Consumer medicine information

FLAMAZINE CREAM

Silver sulfadiazine

BRAND INFORMATION

Brand name

Flamazine Cream

Active ingredient

Silver sulfadiazine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using FLAMAZINE CREAM.

What is in this leaflet ?

This leaflet answers some common questions about FLAMAZINE. It does not contain all of the available information.

It does not take the place of talking to your doctor (or pharmacist).

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you using FLAMAZINE against the benefits they expect it will have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What FLAMAZINE is used for

FLAMAZINE is a topical antibacterial cream with an active ingredient which belongs to the group of antibiotic medicines called sulfonamides.

FLAMAZINE is used to prevent infection in severe burns. Other types of wounds, such as pressure sores and leg ulcers, may also benefit from the application of FLAMAZINE cream.

  • It is soothing when applied and has proven activity against a broad range of organisms including both Gram-positive and Gram-negative bacteria and some viruses and fungi.

Your doctor may have prescribed FLAMAZINE for another reason.

Ask your doctor if you have any questions about why FLAMAZINE has been prescribed for you.

This medicine is available only with a doctor’s prescription (except for Pharmacy-Only 50g tube in NZ).

Before you use FLAMAZINE

When you must not use it

Do not use FLAMAZINE if:

you have an allergy to:

  • FLAMAZINE or any medicine within the Sulfonamide group or any of the ingredients in FLAMAZINE listed at the end of this leaflet.

Ask your doctor or pharmacist if you are not sure.

Do not give

FLAMAZINE to premature infants or newborn infants in the first months of life. Sulfonamides may cause a life-threatening condition known as “kernicterus” (jaundice of the brain) in babies during the first months of life by interfering with normal metabolism.

Tampering and expiry date warnings:

Do not use FLAMAZINE if the tube or jar has been opened or shows signs of tampering before your first application.

Do not use FLAMAZINE if the expiry date (EXP) printed on the tube or jar has passed.

If you use this medicine after the expiry date has passed, it may not work effectively.

Before you start to use it

Tell your doctor if:

  1. you have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.
  2. you are pregnant or intend to become pregnant
    FLAMAZINE should not be used during the last month of pregnancy. Your doctor will discuss the risks and benefits of using FLAMAZINE when pregnant.
  3. you are breast-feeding or intend to breast-feed
    Sulfonamides are excreted in the milk in small amounts and should be used with caution in breast-feeding mothers Your doctor will discuss the risks and benefits of using FLAMAZINE when breastfeeding.
    Do not apply FLAMAZINE to the breasts before breast feeding.
  4. you know you are glucose-6- phosphate deficient
  5. you have or have had any other medical conditions, including:
    - Low white blood cell count: A fall in white blood cell count has been demonstrated very occasionally, but it is not thought to be associated with the treatment. Nevertheless, regular blood counts are advisable if you are on long-term treatment.
    - Problems with your liver and / or kidney. FLAMAZINE should be used with caution in patients with poor liver or kidney function. Reaction to the cream can sometimes cause worsening in these areas but the incidence is lower than with other sulfonamides.

If you have not told your doctor about any of the above, tell them before you use any FLAMAZINE.

Using other medicines

Tell your doctor or pharmacist if you are using other creams, ointments or lotions or taking any medicine. This includes any that you buy without a prescription from a pharmacy, supermarket or health food shop.

How to use FLAMAZINE

How much to use

One jar or tube of FLAMAZINE should be reserved for one person. If you are using jars, discard any remaining cream 24 hours after opening the jar. If you are using tubes, discard the product 7 days after opening.

Follow all directions given to you by your doctor and pharmacist carefully.

These directions may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How to use it

FLAMAZINE should be applied by means of a sterile spatula or by hand, covered with a sterile glove, in a layer approximately 3-5 mm thick. One application at least every 24 hours is normally sufficient but the number of times a day to apply the cream will depend on your own individual needs. Where necessary reapply FLAMAZINE to any area where it has been removed during activity.

It is important to apply FLAMAZINE exactly as your doctor or pharmacist has told you. If you use it less often than you should, it may not work as well and your skin problem may not improve. Using it more often than you should may not improve your skin problem any faster and may cause or increase side effects.

Apply FLAMAZINE at about the same time every day.

How long to use it

Treatment is continued until healing is progressing satisfactorily or the burn site is ready for skin grafting.

Your doctor or pharmacist will tell you how long to keep applying FLAMAZINE cream.

Do not use FLAMAZINE for longer than your doctor tells you.

If you use FLAMAZINE for longer than your doctor or pharmacist tells you, the chance of side effects may increase.

If you are not sure how long to use FLAMAZINE, talk to your doctor.

If you swallow it

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26 in Australia / 0800 POISON or 0800 764 766 in NZ), or go to casualty at your nearest hospital, if you think that you or anyone else may have swallowed FLAMAZINE. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep these telephone numbers handy.

While you are using FLAMAZINE

Things you must do

Tell all doctors and pharmacists who are treating you that you are using FLAMAZINE.

If you feel that FLAMAZINE is not helping your condition, tell your doctor (or pharmacist).

Tell your doctor if, for any reason, you have not used FLAMAZINE exactly as prescribed.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

If you become pregnant while using FLAMAZINE, tell your doctor.

Things you must not do

Do not use FLAMAZINE in or near the eyes.

Do not give FLAMAZINE to anyone else, even if they have similar problems to yours.

Things to be careful of

Do not use large amounts of FLAMAZINE for a long time.

If you use large amounts for a long time, the chance of absorption through the skin and the chance of side effects increases.

Ask your doctor or pharmacist if you are concerned about the length of time you have been using FLAMAZINE.

Side effects

Tell your doctor or pharmacist if you do not feel well while you are using FLAMAZINE.

FLAMAZINE helps most people with skin problems but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • Nausea, vomiting and diarrhoea
  • Skin rash, increasing pain, burning or itching.

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • Red, raised bumps on the face and scalp (lupus erythematosus)
  • Problems with urine volume or colour (Renal or hepatic toxicity)
  • Heart pain (myocarditis),
  • Severe abdominal pain (pancreatitis)
  • Inflammation of the blood vessels causing nodular swellings along length of vessel (vasculitis, including polyarteritis nodosa).
  • Allergy-type reactions such as blistering or angry red rash.
  • Skin discolouration.

These are serious side effects. You may need urgent medical attention.

Serious side effects are rare.

Other side effects not listed above may also occur in some patients.

Tell your doctor if you notice anything else that is making you feel unwell.

Ask your doctor or pharmacist if you don’t understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using FLAMAZINE

Storage

Keep FLAMAZINE in a cool dry place away from light where the temperature stays below 25°C.

Refrigeration is not normally needed but in temperatures in excess of 30°C some form of cooling is desirable. Do not store FLAMAZINE or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills.

Keep FLAMAZINE where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using FLAMAZINE or it has passed its expiry date, ask your pharmacist what to do with any that is left over.

Product description

What it looks like

FLAMAZINE is a sterile white cream. The cream is a semisolid oil in water emulsion.

Ingredients

Active ingredients:
Silver Sulfadiazine 1% (10 mg/g).

Inactive ingredients:
Propylene Glycol, Polysorbate 60, Polysorbate 80, Cetyl Alcohol, Glyceryl Monostearate, Paraffin Liquid and Purified Water.

Supplier

FLAMAZINE is supplied in Australia by:
Smith & Nephew Pty. Ltd.
315 Ferntree Gully Road
Mount Waverley, VIC. 3149
Phone: 03 8540 6777
Fax: 03 9544 5086

FLAMAZINE 50g Tube (AUST R 159342)
FLAMAZINE 500g Jar (AUST R 159338)

FLAMAZINE is supplied in New Zealand by:
Smith & Nephew Ltd.
621 Rosebank Road, Avondale,
Auckland 1026
Phone: 09 828 4059
Fax: 09 820 2868

FLAMAZINE 50g Tube
FLAMAZINE 500g Jar

Prepared June 2010

™Trademark of Smith & Nephew

BRAND INFORMATION

Brand name

Flamazine Cream

Active ingredient

Silver sulfadiazine

Schedule

S4

 

1 Name of Medicine

Silver sulfadiazine.

2 Qualitative and Quantitative Composition

Composition.

Active ingredient.

Silver sulfadiazine 1.0% w/w.

Excipients.

Polysorbate 60 Ph. Eur, Polysorbate 80 Ph. Eur, Glyceryl Monostearate Ph. Eur, Cetyl Alcohol Ph. Eur, Liquid Paraffin Ph. Eur, Propylene Glycol Ph. Eur and Purified Water Ph. Eur.

Description.

A sterile white hydrophilic cream containing silver sulfadiazine 1%. The cream is a semisolid oil-in-water emulsion. The silver sulfadiazine is in a fine micronised form.

3 Pharmaceutical Form

Cream. White to off-white.

4 Clinical Particulars

4.1 Therapeutic Indications

Flamazine cream is indicated for the prevention of infection in severe burns. Other types of wounds, such as pressure sores and leg ulcers, may also benefit from the application of Flamazine cream.

4.2 Dose and Method of Administration

Method of administration.

To be applied topically.

Burns.

The burn wound should be cleaned and Flamazine cream applied over all the affected areas to a depth of 3-5 mm.
This application is best achieved with a sterile gloved hand and/or sterile spatula.
Where necessary, the cream should be reapplied to any area from which it has been removed by patient activity.
In burns, Flamazine cream should be reapplied at least every 24 hours, or more frequently if the volume of exudate is large.

Hand burns.

Flamazine cream can be applied to the burn and the whole hand enclosed in a clear plastic bag or glove which is then closed at the wrist. The patient should be encouraged to move the hand and fingers. The dressing should be changed when an excessive amount of exudate has accumulated in the bag.

Leg ulcers/ pressure sores.

The cavity of the ulcer should be filled with Flamazine cream to a depth of at least 3-5 mm. As Flamazine cream can cause maceration of normal skin on prolonged contact, care should be taken to prevent spread onto nonulcerated areas.
Application of Flamazine cream should be followed by an absorbent pad or gauze dressing, with further application of pressure bandaging as appropriate for the ulcer.
The dressings should normally be changed daily but for wounds which are less exudative, less frequent changes (every 48 hours) may be acceptable. Cleansing and debriding should be performed before application of Flamazine cream.
Flamazine cream is not recommended for use in leg or pressure ulcers that are very exudative.

Fingertip injuries.

Haemostasis of the injury should be achieved prior to the application of a 3-5 mm layer of Flamazine cream. A conventional finger dressing may be used. Alternatively the finger of a plastic or unsterile surgical glove can be used and fixed in place with waterproof adhesive tape. Dressings should be changed every 2-3 days.

4.3 Contraindications

As sulfonamides are known to cause kernicterus, Flamazine cream should not be used at, or near term pregnancy, on premature infants or on newborn infants during the first months of life. Flamazine cream is also contraindicated in patients known to be hypersensitive to silver sulfadiazine or to other components of the preparation such as cetyl alcohol or propylene glycol.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Transient leucopenia has occurred although its association with application of Flamazine has not been confirmed. Nevertheless, regular blood counts are advisable in patients on long-term treatment.
Patients should be watched carefully for sensitivity, especially if there are known reactions to sulfonamides.
Local reactions have been reported in patients treated with silver sulfadiazine; the separation of the eschar may be delayed and fungal invasion of the wound may occur.
In patients with extensive burns, serum sulfonamide concentrations and renal function should be monitored and urine examined for sulfonamide crystals. Absorption of propylene glycol contained in the cream can affect serum osmolality which can interfere with some laboratory tests.
The use of Flamazine cream in some cases of glucose-6-phosphate dehydrogenase deficient patients may be hazardous as haemolysis may occur.
During treatment of burns over a large body area, significant amounts of silver sulfadiazine are systemically absorbed. Therefore, it is possible that any adverse reactions associated with sulfonamides may occur.

Use in hepatic impairment/renal impairment.

Flamazine should be use with caution in patients with impaired renal or hepatic function. Sensitivity has been shown to occur but the incidence is lower than with other sulfonamides.

Use in the elderly.

Of the total number of subjects in clinical studies of silver sulfadiazine cream, seven percent were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Paediatric use.

Flamazine should not be used in premature infants or in newborn infants in the first months of life (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Effects on laboratory tests.

In the treatment of burn wounds involving extensive areas of the body, the serum sulfonamide derivative concentrations may approach adult therapeutic levels (8 mg% to 12 mg%). Therefore, in these patients it would be advisable to monitor serum sulfonamide concentrations. Renal function should be carefully monitored and the urine should be checked for sulfonamide crystals. Absorption of the propylene glycol vehicle has been reported to affect serum osmolality, which may affect the interpretation of laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

As silver may inactivate enzymatic debriding agents, their concomitant use may be inappropriate.
In large area burns where serum sulfadiazine levels may approach therapeutic levels, it should be noted that the effects of systemically administered drugs may be altered.
This can especially apply to oral hypoglycaemic agents and to phenytoin. In the case of these drugs, it is recommended that blood levels should be monitored as their effects can be potentiated.

Cimetidine.

In patients with large area burns, it has been reported that coadministration of cimetidine may increase the incidence of leukopenia.
Sulfonamide may alter the effect of oral anticoagulants, methotrexate, and cyclosporine. There are isolated reports that sulfonamide may also interfere with the effectiveness of hormonal contraceptive.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data were available from studies in animals following topical administration of silver sulfadiazine. No treatment related effects on male or female fertility were documented following subcutaneous administration of silver sulfadiazine to rats at doses up to 500 mg/kg/day for two (females) or ten (males) weeks prior to mating.
(Category C)
Sulfonamides may cause kernicterus in babies during the first month of life by displacing bilirubin from plasma albumin. Sulfonamides should therefore be avoided as far as possible during the last month of pregnancy. Fetal findings (abdominal hernia and laevorotation of the heart) occurred in low incidence in rats at subcutaneous doses of ≥ 250 mg/kg/day during early embryonic development and organogenesis. The significance of these findings for clinical topical administration is unknown.
Flamazine should be used with caution in breastfeeding mothers. Systemically, sulfadiazine can be excreted in breast milk although at concentrations 15-35% of those found in serum.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Blood and lymphatic tissue disorders.

Common: leukopenia.
Leukopenia has been reported in 3-5% of burns patients treated with Flamazine. This may be a drug related effect, and often manifests itself 2-3 days after treatment has commenced. It is usually self limiting and therapy with Flamazine cream does not usually need to be discontinued, although the blood count must be monitored to ensure that it returns to normal within a few days.

General disorders and administration site conditions.

Common: application site burning.

Renal and urinary disorders.

Very rare: renal failure.

Skin and subcutaneous tissue disorders.

Common: pruritus.
Common: application site rash (including eczema and contact dermatitis).
Rare: argyria.
There is evidence that in large area wounds and/or after prolonged application, systemic absorption of silver can occur causing clinical argyria.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Not likely to occur with normal usage.
In extensively burned patients or in patients suspected of showing symptoms of excessive absorption, it is important to optimally maintain fluid balance, not only to prevent dehydration but also to avoid the possibility of renal failure.
If renal function is normal, fluids should be administered to maintain high urine output and assist in the rapid elimination of the drug.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Silver sulfadiazine is a sulfonamide and has broad antimicrobial activity against both Gram positive and Gram negative organisms.
Silver sulfadiazine acts on the cell membrane and cell wall. Unlike sulfadiazine or other sulfonamides, the antibacterial action of the silver salt of sulfadiazine does not appear to depend on inhibition of folic acid synthesis. Its action is not antagonised by p-aminobenzoic acid.
Silver sulfadiazine has broad antimicrobial activity against both Gram positive and Gram negative organisms including Pseudomonas aeruginosa, some yeasts and fungi. It has also been reported to be active in vitro against herpes virus and Treponema pallidum. Sulfonamides act by interfering with the synthesis of nucleic acids in sensitive micro-organisms by blocking the conversion of p-aminobenzoic acid to the coenzyme dihydrofolic acid. Silver sulfadiazine has a bactericidal action; in contrast to sulfadiazine, the silver salt acts primarily on the cell membrane and cell wall and its action is not antagonised by p-aminobenzoic acid. Resistance to silver sulfadiazine has been reported and may develop during therapy.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Silver sulfadiazine is slowly metabolised in contact with wound exudates. Up to about 10% of the sulfadiazine may be absorbed; concentrations in blood of 10 to 20 microgram/mL have been reported although higher concentrations may be achieved when extensive areas of the body are treated. Some silver may be absorbed.
There is evidence that in large area wounds and/or after prolonged application, systemic absorption of silver can occur causing clinical argyria. The sulfadiazine readily diffuses across wounds and enters the general circulation. The degree of uptake will significantly depend upon the nature of the wound and the dosing regime. Sulfadiazine is excreted in the urine.

5.3 Preclinical Safety Data

Genotoxicity.

Silver sulfadiazine was not genotoxic in an in vitro bacterial reverse mutation assay or an in vivo mouse micronucleus test (PO administration), although the doses administered were considered low.

Carcinogenicity.

Long-term carcinogenicity studies of silver sulfadiazine have not been conducted. Silver sulfadiazine is well established in clinical practice in several countries over a number of decades without any grounds for suspicion of carcinogenic potential in humans.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Flamazine should be stored below 25°C. Protect from light. The contents of one container are for the treatment of one person. 250 g and 500 g jars should be discarded 24 hours after opening. Tubes of Flamazine should be discarded 7 days after opening.

6.5 Nature and Contents of Container

Cream: AUST R 159342.
20 g*, 50 g or 80 g* pre-printed cylindrical polyethylene tubes fitted with polypropylene caps.
Cream: AUST R 159338.
250 g* or 500 g black polypropylene jar fitted with a black polyethylene or polypropylene lid. All tubes and jars are tamper-evident. * Pack sizes not marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Silver sulfadiazine is a white or creamy white, odourless or almost odourless crystalline powder, which becomes yellow on exposure to light. Practically insoluble in water; slightly soluble in acetone; practically insoluble in alcohol, chloroform or ether; freely soluble in strong ammonia solution.

Chemical structure.


Chemical name: silver salt of N'-(pyrimidin-2-yl) sulfanilamide. C10H9AgN4O2S. M.W.: 357.1.

CAS number.

22199-08-2.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes