Formoterol Easyhaler 12 micrograms per actuation inhalation powder (Orion Pharma (UK) Limited)

1. Name Of The Medicinal Product

Formoterol Easyhaler® 12 micrograms per actuation Inhalation Powder

2. Qualitative And Quantitative Composition

One metered dose contains 12 micrograms of formoterol fumarate dihydrate.

With the Easyhaler device the delivered dose (ex-actuator) contains the same quantity of active substance as the metered dose (ex-reservoir).

For excipients, see Section 6.1.

3. Pharmaceutical Form

Inhalation powder.

White to yellowish white powder.

4. Clinical Particulars

4.1 Therapeutic Indications

Formoterol Easyhaler 12 micrograms per actuation Inhalation Powder is indicated for use in the treatment of asthma in patients treated with inhaled corticosteroids and who also require a long-acting beta2-agonist in accordance with current treatment guidelines.

Formoterol Easyhaler 12 micrograms per actuation Inhalation Powder is indicated also for the relief of reversible airways obstruction in patients with chronic obstructive pulmonary disease (COPD) and requiring long-term bronchodilator therapy.

4.2 Posology And Method Of Administration

For inhalation use.

ADULTS (INCLUDING THE ELDERLY) AND ADOLESCENTS

Asthma

Regular maintenance therapy:

1 inhalation (12 micrograms) to be inhaled twice daily. For more severe disease this dose regimen can be increased to 2 inhalations (24 micrograms) to be inhaled twice daily.

The maximum daily dose is 4 inhalations (2 inhalations inhaled twice daily).

Chronic Obstructive Pulmonary Disease

Regular maintenance therapy:

1 inhalation (12 micrograms) to be inhaled twice daily.

The maximum daily dose is 2 inhalations (1 inhalation inhaled twice daily).

CHILDREN 6 YEARS AND OLDER

Asthma

Regular maintenance therapy:

1 inhalation (12 micrograms) to be inhaled twice daily. For more severe disease this dose regimen can be increased to 2 inhalations (24 micrograms) to be inhaled twice daily but only after assessment by a physician.

The maximum daily dose is 4 inhalations (2 inhalations inhaled twice daily).

Chronic Obstructive Pulmonary Disease

Not appropriate.

CHILDREN UNDER THE AGE OF 6 YEARS

Formoterol Easyhaler is not recommended for use in children under the age of 6 years.

Renal and hepatic impairment

There is no theoretical reason to suggest that Formoterol Easyhaler dosage requires adjustment in patients with renal or hepatic impairment, however no clinical data have been generated to support its use in these groups.

The duration of action of formoterol has been shown to last for about 12 hours. The treatment should always aim for the lowest effective dose.

Current asthma management guidelines recommend that long-acting inhaled beta2-agonists should be used for maintenance bronchodilator therapy. They further recommend that in the event of an acute attack, a short-acting beta2-agonist should be used.

In accordance with the current asthma management guidelines, long-acting beta2-agonists may be added to the treatment regimen in patients experiencing problems with high dose inhaled steroids. Patients should be advised not to stop or change their steroid therapy when treatment with formoterol is introduced.

If the symptoms persist or worsen, or if the recommended dose of Formoterol Easyhaler fails to control symptoms (maintain effective relief), this is usually an indication of a worsening of the underlying condition.

When transferring a patient to Formoterol Easyhaler from other inhalation devices, the treatment should be individualised. The previous active substance, dose regimen, and method of delivery should be considered.

Instructions for use and handling

Easyhaler is an inspiratory flow driven inhaler, which means that when the patient inhales through the mouthpiece, the substance will follow the inspired air into the airways.

Note: It is important to instruct the patient

- To carefully read the instructions for use in the patient information leaflet which is packed together with each inhaler.

- That it is recommended to keep the device in the protective cover after opening the laminate pouch to enhance the stability of the product during use and make the inhaler more tamper proof.

- To shake and actuate the device prior to each inhalation.

- To breathe in forcefully and deeply through the mouthpiece to ensure that an optimal dose is delivered to the lungs.

- Never to breathe out through the mouthpiece as this will result in a reduction in the delivered dose. Should this happen the patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.

- Never to actuate the device more than once without inhalation of the powder. Should this happen the patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.

- To always replace the dust cap and close the protective cover after use to prevent accidental actuation of the device (which could result in either overdosing or underdosing the patient when subsequently used).

- To clean the mouthpiece with a dry cloth at regular intervals. Water should never be used for cleaning because the powder is sensitive to moisture.

- To replace Formoterol Easyhaler when the counter reaches zero even though powder can still be observed within the device.

4.3 Contraindications

Hypersensitivity to formoterol fumarate dihydrate or to lactose monohydrate (which contains small amounts of milk proteins).

4.4 Special Warnings And Precautions For Use

Patients with asthma who require regular treatment with a beta2-agonist should also be receiving regular and appropriate doses of an inhaled anti-inflammatory drug (e.g. corticosteroids and/or in children sodium cromoglycate) or oral corticosteroids. Formoterol Easyhaler should only be used in patients requiring long-term regular bronchodilator therapy and not as an alternative to short-acting beta2-agonists in the event of an acute asthma attack.

When treatment with formoterol is prescribed, patients should be assessed in respect of the appropriateness of the anti-inflammatory therapy they are receiving. Patients should be instructed to continue taking anti-inflammatory therapy and told that the dose of anti-inflammatory therapy should remain unchanged following the introduction of formoterol, even when symptoms improve. If there is no improvement in symptoms or the number of doses of formoterol required to control symptoms increases, this usually indicates deterioration of the underlying condition and the patients should be told to contact their doctor in order that their asthma and its treatment can be reassessed.

Therapy should not be initiated during an exacerbation. In the event of an acute asthma attack, a short-acting beta2-agonist should be used.

Special care and supervision, with particular emphasis on dosage limits, is required in patients receiving Formoterol Easyhaler when the following conditions may exist:

Severe hypertension, severe heart failure, ischaemic heart disease, cardiac arrhythmias, especially third degree atrioventricular block, idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, thyrotoxicosis, phaeochromocytoma, aneurysm, known or suspected prolongation of the QT interval (QT> 0.44 sec.; see Section 4.5 Interaction with other medicinal products and other forms of interaction) and in patients treated with drugs affecting the QT interval. Formoterol itself may induce prolongation of QT interval.

Caution should be used when co-administering theophylline and formoterol in patients with pre-existing cardiac conditions.

Due to the hyperglycaemic effect of beta2-stimulants, additional blood glucose controls are recommended in diabetic patients.

Potentially serious hypokalaemia may result from beta2-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatment with other medicines, such as xanthine derivatives, steroids and diuretics (see Section 4.5 Interaction with other medicinal products and other forms of interaction). It is recommended that serum potassium levels are monitored in such situations.

As with other inhalation therapy there is a risk of paradoxical bronchospasm. If this occurs the patient will experience an immediate increase in wheezing and shortness of breath after dosing which should be treated straightaway with a fast-acting inhaled bronchodilator. Formoterol Easyhaler inhalation powder should be discontinued immediately, the patient should be assessed and, if necessary, alternative therapy instituted.

Formoterol Easyhaler contains approx. 8 mg of lactose per dose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No specific interaction studies have been carried out with Formoterol Easyhaler.

Drugs such as quinidine, disopyramide, procainamide, phenothiazines, antihistamines and tricyclic antidepressants may be associated with QT interval prolongation and an increased risk of ventricular arrhythmia (see Section 4.4 Special warnings and precautions for use). In addition, levodopa, levothyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2-agonists.

Concomitant administration of other sympathomimetic agents has the potential to produce additive effects both in respect of the desirable effects and the undesirable effects of Formoterol Easyhaler.

Formoterol may interact with monoamine oxidase inhibitors and should not be given to patients receiving treatment with monoamine oxidase inhibitors or for up to 14 days after their discontinuation.

There may be an increased risk of arrhythmias in patients undergoing concomitant treatment with tricyclic antidepressants.

Concomitant administration of formoterol and corticosteroids may increase the hyperglycaemic effect seen with these drugs.

Concomitant treatment with xanthine derivatives, steroids, or potassium-depleting diuretics may potentiate a possible hypokalaemic effect of beta2-agonists. Hypokalaemia may increase susceptibility to cardiac arrhythmias in patients treated with digitalis (see Section 4.4 Special warnings and precautions for use).

There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.

Beta-adrenergic blockers may weaken or antagonise the effect of Formoterol Easyhaler. Therefore Formoterol Easyhaler should not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons for their use.

4.6 Pregnancy And Lactation

Clinical experience with formoterol in pregnant women is limited. No teratogenic effects have been revealed in animal tests. However, until further experience is gained, Formoterol Easyhaler is not recommended for use during pregnancy (particularly at the end of pregnancy or during labour) unless there is no other (safer) established alternative. As with any medicine, use during pregnancy should only be considered if the expected benefit to the mother is greater than any risk to the foetus. The substance has been detected in the milk of lactating rats, but it is not known whether formoterol passes into human breast milk, therefore mothers using Formoterol Easyhaler should refrain from breast-feeding their infants.

4.7 Effects On Ability To Drive And Use Machines

Formoterol has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable Effects

Metabolism and nutrition disorders	Rare >1/10,000, <1/1,000)	Hypokalaemia
Very rare including isolated reports (<1/10,000)	Hyperglycaemia
Nervous system disorders	Common >1/100, <1/10)	Headache
Uncommon >1/1,000, <1/100)	Agitation, dizziness, anxiety, nervousness, insomnia
Cardiac disorders	Common >1/100, <1/10)	Palpitations
Uncommon >1/1,000, <1/100)	Tachycardia
Rare >1/10,000, <1/1,000)	Atrial fibrillation, supraventricular tachycardia, extrasystoles
Very rare including isolated reports (<1/10,000)	Angina pectoris, prolongation of QTc interval
Vascular disorders	Very rare including isolated reports (<1/10,000)	Variation in blood pressure
Respiratory, thoracic and mediastinal disorders	Rare >1/10,000, <1/1,000)	Aggravated bronchospasm, paradoxical bronchospasm (see Section 4.4 Special warnings and precautions for use), oropharyngeal irritation
Gastrointestinal disorders	Very rare including isolated reports (<1/10,000)	Taste disturbance, nausea
Musculoskeletal, connective tissue and bone disorders	Common >1/100, <1/10)	Tremor
Uncommon >1/1,000, <1/100)	Muscle cramps, myalgia
General disorders and administration site conditions	Very rare including isolated reports (<1/10,000)	Hypersensitivity reactions such as severe hypotension, urticaria, angioedema, pruritus, exanthema, peripheral oedema

Treatment with beta₂-agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.

Lactose monohydrate contains small amounts of milk proteins and can therefore cause allergic reactions.

4.9 Overdose

Symptoms:

There is no clinical experience to date on the management of overdose, however, an overdosage of Formoterol Easyhaler would be likely to lead to effects that are typical of beta2-adrenergic agonists: nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalaemia, hyperglycaemia.

Treatment:

Supportive and symptomatic treatment is indicated. Serious cases should be hospitalised.

Use of cardioselective beta-blockers may be considered, but only subject to extreme caution since the use of beta-adrenergic blocker medication may provoke bronchospasm.

Serum potassium should be monitored.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Selective beta2-adrenoreceptor agonists.

ATC code: R03AC13.

Formoterol is a potent selective beta2-adrenergic stimulant. It exerts a bronchodilator effect in patients with reversible airways obstruction. The effect sets in rapidly (within 1−3 minutes) and is still significant 12 hours after inhalation.

In man, formoterol has been shown to be effective in preventing bronchospasm induced by exercise and methacholine.

Formoterol has been studied in the treatment of conditions associated with COPD, and has been shown to improve symptoms and pulmonary function. Formoterol acts on the reversible component of the disease.

5.2 Pharmacokinetic Properties

Absorption:

As reported for other inhaled drugs, it is likely that about 80% of formoterol administered from the Easyhaler inhaler will be swallowed and then absorbed from the gastrointestinal tract. This means that the pharmacokinetic characteristics of the oral formulation largely apply also to the inhalation powder. Following inhalation of therapeutic doses, formoterol cannot be detected in the plasma using current analytical methods.

Absorption is both rapid and extensive: At a higher than therapeutic dose (120 micrograms), the peak plasma concentration is observed at 5 minutes post inhalation whilst at least 65% of a radio-labelled 80 micrograms oral dose is absorbed, and oral doses of up to 300 micrograms are readily absorbed with the peak concentrations of unchanged formoterol at 0.5−1 hour. In COPD patients treated for 12 weeks with formoterol fumarate 12 or 24 micrograms b.i.d. the plasma concentrations of formoterol ranged between 11.5 and 25.7 pmol/L and 23.3 and 50.3 pmol/L respectively at 10 minutes, 2 hours and 6 hours post inhalation.

The pharmacokinetics of formoterol appear linear in the range of oral doses investigated, i.e. 20−300 micrograms. Repeated oral administration of 40−160 micrograms daily does not lead to significant accumulation of the drug. The maximum excretion rate after administration of 12−96 micrograms is reached within 1−2 hours of inhalation.

After 12 weeks administration of 12 micrograms or 24 micrograms formoterol powder b.i.d., the urinary excretion of unchanged formoterol increased by 63−73% in adult patients and by 18−84% in children, suggesting a modest and self-limiting accumulation of formoterol in plasma after repeated dosing.

Studies investigating the cumulative urinary excretion of formoterol and/or its (R,R) and (S,S)-enantiomers, after inhalation of dry powder (12−96 micrograms) or aerosol formulations (12-96 micrograms), showed that absorption increased linearly with the dose.

Distribution:

The plasma protein binding of formoterol is 61−64% (34% primarily to albumin). There is no saturation of binding sites in the concentration range reached with therapeutic doses.

Biotransformation:

Formoterol is eliminated primarily by metabolism, direct glucuronidation being the major pathway of biotransformation, with O-demethylation followed by further glucuronidation being another pathway. Multiple CYP450 isoenzymes (2D6, 2C19, 2C9, and 2A6) catalyze the transformation and so consequently the potential for metabolic drug-drug interaction is low. The kinetics of formoterol are similar after single and repeated administration, indicating no auto-induction or inhibition of metabolism.

Elimination:

Elimination of formoterol from the circulation seems to be polyphasic; the apparent half-life depends on the time interval considered. On the basis of plasma or blood concentrations up to 6, 8 or 12 hours after oral administration, an elimination half-life of about 2−3 hours was determined. From urinary excretion rates between 3 and 16 hours after inhalation, a half-life of about 5 hours was calculated.

After inhalation, plasma formoterol kinetics and urinary excretion rate data in healthy volunteers indicate a biphasic elimination, with the terminal elimination half-lives of the (R,R)- and (S,S)-enantiomers being 13.9 and 12.3 hours, respectively. Approximately 6.4−8% of the dose was recovered in the urine as unchanged formoterol, with the (R,R) and (S,S)-enantiomers contributing 40% and 60% respectively.

After a single oral dose of 3H-formoterol, 59−62% of the dose was recovered in the urine and 32−34% in the faeces. Renal clearance of formoterol is 150 ml/min.

In adult asthmatics, approximately 10% and 15−18% of the dose was recovered in the urine as unchanged and conjugated formoterol, respectively, after multiple doses of 12 and 24 micrograms. In children, approximately 6% and 6.5−9% of the dose was recovered in the urine as unchanged and conjugated formoterol, respectively, after multiple doses of 12 and 24 micrograms. As in healthy volunteers, the (R,R) and (S,S)-enantiomers contributed approximately 40% and 60% of unchanged drug excreted in the urine of adults, respectively, and there was no relative accumulation of one enantiomer over the other after repeated dosing.

5.3 Preclinical Safety Data

Preclinical data reveal no special hazard for humans in the therapeutic dose range based on conventional studies of repeated dose toxicity, genotoxicity, carcinogenicity, and reproduction toxicity. A somewhat reduced fertility in male rats was observed at high systemic exposure to formoterol. In rats and mice a slight increase in the incidence of uterine leiomyomas has been observed. This effect is looked upon as a class-effect observed in rodents after long exposure to high doses of beta2-receptor agonists.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose monohydrate

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

As packaged for sale: 2 years.

After first opening the laminate pouch: 4 months.

6.4 Special Precautions For Storage

After opening the pouch: Do not store above 30°C.

6.5 Nature And Contents Of Container

The multi-dose powder inhaler consists of seven plastic parts and a stainless steel spring. The plastic materials of the inhaler are: polybutylene terepthalate, low density polyethylene, polycarbonate, styrenebutadiene, polypropylene. The inhaler is sealed in a laminate pouch and packed with or without a protective cover in a cardboard box.

Packages:

Formoterol Easyhaler 12 micrograms per actuation inhalation powder:

• 120 actuations + protective cover

• 120 actuations

• 2 x 120 actuations

(Protective cover is available separately)

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Orion Corporation

Orionintie 1

FI-02200 Espoo

Finland

8. Marketing Authorisation Number(S)

PL 27925/0050

9. Date Of First Authorisation/Renewal Of The Authorisation

February 2007

10. Date Of Revision Of The Text

05 August 2009

Fucidin H Ointment

Fucidin H Ointment

sodium fusidate and hydrocortisone acetate

Please read all of this leaflet carefully before you start taking this medicine.

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


• If you have any further questions, ask your doctor or pharmacist.


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


• If any of the side effects become serious, or you notice any side effects not listed in this leaflet please tell your doctor or pharmacist.

In this leaflet:

• 1. What Fucidin H Ointment is and what it is used for


• 2. Before you use Fucidin H Ointment


• 3. How to use Fucidin H Ointment


• 4. Possible side effects


• 5. How to store Fucidin H Ointment


• 6. Further information

What Fucidin H Ointment Is And What It Is Used For

Fucidin H Ointment contains two different types of medicine. One medicine is called sodium fusidate. It is a type of antibiotic. The other medicine is called hydrocortisone acetate. It is a type of corticosteroid (steroid). These two medicines work at the same time in different ways.

Fucidin H Ointment works by:

• The antibiotic killing germs (bacteria) that cause infections.


• The corticosteroid reducing any swelling, redness or itchiness of your skin.

Fucidin H Ointment is used to treat:

• Conditions where the skin is inflamed (eczema or dermatitis) and also infected by germs (bacteria).

Before You Use Fucidin H Ointment

Do not use Fucidin H Ointment

• If you are allergic (hypersensitive) to fusidic acid, sodium fusidate or hydrocortisone acetate.


• If you are allergic (hypersensitive) to any of the other ingredients in your medicine. You can find a list of these ingredients in section 6 of this leaflet.


• To treat a skin condition called acne rosacea. This is redness and inflammation over your nose and cheeks. Ask your doctor if you are unsure.


• To treat a skin condition called perioral dermatitis. This is a red spotty rash around your mouth or chin.


• To treat skin conditions caused by tuberculosis or syphilis.


• To treat skin conditions caused only by bacteria, such as boils or spots.


• To treat a skin condition caused by a virus, such as cold sores or chickenpox.


• To treat a skin condition caused by a fungus, such as athlete’s foot.

Take special care with Fucidin H Ointment

• Take special care if you are going to use this medicine near your eyes or the eyes of a child.


• If you use the ointment over a long time or in large amounts it may make the chance of getting any side effects higher. Also your skin may get more sensitive to this medicine.


• You must not use the medicine for a long time on your face.


• Unless your doctor has told you to, you must not use Fucidin H Ointment on open wounds or sensitive areas such as the nostrils, ears, lips or genitals.


• Unless your doctor has told you to, you must not use Fucidin H Ointment on thin skin, skin ulcers, broken veins or acne.

Taking other medicines

Please tell your doctor or pharmacist if you are taking, or have recently taken any other medicines. This includes any medicines which you have bought without a prescription.

Pregnancy and breast-feeding

Please ask your doctor or pharmacist for advice before using Fucidin H Ointment:

• If you are pregnant, or think you are pregnant.
  You must not use your medicine for a long time or in large amounts. You must ask your doctor for advice.

• If you are breast-feeding.

Tell your doctor if you become pregnant while using this medicine.

Driving and using machines

Usually your medicine will have very little effect on your ability to drive or use machines. Check with your doctor if you feel any side effect that may stop you from driving or using machines.

Important information about some of the ingredients of Fucidin H Ointment

Fucidin H Ointment contains:

• Lanolin (wool fat). This may give you an itchy rash and inflammation on your skin where your medicine is used.


• Cetyl alcohol. This may give you an itchy rash and inflammation on your skin where your medicine is used.

Please ask your doctor if you are worried about any of the ingredients in this medicine.

How To Use Fucidin H Ointment

Always use Fucidin H Ointment exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

How to put on Fucidin H Ointment

This medicine is only for using on your skin or the skin of a child. Do not swallow it. Do not put it inside your body.

Remove the cap. Check the seal is not broken before you first use the ointment. Then push the spike in the cap through the seal on the tube.

Always wash your hands before using Fucidin H Ointment. Rub the medicine gently on the skin. If you use it on your face be careful to avoid your eyes.

Unless you are using the ointment to treat your hands, always wash your hands after using Fucidin H Ointment.

If you accidentally get any medicine in your eye, wash it out with cold water straight away. Then bathe your eye with eyewash if possible. Your eye may sting. If you start to have any problems with your sight or your eye is sore, contact your doctor immediately.

How much Fucidin H Ointment to use

Your doctor will tell you how much Fucidin H Ointment to use.

The usual treatment time is up to two weeks. Ask your doctor before using this medicine for any longer.

You should notice your skin improve after just a few days of using the ointment. If there is no improvement after 7 days you should stop using the ointment and go back to your doctor.

Usually, you should use this medicine twice each day. Use it in the morning and evening. To remind you to use the medicine it may help to use it when you do another regular action, such as brushing your teeth.

If you have been told to cover the skin with any dressings or bandages you may not need to use the medicine so often. A nappy on a baby may act as a dressing. Follow the advice of your doctor.

Adults and children:

Your doctor should tell you the dose that is right for you or the child. If your doctor has told you the amount of ointment to use then keep to this advice. If not, the following guide will help you to use the correct amount.

You can use your first (index) finger to measure how much Fucidin H Ointment to use. Squeeze the ointment along your finger from the tip to the first joint as shown in the diagram. This is called a fingertip unit.

The usual number of finger tip units you need to cover different parts of the body is shown in the diagrams. If you need to use a little more or a little less do not worry. If you are using the ointment on a child still use an adult finger to measure out the fingertip unit.

For an adult:

For application to the face and neck- 2 and a half fingertip units of cream.

For application to the back of the trunk- 7 fingertip units of cream.

For application to the front of the trunk- 7 fingertip units of cream.

For application to one arm (not including the hand)- 3 fingertip units of cream.

For application to both sides of one hand- 1 fingertip unit of cream.

For application to one leg (not including the foot)- 6 fingertip units of cream.

For application to one foot- 2 fingertip units of cream.

For a child under 11 years:

For a child aged three to six months:



For application to the face and neck- 1 fingertip unit of cream.

For application to one arm and hand- 1 fingertip unit of cream.

For application to one leg and foot- 1 and a half fingertip units of cream.

For application to the front of the trunk- 1 fingertip unit of cream.

For application to the back of the trunk, including the buttocks- 1 and a half fingertip units.

For a child aged one to two years:



For application to the face and neck- 1 and a half fingertip units of cream.

For application to one arm and hand- 1 and a half fingertip units of cream.

For application to one leg and foot- 2 fingertip units of cream.

For application to the front of the trunk- 2 fingertip units of cream.

For application to the back of the trunk, including the buttocks- 3 fingertip units.

For a child aged three to five years:



For application to the face and neck- 1 and a half fingertip units of cream.

For application to one arm and hand- 2 fingertip units of cream.

For application to one leg and foot- 3 fingertip units of cream.

For application to the front of the trunk- 3 fingertip units of cream.

For application to the back of the trunk, including the buttocks- 3 and a half fingertip units.

For a child aged six to ten years:



For application to the face and neck- 2 fingertip units of cream.

For application to one arm and hand- 2 and a half fingertip units of cream.

For application to one leg and foot- 4 and a half fingertip units of cream.

For application to the front of the trunk- 3 and a half fingertip units of cream.

For application to the back of the trunk, including the buttocks- 5 fingertip units.

If you forget to use Fucidin H Ointment

If you forget to use this medicine, use it as soon as you remember. Then next use this medicine at the usual time.

If you have any further questions about using this medicine, please ask your doctor or pharmacist.

Possible Side Effects

Like all medicines, Fucidin H Ointment can cause side effects, although not everybody gets them.

Important side effects to look out for:

You must get urgent medical help if you have any of the following symptoms. You may be having an allergic reaction:

• 
  You have difficulty breathing
  


• 
  Your face or throat swell
  


• 
  Your skin develops a severe rash.
  

Other possible side effects:

Any of the problems listed below are more likely if the medicine is used for a long time, in large amounts or on skin folds (such as armpits or under breasts).

These problems are more likely in babies and children. They are also more likely if the skin is covered with a dressing or bandage or nappy.

Skin problems

• Rash.


• Burning and stinging feeling.


• Skin irritation.


• Itching skin.


• Worsening of your eczema.


• Thinning of the skin.


• Small veins near the surface of the skin become visible.


• Stretch marks.


• Itchy rash and skin inflammation in the area where the medicine is used.


• Inflammation or swelling of the hair root (folliculitis).


• Changes in growth of your body hair.


• Red spotty rash around the mouth or chin.


• Lightening of your skin colour.


• Skin of the face may become puffy.

If any of the side effects become serious or you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

How To Store Fucidin H Ointment

• Keep out of the reach and the sight of children.


• Do not use Fucidin H Ointment after the expiry date on the carton. The expiry date is the last day of that month.

Medicines should not be thrown away in waste water or in household waste. Please ask your pharmacist how to throw away any medicine you do not need any more. If you do this you will help
protect the environment.

Further Information

What Fucidin H Ointment contains

• There are two active ingredients, sodium fusidate and hydrocortisone acetate.
  
  Fucidin H Ointment contains 2% sodium fusidate and 1% hydrocortisone.
  

• The other ingredients are cetyl alcohol, lanolin (wool fat), liquid paraffin and white soft paraffin.

You can find important information about some of the ingredients in your medicine near the end of section 2 of this leaflet.

What Fucidin H Ointment looks like and contents of the pack

Fucidin H Ointment is an off-white ointment.

Fucidin H Ointment comes in tubes of 30 g and 60 g.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

LEO Laboratories Limited

Princes Risborough

Bucks.

HP27 9RR

UK

Manufacturer:

LEO Laboratories Limited

Dublin 12

Ireland

This leaflet was last revised in March 2008.

Registered Trade Mark

LEO

017565 - 05

Fortum 2g and 3g Injection

1. Name Of The Medicinal Product

Fortum® for Injection

Ceftazidime (as pentahydrate) (INN) Injection

2. Qualitative And Quantitative Composition

Fortum for Injection: Vials contain 2g or 3g ceftazidime (as pentahydrate) with sodium carbonate (118mg per gram of ceftazidime).

Fortum Monovial in a vial containing 2g ceftazidime pentahydrate.

3. Pharmaceutical Form

Sterile Powder for constitution for Injection

4. Clinical Particulars

4.1 Therapeutic Indications

Single infections

Mixed infections caused by two or more susceptible organisms

Severe infections in general

Respiratory tract infections

Ear, nose and throat infections

Urinary tract infections

Skin and soft tissue infections

Gastrointestinal, biliary and abdominal infections

Bone and joint infections

Dialysis: infections associated with haemo - and peritoneal dialysis and with continuous ambulatory peritoneal dialysis (CAPD)

In meningitis it is recommended that the results of a sensitivity test are known before treatment with ceftazidime as a single agent. It may be used for infections caused by organisms resistant to other antibiotics including aminoglycosides and many cephalosporins. When appropriate, however, it may be used in combination with an aminoglycoside or other beta-lactam antibiotic for example, in the presence of severe neutropenia, or with an antibiotic active against anaerobes when the presence of bacteroides fragilis is suspected. In addition, ceftazidime is indicated in the perioperative prophylaxis of transurethral prostatectomy.

In vitro the activities of ceftazidime and aminoglycoside antibiotics in combination have been shown to be at least additive; there is evidence of synergy in some strains tested. This property may be important in the treatment of febrile neutropenic patients.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology And Method Of Administration

Ceftazidime is to be used by the parenteral route, the dosage depending upon the severity, sensitivity and type of infection and the age, weight and renal function of the patient.

Adults: The adult dosage range for ceftazidime is 1 to 6g per day 8 or 12 hourly (im or iv). In the majority of infections, 1g 8-hourly or 2g 12-hourly should be given. In urinary tract infections and in many less serious infections, 500mg or 1g 12-hourly is usually adequate. In very severe infections, especially immunocompromised patients, including those with neutropenia, 2g 8 or 12-hourly or 3g 12-hourly should be administered.

When used as a prophylactic agent in prostatic surgery 1g (from the 1g vial) should be given at the induction of anaesthesia. A second dose should be considered at the time of catheter removal.

Elderly: In view of the reduced clearance of ceftazidime in acutely ill elderly patients, the daily dosage should not normally exceed 3g, especially in those over 80 years of age.

Cystic fibrosis: In fibrocystic adults with normal renal function who have pseudomonal lung infections, high doses of 100 to 150mg/kg/day as three divided doses should be used. In adults with normal renal function 9g/day has been used.

Infants and children: The usual dosage range for children aged over two months is 30 to 100mg/kg/day, given as two or three divided doses.

Doses up to 150mg/kg/day (maximum 6g daily) in three divided doses may be given to infected immunocompromised or fibrocystic children or children with meningitis.

Neonates and children up to 2 months of age: Whilst clinical experience is limited, a dose of 25 to 60mg/kg/day given as two divided doses has proved to be effective. In the neonate the serum half-life of ceftazidime can be three to four times that in adults.

Dosage in impaired renal function: Ceftazidime is excreted by the kidneys almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function it is recommended that the dosage of ceftazidime should be reduced to compensate for its slower excretion, except in mild impairment, i.e. glomerular filtration rate (GFR) greater than 50ml/min. In patients with suspected renal insufficiency, an initial loading dose of 1g of ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dose.

Renal impairment: For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units, it is recommended that the dosage should be 1g daily in divided doses. For low-flux haemofiltration it is recommended that the dosage should be that suggested under impaired renal function.

Recommended maintenance doses are shown below:

RECOMMENDED MAINTENANCE DOSES OF CEFTAZIDIME IN RENAL INSUFFICIENCY

Creatinine clearance ml/min	Approx. serum creatinine* µmol/l(mg/dl)	Recommended unit dose of ceftazidime (g)	Frequency of dosing (hourly)
50-31	150-200 (1.7-2.3)	1	12
30-16	200-350 (2.3-4.0)	1	24
15-6	350-500 (4.0-5.6)	0.5	24
<5	>500 (>5.6)	0.5	48

* These values are guidelines and may not accurately predict renal function in all patients especially in the elderly in whom the serum creatinine concentration may overestimate renal function.

In patients with severe infections, especially in neutropenics, who would normally receive 6g of ceftazidime daily were it not for renal insufficiency, the unit dose given in the table above may be increased by 50% or the dosing frequency increased appropriately. In such patients it is recommended that ceftazidime serum levels should be monitored and trough levels should not exceed 40mg/litre.

When only serum creatinine is available, the following formula (Cockcroft's equation) may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:

Males:

Creatinine clearance =	Weight (kg) x (140 - age in years)
(ml/min)	72 x serum creatinine (mg/dl)

Females:

0.85 x above value.

To convert serum creatinine in µmol/litre into mg/dl divide by 88.4.

In children the creatinine clearance should be adjusted for body surface area or lean body mass and the dosing frequency reduced in cases of renal insufficiency as for adults.

The serum half-life of ceftazidime during haemodialysis ranges from 3 to 5 hours. The appropriate maintenance dose of ceftazidime should be repeated following each haemodialysis period.

Dosage in peritoneal dialysis: Ceftazidime may also be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD). As well as using ceftazidime intravenously, it can be incorporated into the dialysis fluid (usually 125 to 250mg for 2L of dialysis fluid).

Administration: Ceftazidime may be given intravenously or by deep intramuscular injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh.

4.3 Contraindications

Ceftazidime is contraindicated in patients with known hypersensitivity to cephalosporin antibiotics.

4.4 Special Warnings And Precautions For Use

Hypersensitivity reactions:

As with other beta-lactam antibiotics, before therapy with ceftazidime is instituted, careful inquiry should be made for a history of hypersensitivity reactions to ceftazidime, cephalosporins, penicillins or other drugs. Special care is indicated in patients who have experienced an allergic reaction to penicillins or beta-lactams. Ceftazidime should be given only with special caution to patients with type I or immediate hypersensitivity reactions to penicillin. If an allergic reaction to ceftazidime occurs, discontinue the drug. Serious hypersensitivity reactions may require adrenaline (epinephrine), hydrocortisone, antihistamine or other emergency measures.

Renal function:

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with nephrotoxic drugs, e.g. aminoglycoside antibiotics, or potent diuretics such as furosemide, as these combinations are suspected of affecting renal function adversely. Clinical experience with ceftazidime has shown that this is not likely to be a problem at the recommended dose levels. There is no evidence that ceftazidime adversely affects renal function at normal therapeutic doses: however, as for all antibiotics eliminated via the kidneys, it is necessary to reduce the dosage according to the degree of reduction in renal function to avoid the clinical consequences of elevated antibiotic levels, e.g. neurological sequelae, which have occasionally been reported when the dose has not been reduced appropriately (see 4.2 Dosage in Impaired Renal Function and 4.8 Undesirable Effects).

Overgrowth of non-susceptible organisms:

As with other broad spectrum antibiotics, prolonged use of ceftazidime may result in the overgrowth of non-susceptible organisms (e.g. Candida, Enterococci and Serratia spp) which may require interruption of treatment or adoption of appropriate measures. Repeated evaluation of the patient's condition is essential.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Ceftazidime does not interfere with enzyme-based tests for glycosuria. Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. Ceftazidime does not interfere in the alkaline picrate assay for creatinine. The development of a positive Coombs' test associated with the use of ceftazidime in about 5% of patients may interfere with the cross-matching of blood.

Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but if concurrent administration of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered.

In common with other antibiotics, ceftazidime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. Therefore, alternative non-hormonal methods of contraception are recommended.

4.6 Pregnancy And Lactation

There is no experimental evidence of embryopathic or teratogenic effects attributable to ceftazidime but, as with all drugs, it should be administered with caution during the early months of pregnancy and in early infancy. Use in pregnancy requires that the anticipated benefit be weighed against the possible risks.

Ceftazidime is excreted in human milk in low concentrations and consequently caution should be exercised when ceftazidime is administered to a nursing mother.

4.7 Effects On Ability To Drive And Use Machines

None reported.

4.8 Undesirable Effects

Data from large clinical trials (internal and published) were used to determine the frequency of very common to uncommon undesirable effects. The frequencies assigned to all other undesirable effects were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.

The following convention has been used for the classification of frequency:

very common

common

uncommon

rare

very rare <1/10,000.

Infections and infestations

Uncommon:

Candidiasis (including vaginitis and oral thrush).

Blood and lymphatic system disorders

Common:	Eosinophilia and thrombocytosis.
Uncommon:	Leucopenia, neutropenia, and thrombocytopenia,
Very Rare:	Lymphocytosis, haemolytic anaemia, and agranulocytosis.

Immune system disorders

Very Rare:

Anaphylaxis (including bronchospasm and/or hypotension).

Nervous system disorders

Uncommon:	Headache and dizziness
Very Rare:	Paraesthesia

There have been reports of neurological sequelae including tremor, myoclonia, convulsions, encephalopathy, and coma in patients with renal impairment in whom the dose of ceftazidime has not been appropriately reduced.

Vascular disorders

Common:

Phlebitis or thrombophlebitis with IV administration.

Gastrointestinal disorders

Common:	Diarrhoea
Uncommon:	Nausea, vomiting, abdominal pain, and colitis
Very Rare:	Bad taste

As with other cephalosporins, colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis.

Renal and urinary disorders

Very Rare:

Interstitial nephritis, acute renal failure

Hepatobiliary disorders

Common:	Transient elevations in one or more of the hepatic enzymes, ALT (SGPT), AST (SOGT), LDH, GGT and alkaline phosphatase.
Very Rare:	Jaundice.

Skin and subcutaneous tissue disorders

Common:	Maculopapular or urticarial rash
Uncommon:	Pruritus
Very Rare:	Angioedema, erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis.

General disorders and administration site conditions

Common:	Pain and/or inflammation after IM injection.
Uncommon:	Fever

Investigations

Common:	Positive Coombs test.
Uncommon:	As with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen and/or serum creatinine have been observed.

4.9 Overdose

Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma.

Serum levels of ceftazidime can be reduced by dialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC classification

Pharmacotherapeutic group: cephalosporins ATC code: J01DD02

Mode of action

Ceftazidime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.

Mechanism of Resistance

Ceftazidime is effectively stable to hydrolysis by most classes of beta-lactamases, including penicillinases and cephalosporinases but not extended spectrum beta-lactamases.

Bacterial resistance to ceftazidime may be due to one or more of the following mechanisms:

- hydrolysis by beta-lactamases. Ceftazidime may be efficiently hydrolysed by certain of the extended-spectrum beta-lactamases (ESBLs) including the SHV plasmid mediated ESBLs and by the chromosomally-encoded (AmpC) enzyme that may be induced or stably derepressed in certain aerobic gram-negative bacterial species

- reduced affinity of penicillin-binding proteins for ceftazidime

- outer membrane impermeability, which restricts access of ceftazidime to penicillin binding proteins in gram-negative organisms

- drug efflux pumps.

Breakpoints

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:

- Enterobacteriaceae: S =< 1 mg/l and R > 8 mg/l

- Pseudomonas aeruginosa: S =< 8 mg/l and R > 8 mg/l

Microbiological Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of ceftazidime in at least some types of infections is questionable.

Commonly Susceptible Species

Gram-positive aerobes: Methicillin-susceptible-staphylococci (including Staphylococcus aureus) Streptococcus pneumoniae Streptococcus pyogenes Streptococcus agalactiae

Gram-negative aerobes: Escherichia coli Proteus mirabilis Proteus spp (other) Providencia spp. Pseudomonas aeruginosa Pseudomonas spp. (other) Salmonella spp. Shigella spp Haemophilus influenzae (including ampicillin-resistant strains)

Species for which acquired resistance may be a problem

Gram-negative aerobes: Enterobacter aerogenes Enterobacter spp (other) Klebsiella pneumoniae Klebsiella spp (other) Serratia spp Morganella morganii

Gram-positive anaerobes: Peptococcus spp. Peptostreptococcus spp. Propionibacterium spp. Clostridium perfringens

Gram-negative anaerobes Fusobacterium spp.

Inherently resistant organisms

Gram-positive aerobes: Enterococci including Enterococcus faecalis and Enterococcus faecium Listeria spp Methicillin-resistant-staphylococci

Gram-negative aerobes: Acinetobacter spp Campylobacter spp

Gram-positive anaerobes: Clostridium difficile

Gram-negative anaerobes Bacteroides spp. (many strains of Bacteroides fragilis resistant).

Others: Chlamydia species Mycoplasma species Legionella species

5.2 Pharmacokinetic Properties

Ceftazidime administered by the parenteral route reaches high and prolonged serum levels in man. After intramuscular administration of 500mg and 1g serum mean peak levels of 18 and 37mg/litre respectively are rapidly achieved. Five minutes after an intravenous bolus injection of 500mg, 1g or 2g, serum mean levels are respectively 46, 87 and 170mg/litre.

Therapeutically effective concentrations are still found in the serum 8 to 12 hours after both intravenous and intramuscular administration. The serum half-life is about 1.8 hours in normal volunteers and about 2.2 hours in patients with apparently normal renal function. The serum protein binding of ceftazidime is low at about 10%.

Ceftazidime is not metabolised in the body and is excreted unchanged in the active form into the urine by glomerular filtration. Approximately 80 to 90% of the dose is recovered in the urine within 24 hours. Less than 1% is excreted via the bile, significantly limiting the amount entering the bowel.

Concentrations of ceftazidime in excess of the minimum inhibitory levels for common pathogens can be achieved in tissues such as bone, heart, bile, sputum, aqueous humour, synovial and pleural and peritoneal fluids. Transplacental transfer of the antibiotic readily occurs. Ceftazidime penetrates the intact blood brain barrier poorly and low levels are achieved in the csf in the absence of inflammation. Therapeutic levels of 4 to 20mg/litre or more are achieved in the csf when the meninges are inflamed.

5.3 Preclinical Safety Data

No additional data of relevance.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium carbonate (anhydrous sterile)

6.2 Incompatibilities

Ceftazidime is less stable in Sodium Bicarbonate Injection than other intravenous fluids. It is not recommended as a diluent.

Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe.

Precipitation has been reported when vancomycin has been added to ceftazidime in solution. It is recommended that giving sets and intravenous lines are flushed between administration of these two agents.

6.3 Shelf Life

Fortum Monovial - Two years for the unconstituted product and 24 hours for the constituted product when stored below 30°C and protected from light.

Three years when stored below 25°C and protected from light.

6.4 Special Precautions For Storage

The unconstituted product should be stored below 30°C and protected from light. Constituted solutions may be stored in the refrigerator (2 - 8°C) for up to 24 hours.

6.5 Nature And Contents Of Container

Individually cartoned vials containing 2g ceftazidime (as pentahydrate) for intravenous use in packs of 1 or 5.

Individually cartoned Monovials containing 2g (as pentahydrate) for intravenous infusion.

Individually cartoned vials containing 2g ceftazidime (as pentahydrate) for intravenous infusion in packs of 1 or 5.

Individually cartoned vials containing 3g ceftazidime (as pentahydrate) for intravenous and intravenous infusion use.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Instructions for constitution: See table for addition volumes and solution concentrations, which may be useful when fractional doses are required.

PREPARATION OF SOLUTION

Vial size		Amount of Diluent to be added (ml)	Approximate Concentration (mg/ml)
250mg 250mg	Intramuscular Intravenous	1.0 2.5	210 90
500mg 500mg	Intramuscular Intravenous	1.5 5.0	260 90
1g 1g	Intramuscular Intravenous	3.0 10.0	260 90
2g 2g	Intravenous bolus Intravenous Infusion	10.0 50.0*	170 40‡
3g 3g	Intravenous bolus Intravenous Infusion	15.0 75.0*	170 40‡

*Note: Addition should be in two stages.

‡Note: Use Sodium Chloride Injection 0.9%, Dextrose Injection 5% or other approved diluent (see pharmaceutical precautions) as Water for Injections produces hypotonic solutions at this concentration.

All sizes of vials as supplied are under reduced pressure. As the product dissolves, carbon dioxide is released and a positive pressure develops. For ease of use, it is recommended that the following techniques of reconstitution are adopted.

250mg i.m./i.v., 500mg i.m./i.v., 1g i.m./i.v., and 2g and 3g i.v. bolus vials:

1. Insert the syringe needle through the vial closure and inject the recommended volume of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.

2. Shake to dissolve: carbon dioxide is released and a clear solution will be obtained in about 1 to 2 minutes.

3. Invert the vial. With the syringe plunger fully depressed, insert the needle through the vial closure and withdraw the total volume of solution into the syringe (the pressure in the vial may aid withdrawal). Ensure that the needle remains within the solution and does not enter the head space. The withdrawn solution may contain small bubbles of carbon dioxide; they may be disregarded.

2g and 3g i.v. infusion vials:

This vial may be constituted for short intravenous infusion (e.g. up to 30 minutes) as follows (mini-bag or burette-type set):

Prepare using a total of 50ml (for 2g vials) and 75ml (for 3g vials) of compatible diluent, added in TWO stages as below:-

1. Insert the syringe needle through the vial closure and inject 10ml of diluent for 2g vial and 15ml for 3g vial. The vacuum may assist entry of the diluent. Remove the syringe needle.

2. Shake to dissolve: carbon dioxide is released and a clear solution obtained in about 1 to 2 minutes.

3. Do not insert a gas relief needle until the product has dissolved. Insert a gas relief needle through the vial closure to relieve the internal pressure.

4. Transfer the reconstituted solution to final delivery vehicle (e.g. mini-bag or burette-type set) making up a total volume of a least 50ml (75ml for the 3g vial), and administer by intravenous infusion over 15-30 minutes.

NOTE: To preserve product sterility, it is important that a gas relief needle is not inserted through the vial closure before the product has dissolved.

Fortum Monovial:

The contents of the Monovial are added to small volume infusion bags containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection, or another compatible fluid.

The 2g presentation must be constituted in not less than 100mL infusion bag.

1) Peel off the removable top part of the label and remove the cap.

2) Insert the needle of the Monovial into the additive port of the infusion bag.

3) To activate, push the plastic needle holder of the Monovial down onto the vial shoulder until a "click" is heard.

4) Holding it upright, fill the vial to approximately two-thirds capacity by squeezing the bag several times.

5) Shake the vial to reconstitute the Fortum.

6) On constitution, the Fortum will effervesce slightly.

7) With the vial uppermost, transfer the reconstituted Fortum into the infusion bag by squeezing and releasing the bag.

8) Repeat the steps 4 to 7 to rinse the inside of the vial. Dispose of the empty Monovial safely. Check that the powder is completely dissolved and that the bag has no leaks.

Fortum Monovial is for i.v. infusion only.

These solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids. Ceftazidime is compatible with the most commonly used intravenous fluids.

Vials of Fortum for Injection and Fortum Monovials as supplied are under reduced pressure; a positive pressure is produced on constitution due to the release of carbon dioxide.

Vials of Fortum for Injection should be stored at a temperature below 25°C.

Vials of Fortum for Injection do not contain any preservatives and should be used as single-dose preparations.

In keeping with good pharmaceutical practice, it is preferable to use freshly constituted solutions of Fortum for Injection. If this is not practicable, satisfactory potency is retained for 24 hours in the refrigerator (2 - 8°C) when prepared in Water for Injection BP or any of the injections listed below.

At ceftazidime concentrations between 1mg/ml and 40mg/ml in:

0.9% Sodium Chloride Injection BP

M/6 Sodium Lactate Injection BP

Compound Sodium Lactate Injection BP (Hartmann's Solution)

5% Dextrose Injection BP

0.225% Sodium Chloride and 5% Dextrose Injection BP

0.45% Sodium Chloride and 5% Dextrose Injection BP

0.9% Sodium Chloride and 5% Dextrose Injection BP

0.18% Sodium Chloride and 4% Dextrose Injection BP

10% Dextrose Injection BP

Dextran 40 Injection BP 10% in 0.9% Sodium Chloride Injection BP

Dextran 40 Injection BP 10% in 5% Dextrose Injection BP

Dextran 70 Injection BP 6% in 0.9% Sodium Chloride Injection BP

Dextran 70 Injection BP 6% in 5% Dextrose Injection BP

(Ceftazidime is less stable in Sodium Bicarbonate Injection than in other intravenous fluids. It is not recommended as a diluent)

At concentrations of between 0.05mg/ml and 0.25mg/ml in Intraperitoneal Dialysis Fluid (Lactate) BPC 1973.

When reconstituted for intramuscular use with: 0.5% or 1% Lidocaine Hydrochloride Injection BP

When admixed at 4mg/ml with (both components retain satisfactory potency):

Hydrocortisone (hydrocortisone sodium phosphate) 1mg/ml in 0.9% Sodium Chloride Injection BP or 5% Dextrose Injection BP

Cefuroxime (cefuroxime sodium) 3mg/ml in 0.9% Sodium Chloride Injection BP

Cloxacillin (cloxacillin sodium) 4mg/ml in 0.9% Sodium Chloride Injection BP

Heparin 10u/ml or 50u/ml in 0.9% Sodium Chloride Injection BP

Potassium Chloride 10mEq/L or 40 mEq/L in 0.9% Sodium Chloride Injection BP

Solutions range from light yellow to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations.

Administrative Data

7. Marketing Authorisation Holder

Glaxo Operations UK Ltd

Greenford

Middlesex

UB6 OHE

Trading as

GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex UB11 1BT

8. Marketing Authorisation Number(S)

PL 00004/0294

9. Date Of First Authorisation/Renewal Of The Authorisation

18 May 2001

10. Date Of Revision Of The Text

31^st July 2009

11. Legal Status

POM