Cosmetics with benzoyl peroxide

Pharmacological properties of the drug Benzoyl peroxide

A remedy for the treatment of acne (acne vulgaris). Has an antimicrobial effect against gram-positive bacteria that cause acne. Due to the release of oxygen, it inhibits the development of anaerobic microflora ( Propionibacterium acnes ) in acne, thereby reducing the release of disease-provoking fatty acids in infected follicles. Benzoyl peroxide also has a keratolytic effect, promoting exfoliation of the skin and removal of the stratum corneum around comedones. A small amount, after resorption from the skin surface, is metabolized into benzoic acid and excreted in the urine in the form of benzoate.

Benefits of Benzoyl Peroxide

1. Controls sebum production.
   Benzyl peroxide is known to reduce sebum production, which is the main cause of acne, after which
   facial cleansing
   . Excessive activity of the sebaceous glands clogs pores and provokes acne. Benzoyl peroxide absorbs excess oil and dries it out.
2. Anti-inflammatory and antibacterial properties
   . Bacteria under the top layer of skin cause acne to spread and lead to other problems: swelling, pus, and bleeding. Topical application of benzoyl peroxide kills acne-causing bacteria. Benzoyl peroxide is especially effective at destroying anaerobic bacteria due to its oxidizing properties.

Application of the drug Benzoyl peroxide

Before applying 5 and 10% benzoyl peroxide lotion or gel, the affected areas of the skin are thoroughly washed and dried with a soft, clean towel. Apply to the affected area of ​​the skin and rub until completely absorbed. After using the product, wash your hands thoroughly. At the beginning of treatment, an imaginary worsening may occur due to increased peeling of the skin in the affected areas. Apply the lotion to sensitive skin with caution to avoid hyperemia and flaking. In the first week of treatment, apply 1 time per day; if local reactions do not occur, benzoyl peroxide is used 2 times a day. Should not be used in elderly people. The average duration of treatment with benzoyl peroxide is 8–10 weeks; It should not be used for more than 3 months. In severe cases of the disease, topical use of benzoyl peroxide is combined with other acne treatments (oral antibiotics or retinoids).

Side effects of benzoyl peroxide

1. Benzoyl peroxide is a bleaching agent that can dry out your skin.
2. Application may cause redness and peeling. This means you need to start with a minimum concentration to see how the skin reacts.
3. Too frequent use leads to the appearance of wrinkles and crow's feet, as the dermis is dehydrated.
4. The product causes increased sensitivity to the sun. Therefore, after using it you need to apply a good sunscreen.

To treat acne, you can use various products containing benzoyl peroxide: wash gels, masks, serums.

We will look at the effect salicylic acid has on acne in the next article.

Special instructions for the use of the drug Benzoyl peroxide

Avoid contact with eyes and mucous membranes. To prevent hypersensitivity reactions, a trial application of the solution to a small surface of the skin in the wrist area is recommended. If swelling or itching with severe hyperemia appears in this area within 48 hours, benzoyl peroxide should not be used. With prolonged use, redness or peeling of the skin may occur. If the reaction is severe, the amount of product applied and the frequency of its use should be reduced. Use with caution during pregnancy and breastfeeding. Benzoyl peroxide stimulates mitosis of epidermal cells, which leads to acanthosis and hyperkeratosis; the appearance of peeling and redness of the skin causes a period of apparent deterioration during the first weeks of treatment. Persons with fair skin and blond hair, as well as sensitive skin, are recommended to begin treatment with the use of a 5% solution once a day.

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit and is characterized by non-inflammatory (comedones) and inflammatory lesions (papules, pustules and nodules) that can lead to scar formation and psychological stress. In women who are planning a pregnancy or who are pregnant, this condition can be especially bothersome given the physiological changes as well as the unpredictable nature of acne during this time. Acne often improves during the first trimester, but can worsen during the third trimester due to increased androgen levels and increased sebum production. In addition to hormonal changes, immunological changes may also contribute during pregnancy. Inflammatory lesions tend to be more widespread than noninflammatory lesions, often extending to the trunk. Patients with a history of acne are more likely to develop acne during pregnancy. Treating acne during pregnancy can be challenging, as many commonly used and effective treatment options are contraindicated or not recommended. Therefore, it is important for the physician prescribing therapy for a pregnant woman to be familiar with the treatment restrictions adopted by the US Food and Drug Agency (FDA) (Table 1). Due to the inherent ethical issues associated with the impossibility of clinical trials during pregnancy, pharmacokinetic and pharmacodynamic data to evaluate drug safety during pregnancy are limited, and randomized controlled trials of acne medications do not exist. Thus, most treatment recommendations are based on observational and animal studies. Here we review the data on the safety and effectiveness of common medications for acne and outline a practical approach to treating acne during pregnancy based on the latest available evidence (Table 2). Armed with this information, physicians can develop a safe and effective acne treatment regimen for this unique patient population.

Table 1. Pregnancy Risk Categories (FDA)

Table 2. Algorithm for treating acne during pregnancy

Literature search and data sources

For this review, PubMed was searched using the following key terms: acne, pregnancy, azelaic acid, benzoyl peroxide, salicylic acid, aminolevulinic acid, photodynamic therapy, FDA pregnancy. No publication date restrictions were applied. The search included meta-analyses of randomized controlled trials, clinical trials and reviews. In addition, the search was conducted in the EMBASE, Cochrane and UpToDate databases.

Local treatment

For mild to moderate acne, topical therapy is the standard of care. It is also an important component of treatment for more severe acne and acts synergistically with oral agents. During pregnancy, the degree of systemic absorption of the topical anti-acne drug should be taken into account. The properties of commonly used topical agents are summarized in the following sections and Table 3.

Table 3. Selected topical medications for acne in pregnant women

Azelaic acid

Azelaic acid is classified as pregnancy category B because animal studies have not shown a teratogenic effect and there are no data from human studies. Azelaic acid is a natural dicarboxylic acid with antimicrobial, comedolytic and mild anti-inflammatory properties with the added benefit of reducing post-inflammatory hyperpigmentation. There was no evidence of resistance to azelaic acid in P. acnes. After applying it to the skin, approximately 4% of the drug enters the bloodstream.

Benzoyl peroxide

Benzoyl peroxide is classified as pregnancy category C. Approximately 5% enters the bloodstream and is completely metabolized into benzoic acid, which is also known as a dietary supplement. Due to rapid renal clearance, no systemic toxicity is expected, and the risk of congenital malformations is theoretically low. Benzoyl peroxide has antimicrobial, comedolytic and anti-inflammatory properties. To date, the fact of resistance of P. acnes to benzoyl peroxide has not been established. Benzoyl peroxide is considered safe during pregnancy and helps prevent the development of resistance when used in combination with antibiotics.

Salicylic acid

Salicylic acid is classified as pregnancy category C. There are no studies on the topical use of salicylic acid in humans during pregnancy, although malformations have been described in rat embryos with systemic exposure to salicylic acid and aspirin administration during pregnancy. This is a keratolytic agent. Widespread use of high concentrations of salicylic acid for hyperkeratoses of the skin has resulted in cases of salicylate toxicity, but there are no similar known cases associated with the use of drugs containing it for acne. The risk during pregnancy is low when used on limited areas of the skin for short periods.

Topical antibiotics

Topical antibiotics have long been used to treat inflammatory acne; Erythromycin and clindamycin are the two most commonly prescribed antibiotics for acne in pregnancy. Both are classified as pregnancy category B. Short-term use of topical erythromycin and clindamycin during pregnancy is safe. However, no studies have been conducted on the effects of their long-term use. Given case reports of membranous colitis caused by Clostridia, topical clindamycin should be used with caution in patients with a history of gastrointestinal disease. Topical clindamycin and erythromycin reduce the number of P. acnes in sebaceous follicles by inhibiting bacterial protein synthesis, thereby suppressing inflammatory acne. The combined use of topical antibiotics with benzoyl peroxide reduces the development of bacterial resistance and increases the effectiveness of treatment.

Topical retinoids

Topical retinoids are derivatives of vitamin A and have been used to treat acne for over 30 years. In the United States, these include adapalene, tretinoin, and tazarotene. Adapalene and tretinoin are classified as pregnancy Category C drugs by the FDA, while tazarotene is classified as Category X. This is partly due to the high incidence of birth defects associated with the use of the systemic retinoid isotretinoin. Therefore, tazarotene is not recommended for use during pregnancy. Despite reports of possible birth defects, topical adapalene and tretinoin are unlikely to cause birth defects given their poor cutaneous resorption. A recent meta-analysis excluded the possibility of a significant increase in the incidence of miscarriages, congenital malformations, prematurity and low birth weight. Mechanisms of action include acceleration of keratinocyte differentiation, comedolytic and anti-inflammatory effects. These drugs, however, are not recommended for pregnant women, because their risk-benefit ratio remains questionable.

Topical Dapsone

Topical dapsone is a synthetic sulfone with antimicrobial and anti-inflammatory properties. It is classified as category C in pregnancy. High doses in animals have not shown teratogenic effects. To date, its use during pregnancy has not been associated with an increased risk of fetal defects. The risk of maternal anemia, as well as hyperbilirubinemia and hemolytic anemia in the newborn, is observed with oral dapsone in patients with glucose-6-phosphate dehydrogenase deficiency, but the risk is low with topical dapsone. Topical dapsone was approved for the treatment of acne in 2005. Caution should be exercised given its relatively recent introduction to the market and the lack of controlled studies evaluating its safety during human pregnancy. It should be prescribed during pregnancy only when the benefits clearly outweigh the risks.

Oral medications

Some patients cannot achieve satisfactory results using topical treatments alone. Oral medications are primarily indicated for patients with moderate to severe forms of inflammatory acne and in cases of ineffective topical therapy. The properties of commonly used oral medications are described in the following sections as well as in Table 4.

Table 4. Selected oral antibiotics for acne in pregnant women

Oral antibiotics

Oral antibiotics improve inflammatory acne by inhibiting the growth of P. acnes in the pilosebaceous complex. Tetracycline antibiotics (including doxycycline and minocycline), in addition to antibacterial, have a direct anti-inflammatory effect. The antibiotics most commonly used by patients (other than pregnant women) are doxycycline, minocycline, erythromycin, azithromycin, cephalexin, and trimethoprim-sulfamethoxazole. Because of increased bacterial resistance, it is generally recommended to combine topical benzoyl peroxide with oral antibiotics, limit the use of short courses of oral antibiotics, and not use oral antibiotics for maintenance treatment of acne. To limit the development of bacterial resistance, changes in oral antibiotics should also be avoided whenever possible; if an oral antibiotic has proven effective in the past, it should be prescribed again. Oral antibiotics should be prescribed during pregnancy only when the need has been clearly established.

Erythromycin is a macrolide classified as category B during pregnancy. The drug does not penetrate the placenta well, resulting in low concentrations in fetal tissues. Erythromycin is generally considered safe during any stage of pregnancy when administered over several weeks. It can be considered the antibiotic of choice for the treatment of severe inflammatory acne in pregnant women. However, its effects have not been studied with long-term use (more than 6 weeks). It should be noted that erythromycin estolate is contraindicated due to maternal hepatotoxicity.

Azithromycin is another macrolide classified as pregnancy category B by the FDA. Animal studies have shown that azithromycin crosses the placenta without causing adverse effects in the fetus. Azithromycin is considered acceptable in pregnant women with acne, but has less available safety data than erythromycin.

The FDA has included amoxicillin in pregnancy category B. Its use in early pregnancy may increase the risk of cleft palate. Amoxicillin can be used alone or in combination with other drugs as the drug of choice for the treatment of refractory acne. May cause gastrointestinal side effects such as nausea and vomiting.

Cephalexin is a first-generation cephalosporin with anti-inflammatory properties and is classified as a category B drug for pregnancy. Cephalexin has not been associated with embryonic defects in animal studies. Although it is effective as an anti-acne drug, there is some concern about the development of staphylococcal resistance to it.

Trimethoprim acts as a folate antagonist and is classified as a pregnancy category C drug. A recent study found that use of trimethoprim in the first trimester was associated with a doubled risk of miscarriage. Therefore, the use of trimethoprim-sulfamethoxazole is recommended for use during pregnancy only when there is no alternative and when the benefits outweigh the risks.

Tetracyclines are classified as Category D drugs in pregnancy. Animal studies have found evidence of fetal and fetotoxicity, including toxic effects to fetal teeth and bones. Tetracyclines bind to calcium orthophosphate and are therefore actively deposited in teeth and bones. Deposits of the drug in the teeth persist for a long time, as a result of which the baby teeth of children exposed to the drug after the 20th week of pregnancy become yellow and darken over time. Deposition in bones leads to reversible retardation of fetal growth and suppression of fibula growth, especially with long-term use of the drug. Tetracyclines should be avoided during pregnancy, especially after the first trimester.

It is important to note that more evidence is needed regarding the recommended duration of these treatments. The effects of long-term use of these antibiotics on the fetus are not known. These considerations must be weighed against the severity of the acne and alternative topical treatments. The use of systemic antibiotics should be limited in the second and third trimesters, after completion of organogenesis, with the duration of therapy limited to 4-6 weeks.

Oral corticosteroids

The severity of severe acne that is resistant to antibiotic therapy can be significantly reduced with the use of oral corticosteroids. Prednisone is classified as pregnancy category C by the FDA. The drug has been associated with cleft palate, slowed brain growth, decreased myelination, and decreased head circumference in animal studies. In humans, studies have shown an increased risk of cleft palate and a slight increase in miscarriage and preterm birth. There is little data on the ability of systemic and topical steroids to cross the placental barrier, although topical steroids have been shown to have systemic effects. Prednisolone may be used for severe or fulminant cases of acne after the first trimester. The use of steroids in the form of small numbers of injections and short courses of oral steroids needed for rare, fulminant cases of acne vulgaris is unlikely to pose additional risks to the fetus. The dosage of prednisolone should be no more than 20 mg/day. and no longer than 1 month during the third trimester.

Oral retinoids

Isotretinoin is often prescribed to patients (other than pregnant women) with persistent, conglobate acne vulgaris. The teratogenic effects of isotretinoin are well known and it is classified as category X. The drug causes characteristic deformities associated with the craniofacial region, central nervous system, cardiovascular system, thymus and parathyroid glands. Isotretinoin was approved in 1982 and works by reducing sebum production and normalizing keratinization processes. Isotretinoin is absolutely contraindicated during pregnancy.

Zinc

Zinc provides another option for pregnant acne patients. Zinc sulfate is considered a pregnancy category C drug, while zinc gluconate has not been officially classified. Animal studies and human studies including pregnant women treated for acne have shown no increased risk of fetal abnormalities or risk of fetal harm at doses less than 75 mg/day. Zinc has antibacterial, anti-inflammatory and sebum-reducing effects. Its effectiveness has been established for mild and moderate inflammatory acne when used alone or in combination with other drugs. The recommended amount of zinc during pregnancy is 11 mg/day. Potential side effects include nausea and vomiting, usually dose-related.

Complementary therapy

Glycolic acid

Glycolic acid is classified as pregnancy category N, that is, it is not classified and is used externally for acne. There are no published reports of any adverse effects during pregnancy. Studies have shown improvement in inflammatory acne and comedones, although closed comedones may be slower to respond. It also has the additional benefits of improving post-inflammatory changes and increasing skin absorption of topical medications.

Photodynamic therapy

Photodynamic therapy is classified as category C. There are no reproductive studies in animals. Compared with control treatment, photodynamic therapy resulted in a statistically significant improvement in acne severity, as well as sustained results up to 20 weeks' gestation after multiple treatments. Lack of insurance coverage and the frequency of required sessions at a dermatologist's office may be a barrier to use in pregnant women.

conclusions

In this review, we have highlighted numerous options for clinicians who treat pregnant patients with acne. We offer the following simplified approach as a starting point for clinicians when working with pregnant patients. For mild acne, characterized primarily by non-inflammatory elements of the rash, topical azelaic acid or benzoyl peroxide may be recommended as basic therapy. For inflammatory acne, it is recommended to begin therapy with a combination of topical erythromycin or clindamycin with benzoyl peroxide. For moderate to severe inflammatory acne, oral erythromycin or cephalexin can be prescribed, which are safe when used for only a few weeks. A course of prednisone for no more than a month may be useful for the treatment of fulminant conglobate cystic acne after the first trimester. In general, topical and oral antibiotics should not be used as monotherapy and should be combined with topical benzoyl peroxide to reduce bacterial resistance. The adjunctive therapies discussed in this review should be considered based on patient response and preference. Key recommendations are summarized in Table 5. We hope that this review will be useful for clinicians treating acne in pregnant women.

Table 5. Basic recommendations for acne during pregnancy