Systematic agents

When acne is resistant to topical therapies, oral antibiotics may be used. Oral antibiotics commonly are initial therapy in patients with moderate to severe inflammatory acne. Systemic antibiotics decrease P. acnes colonization and have intrinsic antiinflammatory effects. First-line oral antibiotics have included tetracycline and erythromycin. Because P. acnes resistance to erythromycin is increasing, this antibiotic is becoming a second-line agent that is used when treatment with tetracycline or other macrolide antibiotics fails or is not tolerated. Tetracycline must be taken on an empty stomach. Iron supplements and milk products decrease systemic absorption of the antibiotic. Because of the risk of tooth discoloration and inhibited skeletal growth, tetracycline should not be used in pregnant women or children younger than nine years. Moderate to severe phototoxicity and gastrointestinal intolerance also may limit the use of tetracycline. Doxycycline (e.g., Vibramycin, Doryx) frequently is used to treat moderate to severe acne vulgaris. However, associated photosensitivity may limit its usefulness. Minocycline (Minocin) is a potent acne medication, but treatment with this antibiotic generally is reserved for patients who do not respond to or cannot tolerate aforementioned treatment options. Rare but serious side effects are more common in patients taking minocycline than in patients treated with tetracycline or doxycycline. Oral antibiotics must be taken for six to eight weeks before results are evident, and treatment should be given for six months to prevent the development of microbial resistance. Oral antibiotics may be discontinued after inflammation has resolved. Topical antibiotics may be continued for further treatment. Some patients may require long-term oral antibiotic therapy to control their acne and prevent scarring. A decrease in the effectiveness of OCPs is a concern with coadministration of oral antibiotics. Although this concern has not been supported by research, some package inserts contain a warning about decreased OCP efficacy with concomitant ampicillin or tetracycline therapy. A review of pharmokinetic data showed a reduction of contraceptive steroid hormones only with concomitant  use of rifampin (Rifadin).24 [Evidence level B, nonquantitative systematic review] Nonetheless, it may be wise to inform patients receiving oral antibiotic therapy about the possibility of OCP failure, and to recommend the use of a second method of contraception. OCPs. These contraceptives may be a valuable adjunct in the treatment of acne in female patients. OCPs decrease circulating androgens, thereby decreasing sebum production. The estrogen in OCPs increases the amount of sex hormone-binding globulin, which, in turn, decreases the free testosterone level. The estrogen also decreases secretion of gonadotropins by the anterior pituitary, with a consequent decrease in the amount of androgens
produced by the ovaries. When an OCP is used to treat acne, the physician should prescribe a formulation that contains progestins with low androgenic possibility. Appropriate progestins include norethindrone (Norlutin), norethindrone acetate (Aygestin), ethynodiol diacetate (Zovia), and norgestimate (Ortho- Cyclen). Ultimately, the choice of OCP should be based on tolerability and compliance. Isotretinoin. This vitamin A derivative is used to treat severe, often nodulocystic and nflammatory acne. Isotretinoin (Accutane)
acts against the four pathogenic factors that contribute to acne. It is the only medication with the potential to suppress acne over the long term. To be able to prescribe this medication, the physician must be a registered member of the manufacturer’s System to Manage Accutane-Related Teratogenicity (SMART) program. The SMART program was developed in conjunction with the U.S. Food and Drug Administration (FDA) to minimize unwanted pregnancies and educate patients about the possible severe adverse effects and teratogenicity of isotretinoin, which is a pregnancy category X drug. Hepatitis, hypertriglyceridemia, intracranial hypertension, arthralgia, myalgias, night blindness, and hyperostoses are rare side effects of isotretinoin therapy.Serum liver function tests and triglyceride levels must be monitored monthly in patients receiving isotretinoin. When isotretinoin is present in the gestationalperiod, it can result in severe fetal abnormalities involving several systems.Therefore, two forms of contraception must be used during isotretinoin therapy and for one month after treatment has ended. To ensure that female patients are not pregnant when treatment is initiated, two negative urine pregnancy tests are required before isotretinoin is prescribed. Pregnancy status is rechecked at monthly visits. The link between isotretinoin and depression is controversial. A meta-analysis published in 2000 reviewed the purported risk of depression, suicide, or psychiatric disorders in patients taking isotretinoin and found no evidence that the drug was associated with an increased risk for depression, suicide, or other psychiatric disorders. However, several case reports and case series have described situations in which depression
began on initiation of isotretinoin therapy.

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