Amoxicillin 500mg Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Amoxicillin 500 mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Amoxicillin 500 mg Capsules contain 500mg of amoxicillin as the trihydrate per capsule.
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Capsules.
Amoxicillin 500 mg Capsules are presented as hard gelatin capsules with a maroon cap and yellow body.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of Infection: Amoxicillin is a broad spectrum antibiotic indicated for the treatment of commonly occurring bacterial infections such as: Upper respiratory tract infections Otis 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
Dental abscess (as an adjunct to surgical management)
Helicobacter pylori eradication in peptic (duodenal and gastric) ulcer disease. In children with urinary tract infection the need for investigation should be considered.
Prophylaxis of endocarditis: Amoxicillin may be used for the prevention of bacteraemia associated with procedures such as dental extraction, in patients at risk of developing bacterial endocarditis.
Consideration should be given to official local guidance on the appropriate use of antibacterial agents. Susceptibility of the causative organism to the treatment should be tested (if possible), although the therapy may be initiated before the results are available.
4.2 Posology and Method of Administration
Treatment of infection:
Adult dosage (including elderly patients):
Standard Adult Dose: 250mg three times daily, increasing to 500mg three times daily for more severe infections.
High dosage therapy (maximum recommended oral dosage 6g daily in divided doses): A dosage of 3g 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 3g doses with 10-12 hours between the doses. Dental abscess: two 3g doses with 8 hours between the doses. Gonorrhoea: single 3g dose.
Renal Impairment:
Glomerular filtration rate > 30ml/min: No adjustment necessary.
Glomerular filtration rate 10 - 30ml/min: Amoxicillin max. 500 mg b.d.
Glomerular filtration rate < 10ml/min: Amoxicillin max. 500 mg/day.
Helicobacter eradication in peptic (duodenal and gastric) ulcer disease: Amoxicillin is recommended at a dose of twice daily in association with a proton pump inhibitor and antimicrobial agents as detailed below:
Omeprazole 40mg daily, Amoxicillin 1G BID, Clarithromycin 500mg BID x 7 days or
Omeprazole 40mg daily, Amoxicillin 750mg-1G BID, Metronidazole 400mg TID x 7 days.
Children’s dosage (up to 10 years of age):
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 upper range.
Children weighing more than 40 kg should be given the usual adult dosage.
Dosage in impaired renal function:
The dose should be reduced in patients with severe renal function impairment. In patients with a creatinine clearance of less than 30 ml/min an increase in the dosage interval and a reduction in the total daily dose is recommended (see section 4.4 and 5.2).
Renal impairment in children under 40 kg:
|
Creatinine clearance ml/min |
Dose |
Interval between administration |
|
> 30 |
Usual dose |
No adjustment necessary |
|
10 - 30 |
Usual dose |
12 h (corresponding to 2/3 of the dose) |
|
< 10 |
Usual dose |
24 h (corresponding to 1/3 of the dose) |
Special dose recommendation
Tonsillitis; 50 mg/kg/day in two divided doses.
Acute otitis media: In areas with high prevalence of pneumococci with reduced susceptibility to penicillins, dosage regimens should be guided by national/local recommendations.In severe or recurrent acute otitis media, especially where compliance may be a problem,750 mg twice a day for two days may be used as an alternative course of treatment in children aged 3 to 10 years.
Early Lyme disease (isolated erythema migrans): 50 mg/kg/day in three divided doses, over 14-21days.
Prophylaxis for endocarditis: see table below Administration: Oral
Treatment should be continued for 2 to 3 days following the disappearance of symptoms. It is recommended that at least 10 days treatment be given for any infection caused by beta-haemolytic streptococci in order to achieve eradication of the organism.
Prophylaxis of endocarditis
|
CONDITION |
ADULTS’ DOSAGE (INCLUDING ELDERLY) |
CHILDREN'S DOSAGE ( < 40 kg) |
NOTES | |
|
Dental procedures: prophylaxis for patients undergoing extraction, |
Patient not having general anaesthetic. |
3 g Amoxicillin orally 1 hour before procedure. A second dose may be |
50 mg amoxicillin/kg body weight given as a single dose one |
Note 1. If prophylaxis with ‘Amoxicillin is given twice within one |
|
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). |
given6 hours later, if considered necessary |
hour preceding the surgical procedure |
month, emergence of resistant streptococci is unlikely to be a problem. Alternative antibiotics are recommended if more frequent prophylaxis is required, or if the patient has received a course of treatment with a penicillin during the previous month. Note 2 To minimise pain on injection, ‘Amoxicillin may be given as two injections of 500 mg dissolved in sterile 1% lidocaime solution (see Administration). | |
|
Patient having general anaesthetic: if oral antibiotics considered to be appropriate |
Initially 3 g ‘Amoxicillin orally 4 hours prior to anaesthesia, followed by 3 g orally (or 1 g IV or IM if oral dose not tolerated) as soon as possible after the operation. | |||
|
Patient having general anaesthetic: if oral antibiotics not appropriate |
1 g ‘Amoxicillin IVor 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 Amoxillin IV or IM with 120 mg gentamicin IV or IM immediately prior to anaesthesia (if given) or 15 minutes prior to dental procedure. Followed by (6 hours later): 500 mg ‘Amoxicillin orally |
50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure |
See Note 2. Note 3. ‘Amoxicillin and gentamicin should not be mixed in the same syringe. Note 4. Please consult the appropriate data sheet for full prescribing information on gentamicin. | |
|
Genitourinary Surgery or Instrumentation: prophylaxis for patients who have no urinary tract infection and who are to have genito-urinary surgery or instrumentation under general anaesthesia. In the case of Obstetric and Gynaecological Procedures and Gastrointestinal Procedures - routine prophylaxis is recommended only for patients with prosthetic heart valves. |
Initially: 1 g ‘Amoxicillin IV or IM with 120 mg gentamicin IV or IM, immediately before induction. Followed by (6 hours later): 500 mg ‘Amoxicillin orally or IV or IM according to clinical condition. |
See Notes 2, 3 and 4 above. | ||
|
Surgery or Instrumentation of the Upper Respiratory Trad |
Patients other than those with prosthetic heart valves. |
1 g ‘Amoxicillin IV or IM immediately before induction; 500 mg ‘Amoxicillin IV or IM 6 hours later |
50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure |
See Note 2 above. Note 5. The second dose of ‘Amoxicillin be administered orally as ‘Amoxil’ Syrup SF/DF. |
|
Patients with prosthetic heart valves. |
Initially: 1 g Amoxicillin IV or IM with 120 mg gentamicin IV or IM, immediately before induction; followed by (6 hours later) 500 mg ‘Amoxicillin IV or IM |
50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure |
See Notes 2, 3, 4 and 5 above | |
4.3 Contraindications
Amoxicillin is a penicillin and should not be given to penicillin-sensitive patients, or those sensitive to any of the excipients. Attention should be paid to possible crosssensitivity with other beta-lactam antibiotics e.g. cephalosporins.
Amoxicillin is also contraindicated in viral infections, acute lymphatic leukaemia and infectious mononucleosis due to an increased risk of erythematous skin rashes.
4.4 Special warnings and precautions for use
Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins and cephalosporins.
The excipients tartrazine (E102), sunset yellow (E110), carmosine (E122) and brilliant blue (E133) may cause hypersensitivity reactions.
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.
At high doses relative to urinary output, adequate fluid intake and urinary output must be maintained to minimise the possibility of amoxicillin crystalluria.( see section4.9 )
In patients with renal impairment, the rate of excretion of amoxicillin will be reduced depending on the degree of impairment and it may be necessary to reduce the total daily unit amoxicillin dosage accordingly.(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)
Precaution should be taken in premature children and during the neonatal period: renal, hepatic and haematological functions should be monitored.
4.5 Interactions with Other Medicaments and Other Forms of Interaction
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 literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumaral or warfarin and prescribed course of amoxicillin. If coadministration is necessary, the prothrombin time and international normalised ratio should be monitored with 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.
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin may result in increased and prolonged blood levels of amoxicillin.
4.6 Pregnancy and lactation
Use in Pregnancy: Animal studies with amoxicillin have shown no teratogenic effects. 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.
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
Undesirable effects have been classified using the following convention:
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
Skin and subcutaneous tissue disorders
Clinical Trial Data *Common: Skin rash,
*Uncommon: Pruritis and urticaria.
Post marketing Data
Very rare: Skin reactions such as erythema multiforme and Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP).
Immune system disorders:
Very rare: As with other antibiotics severe allergic reactions ,including angioneurotic oedema, anaphylaxis(see section4.4), serum sickness and hypersensitivity vasculitis.
If a hypersensitivity reaction is reported,the treatment must be discontinued.(see also skin and subcutaneous tissue disorders)
Renal and urinary tract disorders:
Very rare: Interstitial nephritis.
Very rare Crystalluria (see section4.9)
Gastrointestinal disorders:
Clinical Trial Data *Common: Nausea and diarrhoea.
*Uncommon: Vomiting.
Post marketing Data
Very rare: Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic).
Black hairy tongue
Superficial tooth discolouration has been reported in children, mostly with the suspension and chewable tablets. It can usually be removed by brushing.
Hepato -biliary disorders :
Very rare: A moderate rise in AST and/or ALT .hThe significance of rise in AST and /or ALT is unclear.
Hepatitis and cholestatic jaundice.
Blood and lymphatic system disorders:
Very rare: As with other beta lactams, eversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia.
Prolongation of bleeding time and prothrombin time.( see section 4.4)
Nervous system disorders:
Very rare: Hyperkinesias, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
* 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 can lead in some cases to renal failure (see section 4.4).
Amoxicillin may be removed from the circulation by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code: J01CA04 Group: Beta-lactam Antibacterials, Penicillins
General Properties:
Amoxicillin is a broad spectrum antibiotic and kills bacteria by interfering with the synthesis of the bacterial cell wall.
Amoxicillin possesses the safety profile of a penicillin.
Susceptibility:
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. This information gives only approximate guidance on the probability as to whether micro-organisms will be susceptible to amoxicillin or not.
Susceptible:
Gram-positive Gram-negative
Streptococcus faecalis Haemophilus influenze
Streptococcus pneumoniae Escherichia coli
Streptococcus pyogenes Proteus mirabilis
Streptococcus viridans Salmonella species
Staphylococcus aureus Shigella species
(penicillin-sensitive strains only) Bordetella pertussis
Brucella species
Corynebacterium species Neisseria gonorrhoeae
Bacillus anthracis Neisseria meningitides
Listeria monocytogenes Vibrio cholerae
Pasteurella septica Helicobacter pylori
Anaerobes:
Clostridium species Resistant:
Gram-negative
Klebsiella and Enterobacter spp Indole-positive proteus spp
Pseudomonas aeruginosa
Resistance to Enterobacter spp. is reported to be due to poor penetration of amoxicillin into the organisms and its subsequent destruction by P-lactamase. Amoxicillin is therefore not active against penicillinase-producing organisms due to instability to this particular p-lactamase.
Organisms resistant to ampicillin are also resistant to amoxicillin as there is complete cross-resistance between the two compounds.
5.2 Pharmacokinetic Properties
Absorption:
The absolute bioavailability of amoxicillin depends on the dose and ranges between 75 and 90%. In the dose range between 250mg and 750mg the bioavailability (parameters: AUC and/or recovery in urine) is linearly proportional to the dose. At higher doses the extent of absorption decreases. Absorption is not affected by concomitant food intake. Oral administration of a single dose of 500mg amoxicillin results in plasma concentrations of 6-11 mg/l. After administration of a single dose of 3g amoxicillin, the plasma concentrations reach 27mg/l. peak plasma concentrations are present about 1-2 hours after administration.
Distribution:
Protein binding for amoxicillin is approximately 17%. Therapeutic drug levels are rapidly achieved in serum, lung tissue, bronchial secretions, middle ear fluid, bile and urine. Amoxicillin can penetrate inflamed meninges and enter the cerebrospinal fluid. Amoxicillin crosses the placenta and a small percentage is excreted in breast milk.
Biotransformation and Elimination:
The main route of excretion of amoxicillin is the kidney. About 60 - 80% of an oral dose of amoxicillin is excreted in unchanged active form in the urine within 6 hours of administration and a small fraction is excreted in the bile. Approximately 7-25% of the administered dose is metabolised to inactive penicilloic acid. The serum half-life in patients with normal renal function is approximately 1-1.5 hours. In patients with end-stage renal failure the half-life ranges between 5 to 20 hours. The substance is haemodialysable.
Pharmacodynamics in Infants
In preterm infants with gestational age 26-33 weeks, the total body clearance after intravenous dosing of amoxicillin, day 3 of life, ranged between 0.75 - 2 ml/min, very similar to the inuline clearance (GFR) in this population. Following oral administration, the absorption pattern and the bioavailability of amoxicillin in small children may be different to that of adults. Consequently, due to the decreased CL, the exposure is expected to be elevated in this group of patients, although this increase in exposure may in part be diminished by decreased bioavailability when given orally.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Colloidal anhydrous silica
Magnesium stearate Gelatin
Tartrazine (E102)
Sunset yellow (E110)
Carmosine (E122)
Brilliant Blue (E133)
Titanium dioxide (E 171)
6.2 Incompatibilities
None known.
6.3 Shelf-life Blister, 36 months.
Container, 24 months
6.4 Special precautions for storage
Blister: Do not store above 25°C. Store in original package.
Container: Do not store above 25°C, Store in Original Package, Keep container tightly closed
6.5 Nature and contents of container
PVC/Aluminium blister packs containing 3, 6, 12, 15, 21 and 50 capsules.
Polypropylene container with LDPE/HDEP blend Cap containing 100 capsules
6.6 Special precautions for disposal
Not applicable.
7.
Marketing Authorisation Holder
Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/09/2007
10 DATE OF REVISION OF THE TEXT
18/12/2013