According to the FDA-approved labeling (2024), oral tretinoin is indicated for the induction of remission in Acute Promyelocytic Leukemia (APL).
A study published in the Journal of the American Academy of Dermatology (2023) confirms that tretinoin remains the most effective topical therapy for comedonal acne.
Tretinoin was the first retinoid approved by the FDA for the treatment of photoaged skin in 1995 under the brand name Renova.
Data from the National Institutes of Health (NIH) indicates that oral tretinoin achieves complete remission in approximately 70-90% of APL patients when used with chemotherapy.
The World Health Organization (WHO) includes tretinoin on its Model List of Essential Medicines for its critical role in treating leukemia.
According to the iPLEDGE program standards, although primarily focused on isotretinoin, the teratogenic risks of tretinoin are considered equally severe for oral administration.
Clinical trials (2022) showed that tretinoin microsphere gel (0.1%) significantly reduces skin irritation compared to traditional gel formulations.
The American Academy of Dermatology (AAD) recommends tretinoin as a first-line treatment for both adolescent and adult acne (2024 guidelines).
This page is for informational purposes only and does not replace medical advice. Before using any prescription or over-the-counter medication for Tretinoin Cream, you must consult a qualified healthcare professional.
Tretinoin is a potent retinoid (Vitamin A derivative) used topically for acne and photoaging, and orally for acute promyelocytic leukemia (APL). It works by regulating cell growth and differentiation through nuclear receptor activation.
💊Usage & Dosage
Adult Dosage
Topical Dosage for Acne and Photoaging
For most dermatological conditions, tretinoin is applied once daily, typically in the evening.
Acne Vulgaris: A pea-sized amount of cream or gel should be applied to the entire affected area. It is not a 'spot treatment.'
Photoaging: Patients usually start with a lower concentration (0.025%) applied every other night to build tolerance, eventually increasing to 0.05% or 0.1% nightly as tolerated.
Oral Dosage for Acute Promyelocytic Leukemia (APL)
Induction Therapy: The standard dose is 45 mg/m² per day, administered in two evenly divided doses. This is continued until complete remission is documented or for a maximum of 90 days.
Maintenance: Dosage and duration for maintenance therapy vary based on specific oncology protocols and are often combined with anthracycline-based chemotherapy.
Pediatric Dosage
Topical Use: Tretinoin is generally approved for use in pediatric patients aged 12 years and older for acne. Use in children under 12 must be strictly supervised by a pediatric dermatologist, as safety and efficacy have not been formally established for younger populations.
Oral Use (APL): The pediatric dose for APL is also 45 mg/m² per day. However, children may be more susceptible to certain side effects, such as pseudotumor cerebri (increased pressure in the brain), and require close monitoring.
Dosage Adjustments
Renal Impairment
There are no specific dosage adjustment guidelines provided by the manufacturer for patients with renal impairment taking oral tretinoin. However, because metabolites are excreted renally, healthcare providers should exercise extreme caution and monitor for signs of toxicity.
Hepatic Impairment
Since tretinoin is primarily metabolized in the liver, patients with hepatic dysfunction may experience decreased clearance and increased systemic levels. Dose reductions may be necessary for oral therapy, and liver function tests (LFTs) must be monitored frequently.
Elderly Patients
In clinical trials for APL, elderly patients had similar response rates to younger patients. However, for topical use, elderly skin may be thinner and more prone to irritation; therefore, starting with a lower concentration and a less frequent application schedule is often recommended.
How to Take Tretinoin
Topical Application
1Wash and Dry: Wash the skin with a mild, non-medicated soap. Wait at least 20 to 30 minutes for the skin to be completely dry before applying. Applying tretinoin to damp skin can increase absorption and lead to severe irritation.
2Quantity: Use only a pea-sized amount for the entire face. Using more will not speed up results but will increase the risk of peeling and redness.
3Timing: Apply at night, as tretinoin is photolabile (it breaks down in sunlight).
4Sun Protection: Use a broad-spectrum sunscreen (SPF 30+) every morning, as tretinoin increases sensitivity to UV radiation.
Oral Administration
1With Food: Oral capsules should be swallowed whole with a meal to ensure maximal absorption.
2Do Not Crush: Do not open or chew the capsules.
3Storage: Store at room temperature (68°F to 77°F), protected from light and moisture.
Missed Dose
Topical: Skip the missed dose and apply the next dose at the usual time the following evening. Do not double the amount.
Oral: If you miss a dose, take it as soon as possible unless it is almost time for your next scheduled dose. Never take two doses at once.
Overdose
Topical Overdose: Excessive application leads to severe skin redness, peeling, and discomfort. Wash the area and discontinue use for several days until the skin heals.
Oral Overdose: Symptoms may include severe headache, nausea, vomiting, dizziness, and facial flushing. In case of oral overdose, contact a Poison Control Center or seek emergency medical attention immediately.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or frequency of application without medical guidance, as this can lead to treatment failure or increased toxicity.
⚠️Side Effects
Common Side Effects (>1 in 10)
Topical Use
Retinoid Dermatitis: This is the most common reaction, characterized by redness (erythema), dryness, and scaling (peeling). It typically occurs within the first 2-4 weeks of treatment.
Burning/Stinging: A mild sensation of warmth or stinging immediately after application is common.
Increased Photosensitivity: The skin becomes significantly more prone to sunburn.
Acne Flare: Some patients experience a 'purging' phase where acne appears to worsen before it improves.
Oral Use
Headache
🔴Warnings
Important Safety Information
Tretinoin is a highly potent biological modifier. Whether used topically for skin rejuvenation or orally for cancer treatment, it carries significant risks that require careful medical oversight. Patients must be aware that tretinoin is chemically related to Vitamin A; therefore, taking Vitamin A supplements while on tretinoin can lead to additive toxicity (Hypervitaminosis A).
Black Box Warnings
No FDA black box warnings exist for topical tretinoin. However, oral tretinoin carries the following critical warnings:
APL Differentiation Syndrome: Can be fatal if not recognized and treated with steroids immediately.
Pregnancy Risk: Tretinoin is a powerful teratogen. It causes major human fetal abnormalities in a high percentage of pregnancies.
🔄Interactions
Contraindicated Combinations (Do Not Use Together)
Vitamin A (Retinol) Supplements: Taking Vitamin A in doses exceeding the Recommended Dietary Allowance (RDA) while on tretinoin can lead to a toxic syndrome known as Hypervitaminosis A. Symptoms include severe skin peeling, bone pain, and liver damage.
Tetracyclines (e.g., Doxycycline, Minocycline): The combination of oral tretinoin and tetracyclines significantly increases the risk of 'pseudotumor cerebri' (increased pressure in the brain). This combination must be avoided.
Serious Interactions (Monitor Closely)
CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin): These drugs slow the metabolism of tretinoin, leading to increased blood levels and a higher risk of toxicity.
CYP3A4 Inducers (e.g., Rifampin, Phenytoin, St. John's Wort)
🚫Contraindications
Absolute Contraindications
Pregnancy (Oral Use): Tretinoin is strictly contraindicated in pregnancy (Category X). It is a highly potent teratogen that causes severe birth defects, including craniofacial, cardiac, and central nervous system abnormalities. Females of childbearing age must have two negative pregnancy tests before starting oral therapy and use two forms of contraception.
Hypersensitivity: Patients with a known allergy to tretinoin or any of its components (such as parabens in some creams or soybean oil in some capsules) must not use the medication.
Retinoid Hypersensitivity: A history of severe adverse reactions to other retinoids (like isotretinoin or adapalene) is a contraindication.
Relative Contraindications
Eczema or Rosacea
👥Special Populations
Pregnancy
Oral Tretinoin: Classified as FDA Pregnancy Category X. There is a high risk of 'Retinoic Acid Embryopathy.' Even a single dose can cause major malformations. Women must use two independent forms of effective contraception simultaneously for at least one month before, during, and for one month after treatment.
Topical Tretinoin: While systemic absorption is low, it is generally recommended to avoid topical tretinoin during pregnancy as a precautionary measure. There are rare case reports of birth defects following topical use, though a definitive link has not been established.
Breastfeeding
It is not known whether tretinoin is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants (such as growth interference or skin toxicity), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Topical application to the breast area should be strictly avoided to prevent the infant from ingesting the drug.
🧬Pharmacology
Mechanism of Action
Tretinoin (all-trans retinoic acid) is a naturally occurring metabolic product of Vitamin A. Its primary molecular mechanism involves binding to and activating Retinoic Acid Receptors (RAR-alpha, beta, and gamma). Once tretinoin binds to these receptors, they form a complex with Retinoid X Receptors (RXR). This complex moves into the nucleus and binds to DNA, acting as a transcription factor that regulates the expression of genes involved in cell growth and differentiation.
In Acute Promyelocytic Leukemia (APL), the disease is caused by a fusion of the PML gene and the RARα gene. This fusion protein blocks cell maturation. Tretinoin binds to this fusion protein, causing it to break down. This 'releases' the block, allowing the leukemic promyelocytes to mature into normal, functioning white blood cells (neutrophils).
Pharmacodynamics
Onset of Action: In APL, hematologic response is usually seen within 1-2 weeks, with full remission often taking 30-60 days. In acne, improvement is typically seen after 2-3 weeks, but 8-12 weeks are required for maximum benefit.
Frequently Asked Questions
Common questions about Tretinoin Cream
What is Tretinoin used for?
Tretinoin is a versatile medication used in both dermatology and oncology. Topically, it is the gold standard for treating acne vulgaris by preventing clogged pores and is also FDA-approved to reduce fine wrinkles and dark spots caused by sun damage. Orally, it is a life-saving treatment for a specific type of blood cancer called Acute Promyelocytic Leukemia (APL). It works by forcing immature cancer cells to mature into normal white blood cells. Because of its potency, it is only available by prescription and requires careful medical supervision.
What are the most common side effects of Tretinoin?
The side effects of tretinoin depend heavily on whether it is used on the skin or taken as a pill. For topical use, the most common issues are skin redness, peeling, dryness, and a stinging sensation, often called 'retinoid dermatitis.' For the oral form used in leukemia, common side effects include severe headaches, bone pain, dry skin, and nausea. A very serious side effect of the oral form is 'Differentiation Syndrome,' which causes breathing problems and fever. Always report any severe or worsening symptoms to your healthcare provider immediately.
Can I drink alcohol while taking Tretinoin?
It is generally advised to avoid or strictly limit alcohol while taking oral tretinoin for leukemia. Alcohol can increase the levels of triglycerides (fats) in your blood and put extra strain on your liver, both of which are already risks associated with tretinoin therapy. For topical tretinoin, moderate alcohol consumption is unlikely to cause a direct interaction, but alcohol can dehydrate the skin and worsen the dryness and irritation caused by the cream. Consult your doctor for specific guidance based on your treatment plan.
Is Tretinoin safe during pregnancy?
No, tretinoin is not considered safe during pregnancy and is classified as Category X for oral use. Oral tretinoin is a known teratogen, meaning it causes severe and life-threatening birth defects in a high percentage of cases. Women of childbearing age must use two forms of effective birth control and have regular pregnancy tests while taking the oral form. While topical tretinoin is absorbed in very small amounts, most doctors recommend stopping its use during pregnancy as a safety precaution. Always inform your doctor if you are pregnant or planning to become pregnant.
How long does it take for Tretinoin to work?
The timeline for tretinoin results varies by the condition being treated. For acne, you may see an initial 'purge' where skin looks worse, but significant improvement usually takes 6 to 12 weeks of consistent use. For anti-aging benefits like reducing fine lines, it often takes 3 to 6 months of nightly application to see visible changes. In the treatment of leukemia, tretinoin begins working at the cellular level within days, but it may take 30 to 90 days to achieve a full clinical remission. Patience and consistency are essential for this medication.
Can I stop taking Tretinoin suddenly?
If you are using topical tretinoin for acne or aging, you can generally stop using it suddenly without dangerous withdrawal effects, though your skin condition may slowly return to its previous state. However, if you are taking oral tretinoin for leukemia, you must NEVER stop taking it without your oncologist's direct instruction. Stopping the medication early can allow the cancer cells to begin growing again, leading to a relapse. Always follow the full course of treatment as prescribed by your medical team.
What should I do if I miss a dose of Tretinoin?
If you miss a dose of topical tretinoin, simply skip the missed dose and apply it the following evening at your usual time; do not apply extra to make up for it. For oral tretinoin, take the missed dose as soon as you remember, unless it is almost time for your next scheduled dose. Never double your dose to catch up, as this increases the risk of toxicity. If you miss multiple doses of the oral medication, contact your oncology clinic immediately for guidance. Consistency is key to the success of the treatment.
Does Tretinoin cause weight gain?
Weight gain is not a typical side effect of topical tretinoin. However, for patients taking oral tretinoin for leukemia, rapid weight gain can be a sign of a very serious complication called 'Differentiation Syndrome.' This weight gain is usually caused by fluid retention in the lungs or around the heart rather than fat gain. If you are taking oral tretinoin and notice a sudden increase in weight along with shortness of breath or fever, seek emergency medical attention immediately. Most other patients do not experience significant weight changes.
Can Tretinoin be taken with other medications?
Tretinoin has several significant drug interactions that must be managed. It should not be taken with Vitamin A supplements or certain antibiotics like tetracyclines, as this can cause dangerous pressure in the brain. Other medications that affect liver enzymes can also change how tretinoin works in your body. When using topical tretinoin, avoid other harsh skin products like benzoyl peroxide or salicylic acid at the same time of day to prevent severe irritation. Always provide your doctor with a full list of your current medications and supplements.
Is Tretinoin available as a generic?
Yes, tretinoin is widely available as a generic medication in both topical and oral forms. Generic versions are typically much more affordable than brand-name versions like Retin-A, Renova, or Vesanoid. Generic tretinoin is required by the FDA to have the same active ingredient, strength, and effectiveness as the brand-name versions. The appearance of the packaging or the texture of the cream may vary slightly between manufacturers, but the therapeutic benefit remains the same. Check with your pharmacist for the most cost-effective option.
Similar Medications
Other drugs with the same active ingredient (Tretinoin)
: Reported in up to 86% of patients treated for APL.
Mucocutaneous Dryness: Dry skin, dry mouth, and cheilitis (severely chapped lips) are nearly universal.
Bone Pain: Significant musculoskeletal pain, particularly in the long bones.
Nausea and Vomiting: Common gastrointestinal distress during induction therapy.
Less Common Side Effects (1 in 100 to 1 in 10)
Hyperpigmentation or Hypopigmentation: Temporary changes in skin color at the application site.
Pruritus: Intense itching of the skin.
Hypertriglyceridemia: Elevated levels of fats (triglycerides) in the blood (oral use).
Transaminase Elevation: Mild to moderate increases in liver enzymes.
Rare Side Effects (less than 1 in 100)
Pseudotumor Cerebri: Benign intracranial hypertension, characterized by severe headache, papilledema (swelling of the optic nerve), and visual changes. This is more common in pediatric patients.
Alopecia: Thinning of the hair or hair loss (oral use).
Hearing Loss: Rare reports of impaired hearing or tinnitus.
Serious Side Effects — Seek Immediate Medical Attention
> Warning: Stop taking Tretinoin and call your doctor immediately if you experience any of these serious symptoms.
Differentiation Syndrome (Oral Only): This is a life-threatening condition formerly known as Retinoic Acid Syndrome. Symptoms include fever, dyspnea (shortness of breath), weight gain, radiographic pulmonary infiltrates (fluid in lungs), and pleural or pericardial effusions. It requires immediate treatment with high-dose steroids (dexamethasone).
Leukocytosis: An abnormally high white blood cell count (oral use), which can lead to organ damage.
Severe Depression or Suicidal Ideation: While more commonly associated with isotretinoin, any mood changes while on retinoids should be reported immediately.
Pancreatitis: Severe abdominal pain radiating to the back, often associated with very high triglyceride levels.
Vision Changes: Sudden blurring or loss of vision, which may indicate increased brain pressure.
Long-Term Side Effects
Skin Thinning: Prolonged topical use may lead to a perceived thinning of the stratum corneum, though it actually increases dermal thickness over time.
Teratogenicity: The most significant long-term concern is the risk of severe birth defects if pregnancy occurs during or shortly after treatment.
Hyperostosis: Changes in bone density or the formation of bone spurs have been noted with long-term, high-dose oral retinoid therapy.
Black Box Warnings
For oral tretinoin (Vesanoid), the FDA has issued several Black Box Warnings:
1Differentiation Syndrome: Patients may experience fever, respiratory distress, and multi-organ failure. It must be managed with immediate dexamethasone therapy.
2Leukocytosis: About 40% of patients develop high white cell counts, increasing the risk of life-threatening complications.
3Teratogenicity: There is an extremely high risk that a deformed infant will result if tretinoin is administered during pregnancy. Patients must use two forms of effective contraception.
4Experienced Physician: Tretinoin should only be administered under the strict supervision of a physician experienced in the management of leukemia.
Report any unusual symptoms to your healthcare provider immediately. Early intervention is key to managing side effects effectively.
Leukocytosis: Rapid increases in white blood cells can lead to vascular complications.
Major Precautions
Photosensitivity: Tretinoin makes your skin significantly more sensitive to sunlight, wind, and cold. Severe sunburn can occur even on cloudy days. Patients must use protective clothing and SPF 30+ daily.
Eczema and Irritated Skin: Topical tretinoin should not be applied to skin suffering from eczema, as it can cause severe irritation. It should also be kept away from the eyes, mouth, and angles of the nose.
Pseudotumor Cerebri: Oral tretinoin can cause an increase in intracranial pressure. If you experience a persistent, severe headache or vision changes, seek medical help immediately.
Lipid Elevations: Oral tretinoin frequently causes an increase in blood cholesterol and triglycerides. Patients with pre-existing lipid disorders or diabetes must be monitored closely.
Hepatotoxicity: Liver enzyme elevations are common. Baseline and periodic liver function tests are required for oral therapy.
CBC (Complete Blood Count): To monitor for leukocytosis and response to leukemia treatment.
Liver Function Tests (LFTs): Monitored weekly during induction and periodically thereafter.
Lipid Panel: Fasting triglycerides and cholesterol levels should be checked regularly.
Pregnancy Tests: For females of reproductive potential, a pregnancy test must be performed within one week prior to starting therapy and monthly during therapy.
Driving and Operating Machinery
Tretinoin may cause dizziness or severe headaches (especially if intracranial pressure increases). Do not drive or operate heavy machinery until you know how the medication affects you. Visual disturbances, though rare, can also impair the ability to perform these tasks safely.
Alcohol Use
Alcohol should be avoided or strictly limited while taking oral tretinoin. Alcohol can increase triglyceride levels and put additional stress on the liver, potentially worsening the hepatotoxic effects of the medication.
Discontinuation
Topical: Can usually be stopped suddenly, though acne may gradually return if maintenance therapy is not established.
Oral: Discontinuation of oral tretinoin must only be done under the direction of an oncologist. Stopping induction therapy early can lead to a relapse of leukemia.
> Important: Discuss all your medical conditions, including any history of depression, liver disease, or high cholesterol, with your healthcare provider before starting Tretinoin.
: These substances speed up the metabolism of tretinoin, which can reduce its efficacy in treating leukemia.
Antifibrinolytic Agents (e.g., Aminocaproic Acid, Tranexamic Acid): There have been reports of fatal thrombotic (blood clot) complications when these are used with tretinoin.
Moderate Interactions
Photosensitizing Medications (e.g., Thiazides, Sulfonamides, Fluoroquinolones): These drugs can further increase the skin's sensitivity to sunlight, leading to severe phototoxic reactions.
Topical Keratolytics (e.g., Benzoyl Peroxide, Salicylic Acid, Sulfur): Using these alongside topical tretinoin can cause excessive skin irritation and dryness. If used, they should be applied at different times of the day (e.g., Benzoyl Peroxide in the morning, Tretinoin at night).
Food Interactions
High-Fat Meals: For oral tretinoin, a high-fat meal significantly increases absorption. Patients should be consistent in how they take the medication (always with food).
Grapefruit Juice: Grapefruit is a known inhibitor of the CYP3A4 enzyme. Consuming grapefruit juice can increase the systemic concentration of oral tretinoin, potentially leading to increased side effects.
Herbal/Supplement Interactions
St. John's Wort: This herbal supplement induces CYP3A4 enzymes and may decrease the effectiveness of oral tretinoin.
Multivitamins: Many multivitamins contain Vitamin A. Patients must check labels carefully to ensure they are not consuming supplemental Vitamin A while on tretinoin therapy.
Lab Test Interactions
Lipid Profiles: Tretinoin can cause significant elevations in serum triglycerides and cholesterol, potentially interfering with the interpretation of lipid metabolism tests.
Liver Function Tests: It can cause transient elevations in ALT, AST, and bilirubin.
Coagulation Tests: In APL patients, tretinoin may normalize coagulation parameters (like PT and PTT) as the disease goes into remission.
Management Strategy
For major interactions, the primary strategy is avoidance. If a CYP3A4 inhibitor must be used, the physician may reduce the tretinoin dose. For topical interactions, the 'wait and see' approach is used, where the patient spaces out applications of different skin products to minimize irritation.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter skin creams and vitamins.
: Topical tretinoin can cause severe flares of these conditions. It should be used with extreme caution and only under specialist guidance.
Hepatic or Renal Dysfunction: Because the liver metabolizes tretinoin and the kidneys excrete its metabolites, impairment in these organs increases the risk of systemic toxicity.
Leukocytosis: In APL, a baseline white blood cell count > 5,000/µL requires cautious management due to the high risk of Differentiation Syndrome.
History of Depression: While the link is debated, a history of significant psychiatric illness requires careful monitoring during retinoid therapy.
Cross-Sensitivity
Patients who are sensitive to Vitamin A derivatives may show cross-sensitivity to tretinoin. Additionally, because some oral formulations contain soybean oil, patients with severe soy or peanut allergies should check the specific brand's inactive ingredients to avoid anaphylaxis.
> Important: Your healthcare provider will evaluate your complete medical history, including your plans for pregnancy and any skin sensitivities, before prescribing Tretinoin.
Pediatric Use
Dermatology: Safety and effectiveness in children below the age of 12 have not been established. In adolescents, it is widely used for acne, but they must be counseled on the importance of sun protection.
Oncology: Tretinoin is used in children with APL. However, pediatric patients are at a much higher risk for developing pseudotumor cerebri (increased brain pressure). Close monitoring for headaches and nausea is mandatory.
Geriatric Use
Clinical studies of oral tretinoin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In topical use, elderly patients often have more fragile, dry skin (xerosis), making them more susceptible to the irritating effects of tretinoin. Lower concentrations and heavy use of moisturizers are typically required.
Renal Impairment
Metabolites of tretinoin are excreted in the urine. While no specific dose adjustments are mandated, patients with a GFR < 30 mL/min should be monitored for signs of Hypervitaminosis A, such as severe headaches or skin peeling, which may indicate drug accumulation.
Hepatic Impairment
Tretinoin is extensively metabolized by the liver. In patients with significant hepatic impairment (Child-Pugh Class B or C), the half-life of the drug may be significantly prolonged. Physicians may consider a dose reduction (e.g., 25 mg/m² instead of 45 mg/m²) and frequent monitoring of liver enzymes.
> Important: Special populations require individualized medical assessment and more frequent laboratory monitoring to ensure safety.
Duration of Effect: The effects on gene expression can last for several days after a dose, despite the short half-life of the drug in the blood.
Tolerance: There is no evidence of pharmacological tolerance; however, the skin usually 'retinizes' (becomes more tolerant to the irritation) over the first month of topical use.
Pharmacokinetics
| Parameter | Value |
|---|---|
| Bioavailability | ~50% (Oral, increased with food) |
| Protein Binding | >95% (Primarily to Albumin) |
| Half-life | 0.5 to 2 hours |
| Tmax | 1 to 2 hours |
| Metabolism | Hepatic (CYP2C8, 2C9, 3A4) |
| Excretion | Renal 60%, Fecal 30% |
Chemical Information
Molecular Formula: C20H28O2
Molecular Weight: 300.44 g/mol
Solubility: Practically insoluble in water; soluble in dimethyl sulfoxide (DMSO); slightly soluble in ethanol.
Structure: A yellow to light-orange crystalline powder. It is a retinoid consisting of a cyclohexenyl ring, a polyene side chain, and a carboxylic acid group.
Drug Class
Tretinoin is the prototypical First-Generation Retinoid. It is therapeutically related to isotretinoin (Accutane) and alitretinoin. It differs from second-generation retinoids (like acitretin) and third-generation retinoids (like adapalene and tazarotene) in its receptor selectivity and metabolic pathway.