Isotretinoin, or Accunate, is an oral prescription derivative of vitamin A. Originally tested as a chemotherapeutic drug, Isotretinoin earned a new place in the dermatologic market when in 1979 it was discovered to have a dramatic and permanent effect on all acne symptoms.
The medication was first approved by the FDA in 1982 and to date, its efficacy has not been superseded by any other treatment that produces long-term remission and/or substantial improvement in a majority of acne sufferers.
Normally, a course lasts for 15 to 20 weeks, or at a lower dose for six months or longer. It was originally reserved only for the most extreme acne, but with better understanding of the medication, healthcare providers have begun prescribing it more often and for less severe cases.
Some providers are more comfortable prescribing the medication over others, which is typically based on their experiences with patients (or their lack of experience).
How It Works
It’s not known exactly how Isotretinoin works, but it does impact how acne develops in four distinct ways:
- Isotretinoin “shrinks” the skin’s oil glands and reduces the amount of oil they produce. More clinically described, isotretinoin leads to a process called “apoptosis” (destruction) of the sebocytes (oil producing cells), which in turn reduces the oil production.
- The oil reduction therefore reduces the number of P. acnes bacteria living in the follicles. More specifically, the actual size of the oil producing units at the follicles (which turn into pimples) is dramatically reduced and therefore makes the environment for the common acne-causing bacteria undesirable.
- It slows down the creation of new skin cells within the pores, helping to prevent clogging in the first place. In medical terms, this is known as decreased hyperkeratinization. Skin cells that slough off are decreased, therefore reducing comedogenesis.
- Isotretinoin is a strong anti-inflammatory, with the ability to increase one’s defense mechanisms and lower the bacterial population, which in turn decreases inflammation of the skin.
Around 30% of Isotretinoin patients can encounter a few weeks of worsened acne, as their bodies become used to the medication, but the final results are usually quite dramatic.
In fact, 95% of patients who complete an Isotretinoin cycle see a partial or complete improvement of their acne. That said, a high percentage of people who use this acne treatment unfortunately experience long-term relapses of their symptoms as well.
Studies have shown relapse rates from 14% to 52%, with a real-world average of about 1/3 of all patients experiencing some sort of relapse. This often results in a second course. These relapses seem to be dose dependent, with lower doses resulting in more frequent relapses.
Doses of isotretinoin are generally based on weight, with 0.5mg-2mg/kg/day of body weight being the typical guideline (refer to your healthcare provider for their dosing recommendations and schedule). The best results are reached when a cumulative dose of 100-120mg/kg is reached. Most doctors will prescribe high doses of at least 1mg/kg per day for a fairly short period of 15 to 20 weeks.
Because the number of people who suffer from the medication’s side effects can be high, some healthcare providers have recently begun testing lower doses for longer stretches of time. The initial results of this experimentation have shown that patients with mild to moderate acne are able to achieve long-term results with fewer side effects, including scarring, with a lower dose. Similar results have been seen with people suffering from severe cases as well.
If you are prescribed Isotretinoin by your doctor or dermatologist, you’ll need to keep in mind that the price will depend on a number of factors, including where you buy your medication. Commercial insurance can lend itself to little or no out of pocket cost, while out of pocket costs can exceed $100/month, not including required office visits or bloodwork monitoring.
Risks and Side Effects
Clearly, Isotretinoin is exceptionally effective. The problem, however, lies in its numerous and widespread side effects. As a systemic medication, Isotretinoin can impact the entire body and most patients will experience at least some side effects.
These negative effects are almost entirely temporary and typically abate after discontinuation of the medication.
Most common side effects include:
- Dry lips, skin, eyes, nasal mucosa (occasional nose bleeds)
- Rash, likened to eczema, or an activation of previously remiss eczema
- Increased sun sensitivity
- Mild to moderate joint pain
Severe, rare side effects include the following:
- Hair loss (or growth in atypical areas, especially in women)
- Neurological symptoms like headache
- Vision problems (associated with decreased night vision)
- Hearing impairment
- Yellowish deposits on the eyelids
- Bleeding & inflammation of the gums
- Oozing, bleeding bumps
- Severe joint pain
- Acute, long lasting arthritis
- Muscle pain
- Abnormal blood tests
- Low blood platelet count
- Iron deficiency anemia
- Low white blood cell count
- Inflamed pancreas
- Inflammatory bowel disease/Crohn’s disease/Ulcerative colitis
- Abnormal menstrual cycles in women
Pregnancy & Isotretinoin
In addition to the side effects for the patient, there are serious risks to your fetus if you’re pregnant. A “teratogen” is a medication that disrupts the normal development of a fetus in the womb, causing birth defects; isotretinoin is considered a “category X” in terms of pregnancy risk, which equates to known fetal demise or severe, well-documented birth defects in human documented subjects.
Shortly after Isotretinoin became available, the Centers for Disease Control (CDC) warned that a large portion of pregnant women who took the medication suffered from spontaneous abortions and birth defects, leading to:
- Abnormal development of the skull, ears, eyes and/or face
- Central nervous system and cardiovascular system abnormalities
- Thymus and parathyroid abnormalities
The risk of fetal issues is so great that the FDA created the “iPledge program,” which requires women of childbearing age to commit to using two forms of birth control while on Isotretinoin. Let’s keep in mind that the majority of females that suffer from acne are of child-bearing age and the regulations are meant to protect the patient and their offspring.
Exceptions to the iPledge Program include those women who are no longer able to get pregnant (post-tubal ligation, post-hysterectomy, etc.) and in some cases those who are abstinent. With recent transgender focus in medicine, the ability to get pregnant is of most vital importance to the program and whether the patient is born male or female, if the patient is clinically able to get pregnant, they must comply to the regulations of the program accordingly.