Co-Fluampicil Capsules
Out of date information, search anotherPRODUCT SUMMARY
1. TRADE NAME OF THE MEDICINAL PRODUCT Co-fluampicil Capsules
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Ampicillin Trihydrate BP 288.71 mg (equivalent to 250 mg Ampicillin) and Flucloxacillin Sodium BP 272.00 mg (equivalent to 250 mg Flucloxacillin) per capsule.
3. PHARMACEUTICAL FORM
Co-fluampicil capsules are presented as size 0, powder blue opaque (body)/black opaque (cap)
capsules printed with company logo and co-fluam.
4. CLINICAL PARTICULARS
4.1 Therapeutic Indications
Ampicillin/flucloxacillin is indicated for the treatment of severe infections where the causative organism is unknown and for mixed infections involving P 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.
4.2 Posology and method of administration
Adults (including elderly) and children over 10 years:
One capsule to be taken four times daily.
Children under 10 years:
Half the usual adult dose, using a Co-fluampicil Syrup
The above doses for adults and children may be doubled where necessary.
Oral doses should be administered ^ - 1 hour before meals
Route of administration: Oral
4.3 Contra-indications
Patients with a history of hypersensitivity to P-lactam antibiotics ie. penicillins, cephalosporins or to any of the excipients.
Patients with a history of flucloxacillin-associated jaundice/hepatic dysfunction.
Patients with porphyria.
4.4 Special warnings and precautions for use
Before initiating therapy with Co-fluampicil careful enquiry should be made concerning any previous hypersensitivity to P-lactams. Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving P-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. Patients with a history of P-lactam hypersensitivity are more likely to experience these reactions.
Co-fluampicil should be used with caution in patients with evidence of hepatic dysfunction, patients >50 years and those with serious underlying disease. In these patients, hepatic events may be severe, and in very rare circumstances, deaths have been reported (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 the selection of resistant strains of organisms.
Convulsions and other signs of toxicity to the CNS may occur with high doses particularly in infants and the elderly. Occasionally when large doses are administered, nephrotoxicity can result with impaired renal function. Caution should be exercised in patients with impaired renal function and dosage reduction may therefore be necessary.
Cross allergy and cross-resistance between penicillins and cephalosporins is known to exist and therefore the cross contamination of these should be avoided.
Ampicillin should be avoided in patients with infectious mononucleosis and/or acute leukaemia of lymphoid origin are suspected, as they are especially susceptible to ampicillin induced skin rashes.
Sodium content: Each capsule contains 13mg of sodium. To be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interactions
Food may interfere with the absorption of ampicillin/flucloxacillin, doses should therefore be taken thirty minutes to one hour before meals.
The efficacy of oral contraceptives may be reduced and patients should be warned accordingly.
Bacteriostatic drugs such as chloramphenicol, erythromycins, sulphonamides and tetracyclines interfere with the bactericidal effect of ampicillin/ flucloxacillin and should be avoided where rapid bactericidal effect is desired.
Probenecid decreases renal tubular secretion when administered concurrently resulting in increased and prolonged blood levels of both flucloxacillin and ampicillin prolonging half-life and/or toxicity.
Concurrent administration of allopurinol during treatment with ampicillin can increase the likelihood of allergic skin reactions.
Excretion of methotrexate is reduced by penicillins; patients should be monitored for signs of methotrexate toxicity.
It is recommended when testing for the presence of glucose in urine, enzymatic glucose oxidase methods be used because false positive readings are common with chemical methods, due to the high urinary concentrations of ampicillin.
4.6 Use during pregnancy and lactation
Pregnancy: The safety of ampicillin/flucloxacillin combination product in human pregnancy has not been fully established. Animal studies have shown no teratogenic effects. The product may be used in pregnancy only if considered essential by the physician.
Lactation: Trace quantities of ampicillin and flucloxacillin can be detected in breast milk and hence the possibility of hypersensitivity reactions including skin rashes and diarrhoea in breast-fed infants must be considered. Therefore Co-fluampicil should only be administered to a breast-feeding mother when the potential benefit outweighs the potential risk.
4.7 Effects on Ability to Drive and Use Machines
None reported
4.8 Undesirable effects
Hypersensitivity reactions:
Hypersensitivity skin reactions and wheezing occur in sensitive patients.
If any hypersensitivity reactions occur, treatment should be discontinued.
Generalised sensitivity reactions may occur within 1-3 weeks.
Skin rashes are the most common adverse effects encountered and are either urticarial or maculopapular. The urticarial reactions are typical of penicillin hypersensitivity while the maculopapular eruptions are characteristic of ampicillin and often appear about five days after treatment has finished
Skin rash, pruritis, urticaria and exfoliative dermatitis have been reported occasionally. Incidence of rash is higher in patients suffering from infectious mononucleosis and acute or chronic leukaemia of lymphoid origin. Purpura, fever and 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.
Cutaneous reactions subside spontaneously following withdrawal of ampicillin/flucloxacillin.
Reactions such as fever, arthralgia and myalgia can develop more than 48 hours after the start of treatment.
Anaphylaxis has been reported rarely (see 4.4 Special warnings and precautions).
Gastrointestinal reactions:
Minor gastrointestinal disturbances, including occasionally nausea, vomiting and mild diarrhoea may occur.
Pseudomembranous colitis has been reported rarely.
Darkening and discolouration of the tongue can result from fungal overgrowth and hypertrophy of the papilla.
Hepatic effects:
Hepatitis and cholestatic jaundice have been reported rarely. (See 4.4 Special warnings and precautions). Changes in liver function laboratory test results (reversible when treatment is discontinued).
The onset of these effects may be delayed for up to two months posttreatment; in several cases the course of the reactions has been protracted and lasted for some months. Hepatic events may be severe and in very rare circumstances a fatal outcome has been reported. Most reports of deaths have been in patients >50 years and in patients with serious underlying disease.
Renal effects:
Interstitial nephritis may occur.
Haematological effects:
Haematological effects including reversible leucopenia, reversible thrombocytopenia and haemolytical anaemia have been reported rarely. Prolongation of bleeding time and prothrombin time have been reported rarely.
CNS effects:
Convulsions and other signs of CNS toxicity to the CNS may occur with high doses, particularly in infants and the elderly.
4.9 Overdose
Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically.
Co-fluampicil contains flucloxacillin - haemodialysis does not lower the serum levels of flucloxacillin.
Co-fluampicil contains ampicillin, which may be removed from the circulation by haemodialysis.
Cutaneous reactions subside spontaneously following withdrawal of ampicillin/flucloxacillin. Control may be attempted by administering antihistamines. If there is no response, then corticosteroids should be tried.
For an immediate reaction 0.3 to 1.0 ml of adrenalin injection should be given intramuscularly or in severe cases 0.2 ml well diluted intravenously, followed by a further dose if no improvement occurs.
This should be followed by an antihistamine such as diphenhydramine or chlorpheniramine given parenterally and a corticosteroid given intravenously.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic Properties
Ampicillin
Ampicillin is a broad spectrum penicillin for the treatment of a wide range of infections caused by ampicillin-sensitive organisms.
Ampicillin is bactericidal. This action depends on the ability to reach and bind penicillinbinding proteins located in bacterial cytoplasmic membranes. It inhibits bacterial septum and cell wall synthesis, probably by acylation of the transpeptidase enzyme. Transpeptidase is a membrane bound bacterial enzyme responsible for cross-linking of peptidoglycan during the final stage of synthesis of bacterial cell wall hence, cross-linkage of peptidoglycan chains is prevented which is necessary for bacterial cell wall strength and rigidity.
Therefore bacterial cell division and growth are inhibited and lysis and elongation of susceptible bacterial frequently occur. Rapidly dividing bacteria are those growth produce an enzyme penicillinase which inhibits the action of ampicillin.
Minimum inhibitory concentrations for gram-positive organisms have been reported to range from 0.2 to 5 microgram per ml and for gram-negative organisms from 0.02 to 8 microgram per ml. It is inactive against most strains of pseudomonas aeruginosa. Ampicillin is acid stable and may be administered orally. An oral dose of 500 mg produces a peak blood level in one to three hours of about 4 mcg/ml and detectable amounts persist for about six hours. It is widely distributed in the tissues. Within six hours of administration about 30 % of the dose is excreted, for the most part unchanged in the urine, while a concentration at least ten times in excess of plasma levels may be obtained in bile.
Ampicillin crosses the intact meninges in only minute amounts. In bacterial meningitis, higher concentrations are found in the cerebrospinal fluid. Pregnant women given ampicillin may have therapeutic levels of the drug in the amniotic fluid in the later stages of pregnancy.
Flucloxacillin
Flucloxacillin sodium is a bactericidal antibiotic. Chemically, it is similar to dicloxacillin, one of the chlorine atoms replaced by fluorine. It has virtually the same antibacterial spectrum as cloxacillin and its analogues. The main advantage of flucloxacillin is its better absorption after oral administration, peak serum levels being almost double those obtained with cloxacillin after similar doses.
It is a penicillinase - resistant penicillin and is effective only in the treatment of infections caused by pneumococci, group a beta-haemolytic streptococci, and penicillin G-resistant and penicillin G-sensitive staphylococci.
The mechanism of action depends on ability to reach and bind penicillin binding proteins located in bacterial cytoplasmic membranes. This inhibits bacterial septum and 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. Cell division and growth are also inhibited and lysis and elongation of susceptible bacterial frequently occur.
5.2 Pharmacokinetic Properties Ampicillin
Ampicillin is incompletely absorbed from the gastrointestinal tract after oral administration. About 32-53 percent is absorbed. It is stable in acid gastric secretion. Whereas absorption efficiency appears to be independent of dose up to 1000 mg, food appears to delay the onset and reduce the total amount absorbed. Ampicillin should therefore be administered ~ - 1 hour before meals. Peak serum concentration is attained in about two hours and following an oral dose of 500 mg it may range between 2 - 6 mcg/ml.
Protein binding of ampicillin is low. About 20 percent is bound to plasma proteins in circulation and plasma half-life is 1 - 2 hours.
It is widely distributed in most body fluids and bone. Penetration into cells, the eyes and across normal menninges is poor. Inflammation increases the amount which crosses the blood brain barrier. Ampicillin crosses the placenta and appears in cord blood and amniotic fluid. It does not penetrate and is not bound to human erythrocyte.
Ampicillin serum levels in pregnant women are approximately one-half those in non-pregnant women after a comparable dose but urinary recoveries appear similar. Therefore renal clearance rate is doubled during pregnancy. Ampicillin levels in the placenta and umbilical blood are the same as those in maternal serum. Serum clearance in the newborn is about one-half to two-third that of an adult with normal kidney function. Serum half-life is about 2.2 H in infants 2-5 days old, 3.4 H in those under one day and 1.1 H in those older than four months.
About 12-50 per cent is metabolised by the liver. Ampicillin is excreted by the kidneys both as a result of tubular secretion and glomerular filtration. The amount excreted by glomerular filtration depends on the extent of protein binding. Renal concentration range between one-half and twice those in serum and appears to be uniformly distributed among the cortex, medulla and papilla. Within six hours of administration about thirty percent of the dose is excreted for most part unchanged in the urine, about twenty percent of oral dose is excreted in the urine as penicilloic acid. Small amount of ampicillin is excreted in bile and milk. Concomitant probenecid administration effectively reduces the renal clearance of ampicillin to that of glomerular filtration rate, the net effect is to increase mean serum concentrations by a factor of two and to decrease urinary recovery by 18 percent. Concomitant administration of oxacillin or cimetidine has no effect on ampicillin absorption, biotransformation or excretion.
Flucloxacillin
Flucloxacillin is rapidly but incompletely absorbed from the gastro-intestinal tract.
Flucloxacillin is better absorbed from the gastro-intestinal tract than cloxacillin. Its absorption is reduced by food both in stomach and the small intestine.
After an oral dose of 250 to 500 mg, peak serum concentrations are attained within an hour and range between 3 - 27 micrograms per ml with mean peak concentration being 11-15 micrograms per ml. Therapeutic concentration persists for 4 hours. About 95 per cent is bound to plasma proteins. About 50 per cent of the oral dose is excreted in the urine within 6 hours. There is also significant hepatic elimination of flucloxacillin in the bile.
The half life is between 30 and 60 minutes.
5.3 Preclinical safety data
Not applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Starch Glycolate Magnesium Stearate Capsule Body Erythrosine (El27)
Patent Blue V (E131)
Titanium Dioxide (El71)
Water
Sodium Laurilsulfate
Gelatin
Capsule Cap
Black Iron Oxide (E172)
Titanium Dioxide (E171)
Water
Sodium Laurilsulfate
Gelatin
Printing Ink
Titanium Dioxide (E171)
Polyoxyethylene 20 Sorbitan Mono-oleate Shellac
6.2 Incompatibilities
Incompatibilities with colistin sulphomethate sodium, gentamicin, kanamycin and polymyxin B sulphate. Loss of potency after mixing with streptomycin has also been reported.
6.3 Shelf Life
3 years
6.4 Special Precautions for Storage
Protect from heat, light and moisture. Keep out of the reach of children.
6.5 Nature and Contents of Container
1. Opaque plastic containers with plastic caps in pack sizes of 9, 10, 14, 15, 20, 21, 28, 30, 50, 56, 84, 100, 250, 500, 1000 and bulk capsules.
2. Opaque plastic containers composed of either high density polypropylene or high density polyethylene with a tamper-evident or child-resistant tamper-evident closure composed of high density polyethylene with a packing inclusion of polyether foam or polyethylene or polypropylene filler in pack sizes of 9, 10, 14, 15, 20, 21, 28, 30, 50, 56, 84, 100, 250, 500, 1000 and bulk capsules.
3. Opaque plastic containers composed of either high density polypropylene or high density polyethylene with a silica gel sachet inclusion, a laminated aluminium foil seal and a tamper-evident or child-resistant tamper-evident screw-cap composed of high density polyethylene in pack sizes of 9, 10, 14, 15, 20, 21, 28, 30, 50, 56, 84, 100, 250, 500, 1000 and bulk capsules.
4. Blister packs of aluminium/opaque PVC in pack sizes of 9, 10, 14, 15, 20, 21, 28, 30, 56 and 84 capsules.
6.6 Instructions for Use/Handling
No special instructions for use/handling.
ADMINISTRATION DATA
7. MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
UNITS 3 AND 4, QUIDHAMPTON BUSINESS UNITS
POLHAMPTON LANE
OVERTON
HAMPSHIRE
RG25 3ED
8. MARKETING AUTHORISATION NUMBER
PL 20416/0051
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
30/01/2009
10 DATE OF REVISION OF THE TEXT
20/10/2010