Magnapen 250mg/250mg Powder For Solution For Injection Or Infusion

PACKAGE LEAFLET INFORMATION FOR THE USER

Magnapen 250mg/250mg Powder for Solution for Injection or Infusion (Ampicillin and Flucloxacillin)

Read all of this leaflet carefully before you start using this medicine.

- Keep this leaflet. You may need to read it again.

- If you have further questions, please ask your doctor or nurse.

- This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours

The name of your medicine is Magnapen 250mg/250mg Powder for Solution for Injection or Infusion. In the rest of this leaflet it is called Magnapen Injection.

In this leaflet:

1. What Magnapen Injection is and what it is used for

2. Before you are given Magnapen Injection

3. How Magnapen Injection should be given

4. Possible side effects

5. How to store Magnapen Injection

6. Further information

1. WHAT MAGNAPEN INJECTION IS AND WHAT IT IS USED FOR

Magnapen Injection contains two active ingredients, ampicillin and flucloxacillin which together are known as co-fluampicil. Magnapen Injection is an antibiotic medicine. It belongs to the penicillin group of antibiotics and works by killing bacteria that cause infections.

Magnapen Injection is used to treat a wide range of infections caused by bacteria. These infections may affect the chest, ear, nose, throat, skin and soft tissues.

In hospital this medicine may also be used to prevent and treat infections:

• which occur after surgery

• in patients receiving treatment which affects the immune system

• of the blood (septicaemia)

• associated with difficulties in childbirth (septic abortion (abortion complicated by fever, often leading to sepsis) and puerperal fever (an infection of the membrane of the uterus following childbirth or abortion)).

2. BEFORE YOU ARE GIVEN MAGNAPEN INJECTION

Magnapen Injection should not be given if you:

• know that you are allergic to penicillin, cephalosporins, any other antibiotic or any of the ingredients contained in Magnapen Injection (see ‘What Magnapen Injection contains' in section 6)

• have ever had a skin rash or swelling of the face or neck when taking an antibiotic

• have ever had a serious complaint, such as liver problems, when taking an antibiotic.

If any of the above statements apply to you, you should not be given

Magnapen Injection.

1 NAME OF THE MEDICINAL PRODUCT

Magnapen® 250mg/250mg Powder for Solution for Injection or Infusion or Co-fluampicil 250mg/250mg Powder for Solution for Injection or Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Co-fluampicil 500mg Vials contain 250mg ampicillin as ampicillin sodium with 250mg flucloxacillin as flucloxacillin sodium (co-fluampicil 250/250).

3 PHARMACEUTICAL FORM

Powder for Solution for Injection or Infusion

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

Usual adult dosage (including elderly patients and children over ten years): Intramuscular/Intravenous: 500mg four times a day.

Usual children’s dosage:

Intramuscular/Intravenous: Under 2 years: quarter adult dose, four times a day. 2-10 years: half adult dose, four times a day.

The above dosages for adults and children may be doubled where necessary. Therapy may be continued for as long as it is indicated by the nature of infection.

Administration:

Intramuscular: Add 1.5ml Water for Injections to vial contents.

Intravenous: Dissolve 500mg in 10ml Water for Injections.

Administer by slow intravenous injection.

Co-fluampicil Injection may be added to infusion fluids or injected, suitably diluted into the drip tube over a period of 3-4 minutes.

4.3 Contra-indications

Co-fluampicil contains ampicillin and flucloxacillin which are penicillins, and should not be given to patients with a history of hypersensitivity to B-lactam antibiotics (e.g. penicillins, cephalosporins).

Co-fluampicil is contraindicated in patients with a history of flucloxacillin-associated jaundice/hepatic dysfunction.

Ocular administration.

4.4 Special warnings and precautions for use

Before initiating therapy with co-fluampicil careful enquiries should be made concerning previous hypersensitivity reactions to B-lactam antibiotics.

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 hypersensitivity to B-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).

Special caution is essential in the newborn because of the risk of hyperbilirubinemia. Studies have shown that, at high dose following parenteral administration, flucloxacillin can displace bilirubin from plasma protein

Speak to your doctor before being given Magnapen Injection if you:

• are being treated for kidney or liver problems

• have glandular fever

• are having blood tests because your medicine sometimes causes short-term changes in your blood cell counts.

• have syphilis or leptospirosis

Additional monitoring of kidney and liver function is recommended for patients on prolonged treatment e.g. osteomyelitis (bone infection) or endocarditis (infection of the muscle around the heart).

If any of the above apply your doctor may decide to change the dose of Magnapen Injection or prescribe a different medicine.

Taking other medicines

Taking another medicine while you are receiving treatment with Magnapen Injection can affect how it or the other medicine works. Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those you may have bought yourself without a prescription.

Tell your doctor if you are using the following medicines (or any other medicines):

• a contraceptive pill as you will need to take extra precautions such as use of a condom

• probenecid and allopurinol, used in the treatment of gout

• or if you are being treated with any other antibiotic (e.g. penicillins-including ampicillin, or bacteriostatic agents like chloramphenicol, erythromycins or tetracyclines)

• methotrexate, used to treat cancer, autoimmune diseases.

If you are required to have a urine test, please inform your doctor you are taking Magnapen. False positive results can occur with certain tests for sugar in the urine (e.g. the Fehling's test), tests that look for antibodies,

(e.g Coomb's test) or test for protein in the urine (e.g. Copper Sulphate test) whilst taking Magnapen.

If you have any doubts about whether you should take this medicine then discuss matters with your doctor before taking it.

Pregnancy and breast-feeding

You should let your doctor know if you are pregnant, think you might be pregnant or are breast-feeding before being given this medicine. Your doctor will decide if this medicine is suitable for you.

Important information about the sodium content of Magnapen Injection

This medicinal product contains 29.9mg (1.3mmol) of sodium per dose.

To be taken into consideration by patients on a controlled sodium diet.

3. HOW MAGNAPEN INJECTION SHOULD BE GIVEN

Your medicine will be made up before use and given to you by injection into the muscle (intramuscular) or injection into a vein (intravenous) or via a drip (infusion).

The dose of Magnapen Injection your doctor prescribes and the length of time for which you will be given it, will depend on your infection.

The usual dose for treating infection is:

The elderly, adults and children over 10 years

Intramuscular- 500mg four times a day Intravenous- 500mg four times a day

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binding sites, and may therefore predispose to kernicterus in a jaundiced baby. In addition, special caution is essential in the newborn because of the potential for high serum levels of flucloxacillin due to a reduced rate of renal excretion.

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. The intrathecal route should be avoided. 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 500mg vials contains 29.9mg (1.3 mmol) sodium per vial. 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 B-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

Convulsions may be associated with IV administration of high doses to patients with underlying renal failure.

Coma may develop with high doses of Flucloxacillin.

Children

Children two to 10 years receive half the adult dose.

Children under two years receive quarter of the adult dose.

If the infection is severe, your doctor may double these doses.

If you think you have received too much Magnapen Injection

If you think you have received too much Magnapen Injection contact your doctor or nurse immediately. Symptoms of an overdose include feeling sick, being sick and diarrhoea.

If you think you have missed a dose of Magnapen Injection

If you think you have missed a dose of Magnapen Injection, speak to your doctor or nurse.

4. POSSIBLE SIDE EFFECTS

Like many medicines Magnapen Injection may cause side effects in some patients, particularly when treatment is first started, although not everybody gets them.

Treatment with Magnapen Injection should be stopped and medical attention sought immediately if you:

• get severe diarrhoea with bleeding or stomach pain

• notice your urine becoming darker or your faeces becoming paler

• notice your skin or whites of your eyes turning yellow

• notice red or purple discolourations on the skin

• notice that your face is swollen and you have breathing problems

• start to itch or get a rash

• notice blistering of the skin, mouth, eyes or genitals

• notice increased bleeding/bruising, pale skin or weakness (due to changes in the levels of certain blood cells)

• develop nephritis (inflammation ofthe kidneys that can cause swollen ankles or high blood pressure)

• develop a fever

• have porphyria (rare hereditary disease where the blood pigment haemoglobin is abnormally metabolised) as there is a potential of acute attacks

• notice red lumps on both lower legs

• develop pain in your joints

• notice your lymph nodes become enlarged

• notice that you are tired and have shortness of breath

• have blood in your urine

• develop muscle weakness and fatigue

• start to hallucinate

Frequent side effects which are usually mild include:

• nausea (feeling sick)

• vomiting (being sick)

• diarrhoea.

Other side effects

• coma (if you are on very high doses)

• difficulty breathing

If you have Syphilis:

Patients who have syphilis have occasionally suffered from a type of reaction (Jarisch-Herxheimer reaction) shortly after treatment, with fever, chills, headache and reactions at the site of lesions.

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.

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

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

Co-fluampicil is indicated for the treatment of severe infections where the causative organism is unknown, and for mixed infections involving fl-lactamase-producing staphylococci.

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

None

6.2 Incompatibilities

Co-fluampicil should not be mixed with blood products or other proteinaceous fluids (e.g. protein hydrolysates) or with intravenous lipid emulsions.

If co-fluampicil is prescribed concurrently with an aminoglycoside, the antibiotics should not be mixed in the syringe, intravenous fluid container or giving set because of loss of activity of the aminoglycoside can occur under these conditions.

Some of these reactions can be delayed for several weeks after finishing the treatment.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme www.mhra.gov.uk/ yellowcard

By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE MAGNAPEN INJECTION

Keep out of the sight and reach of children.

Do not take the medicine after the expiry date printed on the label.

The expiry date refers to the last day of that month.

Do not store above 25°C. Store in a dry place.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What Magnapen Injection contains

Magnapen Injection contains two active ingredients, ampicillin and flucloxacillin which together are known as co-fluampicil.

Magnapen vials each contain 250 mg ampicillin as ampicillin sodium and 250 mg of flucloxacillin as flucloxacillin sodium (co-fluampicil 250mg/250mg).

The vials for injection contain no other ingredients.

Contents of the pack

The vials are available in packs of 10.

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: Wockhardt Ltd, Ash Road North, Wrexham, LL 13 9UF, UK.

Manufacturer: CP Pharmaceuticals Ltd, Ash Road North, Wrexham,

LL 13 9UF, UK.

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0800 198 5000 (UK Only)

Please be ready to give the following information:

Product Name	Reference
Magnapen 250mg/250mg powder for solution for injection or infusion	PL 29831/0054

This is a service provided by the Royal National Institute of Blind People

This leaflet was last revised 10/2015

107018/3 fwOCKHARDT

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The following drugs are incompatible with Magnapen® 250mg/250mg Powder for Solution for Injection or Infusion or Co-fluampicil 250mg/250mg Powder for Solution for Injection or Infusion:

Amikacin sulphate Amiodarone

Amphotericin B cholesteryl sulphate complex

Atropine Sulphate

Buprenorphine

Calcium gluconate

Chlorpromazine hydrochloride

Ciprofloxacin

Clarithromycin

Diazepam

Dobutamine Hydrochloride Dopamine hydrochloride Erythromycin lactobionate Gentamicin sulphate Heparin sodium Hydralazine hydrochloride Hydrocortisone sodium succinate Kanamycin sulphate Lincomycin hydrochloride Morphine Sulphate Metoclopramide hydrochloride Netilmicin Sulphate Ofloxacin Papaveretum Pethidine Hydrochloride Polymyxin B sulphate Prochlorperazine edisylate Prochlorperazine mesylate Promethazine Hydrochloride Sodium bicarbonate Tobramycin

Verapamil Hydrochloride

6.3 Shelf life

Three years.

6.4 Special precautions for storage

Co-fluampicil Vials for Injection should be stored in a dry place at, or below 25°C.

6.5 Nature and contents of container

5 or 10 ml glass vials fitted with butyl rubber disc and an aluminium seal.

Boxes of 10 vials with instructions for use.

6.6 Special precautions for disposal

Co-fluampicil solutions for injection should be used immediately. Co-fluampicil may be added to most intravenous fluids (e.g. Water for Injections, sodium chloride 0.9%, glucose 5%, sodium chloride 0.18% with glucose 4%).

In intravenous solutions containing glucose or other carbohydrates, co-fluampicil should be infused within two hours of preparation. Intravenous solutions of co-fluampicil in Water for Injections or sodium chloride 0.9% should be infused within 24 hours of preparation. Full particulars are given in the package enclosure leaflet. Preparation of co-fluampicil infusion solutions must be carried out under appropriate aseptic conditions if these extended storage periods are required.

7 MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 29831/0054

7. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

08 May 2000 / 18 June 2007

10 DATE OF REVISION OF THE TEXT 10/2015

107018/3 fmJCKHARDT