Klenzit-MS

Opaque white smooth homogeneous gel.
Each g of gel contains: Adapalene (as microspheres) 1 mg in an aqueous gel base.
Adapalene Gel microsphere, containing Adapalene in a Microsponge delivery system, is used for the topical treatment of acne vulgaris. Each gram of Adapalene Gel microsphere contains adapalene 0.1% (1 mg), a retinoid analogue for the topical treatment of acne vulgaris, as microspheres and preservatives, viz. methyl hydroxybenzoate and phenoxyethanol.
Microsponge is a polymeric delivery system consisting of porous microspheres, which are round microscopic particles made of synthetic polymer. These particles entrap the active drug, Adapalene, in the microsponge system. After the product is applied, the entrapped drug is then delivered to the skin in a controlled time-release pattern or a pre-programmed manner after it has been applied to the skin.
The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naptholic acid. Adapalene is a white to off-white powder which is soluble in tetrahydrofuran, sparingly soluble in ethanol, and practically insoluble in water. The molecular formula of adapalene is C₂₈H₂₈O₃, and its molecular weight is 412.52.

Pharmacotherapeutic Group: D10A Anti-Acne Preparations for Topical Use. ATC code: D10AD03.
Pharmacology: Pharmacodynamics: Adapalene is a retinoid-like compound which in, in vivo and in vitro models of inflammation, has been demonstrated to possess anti-inflammatory properties. Adapalene is essentially stable to oxygen and light and is chemically non-reactive. Mechanically, adapalene binds like tretinoin to specific retinoic acid nuclear receptors but, unlike tretinoin not to cytosolic receptor binding proteins.
Adapalene applied cutaneously is comedolytic in the rhino mouse model and also has effects on the abnormal processes of epidermal keratinization and differentiation, both of which are present in the pathogenesis of acne vulgaris. The mode of action of adapalene is suggested to be a normalisation of differentiation of follicular epithelial cells resulting in decreased microcomedone formation.
Adapalene is superior to reference retinoids in standard anti-inflammatory assays, both in vivo and in vitro. Mechanistically, it inhibits chemotactic and chemokinetic responses of human polymorphonuclear leucocytes and also the metabolism by lipoxidation of arachidonic acid to pro-inflammatory mediators. This profile suggests that the cell mediated inflammatory component of acne may be modified by adapalene.
Microsponge delivery system of microspheres: Microsponge is a polymeric delivery system consisting of solid phase porous microspheres, which are round microscopic particles made of synthetic polymer. These particles entrap the active drug, Adapalene, in the microsponge system. After the product is applied, the entrapped drug is then delivered to the skin in a controlled time-release pattern or a pre-programmed manner after it has been applied to the skin.
The microsphere hold the drug in reserve, allowing the skin to absorb small amounts of active drug over time, thereby reducing irritation or almost no irritation because microspheres themselves remain on top of the skin and are easily washed off when the patient takes a shower or washes the face.
Although the microsponge size may vary usually from 5 to 300 μm in diameter, a typical 25 μm sphere can have up to 250,000 pores and an internal pore structure equivalent to 10 ft. in length, providing a total pore volume of about 1 mL/g. This results in a large reservoir within each Microsponge, which can be loaded with up to its own weight in active agents.
Adapalene microsphere formulation contains 3 to 10 μm sized microparticles of Adapalene entrapped in microspheres less than 150 μm in diameter.
The penetration properties of the microspheres in the skin depend on the size of the particles. Rolland et al (1993) and other studies have reported that microspheres of 310 μm, topically applied to human skin, aggregated in the follicular orifices and pilosebaceous unit. Adapalene microparticles enter selectively into the hair follicle and may yield high local concentrations of the active compound. The controlled destabilization of the microspheres may allow a controlled release of drug and thus provides a highly selective, specific and potent action at the target without irritating the other tissues.
Pharmacokinetics: The pharmacokinetics of topical Adapalene has not been extensively studied. Therapeutic effects of the drug usually appear within 8 to 12 weeks of initiation of treatment. The transdermal absorption of Adapalene is low. Only trace amounts of the parent substance (<0.25 ng/mL) have been found in the plasma of acne patients following chronic topical application of Adapalene gel in controlled clinical trials. The micro particles of Adapalene, being of the size of 3 to 10 μm, achieve follicular targeting and action at the pilosebaceous unit without dispersing into the corneum and causing irritation. Thus enhanced effect as well as safety is achieved with Adapalene microsponge delivery. Excretion of any systemically absorbed Adapalene appears to be primarily by the biliary route.

Adapalene Gel microsphere is proposed for the cutaneous treatment of mild to moderate acne where comedones, papules and pustules predominate.

Adapalene Gel microsphere should be applied to the acne affected areas once a day before retiring and after washing. A thin film of gel should be applied, with the fingertips, avoiding the eyes and lips (see Precautions as follows). Ensure that the affected areas are dry before application.
During the early weeks of therapy, an apparent exacerbation of acne may occur. This is due to the action of the medication on previously unseen lesions and should not be considered a reason to discontinue therapy.
Therapeutic results may be noticed within eight to twelve weeks of treatment.
Since it is customary to alternate therapies in the treatment of acne, it is recommended that the physician assess the continued improvement of the patient after three months of treatment with Adapalene Gel Microsphere.
With patients for whom it is necessary to reduce the frequency of application or to temporarily discontinue treatment, frequency of application may be restored or therapy resumed once it is judged that the patient can again tolerate the treatment.
If patients use cosmetics, these should be non-comedogenic and non-astringent.
Paediatric population: The safety and effectiveness of Adapalene Gel microsphere have not been studied in children below 12 years of age. Adapalene gel microsphere should not be used in patients with severe acne.

Adapalene Gel microsphere is not to be taken orally and is for cutaneous 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.
The acute oral dose of Adapalene Gel microsphere required to produce toxic effects in mice is greater than 10 mg/kg. Nevertheless, unless the amount accidentally ingested is small, an appropriate method of gastric emptying should be considered.
Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.

Hypersensitivity to the active substance or to any of the excipients in the vehicle gel.

If a reaction suggesting sensitivity or severe irritation occurs, use of the medication should be discontinued. If the degree of local irritation warrants, patients should be directed to use the medication less frequently, to discontinue use temporarily, or to discontinue use altogether. Adapalene Gel microsphere should not come into contact with the eyes, mouth, nostrils or mucous membranes.
If product enters the eye, wash immediately with warm water. The product should not be applied to either broken (cut and abrasions) or eczematous skin, nor should it be used in patients with severe acne involving large areas of the body.
Patients with sunburn should be advised not to use the product until fully recovered.
The excipient propylene glycol (E1520) may cause skin irritation and methyl parahydroxybenzoate (E218) may cause allergic reactions which can possibly be delayed.
Effects on Ability to Drive and Use Machines: Adapalene Gel microsphere has no influence on the ability to drive and use machines.

Pregnancy: Animal studies by the oral route have shown reproductive toxicity at high systemic exposure. There have been reports of birth defects among babies born to woman exposed to topical retinoids during pregnancy. Due to the limited available data and because a very weak cutaneous passage of adapalene is possible, this product should not be used in woman of childbearing age, unless an effective means of contraception is used. In case of unexpected pregnancy, treatment should be discontinued.
Breast-feeding: No study on animal or human milk transfer was conducted after cutaneous application of Adapalene. No effects on the suckling child are anticipated since the systemic exposure of the breast-feeding woman to Adapalene is negligible. Adapalene can be used during breastfeeding. To avoid contact exposure of the infant, application of Adapalene to the chest should be avoided when used during breast-feeding.

Adapalene may cause the following adverse drug reactions: See table.

Click on icon to see table/diagram/image

All adverse effects with the use of Adapalene Gel during clinical trials were reversible upon discontinuation of therapy.

There are no known interactions with other medications which might be used cutaneously and concurrently with Adapalene Gel microsphere; however, other retinoids or drugs with a similar mode of action should not be used concurrently with adapalene.
Adapalene is essentially stable to oxygen and light and is chemically non-reactive. Whilst extensive studies in animals and man have shown neither phototoxic nor photoallergic potential for adapalene, the safety of using adapalene during repeated exposure to sunlight or UV irradiation has not been established in either animals or man. Exposure to excessive sunlight or UV irradiation should be avoided. It is advisable to use sunscreen before stepping out in the sunlight. Patients, who normally experience high level of sun exposure, and those with inherent sensitivity to sun, should be warned to exercise caution.
Absorption of adapalene through human skin is low (see Pharmacology: Pharmacokinetics under Actions) and therefore interaction with systemic medications is unlikely. There is no evidence that the efficacy of oral drugs such as contraceptives and antibiotics is influenced by the cutaneous use of Adapalene Gel microsphere.
Adapalene Gel has a potential for mild local irritation, and therefore it is possible that concomitant use of peeling agents, abrasive cleansers, strong drying agents, astringents or irritant products (aromatic and alcoholic agents) may produce additive irritant effects. However, cutaneous antiacne treatment (e.g. erythromycin up to 4%) or clindamycin phosphate (1% as the base) solutions or benzoyl peroxide water based gels up to 10% may be used in the morning when Adapalene Gel microsphere is used at night as there is no mutual degradation or cumulative irritation.
Particular caution should be exercised in using preparations containing sulfur, resorcinol or salicylic acid in combination with Adapalene Gel microsphere. If these preparations have been used, it is advisable not to start therapy with Adapalene Gel microsphere, until the effects of such preparations in the skin have subsided.

Store at temperatures not exceeding 30°C.
Protect from light. Do not freeze.

Acne Treatment Preparations

D10AD03 - adapalene ; Belongs to the class of topical retinoid preparations used in the treatment of acne.

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