Magnapen Hard Capsules
SUMMARY OF PRODUCT CHARACTERISTIC
1. NAME OF THE MEDICINAL PRODUCT
Magnapen® Hard Capsules or Co-fluampicil 250mg/250mg Hard Capsules
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Co-fluampicil Capsules contain 250mg ampicillin as ampicillin trihydrate with 250mg flucloxacillin as flucloxacillin sodium (co-fluampicil 250/250).
3. PHARMACEUTICAL FORM
Capsules
Black and turquoise capsules overprinted Magnapen/Magnapen or CF500/CP
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 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.
The spectrum of activity of co-fluampicil also makes it suitable for the treatment of many mixed infections, particularly those where P-lactamase-producing staphylococci are suspected or confirmed.
Parenteral usage is indicated where oral dosage is inappropriate.
4.2 Posology and method of administration
Usual adult dosage (including elderly patients and children over 10 years):
Oral: 1 capsule four times a day.
Usual children’s dosage:
Oral: Under 10 years: half adult dose, using Co-fluampicil Syrup.
The above dosages for adults and children may be doubled where necessary. Oral doses should be administered half to one hour before meals.
4.3 Contraindications
Co-fluampicil contains 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) or excipients.
Co-fluampicil is contraindicated 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 careful enquiries should be made concerning previous hypersensitivity reactions to P-lactam antibiotics.
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. These reactions are more likely to occur in individuals with a hypersensitivity to P-lactam antibiotics.
Co-fluampicil 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.
In case of severe and persistent diarrhoea, the possibility of pseudomembranous colitis should be considered; flucloxacillin therapy should be discontinued.
Care is required when treating some patients with spirochaete infections such as syphilis or leptospirosis because the Jarisch-Herxheimer reaction may occur shortly after treatment with a penicillin is started.
Co-fluampicil should be used with caution in patients with evidence of hepatic dysfunction (see Section 4.8).
Care is necessary if very high doses of flucloxacillin are given, especially if renal function is poor, because of the risk of nephrotoxicity and/or neurotoxicity. Care is also necessary if large doses of sodium (salts) are given to patients with impaired renal function or heart failure. Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction (see section 4.8). Renal, hepatic and haematological status should be monitored during prolonged and high-dose therapy (e.g. osteomyelitis, endocarditis). Prolonged use may occasionally result in overgrowth of non-susceptible organisms
Sodium Content: Co-fluampicil Capsules contain 13.0mg sodium per capsule. This should be included in the daily allowance of patients on sodium restricted diets.
4.5 Interaction with other medicinal products and other forms of interaction
Other antibacterials: There may be antagonism between penicillins, including ampicillin and bacteriostatic agents such as chloramphenicol, erythromycins or tetracyclines. This may reduce the effectiveness of penicillins particularly in the treatment of infections such as pneumococcal meningitis and scarlet fever.
Cytotoxics: Penicillins reduce the excretion of methotrexate (increased risk of toxicity).
In common with other oral broad-spectrum antibiotics, co-fluampicil may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Probenecid decreases the renal tubular secretion of co-fluampicil. Concurrent use with co-fluampicil may result in increased and prolonged blood levels of both ampicillin and flucloxacillin.
Concurrent administration of allopurinol during treatment with ampicillin can increase the likelihood of allergic skin reactions.
Interference with diagnostic tests: Penicillins may produce false-positive results with the direct antiglobulin (Coombs’) test, falsely high urinary glucose results with the copper sulphate test and falsely high urinary protein results, but glucose enzymatic tests (e.g. Clinistix) and bromophenol blue tests (e.g. Multistix or Albustix) are not affected
4.6 Fertility, pregnancy and lactation
Pregnancy: Animal studies with co-fluampicil 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 effects. The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore co-fluampicil should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.
Lactation: Trace quantities of ampicillin and flucloxacillin can be detected in breast milk. The possibility of hypersensitivity reactions must be considered in breast-fed infants. Therefore co-fluampicil should only be administered to a breast-feeding mother when the potential benefit outweigh the potential risks associated with treatment.
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
Blood and lymphatic system disorders:
As with other P-lactam antibiotics haematological effects including reversible leucopenia, reversible thrombocytopenia and haemolytic anaemia have been reported rarely.
Immune System Disorders:
Anaphylaxis (see Item 4.4-warnings) has been reported rarely.
If any hypersensitivity reaction occurs, the treatment should be discontinued. Late sensitivity reactions may include serum sickness-like reactions (featuring symptoms such as arthralgia, rash, urticaria, fever, angioedema, lymphadenopathy), haemolytic anaemia and acute interstitial nephritis.
Metabolism and nutrition disorders:
Electrolyte disturbances, such as hypokalaemia, due to administration of large amounts of sodium
Psychiatric disorders:
There is a potential for hallucinations to occur rarely with flucloxacillin. Nervous System Disorders
Coma may develop with high doses of Flucloxacillin.
Respiratory, thoracic and mediastinal disorders:
Bronchospasm may occur as a result of penicillin allergy.
There is a potential for acute, severe dyspnoea to occur with flucloxacillin.
Gastrointestinal disorders:
Minor gastrointestinal disturbances, including occasionally nausea, vomiting and diarrhoea may occur during treatment. Pseudomembranous colitis has been reported rarely.
Hepatobiliary disorders:
Hepatitis and cholestatic jaundice have been reported rarely. These may be delayed for up to two months after withdrawal of treatment. In some cases the course of these conditions has been protracted and lasted for several months. Very rarely deaths have been reported from hepatic effects but are mostly limited to patients with serious underlying disease.
As with most other antibiotics, a moderate transient increase in transaminases has been reported.
Skin and subcutaneous tissue disorders:
Skin rash, puritis and urticaria have been reported. The incidence of rash is higher in patients suffering from infectious mononucleosis and acute or chronic leukaemia of lymphoid origin. 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. Reactions such as fever, arthralgia, and myalgia can develop more than 48 hours after the start of the treatment.
Erythema nodosum may occur rarely with flucloxacillin.
Potential for pemphigoid reactions to occur rarely with flucloxacillin.
There is potential for non-thrombocytopenic purpura to occur rarely with flucloxacillin.
Vasculitis may occur rarely with flucloxacillin.
Renal and urinary disorders
Interstitial nephritis may occur but it is reversible when treatment is discontinued.
Congenital, familial and genetic disorders:
Potential for acute attacks of porphyria to occur with flucloxacillin.
General disorders and administration site conditions:
Some patients with spirochaete infections such as syphilis or leptospirosis may experience a Jarisch-Herxheimer reaction shortly after treatment with a penicillin is started. Symptoms include fever, chills, headache and reaction at the site of lesions. The reaction can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy
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
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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Infections encountered in medical practice can involve mixed strains of bacteria and may include P-lactamase-producing strains. Co-fluampicil provides broad spectrum activity.
5.2 Pharmacokinetic properties
Co-fluampicil is excreted via the kidneys with a plasma half-life of approximately one hour.
5.3 Preclinical safety data
Not relevant
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsules. Magnesium Stearate:
Capsule Shells. Gelatin, Black Iron Oxide (E172), Titanium Dioxide (E171), Patent Blue V (E131), Quinoline Yellow (E104).
6.2 Incompatibilities
None known
6.3
Shelf life
Two years
6.4 Special precautions for storage
Do not store above 25°C Store in the original package
6.5 Nature and contents of container
Capsules: Standard polypropylene tube with a polythene closure or standard aluminium canisters or glass bottles fitted with a screw cap with a waxed pulpboard wad. Pack sizes of 20, 50, 100 or 500.
Aluminium foil pack. Pack size 12 capsules.
Aluminium/PVDC blister pack with aluminium overseal. Pack size 20, 28 and 100 capsules.
6.6 Instructions for use/handling
None
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0052
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
18th June 2007
10 DATE OF REVISION OF THE TEXT
10/03/2016