Consumer medicine information

Differin Gel & Cream

Adapalene

BRAND INFORMATION

Brand name

Differin Topical Cream

Active ingredient

Adapalene

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Differin Gel & Cream.

What is in this leaflet

This leaflet answers some common questions about DIFFERIN.

It does not contain all the available information. It does not use the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using DIFFERIN 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 DIFFERIN is used for

DIFFERIN contains the active substance adapalene that belongs to a group of medicines called retinoids.

DIFFERIN is used for the treatment of acne (blackheads, whiteheads and pimples) of the face, chest or back. The product acts against the abnormal skin processes associated with acne.

Your doctor, however may prescribe it for another purpose.

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

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

DIFFERIN is not addictive.

Before you use DIFFERIN

When you must not use it

Do not use DIFFERIN:

  • if you have an allergy to any medicine containing adapalene
    if you have an allergy to the active substance or any of the excipients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives of the skin

Do not use DIFFERIN after the expiry (EXP) date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

DIFFERIN gel contains methyl hydroxybenzoate (E218) which may cause allergic reactions (possibly delayed) and propylene glycol which can cause skin irritation.

DIFFERIN cream contains methyl hydroxybenzoate (E218) and propyl hydroxybenzoate (E216) which may cause allergic reactions (possibly delayed).

Tell your doctor if you have or have had any of the following medical conditions:

  • Eczema
  • Seborrhoeic dermatitis (scaly, flaky itchy and red skin)

Tell your doctor if you are pregnant or plan to become pregnant. Like most medicines of this kind, DIFFERIN is not recommended to be used during pregnancy. Your doctor can discuss with you the risks and benefits involved.

In case of unexpected pregnancy, treatment should be discontinued.

Tell your doctor if you are breast-feeding or planning to breast-feed. Differin can be used during breast feeding It is not known whether DIFFERIN passes into breast milk. To avoid exposure of the infant, do not apply DIFFERIN to your chest if breast-feeding.

If you have not told your doctor about any of the above, tell him/her before you start taking DIFFERIN.

DIFFERIN should only be used on the skin.

DIFFERIN is not recommended for use in children under 12.

Using other medicines

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

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to use DIFFERIN

How much to use

Apply a thin film of DIFFERIN gel or cream to the affected area once a day before bedtime and after washing. Ensure that the affected areas are dry before application.

Ask your doctor or pharmacist if you are not sure how much to apply. They will tell you exactly how much to use for each application.

Follow the instructions they give you.

How to use it

  1. Cleanse the affected skin with a mild cleanser or a mild soap.
  2. Rinse thoroughly and pat dry.
  3. Apply a thin film of DIFFERIN gel or cream to the areas of acne. Do not simply treat the pimples. Let the gel or cream dry.
  4. Do not wash your face after applying the gel or cream. Try not to touch the treated areas overnight.

Avoid the use of of oil-based makeups and creams. Cosmetic products with an abrasive, drying or peeling action may cause an extra irritant effect.

DIFFERIN should not be used on the following areas:

  • eyes
  • lips
  • mouth
  • mucous membranes
  • Angles of the nose
  • open wounds (cuts and abrasions)
  • sunburn
  • skin wth eczema
  • severe acne on large areas of boby

If DIFFERIN comes into contact with these areas, the area should be rinsed immediately with plenty of water.

Hands should be washed after applying DIFFERIN.

How long to use it

Your doctor or pharmacist will tell you how long to use DIFFERIN.

Continue using your medicine for as long as your doctor tells you.

Pimples and spots will be reduced only after several application of this medicine. It may take 4-8 weeks to notice an improvement and more improvement after further use.

It is important that you continue using DIFFERIN as long as prescribed by your doctor.

If you are not sure how long to use DIFFERIN, talk to your doctor or pharmacist.

If you forget to use it

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

Do not use a double dose to make up for the dose that you missed.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you swallow it

Immediately telephone your doctor, or Poisons Information Centre (telephone 13 11 26 in Australia or 0800 POISON or 0800 764 766 in New Zealand), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have swallowed DIFFERIN.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using DIFFERIN

Things you must do

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

If you feel that DIFFERIN is not helping your condition, tell your doctor or pharmacist.

Tell your doctor if, for any reason, you have not used DIFFERIN exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

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

Things you must not do

Do not give DIFFERIN to anyone else, even if they have the same symptoms as yours.

Do not use DIFFERIN to treat other complaints unless your doctor or pharmacist tells you to.

Things to be careful of

Minimise exposure to sunlight and UV lamps. Protect your skin when you are in the sun, especially between 10 am and 3 pm. If outdoors, wear protective clothing and use a non-comedogenic, broad spectrum, SPF 50+ sunscreen.

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

Side effects

All medicines may have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor has weighed the risks of using this medicine against the benefits they expect it will have for you.

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

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

  • Redness
  • Dry skin
  • Skin burning sensation
  • Contact dermatitis
  • Skin irritation
  • Itching of the skin
  • Sunburn
  • Skin discomfort
  • Skin exfoliation
  • Allergic dermatitis
  • Pain of the skin
  • Skin swelling
  • Eyelid irritation
  • Eyelid erythema
  • Eyelid pruritus
  • Eyelid swelling
  • Darkening of fair skin
  • Lightening of dark skin
  • Application site burn

These are mild side effects of the medicine and are usually short-lived.

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

  • contact dermatitis/eczema
  • acne flare
  • swelling of the face or eyelids
  • conjunctivitis

These may be serious side effects of the medicine and may require medical attention.

If you experience sensitivity or irritation when applying this medicine, stop using it and tell your doctor. You may be asked to use the cream less often, or to stop using it until symptoms subside.

If any of the following happen, stop using DIFFERIN and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives of the skin and dizziness
  • Could be a sign of angioedema or a severe allergic reaction

These are very serious side effects. If you have them, you may have had a serious allergic reaction to DIFFERIN. You may need urgent medical attention or hospitalisation.

Serious side effects are very rare.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some patients.

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

After using DIFFERIN

If you have queries about any aspect of your medicine, or any questions regarding the information in this leaflet, discuss them with your doctor or pharmacist.

Storage

Keep the medicine in a cool dry place where the temperature stays below 25°C.

Do not store it, or any other medicine, in a bathroom, near a sink, or on a window-sill.

Do not leave it in the car. Heat and dampness can destroy some medicines.

Keep it where 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 DIFFERIN or it has passed its expiry date, ask your pharmacist what to do with any that is left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

DIFFERIN is a smooth white cream or smooth white gel. It is supplied in plastic tube with a plastic cap containing 3g, 5g, 30 g and 50g of cream or 5g, 30g and 50g of gel.

Ingredients

Each gram of DIFFERIN contains 1 mg (or 0.1%) of adapalene as the active ingredient.

Inactive ingredients for the gel:

  • carbomer 940
  • propylene glycol
  • poloxamer
  • disodium edetate
  • methyl hydroxybenzoate (E218)
  • sodium hydroxide
  • purified water.

Inactive ingredients for the cream:

  • carbomer 934P
  • PEG-20 methyl glucose sesquistearate
  • glycerol
  • squalane
  • methyl hydroxybenzoate (E218)
  • propyl hydroxybenzoate (E216)
  • disodium edetate
  • methyl glucose sesquistearate
  • phenoxyethanol
  • cyclomethicone
  • sodium hydroxide
  • purified water.

Sponsor

Galderma Australia Pty Ltd
13B Narabang Way
Belrose NSW 2085
Ph 1800 800 765

Distributed in New Zealand by:

Healthcare Logistics
58 Richard Pearse Drive
Airport Oaks
Auckland
Ph: 0800 174 104

Made in France

Australian Registration Number:

AUST R 53918 (gel)
AUST R 66174 (cream)

® Registered Trademark

This leaflet was prepared on 12 March 2020.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Differin Topical Cream

Active ingredient

Adapalene

Schedule

S4

 

1 Name of Medicine

Adapalene.

6.7 Physicochemical Properties

Common name.

Adapalene.

Chemical structure.


Chemical name.

6-[3-(1-adamantyl)-4-methoxyphenyl]- 2-naphthoic acid.

Molecular formula.

C28H28O3.

Molecular weight.

412.52.

CAS number.

106685-40-9.

2 Qualitative and Quantitative Composition

Differin Topical cream contains adapalene 1 mg/g in a smooth white cream.

Excipients with known effect.

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

3 Pharmaceutical Form

Topical cream.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Adapalene is a chemically stable compound with retinoid-like pharmacological activity. Biochemical and pharmacological profile studies have demonstrated that adapalene is a potent modulator of cellular differentiation, keratinisation and inflammatory processes all of which represent important features in the pathology of acne vulgaris. Mechanistically, adapalene binds to specific retinoic acid nuclear receptors but unlike tretinoin, does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, current evidence suggests that topical adapalene normalises the differentiation of follicular epithelial cells resulting in decreased microcomedone formation. Adapalene inhibits the chemotactic (directional) and chemokinetic (random) responses of human polymorphonuclear leucocytes in in vitro assay models. It also inhibits the metabolism of arachidonic acid by lipoxidation, to inflammatory mediators.

Clinical trials.

The efficacy of Differin cream has been assessed in 2 randomised, double blind, parallel comparison clinical trials. In the first trial, 350 subjects with acne vulgaris associated with at least 20 facial noninflammatory comedones and 10 inflammatory lesions were enrolled for treatment with Differin cream or the cream vehicle administered once daily. For Differin and vehicle groups respectively after 12 weeks treatment, the mean % reductions from baseline in total lesions were 32% vs 15% (p < 0.05), in noninflammatory lesion counts were 37% vs 15% (p < 0.05) and investigator's global assessment scores were 1.13 vs 1.26 (p < 0.05). The difference between the treatment groups in % reduction in inflammatory lesions (15% vs 5%) was not statistically significant.
In the second trial, 277 subjects with acne vulgaris were enrolled for treatment with Differin cream or tretinoin cream 0.05% administered once daily. For Differin and tretinoin treatment groups respectively after 12 weeks treatment, the mean % reductions from baseline in total lesions were 60% vs 67% (p < 0.05), in noninflammatory lesions were 64% vs 72% (p < 0.05), in inflammatory lesions were 43% vs 56% (p < 0.05) and in the investigator's global assessment scores were 51% vs 57% (p < 0.05).

5.2 Pharmacokinetic Properties

In clinical trials adapalene was seldom detected in plasma, and then only in trace amounts following chronic topical application with an analytical limit of quantification of 0.25 nanogram/mL. After administration of 14C-adapalene to rats, rabbits and dogs, radioactivity was distributed in several tissues, the highest levels being found in liver, spleen, adrenals and ovaries. Metabolism in animals is maintained by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route.
In a human study performed using the gel formulation in which male volunteers followed a course of exaggerated topical application, 30 g (a full tube) was applied all over the body each day for 7 consecutive days, the resultant circulating plasma levels were below the limit of detection (0.15 nanogram.mL-1). There were low quantities of the parent substance in the faeces. In another study healthy volunteers used radiolabelled adapalene 0.1% topical gel, 4 of the subjects received 14 daily topical applications of nonradiolabelled adapalene 0.1% topical gel prior to the single application of radiolabelled adapalene 0.1% topical gel. The other 4 subjects received a single topical application of the radiolabelled product. Levels of radioactivity in all plasma, urine, faeces and skin strip samples analysed were below the limits of reliable quantification, indicating that either very little or no radioactivity was absorbed through the skin.
A further study carried out to investigate the distribution of adapalene in the adipose tissue of women after repeated daily application of adapalene gel for 3 months, found that there was no evidence of circulating adapalene in the plasma (limit of detection 0.15 nanogram.mL-1). On day 90, adapalene levels in the adipose tissue were not quantifiable in 5 of the 6 volunteers (limit of detection 1 nanogram.g-1). In the 6th volunteer the mean concentration at 3 sites was 1.1, 1.3 and 5.5 nanogram.g-1. These concentrations were no longer evident when re-evaluated at the same sites in this subject 1 month after the cessation of treatment.

5.3 Preclinical Safety Data

Genotoxicity.

Adapalene did not demonstrate mutagenic or clastogenic activity in in vitro tests with bacterial and mammalian cells and showed no clastogenic activity in mammalian cells in vitro and an in vitro test in mice.

Carcinogenicity.

Lifetime studies with adapalene have been completed in mice at topical doses of 0.6, 2 and 6 mg/kg and in rats at oral doses of 0.15, 0.5 and 1.5 mg/kg. Phaeochromocytomas were observed in the adrenal medulla of male rats dosed at 1.5 mg/kg but not at the lower doses. This finding was not observed in female rats or in mice. The relevance of the finding in male rats to the use of Differin Topical cream in acne vulgaris is not known.

4 Clinical Particulars

4.1 Therapeutic Indications

Topical treatment of comedo, papular and pustular acne (acne vulgaris) of the face, chest or back.

4.3 Contraindications

Not to be used in patients who are hypersensitive to the active substance or any of the excipients.

4.4 Special Warnings and Precautions for Use

For external use only.
Differin Topical Cream should not come into contact with the eyes, lips, mouth and mucous membranes, angles of the nose or broken skin (cuts and abrasions), sunburn or eczematous skin, nor should it be used in patients with severe acne involving large areas of the body. If product enters the eye, wash immediately with warm water. Because of a potential for increased irritation Differin Cream should not be used by patients with eczema, seborrhoeic dermatitis or severe acne involving large areas of the body.
If a reaction suggesting severe irritation occurs, discontinue use of the medication. If the irritation is not severe, use the medication less frequently, discontinue use temporarily until symptoms subside, or discontinue use altogether. If patients use cosmetics, these should be noncomedogenic and nonastringent. Only oil free moisturisers should be used to relieve dry facial skin.
Because Differin Topical cream may cause some irritation, it is possible that simultaneous use of abrasive cleansers, astringents or strong drying agents or irritant products may cause additive irritant effects.
Animal studies on compounds with a similar mode of action to adapalene have suggested that these may enhance the development of skin cancers caused by UV light. Adapalene is essentially stable to oxygen and light and is chemically nonreactive. Whilst short-term studies have shown no phototoxic to photoallergic potential of adapalene, small numbers of reactions consistent with phototoxicity were reported in clinical studies. The safety of using adapalene during long or repeated exposures to sunlight or UV radiation has not been established in animals or humans. Exposure to sunlight or UV irradiation (including sunlamps) should be avoided during treatment with adapalene. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided.
Efficacy and safety in the treatment of severe pustular or deep cystic acne (acne conglobata) have not been studied.
Differin Cream contains methyl hydroxybenzoate (E218) and propyl hydroxybenzoate (E216) that can cause allergic reactions (can arise after the treatment is completed).

Use in the elderly.

No data available.

Paediatric use.

Safety and efficacy in children below the age of 12 years have not been studied.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There are no known interactions with other medications which might be used topically and concurrently with Differin Topical Cream; however other retinoids or drugs with a similar mode of action should not be used concurrently with adapalene. Exposure of adapalene to other topical antiacne drugs such as erythromycin, clindamycin phosphate or benzoyl peroxide does not produce any mutual degradation.
Absorption of adapalene through human skin is low (see Section 5.2 Pharmacokinetic Properties) and therefore interaction with systemic medication is unlikely.
Differin topical cream has potential for local irritation and it is possible that concomitant use of peeling agents, astringents or irritant products may produce additive irritant effects.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
In pregnant rats and rabbits, adapalene administered orally at relatively high doses (≥ 25 mg/kg leading to exposures ≥ 25 times that anticipated clinically based on AUC) was found to induce foetal abnormalities. In addition the incidences of various skeletal variations were increased at lower oral doses in rats. Topical administration at doses up to 6 mg/kg, resulting in an exposure level about 45 times greater (based on AUC) than that anticipated clinically, was not associated with teratogenicity. Nevertheless, increased incidences of various naturally occurring skeletal variations were still observed following topical administration to rats at 2 mg/kg (AUC exposure about 13 times that anticipated clinically); topical no effect levels were 0.6 and 2 mg/kg respectively (AUC about 5 times that anticipated clinically).
Because of the risk of teratogenicity shown in animals, and since there are no adequately controlled studies in pregnant women, adapalene should not be used by women who are pregnant or who plan to become pregnant during treatment.
In case of unexpected pregnancy, treatment should be discontinued.
It is not known whether adapalene is excreted in human milk. Therefore, the preparation should be used with caution in nursing mothers, and only on areas away from the chest. Cautionary use of Differin during breast feeding should avoid contact exposure of the infant, application of Differin to the chest should be avoided when used during breast-feeding.

4.8 Adverse Effects (Undesirable Effects)

A feeling of warmth, burning, pruritus, dryness, scaling or slight stinging may occur following application. Local adverse events may persist despite cessation of therapy. No systemic reactions have been attributed to the application of the cream to date. The allergic potential of adapalene has not been established.

Side effects.

The incidences of cutaneous side effects reported by patients treated with adapalene 1 mg/g cream during clinical trials were as follows.

Very common (> 10%).

Redness, dry skin, burning sensation at the site of application and scaling.

Common (> 1% and < 10%).

Skin irritation, pruritus and sunburn.

Uncommon (> 0.1% and < 1%).

Contact dermatitis/ eczema, skin discomfort, skin exfoliation, acne flare, facial and eyelid oedema, vesiculobullous eruptions, herpes labialis and conjunctivitis.
Most reactions occurred within 1 month of the initiation of therapy and were generally observed to resolve with continued use of the product or temporary adjustment of the treatment schedule. The incidence of patients withdrawing from the trials because of these topical effects was 7/311 (2.2%). See Table 1.

Postmarketing data.

Differin Cream 0.1% and Differin Gel 0.1% are 2 formulations with the same active ingredient, adapalene. The gel formulation was first marketed in France in September 1995. The postmarketing data detailed below refer to reports collected from the worldwide sales with the gel formulation.

Body as a whole.

Rare (> 0.01% and < 0.1%): allergic reaction and lack of drug effect.

Immune system disorders.

Uncommon (> 0.1% and < 1%): anaphylactic reaction and Angioedema.

Skin and subcutaneous tissue disorders.

Very common (> 10%): irritation, redness, dry skin, burning sensation at the site of application.
Common (> 1% and < 10%): erythema.
Uncommon (> 0.1% and < 1%): contact eczema, contact dermatitis, transient worsening of acne, exfoliative dermatitis - predominantly associated with mechanical abrasion such as waxing, pain of skin, skin swelling, eyelid irritation, eyelid erythema, eyelid pruritus, eyelid swollen, skin discomfort, sunburn, pruritus, skin exfoliation, acne, scaling, application site burn, skin hypopigmentation and skin hyperpigmentation.
Unknown*: dermatitis allergic (allergic contact dermatitis).
*Postmarketing surveillance data.
These events often spontaneously resolve upon adaptation to therapy regimen.

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 Galderma.

4.2 Dose and Method of Administration

Dosage.

A thin film of Differin Topical cream should be applied to the affected areas once a day before bedtime and after washing avoiding the eyes, lips and mucous membranes. The affected areas should be dry before application.
Clinical improvement is expected to be evident in 4 to 8 weeks of treatment, with further improvement to be expected with continued use. Cutaneous safety of Differin topical cream has been demonstrated in 311 patients for up to 12 weeks of treatment. Since it is customary to alternate therapies in the treatment of acne vulgaris, it is recommended that the physician assess continued treatment of the patient with Differin topical cream after 3 months of use.

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.

4.9 Overdose

Differin Topical cream is intended for topical use only. If the medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling or discomfort may occur.
Differin topical cream is not to be taken orally. The oral route toxicity for Differin Topical cream in mice is greater than 10 mL/kg. Unless the amount accidentally ingested is small, an appropriate method of gastric emptying should be considered.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Carbomer 934P, PEG-20 methyl glucose sesquistearate, glycerol, squalane, methyl hydroxybenzoate, propyl hydroxybenzoate, disodium edetate, methyl glucose sesquistearate, phenoxyethanol, cyclomethicone, sodium hydroxide, 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.

6.4 Special Precautions for Storage

Store below 25°C and out of reach of children. Avoid exposure to excessive heat. Replace cap tightly after use.

6.5 Nature and Contents of Container

Collapsible aluminium tube (3 g, 5 g, 30 g and 50 g) coated internally with an epoxy-phenolic resin and fitted with a white polypropylene screw cap.
AUST R 66174.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

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

Summary Table of Changes