Isotretinoin

Aka: Isotretinoin, Accutane

1. Indications
   1. Severe Acne Vulgaris Management ( Cystic Acne)
   2. Treatment resistant Acne Vulgaris
2. Mechanism
   1. Vitamin A derivative (Retinoid) that inhibits sebum production and comedolysis
3. Dosing
   1. Course: 20 weeks
   2. Cummulative dose target: 120 mg/kg total over entire 20 week course
   3. Precautions
      1. Acne may worsen for the first 4 to 6 weeks before it starts to improve
      2. Accutane best absorption is when taken with food
         1. Absorica may be taken with or without food
   4. Initial dosing
      1. Start 0.25 to 0.4 mg/kg/day (or 0.5 mg/kg/day if severe)
      2. Titrate to 1 mg/kg/day as tolerated after the first month
         1. May also maintain at lower dose for moderate Acne Vulgaris
   5. Moderate acne or flares
      1. Lower dosing: 0.3 to 0.5 mg/kg divided twice daily
   6. Facial Acne
      1. Standard dosing: 1 mg/kg divided bid)
   7. Truncal Acne
      1. Higher dosing: 2 mg/kg divided twice daily
      2. Consider repeat 4 month course after 2 month rest
         1. Indicated for severe, refractory truncal acne
4. Adverse Effects
   1. Very Teratogenic (even 1 pill)
      1. See Precautions below
   2. Cheilitis (90%)
      1. Use lip balm
   3. Dry or chapped skin (90%)
      1. Use Skin Lubricant (Moisturizing Lotion)
   4. Dry nose and eyes (80%)
      1. Use artificial tears
      2. Use Nasal Saline and consider petroleum jelly at nasal septum to prevent Epistaxis
   5. Elevated Serum Triglycerides (25%)
   6. Arthralgias and Myalgias (15%)
      1. Take Ibuprofen or Acetaminophen
   7. Elevated liver transaminases (15%)
   8. Hair shedding (10%)
   9. Peeling of palms and soles (5%)
   10. Intracranial Hypertension
       1. Stop medication and return for evaluation if persistent Headache or Vision changes
   11. Night blindness
5. Precautions
   1. Major Depression exacerbation
      1. Increased Suicidality was seen in early studies but have not been confirmed
   2. Teratogenicity
      1. Associated with anomalies of the head, CNS, Cardiovascular System, Thymus and pararthyroid glands
      2. Needs two forms Contraception while taking
      3. Counsel extensively before use
      4. Requires prescribers to to enter into the iPLEDGE program (see below)
6. Drug Interactions
   1. No supplemental Vitamin A intake while on Accutane
   2. Stop topical acne medications (e.g. Benzoyl Peroxide, Keratolytics) to limit skin irritation
7. Monitoring
   1. Serum testing at baseline, 2 months and then as needed (if abnormal labs on initial testing)
      1. Liver transaminases
      2. Lipid panel (esp. Serum Triglycerides)
   2. iPLEDGE Program
      1. http://www.ipledgeprogram.com
      2. Only iPLEDGE registrants can administer Isotretinoin in the United States
      3. Replaces System Manage Accutane Related Teratogenicity (SMART)
         1. Required a Yellow Accutane Qualification Sticker
      4. Pregnancy prevention program per Roche and FDA
      5. Presciption limited to 30 days
      6. Mandates 2 forms of Birth Control
         1. Both forms started >1 month before Accutane
         2. Continue Contraception for 1 month after stopping
         3. One form must be primary Contraception
            1. Tubal Ligation or partner's Vasectomy
            2. Intrauterine Device
            3. Oral Contraceptive
            4. Depo Provera, Norplant or similar
      7. Mandates urine pregnancy timing
         1. Initial Urine Pregnancy Test
         2. Urine Pregnancy Test immediately before Accutane
            1. First five days of Menstrual Cycle
            2. 11 days after last intercourse if Amenorrhea
         3. Urine Pregnancy Test monthly at time of refill
8. References
   1. (2021) Presc Lett 28(12): 70-1
   2. Oge (2019) Am Fam Physician 100(8): 475-84 [PubMed]