Hello, in this post we made a summary of the medications most effective used in the treatment of acne. Here you will find topical and systemic retinoids, antibiotics, keratolytic products, and its dosages, usage indications, etc. Also, we can see some of its contraindications and warnings. A subject that is indispensable when choosing a medicine to treat any disease.
Topical acne drugs
The entire acne affected area is treated, not just the lesions, and long term usage is the rule.
In many patients, topical therapy may be effective as maintenance therapy after initial control is achieved with a combination of oral and topical treatment.
It has long been appreciated that these agents are especially effective in promoting normal desquamation of the follicular epithelium; thus, they reduce comedones and inhibit the development of new lesions. Additionally, they have a marked anti-inflammatory effect, inhibiting the activity of leukocytes, the release of pro-inflammatory cytokines and other mediators. They also help the penetration of other active agents. Thus, they should be utilized in nearly every patient with acne and are the preferred agents in maintenance therapy.
It was the first of this group of agents to be used for acne. Popular forms of tretinoin are 0.025% and 0.05% in a cream base because these are less irritating than the gels and liquids. Its incorporation into microspheres and a polyolpre polymer also help to limit irritation and make the product more stable in the presence of light and oxidizers. Tretinoin treatment may take 8–12 weeks before improvement occurs.
When patients are tolerating the medication and are slow to respond, retinoic acid gel or solution may be utilized. Tretinoin should be applied at night and is in pregnancy category C.
It is a well-tolerated retinoid-like compound, which has efficacy equivalent to the lower concentrations of tretinoin. As it is light stable, it may be applied in either the morning or the evening. It is in pregnancy category C.
Comparatively strong in its action, but also relatively irritating. It should be applied once at night or every other night, and as it is in pregnancy category X, contraceptive counseling should be provided.
Initially utilizing retinoids on an every other night bases, or using a moisturizer with them, may lessen their irritancy. They are also particularly useful in patients with skin of color as they may lighten post inflammatory hyperpigmentation.
Benzoyl peroxide has a potent antibacterial effect. Propionibacterium acnes resistance does not develop during use. Its concomitant use during treatment with antibiotics will limit the development of resistance, even if only given for short 2 to 7 days pulses. While it is most effective in inflammatory acne, some studies have shown it to be comedolytic also. The wash formulations may be utilized for mild trunkal acne when systemic therapies are not required.
Treatment is usually once or twice a day. Benzoyl peroxide may irritate the skin and produce peeling. Water-based formulations of lowest strength are least irritating.
Lessened to once a day or every other day will also help limit this. We recommend not rubbing the medication, only apply it specifically in the damaged area so we will avoid its irritant effect. Allergic contact dermatitis will rarely develop, suggested by the complaint of itch rather than stinging or burning. It is in pregnancy category C.
Erythromycin and Clindamycin
Topical clindamycin and erythromycin are available in a number of formulations. In general, they are well tolerated and are effective in mild to moderate inflammatory acne. These topical products are in pregnancy category B. Use of these topical antibiotics alone, however, is not recommended because of increasing antibiotic resistance.
As mentioned above, concurrent therapy with benzoyl peroxide will limit this problem. Concomitant use with a topical retinoid will hasten the response and allow for more rapid discontinuance of the antibiotic. Dapsone is available topically in a gel formulation. Hemolytic anemia may occur and discoloration of the skin is not uncommon when benzoyl peroxide is applied after topical dapsone. Additionally, concomitant oral use of trimethoprim/sulfamethoxazole will increase the systemic absorption of topical dapsone. It is in pregnancy category C.
Although benzoyl peroxide, retinoids, and topical antibiotics have largely supplanted these older medications, sulfur, resorcin, and salicylic acid preparations are still useful and moderately helpful if the newer medications are not tolerated.
They are frequently found in over-the-counter preparations.
Sulfacetamide–sulfur combination products are mildly effective in both acne and rosacea. The latter should be avoided in patients with known hypersensitivity to sulfonamides.
This dicarboxylic acid is remarkably free from adverse actions and has mild efficacy in both inflammatory and comedonal acne. It may help to lighten post-inflammatory hyperpigmentation and is in pregnancy category B.
Combination topical therapy
Several products are available which combine antibiotics such as clindamycin and benzoyl peroxide, or retinoids and either antibiotics or benzoyl peroxide. In general, these medications increase adherence, as they require less frequent application of medication, and they may also limit irritation compared with the cumulative topical application of each product separately. However, they limit flexibility and may cause more irritation than a single product used alone
These agents are indicated for moderate to severe acne, in patients with inflammatory disease in whom topical combinations have failed or are not tolerated, for the treatment of chest, back, or shoulder acne, or in patients in whom absolute control is deemed essential, such as those who scar with each lesion or develop inflammatory hyperpigmentation. It generally takes 6–8 weeks to judge efficacy. Starting at a high dose and reducing it after control is preferred. Working to maintain control eventually with topical retinoids or retinoid–benzoyl peroxide combination therapy is ideal; however, keeping patients free of disease for 1–2 months before each decrease in dosage is best to prevent flaring. Most courses of oral therapy are of at least 3–6 months’ duration.
There is concern that oral antibiotics may reduce the effectiveness of oral birth control pills. It is appropriate for this as yet unproven (except with rifampin, which is not used for acne) association to be discussed with patients and the second form of birth control offered.
Tetracycline is the safest and cheapest choice and will give a positive response in many patients. It is usually given at an initial dose of 250–500 mg 1–4 times a day, with gradual reduction of the dose, depending on clinical response.
It is best taken on an empty stomach, at least 30 min before meals and 2 h afterward, which often limits dosage to twice a day. Calcium or iron in food supplements combines with tetracycline, reducing absorption by as much as half. Vaginitis or perianal itching may result from tetracycline therapy in about 5% of patients, with Candida albicans usually present in the involved site. The only other common side effects are gastrointestinal symptoms such as nausea. To reduce the incidence of esophagitis, tetracyclines should not be taken at bedtime. Staining of growing teeth occurs, precluding its use in pregnant women and in children under the age of 9 or 10. Tetracycline should also be avoided when renal function is impaired.
The usual dose is 50–100 mg once or twice a day, depending on the disease severity. Photosensitivity reactions are not uncommon with this form of tetracycline and can be dramatic. Sub antimicrobial dose doxycycline, doxycycline hyclate 20 mg, may be given twice daily. The advantage of this is that the anti-inflammatory activity is being utilized but no antibiotic resistance results because of the low dose.
A sustained release 40 mg formulation is also available. These low dose preparations appear to be of low efficacy, however.
Minocycline is the most effective oral antibiotic in treating acne vulgaris. In patients whose P. acnes develops tetracycline resistance, minocycline is an alternative. The usual dose is 50–100 mg once or twice a day, depending on the severity of the disease. Its absorption is less affected by milk and food that is that of tetracycline. Vertigo may occur and beginning therapy with a single dose in the evening may be prudent.
An extended release preparation is also available, which limits the vestibular side effects. Pigmentation in areas of inflammation, or oral tissues, in post-acne osteoma or scars, in a photo distributed pattern, on the shins, in the sclera, nailbed, ear cartilage, teeth, or in a generalized pattern may also be seen (Fig. 139). Additionally, lupus-like syndromes, a hypersensitivity syndrome (consisting of fever, hepatitis, and eosinophilia), serum sickness, pneumonitis, and hepatitis are uncommon but potentially serious adverse effects of minocycline.
For those who cannot take tetracyclines because of side effects or in pregnant women requiring oral antibiotic therapy, erythromycin may be considered. The efficacy is low. Side effects are mostly gastrointestinal upset; vaginal itching is a rare occurrence. The initial dose is 250 – 500 mg 2–4 times a day, reduced gradually after control is achieved. Erythromycin may increase blood levels of other drugs metabolized by the cytochrome P450 system.
Past experience has shown clindamycin to give an excellent response in the treatment of acne; however, the potential for the development of pseudomembranous colitis and the availability of retinoids has limited its use. The initial dose is 150 mg three times a day, reduced gradually as control is achieved
Sulfonamides are occasionally prescribed; however, the potential for severe drug eruptions limits their use. Trimethoprim-sulfamethoxazole (Bactrim, Septra), in double strength doses twice a day initially, is effective in many cases unresponsive to other antibiotics. Trimethoprim alone, 300 mg twice a day, is also useful. Amoxicillin, in doses from 250 mg twice daily to 500 mg three times a day, is also an alternative and may be useful in pregnancy as it falls into pregnancy category B. Dapsone has been used in severe acne conglobata but is rarely used today. Isotretinoin is favored.
Acne antimicrobial resistance has become a clinically relevant problem. Erythromycin and clindamycin resistance is widespread and usually presents simultaneously. Once P. acnes becomes resistant to tetracycline, it is also resistant to doxycycline, so if lack of efficacy due to prolonged oral therapy with one of them is suspected, a switch to minocycline is necessary. While concomitant use of benzoyl peroxide will help limit cutaneous drug resistance problems, it is now appreciated that Staphylococcus aureus in the nares, streptococci in the oral cavity, and enterobacteria in the gut may also become resistant, and close contacts, including treating dermatologists, may harbor such drug-resistant bacteria.
Strategies to prevent antibiotic resistance include limiting the duration of treatment, stressing the importance of adherence to the treatment plan, restricting the use of antibiotics to inflammatory acne, encouraging retreatment with the same antibiotic unless it has lost its efficacy, avoiding the use of dissimilar oral and topical antibiotics at the same time, and using isotretinoin if unable to maintain clearance without oral antibacterial treatment.
Hormonal interventions in women may be beneficial in the absence of abnormal laboratory tests. The workup for the woman with signs of hyperandrogenism, such as acne, menstrual irregularities, hirsutism, or androgenetic alopecia, is presented above. Women with normal laboratory values often respond to hormonal therapy. Results take longer to be seen with these agents, with the first evidence of improvement often not apparent for 3 months and continued improved response seen for at least 6 months. Particularly good candidates for hormonal treatment include women with PCOS, late-onset adrenal hyperplasia, or another identifiable endocrinologic condition; and women with late-onset acne, severe acne, acne that has not responded to other oral and topical therapies, or acne that has relapsed quickly after isotretinoin treatment.
Women with acne primarily located on the lower face and neck, and deep-seated nodules that are painful and long-lasting, are often quite responsive to hormonal intervention
These agents block both adrenal and ovarian androgens. Ortho TriCyclen, Estrostep, Alesse, Yasmin, and Yaz are examples of birth control pills that have beneficial effects on acne. Both the physician and the patient should be familiar with the adverse reactions associated with oral contraceptives, such as nausea, vomiting, abnormal menses, melasma, weight gain, breast tenderness, and rarely thrombophlebitis, pulmonary embolism, and hypertension.
As pregnancy while on anti-androgen treatment will result in feminization of a male fetus, spironolactone is usually prescribed in combination with oral contraceptives. It may be effective in doses from 25–200 mg/day. Most women will tolerate a starting dose of 50–100 mg/day. Most also tolerate 150 mg per day but many will have side effects at 200 mg per day. Side effects are dose-dependent and include breast tenderness, headache, dizziness, lightheadedness, fatigue, irregular menstrual periods, and diuresis. In a study by Shaw in patients treated with 50–100 mg/day, hyperkalemia was measurable, but in the absence of renal or cardiac disease was clinically insignificant. In his series, a third of patients cleared, a third had marked improvement, a quarter showed partial improvement, and 7% had no response.
Spironolactone is often used with other topical or oral acne therapy. Several months of treatment are usually required to see the benefit.
Dexamethasone, in doses from 0.125 to 0.5 mg given once at night, reduces androgen excess and may alleviate cystic acne. Corticosteroids are effective in the treatment of adult-onset adrenal hyperplasia, but anti-androgens are also used increasingly in this setting.
Although steroids may produce steroid acne, they are also effective anti-inflammatory agents in severe and intractable acne vulgaris. In severe cystic acne and acne conglobata, corticosteroid treatment is effective; however, side effects restrict its use. It is generally only given to patients with severe inflammatory acne during the first few weeks of treatment with isotretinoin, for initial reduction of inflammation, and to reduce isotretinoin induced flares.
Other hormonal agents
Finasteride, flutamide, estrogen, gonadotropin-releasing agonists, and metformin (by decreasing testosterone levels) have all been shown to have a beneficial effect on acne but due to side effects, expense, or other considerations are not commonly used.
Oral retinoid therapy
This drug is approved only for severe cystic acne: however, it is useful in less severe forms of acne so as to prevent the need for continuous treatment and the repeated office visits that many patients require. It was a consensus of experts that oral isotretinoin treatment is warranted for severe acne, poorly responsive acne that improves by less than 50% after 6 months of therapy with combined oral and topical antibiotics, acne that relapses off oral treatment, scars, or acne that induces psychological distress. Additionally, other agreed indications were Gram-negative folliculitis, inflammatory rosacea, pyoderma faciale, acne fulminans, and hidradenitis suppurativa.
Many patients in the latter category prefer to be retreated with isotretinoin due to its reliable efficacy and ability to predict side effects, as they will be similar to those experienced in the first course. In Azoulay et al’s study, fully 26% of isotretinoin-treated patients received a second course within a 2year period.
Some subsets of patients tend to relapse more often. In patients under 16, 40% need a second course of isotretinoin within 1 year and 73% within 2 years. Adult women and patients with mild acne tend to relapse more often and more quickly than severely affected 17 to 22 year olds.
Side effects and warnings
It is teratogenic medicine. The use of isotretinoin is related to pregnancy losses and fetal malformations in pregnant women under treatment with isotretinoin. IT IS COMPLETELY CONTRAINDICATED self-medication, as well as the use in pregnant women and it is even advised that both women and men with isotretinoin treatment should refrain from procreation for up to one year after treatment.
Other side effects are observed, such as intestinal diseases (Crohn’s disease), liver damage, depression and tolerances such as drying of the skin and mucosa,
Since the use of isotretinoin leads to a series of unwanted effects in patients, its use should be under strict supervision of medical professionals.
Local surgical treatment is helpful in bringing about a quick resolution of the comedones, although many clinicians wait until after 2 or more months of topical retinoids to extract those that remain. The edge of the follicle is nicked with a No 11 scalpel blade and the contents of the comedo are expressed with a comedo extractor. Scarring is not produced by this procedure. Light electrode desiccation is an alternative. In isotretinoin treated patients, macrocomedones present at weeks 10–15 may be expressed, since they tend to persist throughout therapy.
The use of photodynamic therapy and various forms of light, laser, or radiofrequency energy is under investigation. It is clear that there is an ability to destroy sebaceous glands or kill P. acnes with such interventions; however, the methods to deliver such treatments in an efficient, cost-effective, safe, relatively pain-free, and practical manner are evolving. These treatments will be a welcome addition as they have the potential to provide care without the concerns associated with systemic drugs.