Mechanism of Action
Sinac binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that Sinac is a modulator of cellular differentiation, keratinization, and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of Sinac for the treatment of acne is unknown.
Mechanism of Action
Sinac is a naphthoic acid derivative. Sinac is an active metabolite and therefore requires no metabolic conversion. Sinac, when applied topically, penetrates the hair follicles due to its lipophilic nature. Follicular absorption occurs 5 minutes after topical application. The medication binds to nuclear retinoic acid receptors (RAR), RAR-beta, and RAR-gamma. This complex then binds DNA through retinoic acid response elements and induces gene transcription, leading to downstream keratinocyte proliferation and differentiation. As a result, Sinac decreases microcomedone formations, exfoliates mature comedones, and has anti-inflammatory effects.
The pathogenesis of acne vulgaris is multifactorial. The main factors associated with acneiform lesion development are follicular hyperkeratinization, sebum production by sebaceous glands, and inflammation. In acne-prone patients, keratinocytes accumulate in the lumen of the hair follicle due to increased keratinocyte proliferation and cohesiveness, leading to the formation of a keratotic plug, which results in the microcomedone. The microcomedone is the precursor to all visible acne lesions like open comedones, closed comedones, inflammatory papules, pustules, and nodulocystic lesions. Sinac normalizes the differentiation of follicular epithelial cells to prevent microcomedone formation.
In addition to follicular hyperkeratinization, acne is also a disorder associated with inflammation. Propionibacterium acnes is a gram-positive, anaerobic rod found in the sebaceous follicle. P. acnes is present in both acne-prone individuals and those without acne. The hypothesis is that there may be differences in the strains of P. acnes or in the host response to P. acnes, which leads to its varying degrees of pathogenicity. P. acnes release mediators that contribute to comedone rupture and stimulate inflammatory cells. P. acnes stimulates the toll-like receptor II (TLR-2) pathway, which induces the release of pro-inflammatory modulators. This action leads to neutrophil recruitment and the release of enzymes that result in follicular epithelium rupture. One mediator, IL-12, promotes a TH1 immune response. Sinac is thought to suppress polymorphonuclear lymphocyte chemotaxis and down-regulate15-lipoxygenase and TLR-2, which contributes to its anti-inflammatory effects.
How Sinac Treats Acne
How does a retinoid like Sinac treat acne? Acne like pimples, blackheads and whiteheads start with a clogged pore. Your skin cells are constantly renewing themselves. As old cells die, they shed and reveal fresh skin. But if you have acne-prone skin, the dead cells mix with oil, become sticky and instead of shedding they clog your pores and trap p. acnes bacteria inside.
By unblocking these pores and promoting faster cell turnover, Sinac targets acne at the source, before the blemishes have a chance to form on your skin. As dermatologist Ted Lain describes it, “the dead skin cells do not have the opportunity to collect in the pores which in turn prevents the formation of the earliest acne blemishes.” Austin-based Dr. Ted Lain is one of the nation’s most sought-after dermatologists and is a frequent contributor in print, television, and online discussions of skin health. He was also a paid consultant for The Proactiv Company when he authored this article. Sinac is also anti-inflammatory so it helps with the redness and inflammation of papules and pustules that have already formed.
Local Cutaneous Reactions
Certain cutaneous signs and symptoms of treatment such as erythema, scaling, dryness, and stinging/burning were reported with use of Sinac Gel, 0.3%. These were most likely to occur during the first four weeks of treatment, were mostly mild to moderate in intensity, and usually lessened with continued use of the medication. Depending upon the severity of these side effects, patients should be instructed to either use a moisturizer, reduce the frequency of application of Sinac Gel, 0.3% or discontinue use.
Avoid contact with the eyes, lips, angles of the nose, and mucous membranes. 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 Sinac.
As Sinac Gel has the potential to induce local irritation in some patients, concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect and products with high concentrations of alcohol, astringents, spices, or lime) should be approached with caution.
What Are Side Effects Associated with Using Sinac?
Common side effects of Sinac include:
- Mild burning/stinging
- Skin redness
- Skin discomfort
- A brief sensation of warmth immediately after applying the medication
Less common side effects of Sinac include:
Serious side effects of Sinac include:
- Very red or irritated skin
- An intense burning sensation
- Eye redness and watering (conjunctivitis)
- Eyelid swelling
- Skin discoloration
This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.
Ultraviolet Light and Environmental Exposure
Exposure to sunlight, including sunlamps, should be minimized during use of Sinac Gel, 0.3%. Patients who normally experience high levels of sun exposure, and those with inherent sensitivity to sun, should be warned to exercise caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with Sinac Gel, 0.3%.
Enhancing Healthcare Team Outcomes
Sinac is a topical retinoid that is FDA-approved for the treatment of acne vulgaris and several non-FDA-approved indications, including the treatment of verruca, molluscum contagiosum, Darier disease, Fox-Fordyce disease, Dowling-Degos disease, photoaging, pigmentary disorders, actinic keratoses, and alopecia areata.
Nurse practitioners and primary care physicians who prescribe this agent, as well as pharmacists interacting with patients, must be fully aware of its side effects and contraindications. Pharmacists will also perform through medication reconciliation. Because the drug is teratogenic, clinicians should not prescribe Sinac to women of childbearing age or women who are breastfeeding. Dermatology specialty-trained nursing staff should be on hand to counsel and followup with patients on Sinac therapy. Nursing should assess patient compliance, answer questions regarding dosing/administration, and monitor for adverse events and alert the prescriber promptly if present. Collaboration between all these disciplines in an interprofessional team can optimize Sinac therapy while minimizing adverse effects.
Getting the most from your treatment
- It is recommended that you use a mild soap and lukewarm water to wash with, as very hot or cold water can worsen acne. You cannot clean off blackheads. The black tip of a blackhead is actually a skin pigment and cannot be removed by cleaning or scrubbing.
- If your skin becomes very dry, it may help to use a moisturising cream (preferably a fragrance-free and water-based cream). Do not use ointments or oil-rich creams, as these could clog your pores again.
- You can use make-up and moisturisers, but do not apply them at the same time as you use Sinac. Try to avoid any skin products which exfoliate or dry your skin.
- Sinac may make your skin more sensitive to sunlight than usual. Therefore, it is best to apply it at night and wash it off in the morning. A sun protection cream can also help if you are out in the sun on bright days, even if it is cloudy. Do not use sunbeds.
- It is normal for Sinac treatment to take 1-4 weeks before there is a noticeable improvement in your skin. The most common reason for treatment failure is stopping treatment too soon thinking it is not working. If there is no improvement after 6-8 weeks, speak with your doctor again as there are other treatments which could be more suited to your condition.
- You should avoid getting pregnant while you are using Sinac as there is a slight risk of harm to unborn babies. If necessary, discuss with your doctor which types of contraception are suitable for you and your partner.
- Once your spots have cleared, acne commonly flares up again if you stop treatment. To prevent this, it is usual to carry on with a maintenance treatment after your spots have gone. The dose used to prevent spots from returning is often lower than that used to treat acne. It is common to need maintenance treatment for a number of years to keep acne away.
- The brand of Sinac gel called Epiduo® can cause bleaching. If you have been supplied with this gel, try to avoid it coming into contact with items that could be bleached, such as hair and dyed fabrics.
Sinac: The Bottom Line
Sinac belongs to a class of medication called retinoids. As an acne medication it has been favored by dermatologists for decades, but until recently was only available by prescription. It works on acne by clearing clogged pores and keeping them clear so p. acnes bacteria aren’t trapped inside and blemishes don’t have a chance to form. Sinac also boasts powerful anti-inflammatory properties that can benefit existing pimples.
The following adverse reactions have been identified during post approval use of Sinac: skin irritation, application site pain, face edema, eyelid edema, lip swelling, and angioedema. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.