    4.7 Effects on ability to drive and use machines

     

     

    No studies on the effects on the ability to drive and use machines have been performed.

     

     

     

     

    However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).

     

     

     

     

     

    4.8 Undesirable effects

     

     

    The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.

    The ADRs derived from clinical studies and post-marketing surveillance with amoxicillin, presented by MedDRA System Organ Class are listed below.

     

     

     

     

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

    Very common (≥

     

    1/10),
    c
    Common (≥1/100 to < 1/10),
    u
    Uncommon (≥1/1,000 to < 1/100),
    r
    Rare (≥1/10,000 to < 1/1,000),
    v
    Very rare (< 1/10,000).

     

     

     

     

     

    Not known (cannot be estimated from the available data)

     

     

     

     

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

     

    System Organ Class

    (SOC)

    Frequency

     

    Very common

     

     

    Common

     

     

    Uncommon

     

     

    Rare

     

     

    Very rare

     

     

    Not known

     

     

     

    Infections and infestations

     

     

    Mucocutaneous candidiasis

     

     

    Blood and lymphatic system disorders

     

     

    Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia.

    Prolongation of bleeding time and prothrombin (see section 4.5)

     

     

    Immune System disorders

     

     

    As with other antibiotics, s

     

     

    Severe allergic reactions, including angioneurotic oedema, anaphylaxis (see section 4.4), serum sickness and hypersensitivity vasculitis (see section 4.4).

     

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

     

     

     

    Jarisch-Herxheimer reaction (see section 4.4).

     

     

     

    Nervous system disorders

     

     

    Hyperkinesia, dizziness and convulsions

     

    (see section 4.4). Convulsions may occur in patients with impaired renal function or in those receiving high doses.

    Gastrointestinal disorders

     

     

    *Clinical Trial Data:

     

     

    Diarrhoea and nausea

    *Clinical Trial Data:

     

     

    Vomiting

    Post-marketing Data:

     

     

    Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis) (see section 4.4).

     

    Black hairy tongue

     

     

    Hepatobiliary disorders

     

     

    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:

     

     

    Skin rash

    *Clinical Trial Data:

     

     

    Urticaria and pruritus

    Post-marketing Data:

    Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute

     

     



    System Organ Class

    (SOC)

    Frequency

     


    common

    Common

     

    Uncommon

     

    Rare

     

    Very rare

     

    Not known

     

     

    generalised exanthematous pustulosis (AGEP)

     

    (see section 4.4)

     

    (See also Immune system disorders)

     

     

    .

    Renal and urinary disorders

     

     

    Interstitial nephritis, crystalluria (see section 4.9)

     

     

    *The incidence of these adverse effects was derived from clinical studies involving a total of approximately 6,000 adults

     

     

     



     

    4.9 Overdose

     

     

    Symptoms

     

    and signs of overdose

     

    Gastrointestinal symptoms (such as nausea, vomiting and diarrhoea) and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed. Convulsions may occur in patients with impaired renal function or in those receiving high doses (see sections 4.4 and 4.8).

     

     

    Gross overdose will produce very high urinary concentrations, more so after parenteral administration. Problems are unlikely to occur if adequate fluid intake and urinary output are maintained; however amoxicillin crystalluria in some cases leading to renal failure, has been observed (see section 4.4).

     

    Management

     

     

    Treatment of intoxication

     

    Gastrointestinal

     

     

    Ssymptoms of water/electrolyte imbalance should be treated symptomatically with attention to the water/electrolyte balance. More specific measures may be necessary in patients with impaired renal function: the antibiotic is removed by haemodialysis.

     

     

     

     

    5. PHARMACOLOGICAL PROPERTIES

    5.1 Pharmacodynamic properties

     

     

    Pharmacotherapeutic group:

     

    Beta-lactam antibacterials, penicillins, Ppenicillins with extended spectrum, ATC code: J01CA04

     

     

     

     

    Mechanism of action
    Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.

    Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce

    these enzymes.

     

     

    Amoxicillin trihydrate is a broad spectrum antibiotic which possesses the safety profile of the penicillins and is rapidly bactericidal against a wide range of Gram-negative and Gram-positive organisms.

     

     

     

     

     

    Pharmacokinetic/pharmacodynamic relationship

    The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxicillin.

    Mechanisms of resistance

    The main mechanisms of resistance to amoxicillin are:
    • Inactivation by bacterial beta-lactamases.
    • Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

     

     

     

     

    Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

    Breakpoints

    MIC breakpoints for amoxicillin are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) version 5.0.

     

     

     

    Organism

     

     

    MIC breakpoint (mg/L)

     

     

    Susceptible ≤

     

     

    Resistant >

     

     

    Enterobacteriaceae

     

     

     

    8 1

     

     

     

    8

     

     

     

    Staphylococcus

     

     

    spp.

    Note 2

     

     

     

    Note 2

     

     

     

    Enterococcus

     

     

    spp.3

    4

     

     

     

    8

     

     

     

    Streptococcus groups A, B, C and G

     

     

     

    Note 4

     

     

     

    Note 4

     

     

     

    Streptococcus pneumoniae

     

     

     

    Note 5

     

     

     

    Note 5

     

     

     

    Viridans group steprococci

     

     

     

    0.5

     

     

     

    2

     

     

     

    Haemophilus influenzae

     

     

     

    2 6

     

     

     

    2 6

     

     

     

    Moraxella catarrhalis

     

     

     

    Note 7

     

     

     

    Note 7

     

     

     

    Neisseria meningitidis

     

     

     

    0.125

     

     

     

    1

     

     

     

    Gram positive anaerobes except

     

     

    Clostridium difficile 8

    4

     

     

     

    8

     

     

     

    Gram negative anaerobes

     

     

    8

    0.5

     

     

     

    2

     

     

     

    Helicobacter pylori

     

     

     

    0.125

     

     

    9

    0.125

     

     

    9

    Pasteurella multocida

     

     

     

    1

     

     

     

    1

     

     

     

    Non- species related breakpoints

     

     

    10

    2

     

     

     

    8

     

     

     

    1

     

     

    Wild type Enterobacteriaceae are categorised as susceptible to aminopenicillins. Some countries prefer to categorise wild type isolates of E. coli and P. mirabilis as intermediate. When this is the case, use the MIC breakpoint S ≤ 0.5 mg/L

     

    2

     

     

    Most staphylococci are penicillinase producers, which are resistant to amoxicillin. Methicillin resistant isolates are, with few exceptions, resistant to all beta-lactam agents.

     

    3

     

     

    Susceptibility to amoxicillin can be inferred from ampicillin

     

    4

     

     

    The susceptibility of streptococcus groups A, B, C and G to penicillins is inferred from the benzylpenicillin susceptibility.

     

    5

     

     

    Breakpoints relate only to non-meningitis isolates. For isolates categorised as intermediate to ampicillin avoid oral treatment with amoxicillin. Susceptibility inferred from the MIC of ampicillin.

     

    6

     

     

    Breakpoints are based on intravenous administration. Beta-lactamase positive isolates should be reported resistant.

     

    7

     

     

    Beta lactamase producers should be reported resistant

     

    8

     

     

    Susceptibility to amoxicillin can be inferred from benzylpenicillin.

     

    9

     

     

    The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type



    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.

     

    In vitro susceptibility of micro-organisms to Amoxicillin

    Commonly Susceptible Species

     

     

    Gram-positive aerobes

     

     

    Enterococcus faecalis

    Beta-hemolytic streptococci (Groups A, B, C and G)

    Listeria monocytogenes

     

     

     

    Species for which acquired resistance may be a problem

     

     

    Gram-positive aerobes

     

     

    Coagulase negative staphylococcus

    Staphylococcus aureus

     

     

    £

     

    Streptococcus pneumoniae

    Viridans group streptococcus

     

     

    Gram-negative aerobes

     

     

    Escherichia coli

    Haemophilus influenzae

    Helicobacter pylori

    Proteus mirabilis

    Salmonella

     

     

    typhi

     

    Salmonella

     

     

    paratyphi

     

    Pasteurella multocida

     

     

     

    Gram-positive anaerobes

     

     

    Clostridium

     

     

    spp.

    Gram-negative anaerobes

     

     

    Fusobacterium

     

     

    spp.

    Other

     

     

    Borrelia burgdorferi

     

     

     

    Inherently resistant organisms

     

     

    Gram-positive aerobes

     

     

    Enterococcus faecium

     

     

    Gram-negative aerobes

     

     

    Acinetobacter

     

     

    spp.

     

    Enterobacter

     

     

    spp.

     

    Klebsiella

     

     

    spp.

     

    Pseudomonas

     

     

    spp.

    Gram-negative anaerobes

     

     

    Bacteroides

     

     

    spp. (many strains of Bacteroides fragilis are resistant).

    Other

     

     

    Chlamydia

     

     

    spp.

     

    Mycoplasma

     

     

    spp.

     

    Legionella

     

     

    spp.

     

    Natural intermediate susceptibility in the absence of acquired mechanism of resistance.

     

    £

     

    Almost all S.aureus are resistant to amoxicillin due to production of penicillinase. In addition, all methicillin-resistant strains are resistant to amoxicillin.


     

    5.2 Pharmacokinetic properties

     

     

    Amoxicillin trihydrate is well absorbed by the oral and parenteral routes, peak levels are achieved 1-2 hours after administration.

    Oral administration produces high serum levels independent of the time at which the food is taken. Geramox gives good penetration into the bronchial secretions and the high urinary concentrations of unchanged antibiotic. The average serum half life is 60 minutes. Elimination is mainly via the urine.

    Paediatric population

    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 inulin 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.

     

     

     

     

    Absorption

    Amoxicillin fully dissociates in aqueous solution at physiological pH. It is rapidly and well absorbed by the oral route of administration. Following oral administration, amoxicillin is approximately 70% bioavailable. The time to peak plasma concentration (Tmax) is approximately one hour.

     

     

     

    The pharmacokinetic results for a study, in which an amoxicillin dose of 250 mg three times daily was administered in the fasting state to groups of healthy volunteers are presented below. C

     

     

    max

    T

     

     

    max *

    AUC

     

     

    (0-24h)

    T ½

     

     

     

    (μg/ml)

     

     

     

    (h)

     

     

     

    (μg.h/ml)

     

     

     

    (h)

     

     

     

    3.3 ± 1.12

     

     

     

    1.5 (1.0-2.0)

     

     

     

    26.7 ± 4.56

     

     

     

    1.36 ± 0.56

     

     

     

    *median (range)

     

     

     


     

    In the range 250 to 3000 mg the bioavailability is linear in proportion to dose (measured as Cmax and AUC). The absorption is not influenced by simultaneous food intake.

    Haemodialysis can be used for elimination of amoxicillin.

    Distribution

    About 18% of total plasma amoxicillin is bound to protein and the apparent volume of distribution is around 0.3 to 0.4 l/kg.

    Following intravenous administration, amoxicillin has been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.

    From animal studies there is no evidence for significant tissue retention of drug-derived material. Amoxicillin, like most penicillins, can be detected in breast milk (see section 4.6).

    Amoxicillin has been shown to cross the placental barrier (see section 4.6).

    Biotransformation

    Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose.

    Elimination

    The major route of elimination for amoxicillin is via the kidney.

    Amoxicillin has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the amoxicillin is excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 mg dose of amoxicillin. Various studies have found the urinary excretion to be 50-85% for amoxicillin over a 24 hour period.

    Concomitant use of probenecid delays amoxicillin excretion (see section 4.5).

     

     

     

    Age

    The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

    Gender

    Following oral administration of amoxicillin/ to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of amoxicillin.

    Renal impairment

    The total serum clearance of amoxicillin decreases proportionately with decreasing renal function (see sections 4.2 and 4.4).

    Hepatic impairment

    Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

     

     

     

    5.3 Preclinical safety data

     

     

    Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

    Carcinogenicity studies have not been conducted with amoxicillin

     

     

    There are no non-clinical safety data of relevance to the prescriber that are additional to those included in other sections of the SmPC.

     

     

     

     

     

    7. MARKETING AUTHORISATION HOLDER

     

     

    Generics [UK] Ltd

     

    12 Station Close
    Potters Bar
    Hertfordshire
    EN6 1TL
    United Kingdom.

     

     

     














     

    Updated on 23 February 2016 PIL

    Reasons for updating

    • Change to, or new use for medicine
    • Change to warnings or special precautions for use
    • Change of contraindications
    • Change to instructions about missed dose
    • Change to instructions about overdose
    • Change to side-effects
    • Change to drug interactions
    • Change to further information section
    • Change to date of revision
    • Change to dosage and administration

    Updated on 21 January 2015 PIL

    Reasons for updating

    • Change to warnings or special precautions for use
    • Change to storage instructions
    • Change to side-effects
    • Change to drug interactions
    • Change to information about drinking alcohol
    • Change to information about pregnancy or lactation
    • Change to information about driving or using machinery
    • Change to further information section
    • Change to date of revision

    Updated on 20 January 2015 SmPC

    Reasons for updating

    • Change to section 1 - Name of medicinal product
    • Change to section 2 - Qualitative and quantitative composition
    • Change to section 3 - Pharmaceutical form
    • Change to section 4 - Clinical particulars
    • Change to section 4.2 - Posology and method of administration
    • Change to section 4.3 - Contraindications
    • Change to section 4.4 - Special warnings and precautions for use
    • Change to section 4.8 - Undesirable effects
    • Change to Section 4.8 – Undesirable effects - how to report a side effect
    • Change to section 4.9 - Overdose
    • Change to section 5.1 - Pharmacodynamic properties
    • Change to section 5.2 - Pharmacokinetic properties
    • Change to section 5.3 - Preclinical safety data
    • Change to section 6.1 - List of excipients
    • Change to section 6.6 - Special precautions for disposal and other handling
    • Change to section 9 - Date of renewal of authorisation
    • Change to section 10 - Date of revision of the text

    Legal category: Product subject to medical prescription which may not be renewed (A)

    Free text change information supplied by the pharmaceutical company

    section1:
    Capsule, hard updated to Capsules, Hard

    section 2:
    Amoxicillin Trihydrate updated to amoxicillin trihydrate
    Excipients with known effects: removed

    secion 3:
    Capsules, hard (capsule). updated to Capsule, hard.

    section 4: 4.1
    Therapeutic Indications updated to Therapeutic indications

    section 4.2:
    removed text: Geramox Capsules are for oral use.
    removed text:The absorption of Geramox is virtually unimpaired by the presence of food.
    renal impairment updated to read 'Patients with renal impairment.....'

    Under section: Children weighing<40kg:
    text added: Method of administration
                     Geramox is for oral use
                     The absorption of Geramox is virtually unimpaired by the presence of food.

    section  4.3:
    sentence updated from:
    Use in patients with a history of hypersensitivity to the active substance, beta-lactum antiobiotics including penicillins, or Cephalosporins.
    to:
    Hypersensitivity to the active substance, beta-lactum antiobiotics including penicillins, cephalosporings or to any of the excipients listed in section 6.1.


    section 4.4:
    updated the sentence: Prolonged use of an anti-infective agent may occasionally result in overgroeth of non-susceptible super infection by organisms resistant to that anti-infective.
    to:
    Prolonged use of an anti-infective agent may occasionally result in overgroeth of non-susceptible organisms.

    removed the sentence: Germamox Capsules contain soya oil. If you are allergic to peanut or soya, do not use this medicinal product.

    section 4.8: Table updated
    Gastrointestinal disorders...very rare.....removed 'Superficical tooth discolouration has been reported in children. Good overall hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.'
    Renal and urinary tract disorders updated to Renal and urinary disorders.

    Reporting of suspected adverse reactions updated to new HPRA details

    secion 4.9
    Section divided into 'Symptoms' & 'Management'
    Sentence:' Symptoms of water/electrolyte imbalance should be treated symptomatically' moved under 'Management' section.

    section 5.1:
    added: Pharmacotherapeutic group: Beta-lactam antibacterials, penicillins, Penicillincs, Penicillincs with extended spectrum. ATC code: J01CA04

    section 5.2:
    sentence 'Amoxicillin Trihydrate is well absorbed by the oral and parenteral routes, peak levels are achieved 1-2 hours later after administration' updated to
    'Amoxicillin trihydrate is well absorbed by the oral and parenteral routes, peak levels are achieved 1-2 hours after administration'

    header 'Paediatric population' added

    section 5.3 Preclinical Safety Data updated to Preclinical safety data
    sentence 'There are no pre-clinical safety data.... updated to 'There are no non-clinical data'...

    section 6.1
    List of Excipients updated to List of excipients

    Capsule contents:
    Sodium starch glycolate Type A updated to Sodium starch glycolate
    Microcrystalline cellulose updated to Cellulose, microcrystalline
    Colloidal silicon dioxide updated to Silica, colloidal anydrous

    section 6.6
    removed text: 'of a used medicinal product or waste materials derived from such medicinal product and other handling of the product'.


    Updated on 23 July 2013 PIL

    Reasons for updating

    • Change to warnings or special precautions for use
    • Change of contraindications
    • Change to storage instructions
    • Change to side-effects
    • Change to further information section
    • Change to date of revision

    Updated on 23 July 2013 SmPC

    Reasons for updating

    • Change to section 2 - Qualitative and quantitative composition
    • Change to section 4.4 - Special warnings and precautions for use
    • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
    • Change to section 4.8 - Undesirable effects
    • Change to section 6.1 - List of excipients
    • Change to section 10 - Date of revision of the text

    Legal category: Product subject to medical prescription which may not be renewed (A)

    Free text change information supplied by the pharmaceutical company

    Section 2 Excipients
    Section 4.4 Special Warnings and precautions for use
    Section 4.5 Interaction with other medicinal products & other forms of interaction
    Section 4.8 Reporting of adverse reactions
    Section 6.1 List of Excipients
    Date of Revision

    Updated on 18 July 2012 SmPC

    Reasons for updating

    • Change to section 4.1 - Therapeutic indications
    • Change to section 4.2 - Posology and method of administration
    • Change to section 4.3 - Contraindications
    • Change to section 4.4 - Special warnings and precautions for use
    • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
    • Change to section 4.6 - Pregnancy and lactation
    • Change to section 4.7 - Effects on ability to drive and use machines
    • Change to section 4.9 - Overdose
    • Change to section 5 - Pharmacological properties

    Legal category: Product subject to medical prescription which may not be renewed (A)

    Free text change information supplied by the pharmaceutical company

    Numerous changes made to SPC for Article 45 safety variation & PSUR updates.
    Sections updated:
    4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.9, 5 & revision date

    Updated on 11 July 2012 PIL

    Reasons for updating

    • Change to side-effects
    • Change to date of revision
    • Change due to user-testing of patient information

    Updated on 22 September 2010 PIL

    Reasons for updating

    • Correction of spelling/typing errors

    Updated on 19 July 2010 SmPC

    Reasons for updating

    • Change to section 3 - Pharmaceutical form
    • Change to section 9 - Date of renewal of authorisation
    • Change to section 10 - Date of revision of the text

    Legal category: Product subject to medical prescription which may not be renewed (A)

    Free text change information supplied by the pharmaceutical company

    section 3 Pharmaceutical form updated
    section 9 date of first authorisation/renewal updated to 30April2008
    section 10 Date of revision of text updated to May 2010

    Updated on 7 July 2010 PIL

    Reasons for updating

    • Change to date of revision
    • Change to product name

    Updated on 28 June 2005 PIL

    Reasons for updating

    • Correction of spelling/typing errors
    • Change to date of revision

    Updated on 25 May 2005 SmPC

    Reasons for updating

    • New SPC for medicines.ie

    Legal category: Product subject to medical prescription which may not be renewed (A)

    Updated on 22 September 2004 PIL

    Reasons for updating

    • New PIL for medicines.ie