DUAC - PACKAGE LEAFLET - LEAFLETS

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Duac - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Clindamycin, Benzoyl peroxide anhydrous

Duac 1% - 5% Gel

Indications Why is Duac used? What is it for?

DUAC GEL contains two medicines: clindamycin and benzoyl peroxide.

DUAC GEL belongs to a group of medicines known as "acne preparations".

DUAC GEL is used to treat mild to moderate skin acne.

Clindamycin is an antibiotic that blocks the reproduction of the bacteria involved in acne.
Benzoyl peroxide reduces blackheads and pimples. It also kills the bacteria involved in acne.

Their use in combination in the DUAC GEL works:

fighting the bacteria that cause acne
treating blackheads, pimples and pustules already present
reducing the number of red and inflamed acne pustules DUAC GEL is indicated for the use of adults and adolescents aged 12 years or older.

Contraindications When Duac should not be used

Do not use DUAC GEL

if you are allergic to clindamycin, lincomycin, benzoyl peroxide or any of the other ingredients of DUAC GEL (listed in point 6)

Do not use DUAC GEL if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before you start using DUAC GEL.

Precautions for use What you need to know before taking Duac

Talk to your doctor or pharmacist before using DUAC GEL

Use DUAC GEL only on the skin. Keep away from areas such as eyes, lips, mouth or inside the nose.
Do not use the gel on irritated parts of the skin. For example if there are cuts, abrasions, burns, or broken skin.

→ If DUAC GEL accidentally gets into your eyes, mouth or nose, rinse with plenty of water.

Do not use too much DUAC GEL on sensitive parts of the skin.
Most patients show some redness and peeling of the skin during the first few weeks of treatment. If the skin becomes irritated, it may be necessary to use an oil-free moisturizer, use DUAC GEL less often, or discontinue use for a longer period. short period to allow the skin to recover and then start treatment again.
Stop treatment and see your doctor if skin irritation is severe (severe redness, dryness, itching, stinging, or burning) or if it does not improve.
Try to avoid contact between DUAC GEL and colored garments, including clothing, linen towels and sheets, furniture or carpets. DUAC GEL can whiten these materials.
DUAC GEL can whiten hair.
DUAC GEL can make the skin more sensitive to the harmful effects of the sun. Avoid the use of sun beds / lamps and minimize exposure to the sun. You must use sunscreen and wear protective clothing while using DUAC GEL.

Before using this medicine, talk to your doctor or pharmacist if:

have ever had the following intestinal problems: "regional enteritis", "ulcerative colitis" or "colitis associated with" antibiotic use ".
If you experience stomach cramps or diarrhea that does not improve or worsens, stop using DUAC GEL and contact your doctor immediately. Antibiotics can cause a condition that causes severe diarrhea and stomach cramps. Although this is unlikely to happen with antibiotics applied to the skin.
If you have recently used other medicines containing clindamycin or erythromycin, there is a greater chance that DUAC GEL is not working as well as it should.

→ Tell your doctor or pharmacist if you have recently used any other medicines containing clindamycin or erythromycin.

Children

Do not give this drug to children under the age of twelve. It is not known if it works or if it is safe for them.

Interactions Which drugs or foods can change the effect of Duac

Tell your doctor or pharmacist if you are taking, have recently taken or might use any other medicines.

Tell your doctor or pharmacist if you are using any of the following:

Any acne treatment that contains antibiotics used on the skin
Medicated or "abrasive" soaps and detergents
Soaps or cosmetics that have too much drying effect
Products that contain abundant alcohol or "astringent substances".

This is because when used together with DUAC GEL, over time they can irritate the skin.

DUAC GEL can make some acne medicines less effective when used at the same time. This includes:

some acne medicines that are applied to the skin and that contain tretinoin, isotretinoin or tazarotene.

→ Tell your doctor or pharmacist if you are using even one of these medicines. It may be necessary to use the two products at different times of the day (for example, one in the morning and the other in the evening). Using other anti-acne medicines together with DUAC GEL may increase the risk of skin irritation.

→ Stop treatment and consult your doctor if skin irritation becomes severe (severe redness, dryness, itching, stinging, or burning).

DUAC GEL must not be used at the same time as medicines containing erythromycin.
Applying DUAC GEL at the same time as medicines such as dapsone and sulfacetamide may cause a temporary change in the color of the skin or facial hair (yellow / orange). This will not be permanent.
One of the medicines in DUAC GEL can affect the functioning of certain medicines that are used under general anesthesia (so-called "neuromuscular blocking agents").

→ Tell your doctor or pharmacist if you are going to have surgery.

If you are not sure if any of these conditions apply to you, talk to your doctor or pharmacist before using DUAC GEL.

Warnings It is important to know that:

Pregnancy, breastfeeding and fertility

There is only limited information on the safety of DUAC GEL in pregnant women.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

The doctor will evaluate the benefit for the mother and the risk for the baby of using DUAC GEL during pregnancy.

It is not known whether the components of DUAC GEL can pass into breast milk. One of the medicines contained in DUAC GEL is clindamycin. When clindamycin is taken by mouth or by injection, it can pass into breast milk. If you are breastfeeding, you should consult your doctor before using DUAC GEL.

Do not apply DUAC GEL on your breasts if you are breastfeeding.

Dose, Method and Time of Administration How to use Duac: Posology

Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.

Use DUAC GEL once a day in the evening.
It may take 2 to 5 weeks to see the effect of DUAC GEL.
Do not use for more than 12 weeks at a time. Your doctor will tell you how long the treatment should last.

How to apply DUAC GEL

Remove makeup completely.
Wash the affected area well. Then rinse with warm water and pat gently with a towel.
Apply a light layer of gel over the entire affected skin area, using your fingertips.
Apply to all areas of acne-prone skin, not just individual pimples. If the gel is not absorbed easily, this means that too much has been applied.

For the face only, use the amount of gel that, when it comes out of the tube, reaches the tip of the finger at the first contact (the first wrinkle on the finger). This is a "finger tip".
For the face and back, use two and a half "finger tips" in total.

5. In case of excessive dryness and peeling of the skin, you can use an oil-free moisturizer, use DUAC GEL less frequently or stop the treatment for a short time, to allow the skin to adjust to the treatment. This medicine may not work properly if it is not applied every day.

6. Wash your hands after using the gel.

7. After it has dried, you can use a non-oily make-up.

Always use this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.

Overdose What to do if you have taken too much Duac

If you use more DUAC GEL than you should

Be careful not to apply too much. Applying too much gel or applying more frequently will not help clear the pimples as quickly, and can cause skin irritation. If this happens, use the gel less often, or stop using it for a few days and then start over.

If you accidentally swallow DUAC GEL

If you accidentally swallow the gel, consult a doctor. You may have symptoms similar to taking antibiotics by mouth (stomach pain).

If you forget to use DUAC GEL

do not use a double dose to make up for forgotten individual doses.
Apply the next dose at the usual time.

Do not stop using DUAC GEL without advice.

Do not use the gel for more than 12 weeks at a time without talking to your doctor. Use DUAC GEL for the time recommended by your doctor. Do not stop unless your doctor advises you to.

It is important to continue using the gel as prescribed by your doctor. If you stop too soon, the acne can return.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Side Effects What are the side effects of Duac

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop using DUAC GEL and see a doctor immediately if you notice any of the following serious side effects - you may need urgent medical attention:

Signs of an allergic reaction (such as swelling of the face, eyes, lips or tongue, hives or difficulty in breathing, collapse)
severe or prolonged diarrhea, or abdominal cramps
severe burning, exfoliation, or itching.

Other possible side effects:

If you notice any of these side effects, try using DUAC GEL less often, or stop using it for a day or two and then resume.

Very common side effects

(at least 1 in 10 people are affected)

To the application site:

Redness, exfoliation, dryness

These side effects are usually minor.

Common side effects

(less than 1 in 10 people are affected)

Headache

To the application site:

Burning, pain, sensitivity to light

Uncommon side effects

(less than 1 in 100 people are affected)

Tingling (paraesthesia), worsening of acne, redness of the skin, itchy skin, rash (dermatitis, erythematous rash).

Other side effects

Other side effects have occurred in a very limited number of people, but their exact frequency is not known:

Allergic reactions

Inflammation of the intestine, diarrhea, including haemorrhagic diarrhea, stomach pain

To the application site:

Skin reactions, skin discoloration
Raised itchy rash (hives)

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Expiry and Retention

Keep DUAC GEL out of the sight and reach of children.

Pharmacist: Store in a refrigerator (2 ° C-8 ° C). Do not freeze.

Patient: after receiving DUAC GEL from the pharmacist, do not store it at a temperature above 25 ° C and discard after 2 months from opening.

Do not use this medicine after the expiry date which is stated on the tube and on the label (after "EXP:"). The expiry date refers to the last day of that month.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

What DUAC GEL contains

The active ingredients are: clindamycin phosphate, equivalent to clindamycin 1% weight / weight (10 mg / g) and benzoyl peroxide hydrate, equivalent to anhydrous benzoyl peroxide 5% weight / weight (50 mg / g).
The components are: carbomer, dimethicone, disodium lauryl sulfosuccinate, disodium edetate, glycerol, colloidal hydrated silica, poloxamer 182, purified water and sodium hydroxide.

Description of the appearance of DUAC GEL and contents of the pack

DUAC GEL is supplied in tubes containing - 6, 15, 25, 30, 50, 55, 60 and 70 grams. The gel is yellowish-white in color.
Each pack contains a tube of DUAC GEL.
Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Duac can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on the ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical data of 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 HOLDER OF THE ALL AUTHORIZATION "PLACING ON MARKETING 08.0 AUTHORIZATION NUMBER" PLACING ON MARKET09.0 DATE OF PR IMA AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIOPharmaceuticals, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORAN PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

DUAC 1% - 5% GEL

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 g of gel contains:

10 mg of clindamycin as clindamycin phosphate.

50 mg of anhydrous benzoyl peroxide as hydrated benzoyl peroxide.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Gel.

Homogeneous white to light yellow gel.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Duac 1% - 5% Gel is indicated for the topical treatment of mild to moderate acne vulgaris, especially in the presence of inflammatory lesions, in adults and adolescents 12 years of age and older (see sections 4.4 and 5.1).

Official guidelines on the appropriate use of antibacterial agents should be considered.

04.2 Posology and method of administration

For cutaneous use only.

Dosage

Adults and Adolescents (aged 12 or over)

Duac Gel should be applied only once a day in the evening to the entire affected area.

Patients should be advised that excessive application will not improve efficacy but may increase the risk of skin irritation. If excessive dryness or peeling occurs, the frequency of applications should be reduced or the application temporarily stopped (see section 4.4).

An effect on inflammatory and non-inflammatory lesions can be seen as early as 2-5 weeks of treatment (see section 5.1). The safety and efficacy of Duac Gel have not been studied beyond 12 weeks in the clinical trials of acne vulgaris. Treatment with Duac Gel should not exceed 12 weeks of continuous use.

Pediatric population

The safety and efficacy of Duac Gel have not been established in children below 12 years of age as Duac Gel is not recommended for use in this population.

Elderly patients

There are no particular recommendations.

Method of administration

Duac Gel should be applied in a thin layer after washing the skin with a mild cleanser and drying it completely. If the gel cannot be spread easily on the skin, too much has been applied. Wash hands after application.

04.3 Contraindications

Duac Gel must not be administered in patients with known hypersensitivity to:

- clindamycin

- lincomycin

- benzoyl peroxide

- any of the excipients contained in the product listed in section 6.1.

04.4 Special warnings and appropriate precautions for use

Contact with the mouth, eyes, lips, other mucous membranes or areas where the skin is abraded or injured should be avoided. The application on particularly sensitive areas of the skin must be done with caution.

In case of accidental contact, rinse thoroughly with water.

Duac Gel should be used with caution in patients with a history of segmental enteritis or ulcerative colitis or antibiotic-dependent colitis.

Duac Gel should be used with caution in atopic patients, in whom additional skin dryness may occur.

During the first few weeks of treatment, increased peeling and redness occurs in most patients. Depending on the severity of these side effects, patients may use a non-comedogenic moisturizer, temporarily reduce the frequency of Duac Gel application or temporarily discontinue use; however, efficacy has not been established for dosing frequencies below one. once a day.

Concomitant topical acne therapy should be used with caution because cumulative irritation may occur, which can sometimes be severe, especially with the use of exfoliating, scaling, or abrasive agents. If severe local irritation occurs ( e.g. severe erythema, severe dryness and itching, severe stinging / severe burning pain), Duac Gel should be discontinued.

Since benzoyl peroxide can cause increased sensitivity to sunlight, sunlamps should not be used and intentional or prolonged exposure to the sun should be avoided or minimized.

When exposure to strong sunlight cannot be avoided, patients should be advised to use a sunscreen product and wear protective clothing. If a patient has sunburn, these should be resolved before using Duac Gel.

In the event of prolonged or significant diarrhea or abdominal cramps, treatment with Duac Gel should be discontinued immediately as this may be a manifestation of antibiotic-dependent colitis. We recommend the use of appropriate diagnostic tools, such as the search for "Clostridium difficile" and its toxins and, if necessary, a colonoscopy and the prescription of a possible treatment of colitis.

The product can bleach hair or colored fabrics. Avoid contact with hair, fabrics, furniture or carpets.

Resistance to clindamycin

Patients who have recently used topical or systemic clindamycin or who have used erythromycin are more likely to have developed antimicrobial resistant Propionibacterium acnes and commensal flora (see section 5.1).

Cross resistance

In case of antibiotic monotherapy, cross-resistance with other antibiotics such as lincomycin and erythromycin is possible (see section 4.5).

04.5 Interactions with other medicinal products and other forms of interaction

No formal drug interaction studies have been conducted with Duac Gel.

The concomitant use of topical antibiotics, medicated or abrasive soaps and detergents, soaps and cosmetics that have a strong dehydrating effect, and products with high concentrations of alcohol and / or astringents, can determine a cumulative irritant effect and therefore must be carried out with particular caution.

Duac Gel should not be used in combination with products containing erythromycin due to possible antagonism to the clindamycin component. Clindamycin has been shown to have neuromuscular blocking properties that may potentiate the action of other neuromuscular blocking agents. Therefore, caution should be exercised in concomitant use.

Concomitant application of Duac Gel with tretinoin, isotretinoin and tazarotene should be avoided as benzoyl peroxide can reduce their effectiveness and increase irritation. If combination treatment is required, the products should be applied at different times of the day (for example, one in the morning and the other in the evening). Topical use of preparations containing benzoyl peroxide simultaneously with preparations containing sulphonamide may cause temporary changes in the facial hair and skin color (yellow / orange).

04.6 Pregnancy and lactation

Pregnancy

There are no adequate data from the use of Duac Gel in pregnant women. Animal reproduction / development studies have not been performed with Duac Gel or with benzoyl peroxide. There are limited data on the use of clindamycin and benzoyl peroxide alone in pregnant women. Data from a limited number of pregnancies in which clindamycin was used during the first trimester did not reveal any adverse effects of clindamycin on pregnancy or on the health of the fetus or newborn. Reproduction studies in rats and mice, with the use of subcutaneous and oral doses of clindamycin, did not show an alteration of fertility or damage to the fetus due to clindamycin.

The safety of Duac Gel in pregnancy has not been tested in humans. Therefore, Duac Gel should be prescribed by the doctor to pregnant women only after a "careful evaluation of the risk / benefit ratio.

Feeding time

The use of Duac Gel has not been studied during breastfeeding. However, the percutaneous absorption of benzoyl peroxide and clindamycin is low; it is not known whether clindamycin or benzoyl peroxide are excreted in breast milk following the use of Duac Gel, while the presence of clindamycin has been detected after taking. of clindamycin in breast milk by oral route and parenteral administration. Therefore, the use of Duac Gel for the treatment of breastfeeding patients is permitted only where the expected benefits outweigh the risk to the baby.

If Duac Gel is used during breastfeeding in order to avoid accidental ingestion by the baby, it must not be applied to the breast area.

Fertility

There are no data on the effects of Duac Gel on fertility in men.

04.7 Effects on ability to drive and use machines

Not relevant.

04.8 Undesirable effects

Adverse reactions (ADRs) are summarized below for Duac Gel as a combination of the additional ADRs that have been reported for the individual topical active substances, benzoyl peroxide or clindamycin. Adverse reactions are listed by system, organ class and frequency according to the MedDRA classification. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 and

Medra Very common common Uncommon Not known ** Disorders of the immune system Allergic reactions including hypersensitivity and anaphylaxis Nervous system disorders * Paresthesia Gastrointestinal disorders Colitis (including pseudo-membranous colitis), haemorrhagic diarrhea, diarrhea, abdominal pain Skin and subcutaneous tissue disorders * Erythema, peeling, dryness (generally reported as "mild" in severity) Burning sensation Dermatitis, itching, erythematous rash, worsening of acne Urticaria General disorders and administration site conditions Application site reactions including skin discoloration

* To the application site.

** Based on post-marketing reports.

Since these cases refer to a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency, however systemic reactions are rarely seen.

In addition to the ADRs listed in the table above, photosensitivity reactions at the application site were also commonly reported in the study conducted with topical clindamycin 1% / benzoyl peroxide gel at 3%.

In addition, in addition to the above ADRs, application site headache and pain were commonly reported in studies with topical clindamycin alone.

Local tolerability

During the five clinical trials with Duac Gel, all patients were classified for facial erythema, peeling, burning, dryness on the following scale: 0 = absent, 1 = mild, 2 = moderate and 3 = severe. The percentage of patients who had symptoms present before treatment (baseline) and during treatment was as follows:

Local tolerability assessments for subjects (n = 397) in the Duac Gel group during the Phase 3 studies

Before treatment (baseline) During the treatment Mild Moderate Serious Mild Moderate Serious Erythema 28% 3% 0 26% 5% 0 Desquamation 6% 0 17% 2% 0 Burning 3% 0 5% 0 Dryness 6% 0 15% 1% 0

04.9 Overdose

Excessive use of Duac Gel can cause severe irritation. In this case, discontinue use and wait until the skin has recovered.

Topical benzoyl peroxide is generally not absorbed in sufficient quantities to produce systemic effects.

Excessive application of topical clindamycin may result in the absorption of sufficient quantities to produce systemic effects.

In case of accidental ingestion of Duac Gel, gastrointestinal adverse reactions similar to those seen with systemic clindamycin may occur.

Appropriate measures must be taken to provide relief from irritation caused by overuse.

Cases of accidental ingestion should be treated clinically or as recommended by the National Poison Center, where available.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: clindamycin, combinations.

ATC code: D10 AF51.

Clindamycin is an antibiotic derived from lincosamides with bacteriostatic action on aerobic Gram-positive and a broad spectrum of anaerobic bacteria. Lincosamides, such as clindamycin, bind to the 23S subunit of the bacterial ribosome and inhibit the early stages of protein synthesis. The action of clindamycin is mainly bacteriostatic even if high concentrations can have a slow bactericidal action on sensitive strains.

Although clindamycin phosphate is inactive in vitro, a rapid hydrolysis in-vivo converts the compound into active antibacterial clindamycin. Clinical studies have demonstrated the action of clindamycin on the comedones of acne patients at levels such as to be active against most of the strains of the Propionibacterium acnes. Clindamycin in vitro inhibits all cultures of Propionibacterium acnes tested (MIC 0.4 mcg / ml). Following the application of clindamycin the unsaturated fatty acids of the skin surface decreased from 14% to about 2%.

Benzoyl peroxide has a mild keratolytic action on comedones at any stage of their development. It is an oxidizing agent with bactericidal activity against Propionibacterium acnes, organism involved in the development of acne vulgaris. It is also a sebostatic, and therefore counteracts the excessive production of sebum associated with acne.

Duac Gel has a combination of mildly keratolytic and antibacterial agents that has particular activity against mild to moderate inflammatory lesions of acne vulgaris.

The occurrence of acquired resistance may vary both geographically and over time for selected species. Local information on resistance is desirable, especially in the treatment of severe infections.

The addition of benzoyl peroxide reduces the potential for the emergence of organisms resistant to clindamycin.

The presence of both active substances in a single product is more convenient and ensures greater patient compliance.

Clinical efficacy and safety

In five randomized, double-blind clinical trials of 1318 patients with facial acne vulgaris with both inflammatory and non-inflammatory lesions, 396 used Duac Gel, 396 used benzoyl peroxide, 349 used clindamycin, and 177 used vehicle. Treatment was performed once daily for 11 weeks and patients were evaluated and lesions counted after 2, 5, 8 and 11 weeks.

The average percentage of changes related to the number of lesions after 11 weeks is shown in the table.

Average of the calculated percentage improvements in number of lesions from onset to after 11 weeks

150 (n = 120) 151 (n = 273) 152 (n = 280) 156 (n = 287) 158 * (n = 358) Inflammatory lesions Duac Gel 65 56 42 57 52 Benzoyl peroxide 36 37 32 57 41 Clindamycin 34 30 38 49 33 Excipients 19 -0.4 29 - 29 Non-inflammatory lesions Duac Gel 27 37 24 39 25 Benzoyl peroxide 12 30 16 29 23 Clindamycin -4 13 11 18 17 Excipients -9 -5 17 - -7 Total lesions (inflammatory and non-inflammatory) Duac Gel 41 45 31 50 41 Benzoyl peroxide 20 35 23 43 34 Clindamycin 11 22 22 33 26 Excipients 1 -1 22 - 16

* pivotal study. Statistically significant differences are highlighted in bold.

The reduction in total lesions was significantly greater with the use of Duac Gel than with clindamycin or vehicle in all five studies.

The improvement was significantly greater with Duac Gel than with benzoyl peroxide, but the difference was not statistically significant in the single studies.

In inflammatory lesions, Duac Gel was significantly superior to clindamycin alone in four out of five studies and benzoyl peroxide in three out of five studies. In non-inflammatory lesions, Duac Gel was significantly more effective than clindamycin in four out of five studies and showed a tendency to be more effective than benzoyl peroxide alone.

A general improvement was noted by the physician and was significantly better with Duac Gel than with benzoyl peroxide or clindamycin alone in three out of five studies.

After 2 weeks of treatment, there was an effect on inflammatory lesions. The effect on non-inflammatory lesions was more variable, with efficacy generally evident after 2-5 weeks of treatment.

05.2 "Pharmacokinetic properties

In a study performed under conditions of maximum percutaneous absorption, the mean levels of clindamycin in plasma after a 4-week application period of Duac Gel were insignificant (0.043% of the applied dose).

The presence of benzoyl peroxide in the formulation had no effect on the percutaneous absorption of clindamycin.

Studies with radio-labeled elements have shown that the absorption of benzoyl peroxide through the skin can only occur following conversion to benzoic acid. Benzoic acid is predominantly conjugated, forming hippuric acid, which is eliminated by the kidney.

05.3 Preclinical safety data

Duac Gel

Repeated dose dermal toxicity studies conducted with Duac Gel in two species for up to 90 days have shown no toxic effects other than minimal local irritation.

An eye irritation study found Duac Gel to be only mildly irritating.

No other preclinical studies have been conducted with Duac Gel, but only for the individual substances benzoyl peroxide and clindamycin.

Benzoyl peroxide

In animal toxicity studies, benzoyl peroxide was well tolerated when applied topically.

Although high doses of benzoyl peroxide have been observed to cause breaks in DNA strands, available data from other mutagenicity, carcinogenesis and photocarcinogenesis studies highlight that benzoyl peroxide is neither a carcinogen nor a photo carcinogen.

No data on reproductive toxicity are available.

Clindamycin

In vitro and in vivo studies did not reveal any mutagenic potential of clindamycin. Long-term animal studies have not been performed to investigate the carcinogenic potential of clindamycin. On the other hand, preclinical data show that there is no particular risk for humans based on conventional studies of single and repeated dose toxicity and reproductive toxicity.