AGISPOR SOLUTION

PATIENT PACKAGE INSERT

IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS

(PREPARATIONS) - 1986

The medicine is dispensed without

a doctor’s prescription

Agispor

Cream, Gel,

Solution

Each Agispor tube of cream or gel or

bottle of solution contains:

Bifonazole 1%

Inactive ingredients and allergens in the

preparation - see section 6.

Read this leaflet carefully in its entirety

before using the medicine. This leaflet

contains concise information about the

medicine. If you have further questions,

refer to the doctor or pharmacist.

Refer to the doctor if the symptoms

worsen or if they do not improve within

7 days.

1. WHAT IS THE MEDICINE INTENDED

FOR?

Broad spectrum antifungal medicine.

Therapeutic

group:

Imidazole

antifungal.

2. BEFORE USING THE MEDICINE

Do not use the medicine:

if you are sensitive )allergic( to the

active ingredient or to any of the

other ingredients in the medicine.

for treatment of diaper rash. If your

baby has a diaper rash, refer to a

doctor for appropriate treatment.

for treatment of inflammation of the

nails and scalp.

f o r

t re a t m e n t

v a g i n a l

inflammations.

Special warnings regarding use of the

medicine

Before treatment with Agispor, inform

the doctor if

you have previously had an allergic

reaction to any kind of antifungal

agent.

Agispor

Solution:

Warning!

Flammable, keep away from fire. Do

not light a cigarette or be exposed to

an open flame until the product has

completely dried.

If you are taking, or have recently

taken, other medicines, including

non-prescription medicines and

nutritional supplements, inform the

doctor or pharmacist. It is particularly

important to inform the doctor or

pharmacist if you are taking warfarin.

Pregnancy and breastfeeding

Do not use the medicine if you are

pregnant or breastfeeding, except with

the doctor’s recommendation.

Use in children and infants

Use in infants and toddlers must be done

under medical supervision.

Important information regarding some

of the ingredients of the medicine

The medicine contains cetyl stearyl

alcohol, which may cause local skin

irritation )e.g., rash, itching or redness(

)in the cream and gel only(.

Concentration of the preservative agent:

benzyl alcohol 1% )in the cream and gel

only(.

Do not allow the medicine to come into

contact with the eyes. In case of contact,

wash immediately with water.

3. HOW SHOULD YOU USE THE

MEDICINE?

Check with the doctor or pharmacist if

you are uncertain.

The usual dosage is generally:

Use once a day, preferably in the evening

at bedtime.

Gently massage into the skin.

Continue with the treatment for 2-3

weeks.

Cream: a small amount of cream is

sufficient to treat an area the size of the

palm of the hand.

Gel: a strip of gel half a centimeter long is

sufficient to treat an area the size of the

palm of the hand.

Solution: a few drops )about 3 drops( are

sufficient to treat an area the size of the

palm of the hand.

Do not exceed the recommended

dose

For external use only. Do not put in the

mouth or swallow.

If the medicine accidentally came into

contact with the eyes or mouth, wash

immediately with water and refer to the

doctor.

If a child or anyone else has accidentally

swallowed the medicine, refer immediately

to a doctor or proceed to a hospital

emergency room and bring the package

of the medicine with you.

If you forgot to apply the medicine at

the designated time, apply it as soon

as possible and continue treatment as

usual.

How can you contribute to the success

of the treatment?

Although the affected area will itch, try

to avoid scratching it. Scratching can

damage the surface of the skin and

cause the infection to spread further.

Keep the affected areas clean.

Humidity enhances fungal growth.

Therefore, keep the affected area dry.

Wash the affected area before each

application of the medicine. Between

treatments – antifungal powder can be

used to dry the area.

Always wash your hands after treating

the infection to prevent it from

spreading.

Do not share towels, bath mats, etc.

with other people, as you could spread

the infection to them.

If the treatment is for the feet – take

care to thoroughly wash and dry them,

especially between the toes, but avoid

excessive rubbing. It is recommended

to wear cotton socks; avoid wearing

socks made from wool or from synthetic

materials. It is advisable to change them

several times a day )in accordance with

the amount of sweat(.

Thoroughly wash socks, nylon stockings

and tights in hot water to remove any

peeled skin or fungal spores.

Change your shoes every day, if

possible.

In the appropriate seasons, it is

recommended to wear sandals without

socks.

Do not take medicines in the dark!

Check the label and dose each time

you take a medicine. Wear glasses if

you need them.

If you have further questions regarding

use of the medicine, consult the doctor

or pharmacist.

4. SIDE EFFECTS

As with any medicine, use of Agispor

Cream, Gel or Solution may cause side

effects in some users. Do not be alarmed

when reading the list of side effects. You

may not experience any of them.

As with all medicines, some people may

be allergic to the medicine. If you are

allergic, a reaction will occur immediately

after you start use. If you experience an

allergic reaction, stop use and seek

medical assistance immediately. The signs

of an allergic reaction may include:

Rash.

Swallowing or breathing problems.

Swelling of the lips, face, throat or

tongue.

Weakness, dizziness or faintness.

Nausea.

After applying the medicine, you

might experience one of the following

symptoms:

Slight irritation or burning.

Reddening of the skin.

Peeling.

If the effects are intolerable, stop

treatment and refer to the doctor as soon

as possible.

The medicine may cause local skin

irritation which is very similar to the

symptoms of the infection. If any of the

symptoms worsen, stop treatment and

refer to the doctor as soon as possible.

These symptoms may include:

Skin inflammation.

Burning, pain or itching.

Rash, redness, dryness.

Soft- or soggy-looking skin.

Swelling, edema, hives )red, raised and

itchy lesions(, eczema, blisters.

If any of the side effects worsen, or if you

suffer from a side effect not mentioned in

this leaflet, consult the doctor.

Side effects can be reported to the

Ministry of Health by clicking on the

link “Reporting side effects following

drug treatment” found on the Ministry

of Health homepage )www.health.gov.il(

that directs you to the online form for

reporting side effects, or by entering

the link:

https://forms.gov.il/globaldata/getseque

nce/getsequence.aspx?formType=Adver

sEffectMedic@moh.gov.il

In addition, report to Perrigo via the

following address:

www.perrigo-pharma.co.il

5. HOW SHOULD THE MEDICINE BE

STORED?

Avoid poisoning! This medicine and

any other medicine must be kept in a

safe place out of the sight and reach

of children and/or infants to avoid

poisoning. Do not induce vomiting

without an explicit instruction from

the doctor.

Do not use the medicine after the

expiry date )exp. date( that appears on

the package. The expiry date refers to

the last day of that month.

Store in a cool place below 25°C.

For the cream and gel: after first

opening can be used for 3 months.

Store in the original package.

6. FURTHER INFORMATION

In addition to the active ingredient, the

medicine also contains:

Agispor Cream:

Sorbitan monostearate, polysorbate

60, cetyl esters wax-NF, cetyl stearyl

alcohol, 2-octyldodecanol, benzyl

alcohol, purified water.

Agispor Gel:

Polyoxyethylene 30 cetyl stearyl

alcohol, macrogol 7 glycerol cocoate,

isopropyl isostearate, ethanol, lactic

acid, benzyl alcohol, purified water

Concentration of the preservative:

Benzyl alcohol 1%.

Agispor Solution:

Ethanol, isopropyl myristate.

What the medicine looks like and the

contents of the package:

Agispor Cream: An aluminium tube, 15

grams.

Agispor Gel: An aluminium tube, 15

grams.

Agispor Solution: A brown glass vial

with 15 mL of solution.

Manufacturer and registration holder:

Perrigo Israel Pharmaceuticals Ltd.,

P.O.B. 16, Yeruham.

This leaflet was checked and approved

by the Ministry of Health in January

2016.

Registration number of the medicine

in the National Drug Registry of the

Ministry of Health:

Agispor Cream:

036-82-25608

Agispor Gel:

036-81-25610

Agispor Solution: 036-83-25609

Do not discard medicines via household

waste

wastewater.

pharmacist how to discard medicines

you no longer need. These measures

will help to protect the environment.

Prescribing Information

1.

NAME OF THE MEDICINAL PRODUCT

AGISPOR

Cream, solution, gel, shampoo

AGISPOR ONYCHOSET

Nail ointment

KERATOSPOR

Nail ointment

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

2.1.

Preparations

Qualitative composition in terms of the active ingredient(s) (INN):

Cream, cutaneous solution, gel, shampoo: Bifonazole

Ointment: Bifonazole in combination with urea

Quantitative composition in terms of the active ingredient(s) per dosage form

1g cream contains 10 mg bifonazole

1 ml cutaneous solution contains 10 mg bifonazole

1 g gel contains 10 mg bifonazole

1 g shampoo contains 10 mg bifonazole

1 g nail ointment contains 10 mg bifonazole and 400 mg urea

3. PHARMACEUTICAL FORM

3.1.

Preparations

Pharmaceutical formulation in accordance with standardized terminology:

Cream

Cutaneous solution

Shampoo

Ointment

4. CLINICAL PARTICULARS

4.1.

Therapeutic Indications

AGISPOR cream, solution and gel:

Broad spectrum antimycotic agent.

AGISPOR shampoo:

Pityriorisis versicolor and sebarrrhoeic dermatitis of the scalp caused by pityrosporum.

AGISPOR ONYCHOSET and KERATOSPOR nail ointment:

For nail stripping and antifungal treatment of fungal infections of the finger nails and toe

nails.

4.2.

Posology and Method of Administration

AGISPOR cream, solution and gel:

Posology:

To achieve a lasting cure, treatment with AGISPOR cream, solution and gel must be

carried out reliably and over an adequate period. The usual periods of treatment are

summarized in the table below:

Indication

Duration of treatment

Foot mycoses (Tinea pedis, tinea pedum

interdigitalis)

3 weeks

Mycoses of the trunk, hands and skin

folds (Tinea corporis, tinea manuum,

tinea inguinalis)

2-3 weeks

Pityriasis versicolor

2 weeks

Erythrasma

2 weeks

Superficial candidiasis of the skin

2-4 weeks

Method of administration:

Cream, solution or gel is used once a day, preferably in the evening, before retiring. It

should be applied thinly to the affected skin area and rubbed in.

Cream: A small amount of cream is generally sufficient to treat an area of about the size

of the palm of hand.

Solution: A few drops (about 3 drops) is generally sufficient to treat an area of about the

size of the palm of the hand.

Gel: A strip of gel (1/2 cm long) is generally sufficient to treat an area of about the size of

the palm of the hand.

AGISPOR shampoo:

Posology:

Indication

Duration of treatment

Seborrhoeic dermatitis of the scalp

4 weeks

Method of administration:

Patients should be instructed to shake the bottle well and apply Agispor shampoo to the

hair or affected areas of the skin.

The recommended dose is one scalp wash three times a week, with two applications of

the shampoo each time. The shampoo should be left on the scalp for 5 minutes before

rinsing. Sufficient shampoo should be used to ensure a good lathering of the scalp.

AGISPOR ONYCHOSET and KERATOSPOR nail ointments:

Posology:

The nail ointment is applied in a thin layer to the infected nail once a day in a quantity

sufficient to cover the entire nail surface.

The treatment with AGISPOR ONYCHOSET / KERATOSPOR nail ointment should be

carried out carefully each day and should be continued until no more of the softened,

fungally infected nail substance can be scraped off. This usually takes 7-14 days,

depending on the extent of the infection and the thickness of the nail.

After detachment of the nail, consequent antimycotic treatment of the nail bed should be

carried out with AGISPOR cream once daily for about 4 weeks.

Method of administration:

After application of the nail ointment the treated fingernail or toenail is covered with a

plaster, and this dressing is left in place for 24 hours. The dressing should be changed

daily; the finger or toe (or the hand or foot) should be bathed for about 10 minutes in warm

water after removal of the plaster. After bathing in water, the softened infected nail

substance is removed with the scraper. The treated nails are then dried, further AGISPOR

ONYCHOSET / KERATOSPOR nail ointment is applied as described above, and the nails

are once again covered with the ready-to-use plaster.

It is not necessary to cover the skin surrounding the nail. However, if in exceptional cases

irritation occurs, the edges of skin surrounding the nail should be covered with a suitable

product, such as zinc paste, before fixing the plaster.

After detachment of the nail, i.e. before the start of the antimycotic follow-up treatment,

the treating doctor should check that onycholysis has been completed, and, if necessary,

give the nail bed a final cleaning.

Nail plates that are significantly dystrophic appear to respond better to avulsion with urea.

Cream, solution, gel, shampoo and ointment:

Use in Children

No in-depth studies have been performed in children. From a survey of the clinical data

reported there is no indication that harmful effects should be anticipated in children.

However, in infants and toddlers, the medicinal product should only be used under medical

supervision.

4.3.

Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1

4.4.

Special Warnings and Precautions for Use

Patients with a history of hypersensitivity reactions to other imidazole antifungal agents

(e.g. econazole, clotrimazole, miconazole) must take bifonazole containing products with

caution.

If symptoms continue/persist after treatment, seek medical advice.

Generally:

- Keep medicine out of the reach of children. Avoid contact with eyes.

- Do not swallow.

4.5.

Interactions with Other Medicinal Products and Other Forms of

Interaction

Limited data suggest that an interaction between topical bifonazole and warfarin may be

possible, leading to increases in INR. If bifonazole is used in a patient on warfarin

therapy, they should be appropriately monitored.

4.6.

Fertility, Pregnancy and Lactation

Fertility

Preclinical studies gave no evidence that bifonazole can impair male or female fertility

(see section 5.3).

For nail ointment only:

Preclinical studies gave no evidence that urea would raise concerns for a sperm-

damaging potential (see section 5.3). No information is available on possible effects on

female fertility.

Pregnancy

Preclinical safety data and pharmacokinetic data in humans give no indication that

harmful effects on the mother and child should be anticipated when bifonazole is used

during pregnancy (see section 5.3).

However, no clinical data are available.

As a precautionary measure, it is preferable to avoid the use of bifonazole during the first

trimester of pregnancy.

For nail ointment only:

There are no data from the use of urea in pregnant women. Animal studies do not

indicate direct or indirect harmful effects with respect to reproductive toxicity (see

section 5.3). As a precautionary measure, if is preferable to avoid the use of urea (or the

nail ointment) during the first trimester of pregnancy.

Lactation

It is unknown whether bifonazole is excreted in human breast milk.

The excretion of bifonazole in milk has been studied in animals.

Available pharmacodynamic/toxicological data in animals have shown excretion of

bifonazole/metabolites in milk (see section 5.3). Breast-feeding should be discontinued

during treatment with bifonazole.

For nail ointment only:

It is unknown whether urea is excreted in human milk. Breast-feeding should be

discontinued during treatment with urea or the nail ointment.

4.7.

Effects on Ability to Drive and Use Machines

The medication has no or negligible influence on the ability to drive or use machinery.

4.8.

Undesirable Effects

The following adverse reactions have been identified during post-approval use of

bifonazole. Because these reactions are reported voluntarily from a population of

uncertain size, it is not always possible to reliably estimate their frequency.

General disorders and administration site conditions

Administration site pain, oedema peripheral (at administration site)

Skin and subcutaneous tissue disorders

Dermatitis contact, dermatitis allergic, erythema, pruritus, rash, urticaria, blister, skin

exfoliation, eczema, dry skin, skin irritation, skin maceration, skin burning sensation

These side effects are reversible after discontinuation of the treatment.

Nail ointment only

Skin and subcutaneous tissue disorders

Dermatitis contact, skin maceration, desquamation, nail disorder, nail discoloration,

erythema, skin irritation, application site pain, pain in extremity, pruritus, rash

These side effects are reversible after discontinuation of the treatment.

4.9.

Overdose

No risk of acute intoxication is seen as it is unlikely to occur following a single dermal

application of an overdose (application over a large area under conditions favorable to

absorption) or inadvertent oral ingestion.

5. PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic Properties

Cream, solution, gel and shampoo:

Pharmacotherapeutic group: Anti-fungals for dermatological use – Bifonazole

ATC Code: D01AC10

Bifonazole is an imidazole derivative with a broad antimycotic spectrum, which includes

dermatophytes, yeasts, moulds and other fungi such as Malassezia furfur. It is also

effective against Corynebacterium minutissimum.

Bifonazole exerts its anti-fungal action by inhibiting the biosynthesis of ergosterol on two

different levels, thereby distinguishing bifonazole both from other azole derivatives and

from other anti-fungals which act only on a single level. Inhibition of ergosterol synthesis

leads to structural and functional impairment of the cytoplasmic membrane.

The resistance situation for bifonazole is favorable. Primary resistant variants of sensitive

fungal species are very rare. Investigations so far did not provide any evidence of a

development of secondary resistance in primarily sensitive strains.

Ointment:

Pharmacotherapeutic group: Anti-fungals for dermatological use – Bifonazole,

combinations

ATC Code: D01AC60

Mode of action:

Bifonazole is an imidazole derivative with a broad anti-mycotic spectrum, which includes

dermatophytes, yeasts, moulds and other fungi. Urea is acting as a keratoplastic.

Bifonazole exerts its anti-fungal action by inhibiting the biosynthesis of ergosterol on two

different levels, thereby distinguishing bifonazole both from other azole derivatives and

from other anti-fungals which act only on a single level. Inhibition of ergosterol synthesis

leads to structural and functional impairment of the cytoplasmic membrane.

The resistance situation for bifonazole is favorable. Primary resistant variants of sensitive

fungal species are very rare. Investigations so far did not provide any evidence of a

development of secondary resistance in primarily sensitive strains.

Urea is a naturally occurring substance found e.g. in the human body. With the nail

ointment the infected nail keratin is softened by urea, which allows non-invasive and

painless detachment of the infected nail. Moreover, it was shown by in vitro studies, that

in infected human toenails urea enhances the depth of penetration of bifonazole. Thus,

combination of both enhances the antimycotic effect.

5.2.

Pharmacokinetic Properties

Cream, solution, gel and shampoo:

Absorption

Bifonazole penetrates well into infected skin layers. 6 hours after administration

concentrations in the various skin layers reach from 1000 μg/cm

in the top layer of the

epidermis (stratum corneum) to 5 μg/cm

in the stratum papillare. All concentrations

determined are thus within a range of reliable antimycotic activity.

Ointment:

Absorption:

Respective plasma levels resulting from treatment with bifonazole nail ointment were

always below the detection limit of bifonazole (i.e. < 1 ng/mL).

5.3.

Preclinical Safety Data

Preclinical data reveal no special hazards for humans based on conventional studies

of single dose toxicity and genotoxicity. Effects on the liver (enzyme induction, fatty

degeneration)

were

observed

repeated

dose

toxicity

studies

with

oral

administration but only at exposures in excess of the maximum human exposure

indicating little relevance to clinical use. No carcinogenicity studies were performed

with bifonazole.

In reproduction toxicology studies in rabbits, oral doses of 30 mg/kg body weight

resulted in embryotoxicity including lethality. In the rats, bifonazole at oral doses up to

100 mg/kg body weight was not embryotoxic, but a retarded skeletal development in the

fetuses was observed at the dose of 100 mg/kg. This fetal effect on the skeletal

development can be considered as a secondary effects resulting from the maternal

toxicity (a reduction in body weight). Given the low absorption of the active ingredient

via the skin these results have little relevance to clinical use. No impairment of male or

female fertility was observed in rats at oral doses up to 40 mg/kg body weight.

Bifonazole passes through the placental barrier in rats. A study with lactating rats

administered bifonazole intravenously showed that the drug was secreted into milk.

For nail ointment only:

Non-clinical data reveal no special hazards for humans from urea based on conventional

studies of single dose toxicity, repeated dose toxicity, carcinogenic potential and toxicity

to reproduction and development.

Genotoxicity studies gave mixed results. The genotoxic effects reported in some studies

may be related to the uncoiling DNA at highly non-physiological urea concentration, the

exposures considered sufficiently in excess of the maximum human exposure indicating

little relevance to clinical use.

6. PHARMACEUTICAL PARTICULARS

6.1.

List of Excipients

Cream: 2-octyldodecanol, cetyl stearyl alcohol, cetyl esters wax-NF, sorbitan stearate,

polysorbate 60, benzyl alcohol, purified water.

Solution: Ethanol, isopropyl myristate.

Gel: polyoxyethylene-30-cetyl stearyl alcohol, macrogol 7 glycerol cocoate , isopropyl

isostearate, ethanol, lactic acid, benzyl alcohol, purified water.

Shampoo: Sodium lauryl sulphate, sodium lauryl ether sulphate, ethyl alcohol, lactic

acid, cocamide diethanolamine, cocamidopropylamine oxide,

Perfume 199-95, purified water.

Nail ointment: Beeswax white, paraffin white soft, wool fat.

6.2.

Incompatibilities

Not known

6.3.

Shelf Life

AGISPOR

Cream: 36 months. . Shelf life after first opening: 3 months.

Solution: 60 months.

Gel: 48 months. Shelf life after first opening: 3 months.

Shampoo: 24 months.

AGISPOR ONYCHOSET Nail Ointment: 36 months.

KERATOSPOR Nail Ointment: 36 months.

Shelf life after first opening: 3 months.

6.4.

Special Precautions for Storage

AGISPOR

Cream: store in a cool place, below 25°C.

Solution: store below 25°C.

Gel: store in a cool place, below 25°C.

Shampoo: store in a cool place, below 25°C.

AGISPOR ONYCHOSET Nail Ointment: store in a cool place, below 25°C.

KERATOSPOR Nail Ointment: store in a cool place, below 25°C.

6.5.

Nature and Contents of Container

AGISPOR

Cream: Aluminium tube, 15 gr.

Solution: Brown type III glass bottle.

Gel: Aluminium tube, 15 gr.

Shampoo: HDPE Bottle, 100 ml.

AGISPOR ONYCHOSET Nail Ointment: Aluminium tube, 10 gr. Plasters, scraper

and a metering dispenser.

KERATOSPOR Nail Ointment: Aluminium tube, 10 gr. and a metering dispenser.

6.6.

Special Precautions for Disposal and Other Handling

Instructions for use / handling:

All: If irritation or sensitivity develops, discontinue treatment and institute

appropriate therapy.

Cream: In cases of known. hypersensitivity to cetostearyl alcohol, it is advisable to use a

cetostearyl alcohol-free formulation (e.g. bifonazole solution) instead of the cream.

Solution: The solution is flammable due to ethanol content. Keep away from ignition

sources.

Nail ointment: Lasting therapeutic success depends largely on careful removal of the

diseased nail areas and subsequent consequent treatment of the nail bed with

bifonazole cream or other bifonazole formulations.

Allergy to the plaster is possible, though very rare. Consult your doctor if such an allergy

occurs. You may switch to a different plaster or to rubber finger stalls.

7.

MANUFACTURER AND MARKETING AUTHORISATION

HOLDER

Perrigo Israel Pharmaceuticals, Ltd., P.O.B 16, Yeruham.

8.

MARKETING AUTHORISATION NUMBER

AGISPOR

Cream: 036 82 25608 00

Solution: 036 83 25609 00

Gel: 036 81 25610 00

Shampoo: 126 23 26745 00

AGISPOR ONYCHOSET Nail Ointment: 123 58 26495 00

KERATOSPOR Nail Ointment: 105 78 26596 00

The content of this leaflet was checked and approved by the Ministry of Health in

August 2014.

1.9.2014