OXIDOBEN Gel (Adapalene + Benzoyl peroxide )

Table of Content

Composition

OXIDOBEN Gel Contains:

Adapalene Ph.Eur ............................... 0.1%w/w

Hydrous Benzoyl peroxide Ph.Eur. equivalent to

Anhydrous Benzoyl peroxide ............... 2.5%w/w

In a gel base .................................................... q.s.

Dosage Form

Gel

Description

OXIDOBEN Gel is a combination product for topical use containing adapalene 0.1% and benzoyl peroxide 2.5%.

Adapalene, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties.

Benzoyl Peroxide is a highly lipophilic oxidizing agent that localizes in both bacterial and keratinocyte cell membranes.

Pharmacology

Pharmacodynamics

OXIDOBEN Gel combines two active substances, which act through different, but complimentary, mechanisms of action.

Adapalene

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Benzoyl peroxide

Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects.

Pharmacokinetics

A pharmacokinetic study was conducted in 24 subjects with acne vulgaris who were treated once daily for 30 days with 2 grams/day of a combination gel containing adapalene 0.1% and benzoyl peroxide 2.5% applied to 1000 cm2 of acne involved skin (face, chest and upper back). In 2 subjects (20%), there were quantifiable adapalene plasma concentrations above the limit of quantification (LOQ = 0.1ng/mL). The highest adapalene Cmax and AUC0–24hours was 0.21 ng/mL and 1.99 ng•h/mL, respectively. Excretion of adapalene appears to be primarily by the biliary route.

Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine.

Indications

OXIDOBEN Gel is indicated for the topical treatment of acne vulgaris in patients who are 9 years of age and older (see WARNINGS AND PRECAUTIONS - Paediatric Use).

Dosage and Administration

OXIDOBEN Gel should be applied to the affected areas once daily in the evening. The patient should follow the given instructions while using OXIDOBEN Gel.

  • The affected areas should be thoroughly washed with water.
  • The pin point tube should be squeezed to extract the required amount of OXIDOBEN Gel onto your finger tip
  • A thin film of OXIDOBEN Gel should be gently applied on the entire acne affected areas once a day in the evening.
  • Areas around the eyes, lips and mucous membranes should be avoided.
  • The cap of the tube should be kept tightly closed after use.

Contraindications

Hypersensitivity to the active substances or to any of the excipients

Warnings and Precautions

Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be minimized during the use of OXIDOBEN Gel. Patients with high levels of sun exposure and those with inherent sensitivity to the sun should exercise particular caution. Use of sunscreen products and protective apparel, (e.g., hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with OXIDOBEN Gel.

Local Cutaneous Reactions

Erythema, scaling, dryness, and stinging/burning may be experienced with use of OXIDOBEN Gel. These are most likely to occur during the first 4 weeks of treatment, are mostly mild to moderate in intensity, and usually lessen with continued use of the medication. Irritant and allergic contact dermatitis may occur. Depending upon the severity of these adverse reactions, patients should be instructed to use a moisturizer, reduce the frequency of the application of OXIDOBEN Gel, or discontinue use. The product should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of ‘waxing’ as a depilatory method should be avoided on skin treated with OXIDOBEN Gel. Avoid concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong skin-drying effect and products with high concentrations of alcohol, astringents, spices or limes).

Drug Interactions

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents.

No formal drug-drug interaction studies were conducted with the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%.

Pregnancy

Pregnancy Category C

There are no well-controlled trials in pregnant women treated with the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%. 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, the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5% should be used during pregnancy only if the potential benefit justifies the risk to the foetus.

Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day, up to 25-59 times (mg/m2) the maximum recommended human dose (MRHD) exhibited no foetotoxicity and only minimal increases in supernumerary ribs in both the species and delayed ossification in rabbits.

Lactation

It is not known whether adapalene or benzoyl peroxide is excreted in human milk following the use of the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%. Because many drugs are excreted in human milk, caution should be exercised when OXIDOBEN Gel is administered to a nursing mother.

Paediatric Use

Safety and effectiveness of combination gel containing adapalene 0.1% and benzoyl peroxide 2.5% in paediatric patients below the age of 9 years have not been established.

In a study, 285 pediatric subjects 9 to 11 years of age were randomized to once daily topical application of adapalene 0.1%/benzoyl peroxide 2.5% gel or vehicle gel.  The median age of subjects was 11 years and 24% were males.  At baseline, subjects had a minimum of 20 but not more than 100 total lesions (inflammatory and/or non-inflammatory) with an Investigator Global Assessment score of ‘Moderate’. The efficacy results at week 12 are presented in Table 1.

Table1. Clinical efficacy of adapalene 0.1%/benzoyl peroxide 2.5% gel at week 12

 

Adapalene 0.1%/Benzoyl peroxide 2.5% gel

N=142

Vehicle Gel

N=143

IGA: Two Grade Improvement and Clear or Almost Clear

 

67 (47.2%)

 

22 (15.4%)

Inflammatory Lesions:

Mean Absolute (Percent) Change

 

7.4 (36.0%)

 

0.7 (-13.2%)

Non-inflammatory Lesions: Mean Absolute (Percent) Change

 

20.2 (54.7%)

 

2.9 (2.3%)

Geriatric Use

Clinical studies on the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5% did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.

Undesirable Effects

Clinical Trials Experience

During clinical trials, 1401 subjects were exposed to the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%. A total of 1036 subjects with acne vulgaris, aged 12 years and older, were treated once daily for 12 weeks to 12 months. Related adverse reactions reported within 12 weeks of treatment and in at least 1% of subjects treated with the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%   and those reported in subjects treated with the vehicle gel, are presented in Table 2:

Table 2: Drug related adverse reactions reported in clinical trials by at least 1% of subjects treated for 12 weeks

System Organ Class/ Preferred Term

Adapalene 0.1%/Benzoyl peroxide 2.5% gel

N = 564

Vehicle gel

N = 489

Subjects with adverse events

14%

4%

Dry Skin

7%

2%

Contact dermatitis

3%

<1%

Application site burning

2%

<1%

Application site irritation

1%

<1%

Skin irritation

1%

0%

 

The uncommon side effects were pruritus and sunburn. If skin irritation appeared after application of the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%, the intensity was generally mild or moderate, with local tolerability signs and symptoms (erythema, dryness, scaling, burning and pain of skin ) peaking during the first week and then subsiding spontaneously.

Local tolerability evaluations, presented in Table 3, were conducted at each study visit in clinical trials by assessment of erythema, scaling, dryness, burning and stinging.

Table 3: Incidence of local cutaneous irritation in controlled clinical trials (N = 553) treatment emergent signs and symptoms

 

Maximum Severity During Treatment

End of Treatment Severity (12 Weeks)

 

Mild

Moderate

Severe

Mild

Moderate

Severe

Erythema

27%

13%

1%

8%

2%

1%

Scaling

35%

11%

1%

9%

1%

<1%

Dryness

41%

13%

1%

10%

2%

<1%

Stinging/burning

41%

15%

3%

7%

2%

1%

 

Analysis over the 12-week period showed that the local tolerability scores for erythema, scaling, dryness and stinging/burning peaked at week 1 of therapy and decreased thereafter.

During a pediatric clinical trial, 285 children with acne vulgaris, 9 to 11 years of age were treated with combination gel containing adapalene 0.1% and benzoyl peroxide 2.5% or with the vehicle gel once daily for 12 weeks. Overall, the safety profile of combination gel containing adapalene 0.1% and benzoyl peroxide 2.5% 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 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 tolerability signs and symptoms peaking during the first week and decreasing over time.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of the combination gel containing adapalene 0.1% and benzoyl peroxide 2.5%: eyelid oedema, sunburn, blisters, skin pain, pruritus, swelling face, conjunctivitis, skin discolouration, rash, eczema and allergic contact dermatitis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024. 

By reporting side effects you can help provide more information on the safety of this product.

Overdosage

OXIDOBEN Gel should be applied once daily, and is for cutaneous use only.

In case of accidental ingestion, appropriate symptomatic measures should be taken.

Shelf-Life

2 years

Storage and Handling Instructions

Store below 25°C

Packaging Information

OXIDOBEN Gel: Tube of 15 gm

Last updated: Aug 2015

Last reviewed: Apr 2018