Co-Fluampicil 250/250 Mg Capsules Hard
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-Fluampicil 250/250 mg Capsules, hard
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ampicillin trihydrate, equivalent to 250 mg anhydrous ampicillin Flucloxacillin sodium, equivalent to 250 mg anhydrous flucloxacillin For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, hard.
Hard gelatin capsules, blue body with dark grey cap. Size OE. Marked “G CS 500” containing white granular powder.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Co-Fluampicil is indicated for the treatment of severe infections where the causative organism is unknown, and for mixed infections involving B-lactamase-producing staphylococci. Typical indications include:
In general practice
Chest infections, ENT infections, skin and soft tissue infections, and infections in patients whose underlying pathology places them at special risk.
In hospital (prior to laboratory results being available)
Severe respiratory tract infections, post-operative chest and wound infections; septic abortion, puerperal fever; septicaemia, prophylaxis in major surgery, infections in patients receiving immuno-suppressive therapy.
The spectrum of activity of Co-Fluampicil also makes it suitable for the treatment of many mixed infections, particularly those where B-lactamase-producing staphylococci are suspected or confirmed.
Parenteral usage is indicated where oral dosage is inappropriate.
4.2 Posology and method of administration
For oral administration. Oral doses should be administered half an hour to one hour before meals.
1 capsule four times a day.
Paediatric population
This formulation is not suitable for administration to children under 10 years.
Note
The above dosages for adults may be doubled where necessary.
Abnormal renal function
In common with other penicillins, flucloxacillin usage in patients with renal impairment does not usually require dosage reduction. However, in the presence of severe renal failure (creatinine clearance < 10 ml/minute) a reduction in dose or an extension of dose interval should be considered.
Flucloxacillin is not significantly removed by dialysis and hence no supplementary dosages need to be administered either during, or at the end of the dialysis period.
4.3 Contraindications
Co-Fluampicil Capsules 250/250 contain ampicillin and flucloxacillin which are penicillins, and should not be given to patients with a history of hypersensitivity to P-lactam antibiotics (e.g. penicillins, cephalosporins ...), see section 4.4.
Hypersensitivity to any of the excipients listed in section 6.1.
In patients with a history of flucloxacillin-associated jaundice/hepatic dysfunction.
4.4 Special warnings and precautions for use
Before initiating therapy with Co-Fluampicil Capsules 250/250, careful enquiry should be made concerning previous hypersensitivity reactions to B-lactams.
Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving B-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. These reactions are more likely to occur in individuals with a history of B-lactam hypersensitivity.
Co-Fluampicil Capsules 250/250 contains ampicillin and should be avoided if infectious mononucleosis and/or acute or chronic leukaemia of lymphoid origin are suspected. The occurrence of a skin rash has been associated with these conditions following the administration of ampicillin.
Discontinue treatment if rash appears and change to an alternative non-penicillin antibiotic.
Care should be exercised in patients with a history of allergy or with impaired renal function.
Co-Fluampicil Capsules 250/250 should be used with caution in patients with evidence of hepatic dysfunction (see section 4.8).
During prolonged treatments (e.g. osteomyelitis, endocarditis), regular monitoring of hepatic and renal functions is recommended.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
4.5 Interaction with other medicinal products and other forms of interaction
Bacteriostatic drugs may interfere with the bactericidal action of ampicillin and flucloxacillin.
Probenecid decreases the renal tubular secretion of Co-Fluampicil Capsules 250/250. Concurrent use with Co-Fluampicil Capsules 250/250 may result in increased and prolonged blood levels of both components.
Concurrent administration of allopurinol during treatment with ampicillin can increase the likelihood of allergic skin reactions.
Co-Fluampicil Capsules 250/250 contain ampicillin. It is recommended that when testing for the presence of glucose in urine during ampicillin treatment, enzymatic glucose oxidase methods should be used. Due to high urinary concentrations of ampicillin, false positive readings are common with chemical methods.
Oral courses of broad spectrum anti-bacterials affect the hypoprothrombinaemic response to oral anticoagulants.
Pseudomembranous colitis has been reported rarely and has usually been associated with use of flucloxacillin in combination with other antibiotics.
Methotrexate excretion is reduced by penicillins. Patients should be monitored carefully for signs of methotrexate toxicity.
4.6 Fertility, pregnancy and lactation
Pregnancy: The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore ‘Co-Fluampicil Capsules 250/250' should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.
Animal studies have shown no teratogenic effects. The product has been in clinical use since 1971 and the limited number of reported cases of use in human pregnancy have shown no evidence of untoward effect. The use of Co-Fluampicil in pregnancy should be reserved for cases considered essential by the physician.
Breast-feeding: Co-Fluampicil Capsules 250/250 should only be administered to a breast-feeding mother when the potential benefits outweigh the potential risks associated with treatment.
Breast-feeding is not contraindicated with flucloxacillin and ampicillin. Trace quantities of penicillins can be detected in breast milk. While adverse effects are apparently rare, three potential problems exist for the nursing infant:
> modification of bowel flora
> direct effects on the infant such as allergy / sensitisation
> interference with interpretation of culture results when
> pyrexia of unknown origin occurs.
4.7 Effects on ability to drive and use machines
None known
4.8 Undesirable effects
Side-effects as with other penicillins, are uncommon and mainly of a mild and transitory nature.
Hypersensitivity reactions:
If a rash or any hypersensitivity reaction occurs, the treatment should be discontinued.
Skin rash, pruritus and urticaria have been reported occasionally. The incidence of rash is higher in patients suffering from infectious mononucleosis and acute or chronic leukaemia of lymphoid origin. An urticarial rash suggests penicillin hypersensitivity; an erythematous rash may arise in patients receiving ampicillin who have glandular fever. Purpura, fever, eosinophilia and sometimes angioneurotic oedema have also been reported. Rarely, skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. Certain reactions (fever, arthralgia, myalgia) sometimes develop more than 48 hours after the start of the treatment.
As with other B-lactam antibiotics, anaphylaxis (see section 4.4) and angioedema has been reported rarely.
Gastrointestinal reactions:
Minor gastrointestinal disturbances, including occasionally nausea, vomiting and diarrhoea may occur during treatment. As with other antibiotics, pseudomembranous colitis has been reported rarely.
Hepatic effects:
Hepatitis and cholestatic jaundice have been reported rarely. These reactions are related neither to the dose nor to the route of administration. These may be delayed for up to two months post-treatment. In some cases the course has been protracted and lasted for several months. Very rarely deaths have been reported almost always in patients with serious underlying disease.
As with most other antibiotics, a moderate and transient increase in transaminases has been reported.
Renal effects:
Interstitial nephritis may occur.
Haematological effects:
As with other B-lactams, haematological effects including reversible leucopenia, reversible thrombocytopenia and haemolytic anaemia has been reported rarely.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov .uk/yellowcard
4.9 Overdose
Problems of overdosage with Co-Fluampicil are unlikely to occur. If encountered they may be treated symptomatically.
Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically.
More specific measures may be necessary in patients with impaired renal failure.
Co-Fluampicil Capsules 250/250 contains flucloxacillin. Haemodialysis does not lower the serum levels of flucloxacillin.
Co-Fluampicil Capsules 250/250 contains ampicillin, which may be removed from the circulation by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ampicillin is bactericidal and flucloxacillin is a semi-synthetic penicillin of the isoxazolyl group which is bacterial and staphylococcal penicillinase resistant.
They both act by inhibiting cell wall synthesis, probably by acylation of membrane -bound transpeptidase enzymes. This prevents cross linkage of peptidoglycan chains which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited and lysis and elongation of susceptible bacteria frequently occur. Rapidly dividing bacteria are most susceptible to the action of penicillins.
5.2 Pharmacokinetic properties
Flucloxacillin
Flucloxacillin is rapidly but incompletely absorbed (30 - 80 %) after oral administration and the presence of food impairs absorption.
Flucloxacillin in common with other penicillins, is widely distributed throughout the body. It is highly bound (90 - 95 %) to plasma proteins. The half-life of flucloxacillin is 30 to 60 minutes. It is rapidly excreted by the kidneys. Hepatic and billiary elimination also occur.
Ampicillin
Oral absorption of ampicillin (35-50 %) is impaired by presence of food in the stomach. When ampicillin is administered i.m. a much higher peak level is reached within 30 minutes than by the oral route. Ampicillin is evenly distributed throughout most body tissues and with the exception of the kidney and liver, tissue concentrations are lower than simultaneous plasma levels in healthy individuals. Ampicillin exhibits low plasma protein binding (17-18 %). 12-50 % of an ampicillin dose undergoes hepatic biotransformation. About 20-60 % of an oral dose and 50-85 % of an i.m. dose of ampicillin is excreted unchanged in the urine. A small amount of ampicillin is excreted in the bile.
5.3 Preclinical safety data
Flucloxacillin sodium
Flucloxacillin is described as moderately toxic by intravenous, intraperitoneal and subcutaneous routes. It is mildly toxic by ingestion and capable of experimental reproductive effects.
Acute toxicity studies have shown that the ld50 was determined as 11 g / kg when flucloxacillin was orally administered to rats whilst for mice an oral dose of 7600 mg / kg represented the lethal dose. However, for subcutaneous administration to rats and mice the ld50 was reported as 2800 mg / kg and 1450 mg / kg, respectively.
Ampicillin trihydrate
Ampicillin can produce experimental teratogenic and reproductive effects.
Reproductive studies have shown that a tdl0 of 1500 mg / kg was reported when ampicillin was administered orally to rats who were between 6 to 11 days pregnant.
Also, oral dosing of 28 g / kg in 7 to 13 days pregnant mice have shown teratogenic effects.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule contents Magnesium stearate
Capsule shell Quinoline yellow (E104)
Patent Blue V (E131)
Titanium dioxide (E171),
Gelatin
Yellow iron oxide (E172)
Black iron oxide (E172)
6.2. Incompatibilities
None known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store below 25 °C.
Store in the original package and keep the container tightly closed in order to protect from moisture.
6.5 Nature and contents of container
Polypropylene containers with polyethylene caps (with optional polyethylene ullage filler), amber glass bottles, PVC/foil blister packs and high density polyethylene (HDPE) containers with polyethylene snap closures.
All pack types are available in pack sizes of 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 50, 56, 60, 84, 90, 100, 250, 500 and 1000.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Ltd t/a Mylan
Station Close
Potters Bar
Herts
EN6 1TL
8. MARKETING AUTHORISATION NUMBER(S)
PL 4569/0082
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12 December 1995
10 DATE OF REVISION OF THE TEXT
12/04/2016