TactuPump: Indications, Dosage, Precautions, Adverse Effects
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TactuPump - Product Information

Manufacture: Galderma Laboratories
Country: Canada
Condition: Acne, Acne rosacea (Rosacea), Acne Vulgaris (Acne), Pimples (Acne)
Class: Topical acne agents
Form: Cream, gel, liniment or balm, lotion, ointment, etc
Ingredients: Adapalene, benzoyl peroxide, hydrous, acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, sorbitan oleate, and purified water

Summary Product Information

Route of Administration Dosage Form / Strength Clinically Relevant Nonmedicinal Ingredients
Topical Gel, 0.1% adapalene / 2.5% benzoyl peroxide
Gel, 0.3% adapalene / 2.5% benzoyl peroxide
None

For a complete listing see Dosage Forms, Composition and Packaging section.

Indications and Clinical Use

TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) Topical Gel is indicated for:

  • Treatment of mild and moderate acne vulgaris, characterized by comedones, inflammatory papules/ pustules in patients 9 years of age and older.

TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel is indicated for:

  • Treatment of moderate and severe acne vulgaris, characterized by comedones, inflammatory papules/pustules with or without occasional nodules in patients 12 years of age and older.

Clinical Use

Physicians should be able to choose between the two concentrations TACTUPUMP FORTE Topical Gel and TACTUPUMP Topical Gel based on the presenting patient’s clinical condition and confounding factors that could worsen acne severity.

TACTUPUMP FORTE may also be considered for those patients who have moderate and severe acne vulgaris, who may have risk factors that worsen acne prognosis such as tendency toward cyclical relapses, pre -pubertal onset or long term history of acne, positive family / genetic history, those prone to or at risk for scarring, and those who may have intolerance or contraindication to systemic treatment. In these cases, physicians have the option to choose between the 2 concentrations. Clinical surveillance of these patients is recommended to ensure sufficient therapeutic response.

Geriatrics (> 65 Years of Age)

Safety and effectiveness of TACTUPUMP and TACTUPUMP FORTE in geriatric patients aged 65 years and above have not been established.

Pediatrics (< 9 Years of Age)

Safety and effectiveness of TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) in children below the age of 9 years have not been established.

Safety and effectiveness of TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) in children below the age of 12 years have not been established.

Contraindications

  • Patients who are hypersensitive to adapalene, benzoyl peroxide or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.
  • Application to areas of skin affected by eczema or seborrhoeic dermatitis

Warnings and Precautions

General

For external use only. Not for ophthalmic use.

Avoid contact with the eyes, lips, angles of the nose, mucous membranes, abraded skin and open wounds. If contact occurs, rinse thoroughly with water.

If a reaction suggesting allergic / hypersensitivity reactions to any component of the formula occurs, the use of the product should be discontinued.

Concomitant topical acne therapy is not recommended because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents (see DRUG INTERACTIONS, Drug-Drug Interactions). Avoid concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes).

The product should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of electrolysis, “waxing” and chemical depilatories for hair removal should be avoided on skin treated with TACTUPUMP or TACTUPUMP FORTE (see DRUG INTERACTIONS, Drug-Lifestyle Interactions).

TACTUPUMP and TACTUPUMP FORTE may bleach hair and coloured fabric. Use caution when applying near hairline (see DRUG INTERACTIONS, Drug-Lifestyle Interactions).

Patients should be advised to use non-comedogenic cosmetics (see DRUG INTERACTIONS, Drug-Lifestyle Interactions).

Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning or pruritus are associated with the topical application of retinoids and can also be expected with the use of TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) or TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel. These treatment-related effects generally occur during the first four weeks of therapy, are mostly mild to moderate in intensity, and usually lessen as the skin adjusts with continued use. Depending on the degree of the side effects, patients can be directed to use a moisturizer, use the medication less frequently or temporarily discontinue use until the symptoms subside (see DOSAGE AND ADMINISTRATION).

As with any retinoid, exposure to excessive sunlight, including sunlamps, should be avoided while using the preparation, or a suitably effective sunscreen product and protective clothing over the treated areas is recommended when exposure cannot be avoided. In case of sunburn, allow the skin to heal before using TACTUPUMP or TACTUPUMP FORTE. Weather extremes, such as wind or cold, may also be irritating to patients under treatment with adapalene. 

Carcinogenesis and Mutagenesis

See TOXICOLOGY.

Special Populations

Pregnant Women

It is recommended that topical adapalene/benzoyl peroxide should not beused by pregnant women. Topical adapalene/benzoyl peroxide should be used by women of childbearing years only after contraceptive counselling.

There are no well-controlled trials in pregnant women treated with TACTUPUMP or TACTUPUMP FORTE. Animal reproduction studies have not been conducted with the combination gel or benzoyl peroxide. Furthermore, such studies are not always predictive of human response; therefore, TACTUPUMP and TACTUPUMP FORTE should not be used by pregnant women.

There have been rare reports of birth defects among babies born to women exposed to topical retinoids during pregnancy. However, there are no well-controlled prospective studies of the use of topical retinoids, including adapalene, in pregnant women. A retrospective study of mothers exposed to topical tretinoin during the first trimester of pregnancy found no increase in the incidence of birth defects.

Adapalene administered orally at doses of ≥25 mg/kg/day has been shown to be teratogenic. No teratogenic effects were seen in rats at oral doses of up to 5.0 mg/kg/day.

Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day exhibited no foetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits (see TOXICOLOGY). The AUC at the No Observable Adverse Effect Level in the rat (6.0 mg/kg/ day, the most sensitive species) corresponds to safety margins of 32 and 102 when compared respectively to the exposure data in humans with TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel and TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) Topical Gel

Nursing Women

It is not known whether adapalene or benzoyl peroxide is excreted in human milk following use of TACTUPUMP or TACTUPUMP FORTE Topical Gel. Animal pharmacology studies indicate that adapalene is excreted in milk at levels lower than plasma levels. Because many drugs are excreted in human milk, caution should be exercised when TACTUPUMP or TACTUPUMP FORTE are administered to a nursing mother. If applied to the chest, facial contact and oral ingestion by the infant from maternal skin may occur.

Pediatrics (9-16 Years of Age)

No specific monitoring or hazards are associated with the use of TACTUPUMP in pediatric patients between the ages of 9 and 16 years.

Safety and effectiveness of TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) in children below the age of 9 years have not been established.

Safety and effectiveness of TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) in children below the age of 12 years have not been established.

Geriatrics (> 65 Years of Age)

Safety and effectiveness of TACTUPUMP and TACTUPUMP FORTE in geriatric patients age 65 years and above have not been established.

Adverse Reactions

Adverse Drug Reaction Overview

Treatment-related adverse reactions typically associated with use of TACTUPUMP or TACTUPUMP FORTE include mild to moderate application site reactions, such as skin irritation characterized by scaling, dryness, erythema, and burning/stinging. These reactions usually occur early in the treatment, and tend to gradually lessen over time (see WARNINGS AND PRECAUTIONS). Local adverse reactions during the treatment period were more pronounced with TACTUPUMP compared to adapalene or benzoyl peroxide alone.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

During clinical trials, 2077 subjects were exposed to TACTUPUMP or TACTUPUMP FORTE Topical Gel formulations.

A total of 1470 patients with acne vulgaris, 12 years and older, were treated once daily for 12 weeks to 12 months.

TACTUPUMP and TACTUPUMP FORTE efficacy and safety were assessed in subjects 12 years of age or older presenting with acne vulgaris. In these studies, TACTUPUMP and TACTUPUMP FORTE and their comparators were applied once daily over a treatment period of 12 weeks.

In two 12-week studies, related adverse events that were reported in at least 1% in any treatment group of 564 patients treated with TACTUPUMP Topical Gel are captured in Table 1.

Related adverse events reported in at least 1% of patients 12 years and older, in a 12-week study conducted with TACTUPUMP FORTE Topical Gel or TACTUPUMP Topical Gel are summarized in Table 2.

Table 1 Drug Relateda Adverse Events Reported in Clinical Trials by At Least 1% of Patients treated with TACTUPUMP (12 Weeks)
System Organ Class / Preferred Termb TACTUPUMP Gel
(N=564)
n (%)
Adapalene 0.1% Gel
(N=568)
n (%)
Benzoyl Peroxide 2.5% Gel
(N=564)
n (%)
Vehicle Gel
(N=489)
n (%)
Total number of AE(s) 104 87 40 23
Total number (%) of subjects with AE(s)c 81 (14.4) 70 (12.3) 29 (5.1) 21 (4.3)
Skin and Subcutaneous Tissue Disorders
Dry skin 36 (6.9) 33 (5.8) 11 (2.0) 10 (2.0)
Contact dermatitis 16 (2.8) 14 (2.5) 1 (0.2) 1 (0.2)
Skin irritation 6 (1.1) 1 (0.2) 3 (0.5) 0
Pruritus 4 (0.7) 4 (0.7) 10 (1.8) 4 (0.8)
General Disorders and Administration Site Conditions
Application site burning 13 (2.3) 3 (0.5) 2 (0.4) 2 (0.4)
Application site irritation 8 (1.4) 6 (1.1) 2 (0.4) 1 (0.2)

aDrug-related adverse events do not include known local adverse events (local tolerability) of retinoids.

bMultiple occurrences of a Preferred Term by a subject were counted once per Preferred Term.

cA subject was counted once even if the subject experienced more than one AE during the study.

Table 2 Drug Relateda Adverse Events Reported in at least 1% of patients 12 years and older, in a 12-week study conducted with TACTUPUMP FORTE Topical Gel or TACTUPUMP Topical
System Organ Class/Preferred Term TACTUPUMP FORTE Gel
(N=217
n(%)
TACTUPUMP Gel
(N=217)
n(%)
Vehicle Gel
(N=69)
n(%)
Total Number (%) of Subjects with at least one adverse reaction 15 (6.9) 0 0
Skin and Subcutaneous Tissue Disorders
Skin irritation 9 (4.1) 0 0
Eczema 3 (1.4) 0 0
Skin burning sensation 2 (0.9) 0 0
Dermatitis atopic 2 (0.9) 0 0

a Drug-related adverse events do not include known local adverse events (local tolerability) of retinoids.

In the two 12-week studies conducted with TACTUPUMP Topical Gel, local tolerability evaluations were conducted at each study visit by assessment of erythema, scaling, dryness and stinging/burning. Analysis over the 12-week period showed that local tolerability scores peaked at Week 1 of therapy and subsided thereafter. Most local tolerability signs for TACTUPUMP Topical Gel were mild or moderate in severity (Table 3).

Table 3 Highest Severity of Local Tolerability Scores Worse than Baseline, Safety Population, in Clinical Trials with TACTUPUMP
TACTUPUMP Gel
Na= 553
nb (%)
Adapalene 0.1% Gel
Na= 562
nb (%)
Benzoyl Peroxide 2.5% Gel
Na= 557
nb (%)
Gel Vehicle
Na= 481
nb (%)
Erythema 225 (40.7) 174 (31.0) 104 (18.7) 97 (20.2)
1 = mild 148 (26.8) 121 (21.5) 73 (13.1) 72 (15.0)
2 = moderate 72 (13.0) 51 (9.1) 30 (5.4) 24 (5.0)
3 = severe 5 (0.9) 2 (0.4) 1 (0.2) 1 (0.2)
Scaling 253 (45.7) 211 (37.5) 100 (18.0) 88 (18.3)
1 = mild 192 (34.7) 175 (31.1) 89 (16.0) 84 (17.5)
2 = moderate 58 (10.5) 35 (6.2) 11 (2.0) 4 (0.8)
3 = severe 3 (0.5) 1 (0.2) 0 0
Dryness 302 (54.6) 244 (43.3) 135 (24.2) 87 (18.1)
1 = mild 224 (40.5) 202 (35.9) 202 (35.9) 80 (16.6)
2 = moderate 74 (13.4) 39 (6.9) 14 (2.5) 7 (1.5)
3 = severe 4 (0.7) 3 (0.5) 0 0
Stinging/Burning 328 (59.3) 178 (31.6) 79 (14.2) 53 (11.1)
1 = mild 225 (40.7) 139 (24.7) 72 (12.9) 45 (9.4)
2 = moderate 84 (15.2) 31 (5.5) 5 (0.9) 8 (1.7)
3 = severe 19 (3.4) 8 (1.4) 2 (0.4) 0

aN = Total number of subjects with data available.

bn = Number of subjects with data worse than baseline.

At the end of treatment period (12 weeks), the incidence of local signs and symptoms of tolerability of TACTUPUMP Topical Gel is comparable to adapalene 0.1% gel with regard to the signs of erythema, scaling and dryness, but induces slightly more stinging (see Table 4).

Table 4 Comparison of Local Tolerability at End of Treatment Period (Last Score Observed Worse than Baseline): Combined Data from two Clinical Trials with TACTUPUMP
Final Scorea TACTUPUMP Gel
n (%)
Adapalene 0.1% Gel
n (%)
Benzoyl Peroxide 2.5% Gel
n (%)
Vehicle Gel
n (%)
Nb 553 562 557 481
Erythemac 60 (10.8) 56 (10.0) 27 (4.8) 39 (8.1)
Scalingc 55 (9.9) 54 (9.6) 34 (6.1) 30 (6.2)
Drynessc 65 (11.8) 65 (11.6) 32 (5.7) 28 (5.8)
Stinging/burningc 51 (9.2) 33 (5.9) 20 (3.6) 17 (3.5)

aLast score observed during post-baseline period and worse than baseline.

bN = Total number of subjects with data at baseline and at least one post-baseline observation.

cCombined for ‘mild’, ‘moderate’ and ‘severe’.

In the 12-week study conducted with both TACTUPUMP Topical Gel and TACTUPUMP FORTE Topical Gel, the incidence of local cutaneous irritation, for worst and final scores was comparable for all tolerability parameters between the active arms for the combined (moderate and severe) acne population (Table 5).

Table 5 Summary of Local Tolerability, observed data, worst and final scores, in the combined (moderate and severe IGA acne populations) treated with TACTUPUMP FORTE Topical Gel or TACTUPUMP Topical Gel
Worst Score Final Score
Sign/Symptom TACTUPUMP FORTE Gel
N= 217
n (%)
TACTUPUMP Gel
N= 217
n (%)
Gel Vehicle
N= 69
n (%)
TACTUPUMP FORTE Gel
N= 217
n (%)
TACTUPUMP Gel
N= 217
n (%)
Gel Vehicle
N= 69
n (%)
Erythema 104 (48.8) 93 (43.9) 25 (36.8) 40 (18.8%) 27(12.7%) 6 (8.8%)
Scaling 116 (54.5) 101 (47.6) 21 (30.9) 31 (14.6) 28 (13.2) 6 (8.8)
Dryness 137 (64.3) 132 (62.3) 27 (39.7) 38 (17.8) 35 (16.5) 6 (8.8)
Stinging/Burning 141 (66.2) 138 (65.1) 19 (27.9) 26 (12.2) 26 (12.3) 2 (2.9)

n = Number of subjects with data worse than baseline

Worst Score: The highest severity score observed during post-Baseline period for a subject.

Final Score: The last data observed during the post-Baseline period for a subject.

Signs/symptoms of local irritation in the Moderate stratum at the final visit occurred in a greater proportion of subjects in the TACTUPUMP FORTE Topical Gel group than in the TACTUPUMP Gel group. Similar trend was observed in the Severe stratum. Scaling had a higher increase in incidence between the Moderate and Severe acne strata (Table 6). Severity was mostly mild or moderate with few subjects experiencing severe signs/symptoms.

Table 6 Summary of Local Tolerability, observed data, final scores, in the moderate and severe IGA acne populations treated with TACTUPUMP FORTE Topical Gel or TACTUPUMP Topical Gel
Final Scores
Sign/Symptom Moderate acne Severe acne
TACTUPUMP FORTE Gel
 N= 110
n (%)
TACTUPUMPGel
N= 101
n (%)
Gel Vehicle
N= 35
n (%)
TACTUPUMP FORTE Gel
N= 103
n (%)
TACTUPUMP Gel
N= 111
n (%)

Gel Vehicle
N= 33
n (%)
Erythema 20 (18.2) 13 (12.9) 4 (11.4) 20 (19.4) 14 (12.6) 2 (6.1)
Scaling 13 (11.8) 11 (10.9) 3 (8.6) 18 (17.5) 17 (15.3) 3 (9.1)
Dryness 18 (16.4) 17 (16.8) 3 (8.6) 20 (19.4) 18 (16.2) 3 (9.1)
Stinging/Burning 13 (11.8) 12 (11.9) 0 13 (12.6) 14 (12.6) 2 (6.1)

n = Number of subjects with data worse than baseline

Final Score: The last data observed during the post-Baseline period for a subject.

Over the course of the long-term (12-month) study conducted with TACTUPUMP, no unexpected events or treatment emergent safety signals appeared. A total of 147 subjects (32.5%) reported related adverse events and most of the adverse events occurred within the first three months of treatment (see Table 7).

Table 7 Drug Relateda Adverse Events Reported in Long-Term Clinical Trial by At
Least 1% of Patients treated with TACTUPUMP (12 Months)
System Organ Class / Preferred Termb Baseline to Month 3
(n = 452)
Month 3 to Month 6
(n = 397)
Month 6 to Month 9
(n = 366)
Month 9 to 1 Year
(n = 334)
Total
(n = 452)
Total number of AE(s) 233 18 15 9 276
Total number (%) of subjects with AE(s)c  127 (28.1%) 16 (4.0%) 11 (3.0%) 5 (1.5%) 147 (32.5%)

Skin and Subcutaneous Tissue Disorders

94 (20.8) 8 (2.0) 8 (2.2) 4 (1.2) 110 (24.3)
Dry skin 69 (15.3) 5 (1.3) 6 (1.6) 3 (0.9) 78 (17.3)
Erythema 21 (4.6) 0 2 (0.5) 1 (0.3) 24 (5.3)
Skin desquamation 21 (4.6) 0 1 (0.3) 0 22 (4.9)
Skin discomfort 5 (1.1) 0 0 0 5 (1.1)
General Disorders and Administration Site Conditions 59 (13.1) 4 (1.0) 4 (1.1) 2 (0.6) 68 (15.0)
Application site burning 54 (11.9) 3 (0.8) 4 (1.1) 1 (0.3) 61 (13.5)
Application site irritation 16 (3.5) 1 (0.3) 0 1 (0.3) 18 (4.0)
Injury, Poisoning & Procedural Complications 5 (1.1) 4 (1.0) 0 0 9 (2.0)
Sunburn 5 (1.1) 4 (1.0) 0 0 9 (2.0)

aDrug-related adverse events do not include known local adverse events (local tolerability) of retinoids.

bMultiple occurrences within a System Organ Class (SOC) by a subject were counted once per SOC. Multiple occurrences of a Preferred Term by a subject were counted once per Preferred Term.

cA subject was counted once even if the subject experienced more than one Adverse Event during the study. Subjects may be counted in more than one period due to multiple Adverse Events.

Adverse Event(s) with incomplete onset date(s) or onset date(s) prior to the first application are only included in the Total column.

Less Common Clinical Trial Adverse Drug Reactions (<1%)

The following less common events have been designated as related (possibly, probably, definitely) to treatment with TACTUPUMP and TACTUPUMP FORTE, considering all patients in the clinical trials in acne vulgaris:

Blood and Lymphatic: Lymphadenopathy.

General and Administration Site: Pyrexia, xerosis, application site pruritus.

Gastrointestinal: Vomiting, diarrhea.

Nervous system: Dizziness, headache, paraesthesia (tingling at the application site)

Ophthalmologic: Eyelid edema, eye discharge, eyelid erythema.

Skin: Facial edema, worsening of acne, dermatitis, dermatitis contact, dermatitis exfoliative, pain of skin, skin desquamation, urticaria, swelling of face, skin hypopigmentation, cystic acne, acne, skin burning sensation, photosensitivity reaction, sunburn, rash, erythema, eczema.

Abnormal Hematologic and Clinical Chemistry Findings

No significant abnormal values were observed in the short term controlled studies or the long-term safety study.

Pediatrics

During a pediatric clinical trial, 285 children with acne vulgaris, 9 to 11 years of age were treated with TACTUPUMP or with the vehicle gel once daily for 12 weeks. Overall, the safety profile of TACTUPUMP in these subjects is comparable to the safety profile observed in older subjects 12 years of age and above, both in the nature and frequency of the observed adverse events.

Analysis of local tolerability evaluations shows similar incidence of treatment emergent signs and symptoms as in subjects 12 years of age and above, with local tolerance signs and symptoms peaking during the first week and decreasing over time.

No data is available for TACTUPUMP FORTE in children 9 to 11 years of age.

Post-Market Adverse Drug Reactions

The following events have been reported since the global launch of TACTUPUMP topical gel. These events have been chosen for inclusion due to either their seriousness, causal connection to TACTUPUMP or frequency of reporting. Post -market adverse events are reported spontaneously from a population of unknown size, thus estimates of frequency cannot be made.

Skin: Acne, pain of skin, eczema vesicular, allergic contact dermatitis, skin oedema, swelling of face, photosensitivity reaction, blister (vesicles), skin discoloration, rash, pruritus.

Ophthalmologic: Eyelid oedema, conjunctivitis.

Respiratory, thoracic and mediastinal disorders: Throat tightness

There is no post-marketing experience with TACTUPUMP FORTE.

Drug Interactions

Overview

There are no known interactions with other medications which are likely to be used topically and concurrently with TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) or TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel. Absorption of adapalene through human skin is low, and therefore interaction with systemic medications is unlikely.

The percutaneous penetration of benzoyl peroxide in the skin is low and the drug substance is completely metabolised into benzoic acid which is rapidly eliminated. Therefore, the potential interaction of benzoic acid with systemic medicinal products is unlikely to occur.

Drug-Drug Interactions

No formal drug-drug interaction studies were conducted with TACTUPUMP or TACTUPUMP FORTE.

As TACTUPUMP and TACTUPUMP FORTE have the potential for local irritation, it is possible that concomitant use of abrasive cleansers, strong drying agents, or irritant products may produce additive irritant effects. Particular caution should be exercised in using preparations containing sulphur, resorcinol, or salicylic acid in combination with TACTUPUMP or TACTUPUMP FORTE Topical Gel. If these preparations have been used, it is advisable not to start therapy with TACTUPUMP or TACTUPUMP FORTE until the effects of such preparations have subsided.

Drug-Food Interactions

Interactions of TACTUPUMP or TACTUPUMP FORTE with food products have not been established.

Drug-Herb Interactions

Interactions of TACTUPUMP or TACTUPUMP FORTE with herbal products have not been established.

Drug-Laboratory Interactions

Interactions of TACTUPUMP or TACTUPUMP FORTE with laboratory tests have not been established.

Drug-Lifestyle Interactions

TACTUPUMP and TACTUPUMP FORTE should not come into contact with any coloured material including hair and fabrics as this may result in bleaching and discolouration.

As with other retinoids, use of electrolysis, “waxing” and chemical depilatories for hair removal should be avoided on skin treated with TACTUPUMP or TACTUPUMP FORTE.

Patients should be advised to use non-comedogenic cosmetics. Colour cosmetics such as blushers and powders are acceptable; however, make-up cosmetics should be water based. Cosmetics must be removed by thorough cleansing before the area is treated.

Dosage and Administration

Recommended Dose and Dosage Adjustment

TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) Topical Gel ( patients 9 years of age and older) and TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel ( patients 12 years of age and older), should be applied to affected areas of the face, chest and back once daily in the evening, after washing gently with a non-medicated cleanser.

In subjects with moderate acne vulgaris, the choice between the two concentrations of adapalene/benzoyl peroxide fixed-dose combination should be based on the patient’s clinical condition and risk factors for acne severity.

A small amount of either TACTUPUMP or TACTUPUMP FORTE should be applied to provide a thin film, avoiding eyes, lips and mucous membranes. These medications should not be applied to cuts, abrasions, eczematous, or sunburned skin.

If irritation occurs, the patient should be directed to apply non-comedogenic moisturizers. Discontinue treatment if a severe local inflammatory response is experienced. Reinstitute therapy when the reaction has subsided, initially applying the preparation less frequently (e.g. every other day). Once-daily application may be resumed if it is judged that the patient is able to tolerate the treatment.

Missed Dose

If a single dose is missed, dosing should continue as per usual the following day, and the usual amount should be applied.

Overdosage

For management of a suspected drug overdose, contact your regional Poison Control Centre.

In the event of an acute oral overdose, activated charcoal may be administered to aid in the removal of unabsorbed drug. General supportive measures are recommended.

TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) Topical Gel and TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel are intended for cutaneous use only. Acute overdosage with the topical use is unlikely. If the medications are applied excessively, no more rapid or better results will be obtained and marked redness, peeling or discomfort may occur.

The acute oral toxicity of adapalene topical gel, 0.1% in mice and rats is greater than 10 mL/kg (10 mg/kg). Inadvertent oral ingestion of adapalene may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A, including teratogenesis in women of childbearing years. Therefore, pregnancy testing should be carried out in women of childbearing potential who have ingested the product.

Action and Clinical Pharmacology

Mechanism of Action

Adapalene and benzoyl peroxide, have complementary mechanisms of action targeting the pathology of acne vulgaris. The actives have an effect on three pathophysiologic factors known to contribute to acne vulgaris: altered follicular growth and differentiation (comedogenesis), colonization of the pilosebaceous unit with Propionibacterium acnes (P. acnes), and inflammation.

Adapalene

Adapalene is a chemically stable, retinoid-like compound. Biochemical and pharmacological profile studies have demonstrated that adapalene is a potent modulator of cellular differentiation, keratinization 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 normalizes the differentiation of follicular epithelial cells resulting in decreased microcomedone formation. In vitro studies with adapalene 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 (BPO)

Benzoyl peroxide is an oxidizing agent with a broad spectrum bactericidal activity, in particular against Propionibacterium acnes (P. acnes), which is abnormally present in the acne-affected pilosebaceous unit. Additionally benzoyl peroxide has demonstrated exfoliative and keratolytic activities.

Pharmacodynamics

TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) and TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gels combine two active substances, which have complementary mechanisms of action. The targets of this action are distinct, with no known pharmacodynamic interactions.

Adapalene

Studies in acne patients provide clinical evidence that topical adapalene is effective in reducing noninflammatory acne lesions (open and closed comedones). 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. This suggests that the cell-mediated inflammatory component of acne is modified by adapalene. Studies in human patients provide clinical evidence that topical adapalene is effective in reducing the inflammatory components of acne (i.e., papules and pustules).

Benzoyl Peroxide

Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects. As it exerts its antimicrobial effect through its oxidizing properties, resistance to this agent is unlikely to develop and has not been reported in the literature. In addition, benzoyl peroxide has keratolytic properties, which may improve efficacy.

Pharmacokinetics

The pharmacokinetic studies for TACTUPUMP evaluated systemic exposure to adapalene when applied in fixed combination with benzoyl peroxide or as monad. Plasma benzoyl peroxide was not measured because the skin rapidly metabolizes benzoyl peroxide into benzoic acid. Benzoic acid is an endogenous compound synthesized in the intestine from phenylalanine; the absorbed dose of benzoic acid after topical application of TACTUPUMP under maximized use conditions (i.e. 2 g/day) is less than 10% of the Acceptable Daily Intake established by the World Health Organization (WHO).

Topical application of either TACTUPUMP Topical Gel or adapalene gel (at corresponding equivalent adapalene strengths, i.e., 0.1% or 0.3%) under conditions of maximized use generated similar results. The studies confirmed low systemic exposure to adapalene when applied topically in TACTUPUMP Topical Gel or in adapalene gel. Benzoyl peroxide in fixed-combination with adapalene did not increase the systemic exposure of adapalene.

Absorption

Absorption of adapalene through human skin is low. No quantifiable levels of parent substance have been found in the plasma of patients following chronic adapalene gel 0.1% application in controlled clinical trials (limit of quantification = 0.25 ng/mL).

A pharmacokinetic study was conducted with TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) gel or adapalene gel under maximized conditions for 30 days (2 g applied to 1000 cm²). Daily application of TACTUPUMP resulted in low systemic exposure to adapalene, with observed plasma concentrations below 0.1 ng/mL in most subjects. Adapalene concentrations reached quantifiable levels (between 0.1 and 0.2 ng/mL) in two subjects treated with adapalene 0.1% /benzoyl peroxide 2.5% gel and three subjects with adapalene gel. The highest adapalene AUC0-24h determined in the fixed-combination group was 1.99 ng.h/mL compared to an AUC0-24h of 2.65 ng.h/mL with adapalene gel 0.1%.

An additional pharmacokinetic study was conducted with TACTUPUMP FORTE in 28 adult and adolescent subjects (12 to 33 years of age) with severe acne vulgaris. The subjects were treated with once-daily applications on all potentially affected areas during a 4-week period with, on average, 2.3 grams/day (range: 1.6-3.1grams/day) of TACTUPUMP FORTE gel applied as a thin layer to the face, shoulders, upper chest and upper back. After 4 weeks of treatment, 16 subjects (62%) had quantifiable adapalene plasma concentrations above the limit of quantification (LOQ of 0.1 ng/mL), with a mean Cmax of 0.16 ± 0.08 ng/mL and a mean AUC0-24h of 2.49 ± 1.21 ng.h/mL. The most exposed subject had adapalene Cmax and AUC0-24h values of 0.35 ng/mL and 6.41 ng.h/mL, respectively.

The percutaneous penetration of benzoyl peroxide is low; when applied topically, it is rapidly and completely converted into benzoic acid in the skin and eliminated in the urine.

Distribution

Classical plasma protein binding techniques were not feasible due to the physiochemical properties of adapalene. However, an alternative method was adopted that measured the partitioning of the drug between plasma or protein solutions and erythrocytes. When 3H-adapalene was incubated with human whole blood, 26% was bound to erythrocytes and total binding of adapalene in blood was > 99%. Adapalene bound primarily to lipoproteins and human serum albumin. The distribution for benzoyl peroxide could not be determined since it is converted into benzoic acid, which is an endogenous substance.

Metabolism

Following 24 -hour incubation with human hepatocytes, more than 90% of adapalene was metabolized. Both metabolites and adapalene showed a possibility for conjugation - predominantly glucuronidation and sulfation.

Benzoyl peroxide undergoes a copper-dependent metabolism in the skin to radical and non-radical metabolites. The initial cleavage of the peroxide bond yields short-lived hydroxyl benzoyloxyl free radicals. Benzoyloxyl radicals can fragment to form phenyl radicals plus carbon dioxide, or can attract hydrogen atoms to form the stable metabolite, benzoic acid. The metabolism of benzoyl peroxide metabolism evaluated in vitro in human skin confirmed benzoyl peroxide is metabolized into benzoic acid before passing into circulation.

Excretion

Excretion of adapalene appears to be primarily by the biliary route. The majority of an administered dose of 0.3% adapalene gel was excreted by 144 hours post dose and no drug was detected after the 6th day following last application. Under maximized conditions, the mean total unchanged drug substance excreted in the feces was 0.07% ± 0.06% of the total dose applied (range, 0.02% to 0.19%).

After topical administration in animal models, benzoyl peroxide was mainly and rapidly excreted in urine (45% of applied dose), nearly exclusively in the form of benzoic acid.

Special Populations and Conditions

Pharmacokinetic studies have not been conducted in subjects with a medical condition which might interfere with the absorption, distribution, metabolism, or excretion of TACTUPUMP or TACTUPUMP FORTE, in particular, a history of hepatic or renal disease.

Storage and Stability

TACTUPUMP (adapalene 0.1%/benzoyl peroxide 2.5%) and TACTUPUMP FORTE (adapalene 0.3%/benzoyl peroxide 2.5%) Topical Gel should be stored at room temperature (15˚ to 25˚C). The product should be used within a period of 12 months after first opening. Any unused portion should be discarded 12 months after opening or at product expiry date (whichever comes first). Keep container tightly closed. Keep in a safe place out of the reach of children.

Special Handling Instructions

There are no special handling instructions for TACTUPUMP and TACTUPUMP FORTE topical gels.

Dosage Forms, Composition and Packaging

TACTUPUMP (adapalene 0.1% /benzoyl peroxide 2.5%) topical gel is available in 70 g polypropylene and high density polyethylene (HDPE) bottle with a polypropylene pump. Physician samples are available in a 15 g bottle with a pump.

TACTUPUMP FORTE topical gel (adapalene 0.3% /benzoyl peroxide 2.5%) is available in 70 g polypropylene and high density polyethylene (HDPE) bottle with a polypropylene pump. Physician samples are available in a 15 g bottle with a pump.

TACTUPUMP and TACTUPUMP FORTE are white to very pale yellow opaque gels.

Each gram of TACTUPUMP or TACTUPUMP FORTE topical gel contains respectively adapalene 0.1% w/w (1 mg/g) or adapalene 0.3% w/w (3 mg/g) in addition to benzoyl peroxide 2.5% w/w (25 mg/g) in a vehicle consisting of acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, sorbitan oleate, and purified water.