Pharmacologic Therapy for Acne: A Primer for Primary Care

Isotretinoin

Isotretinoin is an oral systemic retinoid that modulates nuclear receptors and regulates gene transcription in the epidermis.¹⁶ Isotretinoin’s mechanisms of action target the main pathogenic factors underlying acne, including reduction of follicular hyperkeratosis, comedogenesis, sebum production, and inflammation and suppression of P acnes.²² These combined actions make isotretinoin a highly effective treatment option for acne.

The drug is approved by the FDA for treatment of nodular acne refractory to traditional acne therapies.²³ Isotretinoin is available in 10, 20, 25, 30, and 40 mg capsules, and the recommended dosing is 0.5 to 2.0 mg/kg/d. The usual course of therapy is 15 to 20 weeks or until an accumulative dosage of 120 to 150 mg/kg is attained.²³ Patients should be instructed to take isotretinoin with meals, as oral availability is increased with high-fat foods.²³

Isotretinoin has major adverse effects. It is a teratogenic medication that can cause congenital anomalies in exposed fetuses, including craniofacial, cardiac, and neurologic issues.¹⁶ Due to the seriousness of the congenital anomalies, all prescribers must be registered in the iPledge program, a computer-based risk management program instituted in 2006 by the FDA and the companies that manufacture isotretinoin to eliminate congenital risks associated with isotretinoin. All patients, both male and female, must sign an informed consent form when they register in the program.

Although the iPledge program does not mandate consistent condom use for male patients, they should be informed that minute amounts of isotretinoin can be found in semen. The risk for fathering a fetus with congenital anomalies when taking isotretinoin appears to be extremely low.¹⁶ Women of childbearing potential must commit to the use of two highly reliable forms of birth control when taking the medication, including one month before starting therapy and one month after completing therapy.¹⁶ Monthly pregnancy testing is mandatory throughout the course of treatment.²⁴ Further information regarding the risk management program can be found at iPledgeprogram.com.

Isotretinoin is metabolized by the liver and may cause lipid abnormalities and hepatic enzyme elevations. Baseline and monthly laboratory monitoring of liver enzymes and cholesterol and triglyceride levels are recommended.²⁴ The process of initiating and monitoring isotretinoin therapy is quite complex, and unless the practitioner plans to routinely prescribe this medi­cation, patients needing isotretinoin therapy should be referred to a dermatology practice.

PATIENT EDUCATION

Patients are more likely to adhere to treatment when simplified regimens are used and when they have realistic expectations for therapy outcomes. Providers need to educate patients that all treatments may require at least two to three months of use before visible results occur. Initial and subsequent visits should include discussions about clear expectations and strategies to reduce potential adverse effects.

PUTTING IT ALL TOGETHER

Acne therapy starts with the use of a topical retinoid in mild acne cases, unless the patient is unable to tolerate the associated skin irritability. Addition of a topical antibiotic or anti-inflammatory agent, preferably BPO, either alone or with a combination product, is also recommended for mild to moderate acne. Patients with moderate to severe acne may benefit from a short course (three months or less) of antibiotics.

Oral hormones may be an excellent therapy choice when acne treatment is needed for women of childbearing age. Isotretinoin is indicated in select cases of severe acne resistant to other treatments.