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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Retinoid [EPC]
Isotretinoin is a potent systemic retinoid (Vitamin A derivative) indicated for the treatment of severe, recalcitrant nodular acne. It works by significantly reducing sebum production and shrinking sebaceous glands.
Name
Isotretinoin
Raw Name
ISOTRETINOIN
Category
Retinoid [EPC]
Drug Count
7
Variant Count
94
Last Verified
February 17, 2026
RxCUI
197843, 197844, 197845, 403930, 1299203, 1300006, 1300014, 1300016, 1547561, 1547563, 1547565, 1547567, 2262711, 2262713, 2262714, 2262715, 2262717, 2262719, 2262721, 2262723, 2262725, 2262727, 2262729, 2262731, 1373333, 1373335, 1373337, 1605088, 206880, 206883, 206902, 2473107, 404058, 404061, 404064, 2711694, 404059, 404062, 404065, 643488
UNII
EH28UP18IF
About Isotretinoin
Isotretinoin is a potent systemic retinoid (Vitamin A derivative) indicated for the treatment of severe, recalcitrant nodular acne. It works by significantly reducing sebum production and shrinking sebaceous glands.
Detailed information about Isotretinoin
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Isotretinoin.
First approved by the FDA in 1982 under the brand name Accutane, isotretinoin has since become the gold standard for treating acne that causes permanent scarring or significant psychological distress. While the original Accutane brand was discontinued for business reasons, several generic versions and branded formulations (such as Absorica, Claravis, and Amnesteem) remain widely available. It is important to note that isotretinoin is not a first-line treatment; healthcare providers typically reserve it for cases where other treatments have failed due to its significant side effect profile and the stringent regulatory requirements surrounding its prescription.
Isotretinoin is unique among acne treatments because it is the only medication that addresses all four major factors involved in the pathogenesis (development) of acne. At the molecular level, isotretinoin works by inducing apoptosis (programmed cell death) in sebaceous gland cells. This leads to a dramatic reduction in the size and activity of these glands.
Isotretinoin is highly lipophilic (fat-soluble). For most formulations, absorption is significantly enhanced when taken with a high-fat, high-calorie meal. Without food, the bioavailability (the amount of drug that reaches the bloodstream) can be reduced by as much as 50%. However, newer formulations like Absorica use Lidose technology to improve absorption even in a fasted state. Peak plasma concentrations (Tmax) are typically reached within 3 to 5 hours after oral administration.
Isotretinoin is extensively bound to plasma proteins, primarily albumin, at a rate exceeding 99.9%. Because of its lipophilic nature, it does not easily cross the blood-brain barrier in significant amounts, though it can distribute into various tissues, particularly the liver and skin.
Metabolism occurs primarily in the liver via several cytochrome P450 enzymes, including CYP2C8, 2C9, 3A4, and 2B6. The major active metabolite is 4-oxo-isotretinoin, which also contributes to the drug's therapeutic effects. Through a process of isomerization, isotretinoin can also be converted into tretinoin (all-trans-retinoic acid).
The mean elimination half-life of isotretinoin is approximately 10 to 20 hours, while the half-life of its 4-oxo metabolite is longer, ranging from 17 to 50 hours. The drug and its metabolites are excreted in nearly equal proportions through both renal (urine) and biliary (feces) pathways. Most of the drug is cleared from the body within 2 to 4 weeks after the final dose.
The primary FDA-approved indication for isotretinoin is the treatment of severe recalcitrant nodular acne. "Severe" is defined by the presence of many cysts and nodules (often 5 mm in diameter or greater), while "recalcitrant" means the condition has not improved after at least one course of systemic antibiotic therapy.
Off-label uses, which your doctor may consider based on clinical judgment, include:
Isotretinoin is available exclusively as an oral medication. Common forms include:
> Important: Only your healthcare provider can determine if Isotretinoin is right for your specific condition. Because of its potential for severe birth defects, all patients in the U.S. must be enrolled in the iPLEDGE risk management program.
The dosage of isotretinoin is highly individualized based on the patient's body weight and the severity of the condition. Healthcare providers typically aim for a total cumulative dose of 120 mg/kg to 150 mg/kg over the course of treatment to minimize the risk of relapse.
A typical course of treatment lasts 15 to 20 weeks. If the total nodule count has been reduced by more than 70% before the full cumulative dose is reached, the provider may choose to discontinue therapy, though completing the full course is generally recommended for long-term remission.
Isotretinoin is FDA-approved for use in pediatric patients aged 12 years and older. The dosing guidelines for adolescents are identical to those for adults (0.5 to 1.0 mg/kg/day). Use in children under the age of 12 is considered off-label and must be approached with extreme caution due to the potential for premature epiphyseal closure (premature stopping of bone growth).
There are no specific dosage adjustment guidelines provided by the manufacturer for patients with renal impairment. However, since isotretinoin is partially excreted renally, patients with severe renal failure should be started at a lower dose and titrated slowly while monitoring for toxicity.
Isotretinoin is contraindicated in patients with significantly impaired hepatic (liver) function. If a patient develops elevated liver enzymes (transaminases) during treatment, the dose should be reduced or the medication discontinued until levels normalize.
Clinical studies of isotretinoin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range.
If you miss a dose, skip the missed dose and take your next dose at the regularly scheduled time. Do not double the dose to catch up. Consistency is important, but an occasional missed dose will not significantly impact the long-term outcome of the 20-week course.
Signs of an isotretinoin overdose are similar to those of acute Vitamin A toxicity (hypervitaminosis A). Symptoms may include:
In the event of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately. Because isotretinoin remains in the blood for some time, female patients of childbearing potential must adhere to strict pregnancy prevention measures even after an overdose.
> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.
Nearly all patients taking isotretinoin will experience some degree of mucocutaneous (skin and mucous membrane) side effects. These are typically dose-dependent and manageable with supportive care.
> Warning: Stop taking Isotretinoin and call your doctor immediately if you experience any of these.
Most side effects of isotretinoin resolve within a few weeks of stopping the medication. However, some effects may be long-lasting:
Isotretinoin carries a Black Box Warning for Teratogenicity (risk of birth defects). There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking isotretinoin in any amount, even for short periods. Potentially any fetus exposed during pregnancy can be affected. The warning also mandates participation in the iPLEDGE program to ensure no patient starts the drug while pregnant or becomes pregnant during therapy.
Report any unusual symptoms to your healthcare provider.
Isotretinoin is one of the most strictly regulated medications in the United States. Patients must understand that this drug can cause life-threatening birth defects and serious mental health issues. It is essential to keep all follow-up appointments and complete all required laboratory testing. You must not share this medication with anyone else, even if they have similar acne symptoms, as the risks are too great.
CONTRAINDICATION AND IPLEDGE PROGRAM: Isotretinoin must not be used by patients who are pregnant or who may become pregnant. There is an extremely high risk of life-threatening birth defects. These defects include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Because of these risks, isotretinoin is available only through a restricted program called iPLEDGE. Under this program, only prescribers and pharmacies registered with iPLEDGE can prescribe and dispense the drug.
To ensure safety, your healthcare provider will require the following tests:
Use caution when driving at night. Isotretinoin can cause a sudden decrease in night vision. If you experience any visual changes, avoid driving or operating heavy machinery until you have consulted an ophthalmologist.
Alcohol consumption should be strictly limited or avoided while taking isotretinoin. Both alcohol and isotretinoin are processed by the liver and can increase triglyceride levels. Combining them significantly increases the risk of liver damage and pancreatitis.
Isotretinoin does not require a tapering period. However, you should not stop taking it prematurely without consulting your doctor, as this increases the likelihood of your acne returning. If you experience serious side effects (psychiatric, visual, or abdominal pain), stop the drug immediately and contact your provider.
> Important: Discuss all your medical conditions with your healthcare provider before starting Isotretinoin.
Isotretinoin can cause several laboratory abnormalities that do not necessarily reflect a drug-drug interaction but are critical to monitor:
For each major interaction, the clinical consequence is typically an increase in systemic toxicity (such as Vitamin A toxicity) or a failure of a secondary therapy (such as birth control). Management always involves strict avoidance of contraindicated drugs and vigilant laboratory monitoring for others.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.
> Important: Your healthcare provider will evaluate your complete medical history before prescribing Isotretinoin.
Isotretinoin is classified as Pregnancy Category X. It is one of the most dangerous drugs for a developing fetus. If pregnancy occurs, the medication must be stopped immediately, and the patient should be referred to an obstetrician-gynecologist experienced in reproductive toxicity. There is no "safe" dose or "safe" trimester. Birth defects can occur even if the drug is taken for a single day. Females must use two effective forms of birth control simultaneously for at least one month before starting, during the entire course, and for one full month after the last dose.
It is not known if isotretinoin is excreted in human milk. However, because it is highly lipophilic, it is very likely to pass into breast milk. Due to the potential for serious adverse reactions in the nursing infant (similar to the side effects seen in adults), breastfeeding is strictly contraindicated during treatment and for one month after the final dose.
Isotretinoin is approved for children 12 years of age and older. In this population, the primary concern is the effect on bone health. There have been reports of premature epiphyseal closure (fusion of the growth plates), which can result in permanent shortening of stature. Pediatric patients should be monitored for any bone or joint pain. It is not approved for use in children under 12, as the risks to developing skeletal systems have not been adequately studied.
Acne is less common in the elderly, but isotretinoin may be used for conditions like rosacea or rhinophyma. Geriatric patients are more likely to have pre-existing liver or kidney issues and are often taking multiple other medications (polypharmacy). They should be monitored closely for changes in liver function and lipid levels. There is also a theoretical risk that the drying effects could increase the risk of skin infections or corneal abrasions in older adults with naturally drier skin and eyes.
In patients with renal failure, the pharmacokinetics of isotretinoin are not significantly altered because it is primarily metabolized by the liver. However, caution is advised. Some studies suggest starting at a very low dose (e.g., 10 mg/day) and monitoring the GFR (Glomerular Filtration Rate) and electrolyte balance, as the drug's metabolites can occasionally accumulate in the setting of severe kidney disease.
Isotretinoin is contraindicated in patients with severe hepatic impairment. In those with mild to moderate impairment, the drug should be used only if the benefits clearly outweigh the risks, with frequent monitoring of AST, ALT, and alkaline phosphatase levels. If transaminase levels rise above three times the upper limit of normal, the drug should be stopped.
> Important: Special populations require individualized medical assessment.
Isotretinoin is a systemic retinoid that acts as a non-selective agonist for nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Once it binds to these receptors in the nucleus of sebaceous gland cells, it alters gene expression. Specifically, it downregulates the expression of genes involved in lipid synthesis and cell proliferation. This leads to the shrinking of sebaceous glands and a reduction in the production of sebum. Furthermore, it exhibits anti-inflammatory effects by inhibiting the chemotaxis of neutrophils and monocytes into the dermis.
The onset of action for sebum suppression is rapid, typically occurring within 2 to 4 weeks. However, the visible improvement in acne nodules often takes 8 to 12 weeks. Some patients experience an "initial flare" or "purging" phase where acne temporarily worsens as the drug begins to normalize skin cell turnover. The duration of the drug's effect is long-lasting; many patients remain clear of acne for years after a single 20-week course, suggesting that the drug induces permanent or semi-permanent structural changes in the skin's architecture.
| Parameter | Value |
|---|---|
| Bioavailability | ~25% (fasted), ~50% (fed) |
| Protein Binding | >99.9% (primarily albumin) |
| Half-life | 10-20 hours (parent drug) |
| Tmax | 3-5 hours |
| Metabolism | Hepatic (CYP2C8, 2C9, 3A4, 2B6) |
| Excretion | Renal 50%, Fecal 50% |
Isotretinoin is classified as a first-generation systemic retinoid. It is closely related to other retinoids like tretinoin (topical), acitretin (used for psoriasis), and adapalene. Within the therapeutic hierarchy, it is categorized as an anti-acne agent and a keratolytic.
Medications containing this ingredient
Common questions about Isotretinoin
Isotretinoin is primarily used to treat severe, recalcitrant nodular acne that has not responded to other treatments like antibiotics or topical creams. It is reserved for cases where the acne is causing permanent scarring or significant psychological distress for the patient. By targeting all four causes of acne—excess oil, clogged pores, bacteria, and inflammation—it provides a comprehensive solution. Most patients undergo a 4 to 6-month course of treatment to achieve long-term remission. It is also occasionally used off-label for severe rosacea or other chronic skin conditions under strict medical supervision.
The most common side effects are related to the drying of the skin and mucous membranes, which affects nearly every patient. This includes severely dry and cracked lips (cheilitis), dry and itchy skin, dry eyes, and frequent nosebleeds due to dry nasal passages. Many patients also report muscle aches and joint pain, particularly in the lower back, which can be exacerbated by physical activity. These effects are usually dose-dependent and typically resolve within a few weeks after the treatment course is completed. While bothersome, they are generally manageable with moisturizers, lip balms, and saline nasal sprays.
It is strongly recommended that you avoid or strictly limit alcohol consumption while taking isotretinoin. Both alcohol and isotretinoin are processed by the liver, and combining them can place excessive stress on the organ, potentially leading to hepatotoxicity. Furthermore, both substances can significantly raise your triglyceride levels, increasing the risk of developing acute pancreatitis, a serious and painful condition. Alcohol can also worsen the dehydrating effects of the medication on your skin and eyes. To ensure your safety and the effectiveness of the treatment, it is best to abstain from alcohol during your course.
No, isotretinoin is extremely dangerous during pregnancy and is classified as a known human teratogen. Even a single dose taken during pregnancy can cause severe, life-threatening birth defects or miscarriage. These defects can affect the brain, heart, face, and various glands of the developing fetus. Because of this risk, the FDA mandates that all patients, regardless of gender, participate in the iPLEDGE program to prevent fetal exposure. Females of reproductive potential must use two forms of effective birth control and pass monthly pregnancy tests to continue receiving the medication.
While some patients see an improvement in their skin within the first month, it often takes 2 to 3 months to see significant results. In fact, many patients experience a temporary worsening of their acne, known as a 'flare' or 'purge,' during the first few weeks as the drug begins to clear out clogged pores. The full benefits are usually realized toward the end of a 15 to 20-week course. Even after you stop taking the medication, your skin may continue to improve for several weeks. The goal of the treatment is to reach a cumulative dose that provides long-term clearance of acne.
You can stop taking isotretinoin suddenly without experiencing physical withdrawal symptoms, as it is not an addictive substance. However, you should only do so if you are experiencing serious side effects, such as severe depression or vision changes, and you must notify your doctor immediately. If you stop the medication prematurely simply because your skin looks clear, there is a much higher risk that your acne will return. To achieve permanent results, it is crucial to complete the full cumulative dose prescribed by your dermatologist. Always consult your healthcare provider before making any changes to your treatment plan.
If you miss a dose of isotretinoin, you should skip the missed dose and simply take your next scheduled dose at the normal time. You should never take two doses at once or 'double up' to make up for the one you missed, as this can increase the risk of acute side effects. Because isotretinoin is a long-term treatment that builds up in your system, a single missed dose will not negatively impact the overall success of your therapy. Try to take your medication with a meal at the same time each day to help you remember. If you find yourself missing doses frequently, talk to your pharmacist about tools to help you stay on track.
Weight gain is not a commonly reported side effect of isotretinoin in clinical trials. However, because the medication must be taken with a high-fat, high-calorie meal to be properly absorbed, some patients may inadvertently increase their caloric intake, leading to minor weight changes. If you notice significant weight gain, it is more likely related to lifestyle changes or other factors rather than the medication itself. It is important to focus on healthy fats, such as avocados or nuts, to aid absorption without consuming excessive empty calories. If you have concerns about your weight during treatment, discuss them with your healthcare provider.
Isotretinoin has several significant drug interactions that must be avoided. You should never take it with Vitamin A supplements or tetracycline-class antibiotics, as these combinations can lead to severe toxicity or increased pressure in the brain. It may also interact with certain types of birth control and anti-seizure medications like phenytoin. Because of these risks, it is essential to provide your doctor with a complete list of all prescription drugs, over-the-counter medicines, and herbal supplements you are taking. Your pharmacist can also help screen for potential interactions every time you fill a new prescription.
Yes, isotretinoin is available as a generic medication and is sold under several different brand names, including Claravis, Amnesteem, Myorisan, and Zenatane. The original brand-name version, Accutane, is no longer on the market, but the generic versions contain the same active ingredient and are just as effective. There is also a specialized brand called Absorica, which is formulated to be absorbed better without food. Regardless of the brand or generic version you are prescribed, you will still be required to participate in the iPLEDGE program. Generic versions are typically more cost-effective for patients while providing the same clinical results.