Consumer medicine information

APOC-5FU Cream

Fluorouracil

BRAND INFORMATION

Brand name

APOC-5FU Cream

Active ingredient

Fluorouracil

Schedule

SUMMARY CMI

APOC-5FU CREAM

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using APOC-5FU?

APOC-5FU contains the active ingredient fluorouracil. APOC-5FU is used to treat solar keratoses, also known as actinic keratoses or sunspots and Bowen's disease (type of skin cancer).

For more information, see Section 1. Why am I using APOC-5FU? in the full CMI.

2. What should I know before I use APOC-5FU?

Do not use if you have ever had an allergic reaction to fluorouracil or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use APOC-5FU? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with APOC-5FU and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use APOC-5FU?

Carefully follow all directions given by your doctor or other healthcare professionals.

Apply APOC-5FU once or twice daily as advised by your doctor.

More instructions can be found in Section 4. How do I use APOC-5FU? in the full CMI.

5. What should I know while using APOC-5FU?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using APOC-5FU. Limit your exposure to sun during and immediately following treatment with APOC-5FU. Apply a broad-spectrum sunscreen every day before going outdoors, and regularly reapply during the day, except directly on the treatment area. If you become pregnant while using APOC-5FU stop using it and tell your doctor immediately.
Things you should not do	Do not let APOC-5FU come into contact with the eyes, eyelids, nostrils or mouth. APOC-5FU is highly irritating to skin and the eyes.
Looking after your medicine	Keep APOC-5FU in a cool dry place where the temperature stays below 25°C and protect from heat. Keep out of reach of children and pets.

For more information, see Section 5. What should I know while using APOC-5FU? in the full CMI.

6. Are there any side effects?

Common side effects include soreness and pain, itchiness or irritation, darkening or reddening of the skin, burning, crusting, increased sensitivity of the skin to the sun, rash, dermatitis, and scarring.

Serious side effects include stomach problems such as severe pain, cramps, bloody diarrhoea and vomiting, swelling and soreness of the mouth and tongue, fever and chills, or severe pain or ulceration at the site of application.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

APOC-5FU CREAM

Active ingredient: Fluorouracil

Consumer Medicine Information (CMI)

This leaflet provides important information about using APOC-5FU. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using APOC-5FU.

Where to find information in this leaflet:

1. Why am I using APOC-5FU?
2. What should I know before I use APOC-5FU?
3. What if I am taking other medicines?
4. How do I use APOC-5FU?
5. What should I know while using APOC-5FU?
6. Are there any side effects?
7. Product details

1. Why am I using APOC-5FU?

APOC-5FU contains the active ingredient fluorouracil.

APOC-5FU belongs to a group of anti-cancer medicines that are applied to the skin. It works by destroying precancerous and cancerous cells, while having little effect on normal cells.

APOC-5FU is used to treat the following skin conditions:

Solar keratoses, also known as actinic keratoses or sunspots.
Bowen's disease (type of skin cancer).

Solar keratoses are rough, red, scaly, or crusty spots on the skin that are caused by too much exposure to sunlight. They are more common on sun-exposed areas, such as the face, nose, ears, chest, forearms, and back of the hands.

Solar keratoses are usually harmless, but there is a small risk that they may eventually turn into skin cancer.

Bowen's disease causes one or more small patches of scaly red skin. It occurs when there is a growth of abnormal cells in the outer layer of skin. It is most commonly found on the lower leg.

2. What should I know before I use APOC-5FU?

Warnings

Do not use APOC-5FU if:

You are allergic to fluorouracil, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
You have a dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.

Check with your doctor if you:

Have any other medical conditions including inflammatory skin conditions such as darkening of skin during pregnancy (chloasma) or a chronic rash (rosacea).
Work outside for long periods of time during the day. Exposure to UV radiation from the sun or tanning salons may increase the intensity of skin reactions at the sites where APOC-5FU is applied.
Take any medicines for any other condition.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not use APOC-5FU if you are pregnant or intend to become pregnant. APOC-5FU may affect your developing baby if you use it during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Nursing mothers should avoid using APOC-5FU as it is not known if the active ingredient in APOC-5FU passes into breast milk, and if there is a possibility that your baby may be affected.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with APOC-5FU and affect how it works.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect APOC-5FU.

4. How do I use APOC-5FU?

How much to use

Apply APOC-5FU to the affected skin once or twice daily as advised by your doctor.

Follow the instructions below and use APOC-5FU until your doctor tells you to stop.

Wash the skin to be treated using lukewarm water. Avoid soap or other cleansing products which may sting or irritate your skin, especially as treatment progresses.
Pat dry the affected area with a soft white paper towel.
Allow 15 minutes for your skin to completely dry.
Using a non-metal applicator, cotton bud or a rubber glove apply a thin film of APOC-5FU, smoothing it gently onto your affected skin. Do not use too much cream.
Be very careful not to allow APOC-5FU to come into contact with mucous membranes, such as eyes, eyelids, nostrils and lips.
Do not apply APOC-5FU to broken skin or open cuts as it may be absorbed into the bloodstream and may cause side effects.
Wash your hands carefully and thoroughly immediately after using APOC-5FU.
Do not cover the treated area unless your doctor tells you to.
If your doctor asks you to apply a dressing after using APOC-5FU, apply a fresh dressing to the area(s) daily.
The total area of skin treated with APOC-5FU at any time should not exceed 500 sq cm (approx. 23 cm x 23 cm). Treat larger areas a section at a time

When to use APOC-5FU

Apply in the morning and then again in the late afternoon or early evening.
Do not apply APOC-5FU immediately before going to bed.
Apply APOC-5FU at least 1.5 - 2 hours before bedtime to enable complete absorption and prevent wiping off onto pillowcases and sheets. Contact with pillowcases or sheets may result in undesirable spreading of APOC-5FU to normal skin that does not need treatment.

How long to use APOC-5FU

Unless your doctor tells you to stop using APOC-5FU continue treatment up until the ulceration stage, usually 3 to 4 weeks.

The healing process is usually complete 1 to 2 months after the end of treatment. The healthy skin surrounding the treated area may occasionally become reddened but will soon resume its normal colour once treatment is stopped.

If you forget to use APOC-5FU

APOC-5FU should be used regularly at the same time each day.

If you miss your dose at the usual time and it is almost time for your next dose, skip the dose you missed and apply your next dose when you are meant to.

Do not try to make up the dose you missed by applying more the next time.

If you use too much APOC-5FU

If you think that you have used too much APOC-5FU, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using APOC-5FU?

What you should expect

Expect your appearance to look worse and to feel uncomfortable while treatment is in progress.

Sometimes it can take several weeks after treatment with APOC-5FU has stopped before you see any improvement in your condition.

When APOC-5FU is applied to the skin, the following usually happens:

Redness of the affected area occurs (generally within 3 to 5 days).
This is followed by blistering, peeling, and cracking (within 11 to 14 days) with occasional open sores and some discomfort.
The treated skin will then flake away.
Some redness of the skin will continue for some time after APOC-5FU is stopped. Scarring is not expected.

Things you should do

Limit your exposure to sun during and immediately following treatment with APOC-5FU.
This will help reduce the likelihood and severity of unwanted side effects.
Apply a broad-spectrum sunscreen (SPF 30 or higher) every day before going outdoors, and regularly reapply during the day, except directly on the treatment area.
APOC-5FU can make you more sensitive to sunlight. In addition to sunscreen, wear wide-brimmed hat, long sleeves, and trousers (or a long skirt) to protect your skin.

Call your doctor straight away if you:

Become pregnant while using APOC-5FU.

Remind any doctor, dentist or pharmacist you visit that you are using APOC-5FU.

Things you should not do

Do not let APOC-5FU come into contact with the eyes, eyelids, nostrils or mouth. APOC-5FU is highly irritating to sensitive skin and the eyes.

Do not allow pets to contact the APOC-5FU container or your skin where APOC-5FU has been applied.

Safely discard or clean any cloth or applicator that may retain APOC-5FU and avoid leaving any residues of APOC-5FU on your hands, clothing, carpeting or furniture. APOC-5FU may be fatal if ingested by pets.

Things to be careful of

While treatment is in progress follow these personal care tips:

Avoid using cosmetics or other topical medications, including sunscreens, directly on the treatment area, unless directed by your doctor.
Your treated skin is expected to become irritated and uncomfortable whilst using APOC-5FU. Applying other products directly on the treatment area may make your discomfort worse.
You may continue to shave whilst using APOC-5FU but take care not to cut your skin in the treatment area.
As facial skin becomes inflamed during APOC-5FU treatment shaving with a conventional razor may become unpleasant. You may prefer instead to lightly shave with an electric razor or clip the facial hair

Looking after your medicine

Store below 25°C. Protect from heat.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on window sills.

Keep it where young children and pets cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use APOC-5FU after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

During treatment with APOC-5FU expect to have a temporary unsightly appearance and discomfort at the sites where you apply the cream.

Less serious side effects

Less serious side effects	What to do
Soreness and pain Itchiness and irritation Darkening or reddening of the skin Burning Crusting Increased sensitivity of the skin to the sun Rash Dermatitis Scarring.	Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects	What to do
Stomach problems such as severe pain, cramps, bloody diarrhoea and vomiting Swelling and soreness of the mouth and tongue Fever and chills.	Discontinue APOC-5FU immediately and call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What APOC-5FU contains

Active ingredient (main ingredient)	5% w/w (50mg/g) of fluorouracil
Other ingredients (inactive ingredients)	Methyl hydroxybenzoate White soft paraffin Polysorbate 60 Propyl hydroxybenzoate Propylene glycol Stearyl alcohol Purified water
Potential allergens	Hydroxybenzoates.

This medicine does not contain gluten, lactose, sucrose, tartrazine and other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What APOC-5FU looks like

APOC-5FU is a white cream in a 20 g aluminium tube
(AUST R 231556).

Who distributes APOC-5FU

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel St,
Cremorne VIC 3121
www.arrotex.com.au

APOC-5FU is a registered trade mark used under licence.

This leaflet was prepared in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

APOC-5FU Cream

Active ingredient

Fluorouracil

Schedule

1 Name of Medicine

Fluorouracil.

2 Qualitative and Quantitative Composition

Cream containing fluorouracil 5% w/w.

Excipients with known effect.

Methyl hydroxybenzoate, propyl hydroxybenzoate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APOC-5FU is a homogenous, white cream.

4 Clinical Particulars

4.1 Therapeutic Indications

Solar and senile keratoses, Bowen's disease.

4.2 Dose and Method of Administration

APOC-5FU cream is intended for topical administration.

Dosage.

APOC-5FU should only be used under medical supervision.
APOC-5FU is well tolerated. The healthy skin surrounding the area being treated may occasionally become reddened, but soon resumes its normal colour on cessation of treatment.
In cases of senile and solar keratoses a thin layer of the cream is applied to the affected areas once or twice daily, generally without a dressing. In the treatment of other conditions (including keratosis palmaris) a fresh occlusive dressing should be applied daily. Treatment should be continued up to the erosion stage. Duration of therapy is usually 3-4 weeks, but it may prove necessary to exceed this on occasion. In-use stability studies have confirmed that the cream can be used for up to 8 weeks after opening the tube. When APOC-5FU is applied to the skin, the following usually happens: a redness of the affected area (generally within 3 to 5 days) followed by blistering, peeling, and cracking (within 11 to 14 days) with occasional open sores and some discomfort. Although the skin seems to be worse, it is a sign that the medication is working. The treated skin will flake away. Some redness of the skin will continue for some time after the drug is stopped.

Limitation of treatment area.

The total area of skin being treated with APOC-5FU at any time should not exceed 500 sq cm (approx. 23 x 23 cm). Larger areas should be treated a section at a time.

4.3 Contraindications

Fluorouracil is contraindicated in women who are or may become pregnant during therapy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Fluorouracil should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the enzyme dihydropyrimidine dehydrogenase (DPD). DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities.
Rarely, life-threatening toxicities such as stomatitis, diarrhoea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency.
A case of life-threatening systemic toxicity has been reported with the topical use of fluorouracil 5% in a patient with DPD enzyme deficiency. Symptoms included severe abdominal pain, bloody diarrhoea, vomiting, fever, and chills. Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the oesophagus, stomach, and small bowel. Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.
Known hypersensitivity to fluorouracil or any of its excipients.

4.4 Special Warnings and Precautions for Use

Identified precautions.

The normal pattern of response includes: early and severe inflammatory phases (typically characterised by erythema, which may become intense and blotchy), a necrotic phase (characterised by skin erosion) and finally healing (when epithelialisation occurs). The clinical manifestation of response usually occurs in the second week of fluorouracil treatment. However, these treatment effects sometimes are more severe and include pain, blistering and ulceration.
Highly irritant and so should not be allowed to come in contact with mucous membranes (eyes, nose or mouth) due to the possibility of irritation, local inflammation and ulceration. There is a possibility of increased absorption through ulcerated or inflamed skin.
Treatment of perioral area or nasolabial fold should be avoided, or treated carefully. Because of its irritant nature, care should be taken to see that fluorouracil does not come into contact with normal skin. Fluorouracil should be applied with a non-metal applicator or rubber glove. Should a glove not be worn and the hands come in contact with fluorouracil during application they should be washed thoroughly.
Exposure to UV radiation (e.g. natural sunlight or tanning salon) should be avoided. Fluorouracil therapy is not advisable in persons who work outdoors for prolonged periods in the sun. Excessive sun exposure may produce a diffuse phototoxic response in the areas of application; therefore, exposure should be minimised during and immediately following treatment with fluorouracil because the intensity of the reaction may be increased.
While treatment is in progress, avoid cosmetics on treated areas and other topical medication applied to the same area, unless otherwise directed.
Occlusion of the skin with resultant hydration has been shown to increase percutaneous penetration of several topical preparations. If any occlusive dressing is to be used, there may be an increase in the severity of inflammatory reactions in the adjacent normal skin. A porous gauze dressing may be applied for cosmetic reasons without increase in reaction.
The excipients stearyl alcohol and propylene glycol may cause local skin irritations (e.g. contact dermatitis); the excipients methyl hydroxybenzoate and propyl hydroxybenzoate may cause allergic reactions (possibly delayed).

Information for patients.

Fluorouracil may be fatal if ingested by pets. Avoid allowing pets to contact the APOC-5FU container or the skin where APOC-5FU has been applied. Store APOC-5FU out of reach of pets. Safely discard or clean any cloth or applicator that may retain APOC-5FU and avoid leaving any residues of APOC-5FU on your hands, clothing, carpeting or furniture.

Use in the elderly.

No data available.

Paediatric use.

Safety and effectiveness in children have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Although no significant medicine interactions with fluorouracil have been reported, potential medicine interactions are possible, caution should be taken with medicines that may have an effect on the DPD enzyme.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
Studies in animals have shown that fluorouracil is teratogenic. The potential risk for humans is unknown, hence fluorouracil is contraindicated in pregnancy or where pregnancy cannot be excluded (see Section 4.3 Contraindications).
It is not known whether fluorouracil is excreted in human milk. Because there is some systemic absorption of fluorouracil after topical administration, because many medicines are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, fluorouracil use should be avoided in nursing mothers.

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. However, adverse effects of APOC-5FU include dizziness which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

The most frequently encountered reactions are often related to an extension of the pharmacological activity of the medicine. These include pain, pruritus, hyperpigmentation, burning, crusting, allergic contact dermatitis, erosions, erythema, hyperpigmentation, irritation, photosensitivity, scarring, rash, soreness and ulceration at the site of application. Leukocytosis is the most frequent haematological adverse effect.
Application site haemorrhage has also been reported (frequency unknown).
The patient should be advised of the temporary unsightly appearance and local discomfort to be expected during treatment with this drug (see Section 4.4 Special Warnings and Precautions for Use). Patients with chloasma and rosacea and other inflammatory dermatoses may encounter accentuation of their condition and should first be treated with appropriate therapy before using the medication. While absorption of fluorouracil through healthy skin is negligible, absorption is considerably increased when it is applied to diseased skin.
Although a causal relationship is remote, other adverse reactions which have been reported infrequently are:

Nervous system disorders.

Emotional upset, insomnia, irritability, dizziness, headache.

Gastrointestinal disorders.

Nausea.

Skin and subcutaneous tissue disorders.

Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticarial, skin rash.

Special senses.

Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.

Miscellaneous.

Herpes simplex.

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 and contact Arrotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

Symptoms.

If fluorouracil is accidentally ingested, signs of fluorouracil overdosage may include nausea, vomiting and diarrhoea. Stomatitis and blood dyscrasias may occur in severe cases.

Treatment.

Appropriate measures should be taken for the prevention of systemic infection and daily white cell counts should be performed.
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.

When the preparation is applied to keratotic and preneoplastic lesions it produces the following pattern of response: first erythema, then, usually, vesiculation, erosion, ulceration, necrosis and epithelialisation.

Clinical trials.

A therapeutic equivalence clinical study was performed which has proven the equivalence of APOC-5FU 5% cream to the registered Australian Efudix cream. The primary objective of this randomized, double-blind, parallel-group, vehicle-controlled study was to evaluate the clinical efficacy and safety of the formulations of 5% fluorouracil cream in patients with lesions of actinic keratosis (AK) on the face and/or scalp. In addition, the efficacy of both test and reference creams were compared to a vehicle control (placebo) cream. A total of 308 patients with lesions of AK on the face and/or scalp applied the cream (test, reference or placebo) to the affected areas twice per day for 14 days. On days 0, 14 and 42, all lesions were counted and irritation scored using a standardized rating scale. The primary endpoint was the number and proportion (%) of patients in the per protocol population (PPP) in the test and reference groups who had complete clearance of baseline lesions on Day 42. The results for the test and reference products were 48 patients (40.34%) and 51 patients (46.36%) respectively. The difference between the test and reference groups was -6.03% and the 90% CI was -17.67% to +5.61%, within the pre-determined limits of bioequivalence of -20% to +20%. Furthermore, the results demonstrate the non-inferior efficacy of the test product in terms of the proportion of patients with treatment success (100% clearance of all AK lesions within the treatment area) at study week 6 (4 weeks after completion of 2 weeks of treatment). Both the test and reference products were shown to be superior to placebo, and the safety profile of the test product was not clinically different to that of the reference product.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Methyl hydroxybenzoate, white soft paraffin, polysorbate 60, propyl hydroxybenzoate, propylene glycol, stearyl alcohol, purified water.

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.
Discard 8 weeks after opening the tube.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Aluminium tube containing 20 g of cream.
AUST R: 231556.
APOC-5FU is a registered trade mark used under licence.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

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APOC-5FU Cream

Fluorouracil

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