Panalene Duo is for once-daily cutaneous use only.
In case of accidental ingestion, appropriate symptomatic measures should be taken.
Not applicable.
Panalene Duo may cause the following adverse reactions at the site of application:
| System Organ Class (MedDra) | Frequency | Adverse Drug Reaction |
| Eye disorders | Not known (cannot be estimated from the available data)* | Eyelid oedema |
| Immune system | Not known (cannot be estimated from the available data)* | Anaphylactic reaction |
| Respiratory, thoracic and mediastinal disorders | Not known (cannot be estimated from the available data)* | Throat tightness, dyspnoea |
| Skin and subcutaneous tissue disorders | Common (>1/100 to <1/10) | Dry skin, irritative contact dermatitis, skin irritation, skin burning sensation, erythema, skin exfoliation (scaling) |
| Uncommon (>1/1000 to <1/100) | Pruritus, sunburn | |
| Not known (cannot be estimated from the available data)* | Allergic contact dermatitis, swelling face, pain of skin (stinging pain), blisters (vesicles), skin discolouration, (hyperpigmentation and hypopigmentation), urticaria. |
*Post marketing surveillance data
If skin irritation appears after application of Panalene Duo, the intensity is generally mild or moderate, with local tolerability signs and symptoms (erythema, dryness, scaling, burning and pain of skin (stinging pain) peaking during the first week and then subsiding spontaneously.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard
Cutaneous treatment of Acne vulgaris when comedones, papules and pustules are present
Panalene Duo is indicated in adults and adolescents aged 9 years and over.
Pharmacotherapeutic group: Anti-Acne Preparations for Topical Use, D10AD Retinoids for topical use in acne;
ATC code: D10AD53
Mechanism of action and Pharmacodynamic effects:
Panalene Duo combines two active substances, which act through different, but complementary, mechanisms of action.
- Adapalene: Adapalene is a chemically stable, naphthoic acid derivative with retinoid-like activity. Biochemical and pharmacological profile studies have demonstrated that adapalene acts in the pathology of Acne vulgaris: it is a potent modulator of cellular differentiation and keratinisation and it has anti-inflammatory properties. Mechanistically, adapalene binds to specific retinoic acid nuclear receptors. Current evidence suggests that topical adapalene normalizes 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 to inflammatory mediators. In vitro studies have shown inhibition of the AP-1 factors and the inhibition of the expression of toll like receptors 2. This profile suggests that the cell mediated inflammatory component of acne is reduced by adapalene.
- Benzoyl peroxide: Benzoyl peroxide has been shown to have antimicrobial activity; particularly against P. acnes, which is abnormally present in the acne-affected pilosebaceous unit. Additionally benzoyl peroxide has demonstrated exfoliative and keratolytic activities. Benzoyl peroxide is also sebostatic, counteracting the excessive sebum production associated with acne.
Clinical efficacy of Panalene Duo in patients aged 12 years and older:
The safety and efficacy of Panalene Duo applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing Panalene Duo to its individual active components, adapalene and benzoyl peroxide, and to the gel vehicle in acne patients. A total of 2185 patients were enrolled in Study 1 and Study 2. The distribution of patients in the two studies was approximately 49% male and 51% female, 12 years of age or older (mean age: 18.3 years; range 12 - 50), presenting 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions at baseline. The patients treated the face and other acne affected areas as needed once daily in the evening.
The efficacy criteria were:
(1) Success rate, percentage of patients rated 'Clear' and 'Almost Clear' at Week 12 based on the Investigator's Global Assessment (IGA);
(2) Change and Percent Change from baseline at Week 12 in
- Inflammatory lesion counts
- Non-inflammatory lesion counts
- Total lesion count
The efficacy results are presented for each study in Table 1 and combined results in Table 2. Panalene Duo was shown to be more effective compared to its monads and gel vehicle in both studies. Overall, the net beneficial effect (active minus vehicle) obtained from Panalene Duo was greater than the sum of the net benefits obtained from the individual components, thus indicating a potentiation of the therapeutic activities of these substances when used in a fixed-dose combination. An early treatment effect of Panalene Duo was consistently observed in Study 1 and Study 2 for Inflammatory Lesions at Week 1 of treatment. Noninflammatory lesions (open and closed comedones) noticeably responded between the first and fourth week of treatment. The benefit on nodules in acne has not been established.
Table 1 Clinical efficacy in two comparative trials
| Study 1 | ||||
| Study 1 Week 12 LOCF; ITT | Adapalene+BPO N=149 | Adapalene N=148 | BPO N=149 | Vehicle N=71 |
| Success (Clear, Almost Clear) | 41 (27.5%)
| 23 (15.5%) p=0.008 | 23 (15.4%) p=0.003 | 7 (9.9%) p=0.002 |
| Median Reduction (% Reduction) in |
|
|
|
|
| Inflammatory Lesion Count | 17 (62.8 %) | 13 (45.7 %) p<0.001 | 13 (43.6 %) p<0.001 | 11 (37.8 %) p<0.001 |
| Noninflammatory Lesion Count | 22 (51.2 %) | 17 (33.3 %) p<0.001 | 16 (36.4 %) p<0.001 | 14 (37.5 %) p<0.001 |
| Total lesion Count | 40 (51.0 %) | 29 (35.4 %) p<0.001 | 27 (35.6 % p<0.001 | 26 (31.0 %) p<0.001 |
| Study 2 | ||||
| Study 2 Week 12 LOCF; ITT | Adapalene+BPO N=415 | Adapalene N=420 | BPO N=415 | Vehicle N=418 |
| Success (Clear, Almost Clear) | 125 (30.1%) | 83 (19.8%) p<0.001 | 92 (22.2%) p=0.006 | 47 (11.3%) p<0.001 |
| Median Reduction (% Reduction) in |
| |||
| Inflammatory Lesion Count | 16 (62.1 %) | 14 (50.0 %) p<0.001 | 16 (55.6 %) p=0.068 | 10 (34.3 %) p<0.001 |
| Noninflammatory Lesion Count | 24 (53.8 %) | 22 (49.1 %) p=0.048 | 20 (44.1 %) p<0.001 | 14 (29.5 %) p<0.001 |
| Total Lesion Count | 45 (56.3 %) | 39 (46.9 %) p=0.002 | 38 (48.1 %) p<0.001 | 24 (28.0 %) p<0.001 |
Table 2 Clinical efficacy in combined comparative trials
| Adapalene+BPO N=564 | Adapalene N=568 | BPO N=564 | Gel Vehicle N=489 | |
| Success (Clear, Almost Clear) | 166 (29.4%) | 106 (18.7%) | 115 (20.4%) | 54 (11.1%) |
| Median Reduction (% Reduction) in |
| |||
| Inflammatory Lesion Count | 16.0 (62.1) | 14.0 (50.0) | 15.0(54.0) | 10.0 (35.0) |
| Noninflammatory Lesion Count | 23.5 (52.8) | 21.0 (45.0) | 19.0 (42.5) | 14.0 (30.7) |
| Total Lesion Count | 41.0 (54.8) | 34.0 (44.0) | 33.0 (44.9) | 23.0 (29.1) |
Clinical efficacy of Panalene Duo in children 9 to 11 years old
During a paediatric clinical trial, 285 children with acne vulgaris, aged 9 - 11 years (53% of the subjects were 11 years old, 33% were 10 years old and 14% were 9 years old) with a score of 3 (moderate) on the IGA scale and a minimum of 20 but not more than 100 total lesions (Non-inflammatory and/or Inflammatory) on the face (including the nose) at baseline were treated with Panalene Duo Gel once daily for 12 weeks.
The study concludes that the efficacy and safety profiles of Panalene Duo Gel in the treatment of facial acne in this specific younger age group are consistent with results of other pivotal studies in subjects with acne vulgaris aged 12 years and older showing significant efficacy with an acceptable tolerability. A sustained early treatment effect of Panalene Duo Gel compared to Gel Vehicle was consistently observed for all Lesions (Inflammatory, Non-Inflammatory, and Total) at Week 1 and continuing to Week 12.
| Study 3 | ||
| Week 12 LOCF; ITT | Adapalene + BPO N=142 | Vehicle Gel N=143 |
| Success (Clear, Almost Clear) | 67 (47.2%) | 22 (15.4%) |
| Median Reduction (% Reduction) in | ||
| Inflammatory Lesion Count | 6 (62.5%) | 1 (11.5%) |
| Noninflammatory Lesion Count | 19 (67.6%) | 5 (13.2%) |
| Total Lesion Count | 26 (66.9%) | (18.4%) |
The pharmacokinetic (PK) properties of Panalene Duo are similar to the PK profile of Adapalene 0.1% gel alone.
In a 30-day clinical PK study, conducted in patients with acne who were tested with either the fixed-combination gel or with an adapalene 0.1% matched formula under maximised conditions (with application of 2 g gel per day), adapalene was not quantifiable in the majority of plasma samples (limit of quantification 0.1 ng/ml). Low levels of adapalene (Cmax between 0.1 and 0.2 ng/ml) were measured in two blood samples taken from the subjects treated with Panalene Duo and in three samples from the subjects treated with Adapalene 0.1% Gel. The highest adapalene AUC 0-24h determined in the fixed-combination group was 1.99 ng.h/ml.
These results are comparable to those obtained in previous clinical PK studies on various Adapalene 0.1% formulations, where systemic exposure to adapalene was consistently low.
The percutaneous penetration of benzoyl peroxide is low; when applied on the skin, it is completely converted into benzoic acid which is rapidly eliminated.
Panalene Duo Gel should not be applied to damaged skin, either broken (cuts or abrasions), eczematous or sunburned.
Panalene Duo should not come into contact with the eyes, mouth, nostrils or mucous membranes. If product enters the eye, wash immediately with warm water.
This product contains propylene glycol (E1520) that may cause skin irritation.
If a reaction suggesting sensitivity to any component of the formula occurs, the use of Panalene Duo should be discontinued.
Excessive exposure to sunlight or UV radiation should be avoided.
Panalene Duo should not come into contact with any coloured material including hair and dyed fabrics as this may result in bleaching and discoloration.
Not relevant.
Panalene Duo should be applied to the entire acne affected areas once a day in the evening on a clean and dry skin. A thin film of gel should be applied, with the fingertips, avoiding the eyes and lips.
If irritation occurs, the patient should be directed to apply non-comedogenic moisturizers, to use the medication less frequently (e.g. every other day), to suspend use temporarily, or to discontinue use altogether.
The duration of treatment should be determined by the Doctor on the basis of the clinical condition. Early signs of clinical improvement usually appear after 1 to 4 weeks of treatment.
The safety and effectiveness of Panalene Duo have not been studied in children below 9 years of age.
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
