Amoxicillin 500mg Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Amoxicillin 500mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains Amoxicillin Trihydrate BP 586mg equivalent to Amoxicillin 500mg
3 PHARMACEUTICAL FORM
Capsules for oral administration
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of infection: Amoxicillin is a broad spectrum antibiotic indicated for the treatment of commonly-occurring bacterial infections such as:
Upper respiratory tract infections Otitis media
Acute and chronic bronchitis Chronic bronchial sepsis Lobar and bronchopneumonia Cystitis, urethritis, pyelonephritis Bacteriuria in pregnancy
Gynaecological infections including puerperal sepsis and septic abortion
Gonorrhoea
Peritonitis
Intra abdominal sepsis Septicaemia Bacterial endocarditis Typhoid and paratyphoid fever Skin and soft tissue infections Osteomyelitis
Dental abscess (as an adjunct to surgical management)
Invasive Salmonellosis Meningitis
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.
In some of these infections initiation of treatment or indeed the whole course of treatment may need to be by the partentral route.
In children with urinary tract infection, the need for further clinical investigation should be considered.
4.2 Posology and method of administration Adult (including elderly patients):
Normal adult dosage:
250 mg every eight hours which may be doubled in severe infections.
High dosage therapy
Up to a maximum of 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.
Simple acute urinary tract infections:
Two 3g doses with 10-12 hours between the doses.
Gonorrhoea:
3g single dose in combination with 1G Probenecid.
Dental Prophylaxis
For patients undergoing extraction, scaling or surgery involving gingival tissues and who have not received penicillin treatment in the previous month. (if penicillin has been given within the previous month, prophylaxis with an alternative type of antibiotic should be considered.)
The following categories of patients should be referred to the hospital:
A) Patients who will require a general anaesthetic who have been given penicillin in the previous month.
B) Patients with a prosthetic heart valves whether or not they are to receive a general anaesthetic.
C) Patients who have had one or more attacks of endocarditis.
In dental prophylaxis, the normal adult is 3G orally given one hour before treatment with a second dose if condsidered necessary given six hours later.
Children (up to 10years):
It is recommended that the alternative oral liquid formulation is used.
In dental prophylaxis, the same precautions apply as with adults, the normal dosage in children, 5-10 years is half the adult dose and quarter the adult dose in children under 5 years.
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 weighing more than 40 kg should be given the usual adult dosage.
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 14-21days.
Prophylaxis for endocarditis: 50 mg amoxicillin/kg body weight given as a single dose one hour preceding the surgical procedure.
Dosage in impaired renal function:
The dose should be reduced in patients with severe renal function impairment. In patients with a creatinine clearance of less than 30 ml/min an increase in the dosage interval and a reduction in the total daily dose is recommended (see section 4.4 and 5.2).
Renal impairment in children under 40 kg:
|
Creatinine |
Dose |
Interval |
between |
|
clearance |
administration |
|
ml/min | ||
|
> 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) |
Dental prophylaxis involving general anaesthesia
In patients undergoing general anaesthesia, if oral amoxicillin is considered appropriate, the 3G may be given 4 hours prior to anaesthesia.
Route of administration
Oral
4.3 Contraindications
Amoxicillin is a penicillin and should not be given to penicillin-hypersensitive patients and patients with hypersensitivity to the listed ingredients. Attention should be paid to possible cross-sensitivity with other beta-lactam antibiotics e.g. cephalosporins.
4.4 Special warnings and precautions for use
Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins. 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 4.3).
Erythematous (morbilliform) rashes have been associated with glandular fever in patients receiving amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (see Section 4.9 Overdose).
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.
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
When given to patients taking combination oral contraceptives, amoxicillin can cause a reduction in their effect and patients should be warned accordingly.
Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.
Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.
Penicillins reduce excretion of methotrexate (increased risk of toxicity) Excretion of penicillins reduced by sulfinpyrazone
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 Fertility, Pregnancy and lactation
It is understood that animal studies with amoxicillin have shown no teratogenic effects. The product has been in extensive clinical use since 1972 and its suitability in human pregnancy has been well documented in clinical studies. When antibiotic therapy is required during pregnancy, 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
No known adverse effects are reported.
4.8 Undesirable effects
The following convention has been utilised for the classification of undesirable effects:-
Very common (>1/10), common (>1/100, <1/10), uncommon
(>1/1000,<1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000)
The majority of side effects listed below are not unique to amoxicillin and may occur when using other penicillins.
Unless otherwise stated, the frequency of adverse events has been derived from more than 30 years of post-marketing reports.
Blood and lymphatic system disorders
Very rare: Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia. Prolongation of bleeding time and prothrombin (see Section 4.5 - Interaction with other Medicaments and other Forms of Interaction)
Immune system disorders
Very rare: As with other antibiotics, severe allergic reactions, including angioneurotic oedema, anaphylaxis (see Section 4.4 - Special Warnings and Precautions for Use), serum sickness and hypersensitivity vasculitis.
If a hypersensitivity reaction is reported, the treatment must be discontinued. (See also Skin and subcutaneous tissue disorders).
Nervous system disorders
Very rare: Hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Gastrointestinal disorders
Clinical Trial Data
*Common: Diarrhoea and nausea. *Uncommon: Vomiting.
Post-marketing Data
Very rare: Mucocutaneous candidiasis and antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis).
Superficial tooth discolouration has been reported in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.
Hepato-biliary disorders
Very rare: Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT.
The significance of a rise in AST and/or ALT is unclear.
Skin and subcutaneous tissue disorders
Clinical Trial Data
*Common: Skin rash *Uncommon: Urticaria and pruritus
Post-marketing Data
Very rare: Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP)
(See also Immune system disorders).
Renal and urinary tract disorders
Very rare: Interstitial nephritis.
Very rare: Crystalluria (see Section 4.9 Overdose)
*The incidence of these AEs was derived from clinical studies involving a total of approximately 6,000 adult and paediatric patients taking amoxicillin.
4.9 Overdose
Gross overdosage will produce very high urinary concentrations. Problems are unlikely if adequate fluid intake and urinary output are maintained; however, crystalluria is a possibility. More specific measures may be necessary in patients with impaired renal function: the antibiotic is removed by haemodialysis.
5.1 Pharmacodynamic properties
Amoxicillin is well absorbed by the oral route. Oral administration, usually at convenient t.d.s. dosage, produces high serum levels independent of the time at which food is taken. Amoxicillin gives good penetration into bronchial secretions and high urinary concentrations of unchanged antibiotic. It is rapidly bactericidal and possesses the safety profile of a penicillin.
5.2 Pharmacokinetic properties
Amoxicillin is rapidly absorbed when given by mouth; it is not converted to ampicillin. It is widely distributed and is reported to produce peak antibiotic plasma concentrations that are up to twice as high as those from the same dose of ampicillin. Peak plasma-amoxicillin concentrations of about 5 ug per ml have been observed 2 hours after a dose of 250 mg, with detectable amounts present for up to 8 hours. Doubling the dose can produce double the concentration. The presence of food in the stomach does not appear to diminish absorption significantly.
Up to 20% is bound to plasma proteins in the circulation and plasma half-lives of about one hour have been reported.
Amoxicillin diffuses across the placenta; little appears to be excreted in breast milk. It penetrates well into purulent and mucoid sputum and low concentrations have been found in ocular fluid.
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
6.1 List of excipients
Magnesium Stearate BP Capsule Shell:
Gelatin EP E172 (Ferric Oxide) E127 (Erythrosine BS) Titanium dioxide E171
6.2 Incompatibilities
None known
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store below 25 °C.
6.5 Nature and contents of container
Blister packages of PVDC (60gsm) coated PVC (250pm)/aluminium blisters in the following pack sizes: 12, 15 and 21 capsules.
Blister packages of PVC (250pm)/aluminium blisters in the following pack sizes: 12, 15 and 21 capsules.
Polypropylene tubular container with an open end equipped to accept a polyethylene closure, with a tamper-evident tear strip, and is of the appropriate size to accommodate 4 , 100, 500 and 1000 capsules.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Special Concept Development (UK) Limited,
Unit 1-7 Colonial Way,
Watford, Hertfordshire,
WD24 4YR United Kingdom.
8 MARKETING AUTHORISATION NUMBER(S)
PL 36722/0020
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
7th February 2005
10 DATE OF REVISION OF THE TEXT
16/01/2014