Tretinoin - StatPearls - NCBI Bookshelf - Continuing Education Activity
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It is mandatory to procure user consent prior to running these cookies on your website. Tretinoin is also used systemically in the management of acute promyelocytic leukemia APL. Tretinoin is a vitamin A derivate in the retinoids class of medications. This activity outlines and reviews the indications, actions, and contraindications of tretinoin as a valuable agent in treating acne vulgaris and APL management and therapy.
This activity will highlight the mechanism of action, adverse event profile, and other key factors such as off-label uses, including some indications of APL, pre-malignant and malignant skin conditions, and other common skin conditions such as psoriasis, dosing of both oral and topical treatment options, monitoring of both topical and oral tretinoin use i.
Objectives: Explain the importance of monitoring for patients on tretinoin therapy, including target triglyceride and liver function concentrations.
Summarize the risks associated with initiating tretinoin treatment along with key patient counseling points. Identify the most common adverse events associated with tretinoin treatment. Outline the importance of how collaboration and coordination among the interprofessional team can enhance patient care when dosing and monitoring tretinoin to improve patient outcomes for patients receiving topical anti-acne and palliative for photoaging and oral antineoplastic tretinoin.
Access free multiple choice questions on this topic. Tretinoin is a generic name for a medication derivative of vitamin A retinol , also commonly known as all-trans retinoic acid ATRA.
Tretinoin can be given systemically or topically for various indications. The exact mechanism by which topical tretinoin functions are not completely understood, but current evidence suggests mediation through binding of retinoic acid receptors RARs alpha, beta, and gamma along with retinoid X receptors RXRs by blocking inflammatory mediators. By doing this, the production of procollagen increases to augment collagen type I and III formations.
RAR-gamma effects are associated with mucocutaneous tissues and bone. Tretinoin's effectiveness as an acne medication is because of its ability to modify the abnormal follicular formation that comes from excessive keratinization of epithelial cells. Tretinoin promotes cornified cell detachment and enhances shedding. Tretinoin increases mitotic activity, thereby increasing loosely-adherent corneocytes turnover. By doing so, the comedo contents can be expelled, with a reduction of microcomedo precursor lesion of acne vulgaris.
RAR-alpha and -beta has presented in associated with APL and squamous cell malignancies, respectively. Retinoic acid binds to retinoic acid receptor alpha, a member of the steroid-thyroid hormone receptor superfamily. Again, like topical tretinoin, the exact mechanism of systemic tretinoin is unclear but is hypothesized to include the following:. Systemic tretinoin produces complete remission by inducing an initial primitive promyelocyte maturation followed by bone marrow and peripheral blood repopulation occurring by normal, polyclonal hematopoietic cells.
For the treatment of APL, the administration is typical with a meal; capsules are not to be opened or crushed. According to the FDA drug labeled guidelines of orally administered tretinoin, most patients will experience drug-related toxicity, such as headaches, weakness, fever, and fatigue. Interruption of therapy is rarely required as these adverse effects are rarely permanent or irreversible. According to FDA labeled drug guidelines, contraindications include patients with evidence of hypersensitivity to tretinoin or any of its components.
If administered during pregnancy, there is a significantly high risk of fetal loss and malformations, including the musculoskeletal system, thymus, central nervous system, external ear, eye, great vessel abnormalities, a cleft palate, facial dysmorphia, and parathyroid hormone deficiency.
In all females undergoing tretinoin therapy, effective contraception must be used throughout treatment then continued for one month following discontinuation. Even if the patient has a history of infertility or menopause, contraception must be used, the patient has undergone a hysterectomy.
Two 2 reliable forms of contraception are the recommendation to be used simultaneously, even in patients who have a history of infertility or menopause. Abstinence may also be a chosen method of contraception. Patients who have undergone hysterectomy do not need a form of contraception. Discussion of continuing or terminating the pregnancy should occur between patient and physician if there is contraception during treatment.
In patients who lack genetic markers t 15;17 translocation, alternative treatment options should be considered. Oral tretinoin is also contraindicated during breastfeeding, pregnancy during the first trimester caution if pregnancy in the second or third trimester , caution in females of reproductive potential, caution in pediatric patients.
Patients with acute promyelocytic leukemia APL should be under strict supervision by an APL experienced physician, facility as well as supportive services to monitor drug tolerance and toxicity properly as there can be severe adverse reactions to taking oral tretinoin.
Monitor for hypersensitivity, photosensitivity, and any other skin irritation or allergies. Monitor APL for side effects including major, life-threatening side effects such as retinoic acid RA-APL syndrome and leukocytosis and response to treatment. Monthly follow-ups visits are required. Fasting lipid checks are recommended weekly or biweekly to monitor lipid response, but this is relative to the individual's health.
Asymptomatic, young patients without a personal or significant family history of dyslipidemia or diabetes mellitus require less frequent laboratory draws mentioned above. Clinical assessment of the following areas is necessary to assess for treatment response and adverse effects:. Monthly follow-up visits are typical to fulfill the requirements of the iPLEDGE program a program to eliminate fetal exposure to isotretinoin. Due to tretinoin teratogenicity, women of childbearing potential are recommended the use two dependable forms of contraception while on oral tretinoin therapy for APL and one month following discontinuation of treatment; monitoring for pregnancy and contraception counseling repeated monthly while on medication.
Delay of treatment should occur until obtaining a negative pregnancy result. If treatment cannot be delayed in the case of APL treatment , the patient should use two forms of contraception. Symptoms of overdose with topical tretinoin use may include excessive redness, peeling, and discomfort.
Symptoms of overdose with oral tretinoin include the following: cracked and sore lips, redness, headache, flushing, stomach pain, dizziness, loss of coordination. Case Report: year-old overdosed on mg of ingested tretinoin in a suicide attempt and developed nothing besides some non-bloody diarrhea, which received treatment with hydration and activated charcoal.
If liver enzymes increase to more than three times over baseline, the recommendation is to discontinue isotretinoin.
ATRA initiation should be immediate once APL is suspected, especially if the diagnosis supports genetic or molecular data. If molecular or genetic data do not support the diagnosis, then ATRA should no longer be given. Before tretinoin prescription and eventual use, pregnancy status should be negative through a urine pregnancy test before eventual prescribing and use of tretinoin; this is due to the routine use of urine pregnancy tests, complications such as fetal malformations, and risk of fetal loss.
It is still unknown as to whether oral tretinoin appears in breast milk, but because of potentially serious adverse effects that may take place in breastfed infants, breastfeeding should be strongly discouraged.
Swift identification of RA-APL syndrome, an unpredictable but frequent complication, includes symptoms such as dyspnea, fever, weight gain, pleural and pericardial effusions, acute respiratory distress, pulmonary infiltrates on chest x-ray, edema, and multi-organ failure. After resolved, treatment may continue. Sunscreen is a requirement for all patients on tretinoins, as there is an increased risk of photosensitivity.
Encourage avoidance of exposure to sunlight or tanning beds. Patients should be encouraged to wear protective clothing and use sunscreen recommended SPF 15 or higher according to the tretinoin drug label when they are outdoors, even on a cloudy day. Advise patients to avoid using skin products that may cause skin irritation and dryness, such as harsh soaps, shampoos, hair coloring chemicals, hair removers, or skin products that contain alcohol, spices, astringents, or lime.
The healthcare team, e. This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. Help Accessibility Careers. StatPearls [Internet]. Search term. Tretinoin Athina L. Author Information Authors Athina L. Affiliations 1 University of Miami. Continuing Education Activity Tretinoin is a valuable medication in treating mild, moderate, and severe acne that can be used topically or systemically. Indications Tretinoin is a generic name for a medication derivative of vitamin A retinol , also commonly known as all-trans retinoic acid ATRA.
Adjunctive palliative treatment of photoaging: Fine facial wrinkles [2]. Facial mottled hyperpigmentation i. In acute promyelocytic leukemia APL , patients with refractory disease for remission induction who have previously relapsed from anthracycline chemotherapy or those who have a contraindication to anthracycline-based therapy [3]. Moderate to severe and cystic acne [7] [8] [9].
Acute promyelocytic leukemia APL patients during the consolidation phase of treatment with combination chemotherapy [10] [11] In adults with APL, tretinoin, in combination with arsenic trioxide, supports tretinoin as a part of the consolidation phase of treatment [12]. Acute promyelocytic leukemia patients during the maintenance phase of therapy in intermediate- and high-risk patients on combination chemotherapy [13] [14] Combination chemotherapy in pediatrics with APL supports tretinoin use as part of the maintenance phase of treatment [15].
Treatment of pre-malignant and malignant skin conditions in high-risk patients diagnosed with actinic keratosis, basal, and squamous cell carcinoma [16] [17] [18] [19]. Ichthyosis congenita, ichthyosis vulgaris, lamellar ichthyosis [22].
The combination of minoxidil with topical tretinoin may show increased hair growth due to increased penetrating ability. Mechanism of Action The exact mechanism by which topical tretinoin functions are not completely understood, but current evidence suggests mediation through binding of retinoic acid receptors RARs alpha, beta, and gamma along with retinoid X receptors RXRs by blocking inflammatory mediators. Again, like topical tretinoin, the exact mechanism of systemic tretinoin is unclear but is hypothesized to include the following: Apoptosis and degradation of PML-RAR alpha protein occur by both caspase-mediated cleavage and proteasome-dependent degradation;.
Administration Topical Tretinoin Topical administration of tretinoin includes applying a thin layer once daily, before bedtime, to the skin where lesions are present. Patients need to keep the medication away from eyes, mouth, nasal creases, and mucous membranes.
Dosages vary amongst different brands. A commonly used topical tretinoin consisting of 0. Tretinoin has also been sublingually administered by squeezing the contents from the capsule beneath the tongue as well as through enteric and nasogastric tubes. ATRA must be used in combination with other medications i.
Nursing mothers should discontinue nursing before starting oral tretinoin, as nursing infants have potentially serious adverse effects. Patients should take a missed dose as soon as possible unless it is time for the next dose, at which point it's recommended to skip the missed dose and proceed with the regular schedule of medication; patients should not take a doubled dose. The recommendation is to take isotretinoin with food especially with high-fat meals , as this will increase absorption.
A lipid encapsulation of isotretinoin exists and demonstrates increased bioavailability even if the patient has fasted. This form of the medication can be dosed twice daily regardless if fasted or not. The initial dose is 0. APL, relapsed or refractory APL, newly diagnosed Induction treatment Consolidation treatment APL, relapsed or refractory 1-year-old and older Do not administer tretinoin with vitamin A due to symptoms of syndrome of hypervitaminosis A.
Myocardial contractility impairment, along with episodic hypotension, was observed with or without leukocytosis. Most commonly occurs during the first month of treatment; however, some cases have been reported after the first dose. Management: patients should receive high-dose steroids if there is any clinical suspicion as a means to reduce morbidity and mortality related to the syndrome. Teratogen There is an increased risk of severe fetal deformities with oral tretinoin.
Pregnant women or those of child-bearing age are at an increased potential of fetal risk and contraception failure risk. Patients must be on two 2 dependable forms of contraception throughout treatment, followed by one 1 month after discontinuation of tretinoin.
Patients must have a negative pregnancy test less than one 1 week before starting tretinoin, or if unable to delay treatment, may start with two forms of contraception, as previously mentioned. Pregnancy testing and counseling on contraception should continue every month during treatment. There is no FDA boxed warning for topical tretinoin.
All Rights Reserved. Since then, other uses have been described, including the treatment of lesions of the oral mucosa and the ocular surface epithelia, hypertrophic scarring, various infections, and pigmentation disorders. Kligman and colleagues 3 at the University of Pennsylvania reported on the effectiveness of topical tretinoin in treating acne in Soon after topical tretinoin became available to the public, elderly patients using it to treat acne reported noticing a general improvement in the condition of their skin.
Beneficial results were subsequently verified by large multicenter trials and clinical experience supporting the efficacy and safety of topical tretinoin to treat photodamaged skin. The aim of this review is to provide an overview of the history and current uses of topical tretinoin, including likely mechanisms of action, approved indications and dosing, and associated safety and tolerability issues, as well as to speculate on potential therapeutic areas that may be targets for further research and future clinical applications.
These receptors can act to modify gene expression, protein synthesis, and epithelial cell growth and differentiation. Topical tretinoin has the ability to modify abnormal follicular keratinization and promote comedolysis, modulate the proliferation and differentiation of epidermal cells, stimulate the formation of new collagen, reduce inflammation, stimulate fibroblasts, prevent collagen loss, and inhibit the induction of skin metalloproteinases ie, collagenase, kd gelatinase, and stromelysin, which are induced by ultraviolet [UV] irradiation and may degrade skin collagen.
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Topical tretinoin gel and cream FDA approved for: Topical application for treatment of acne vulgaris[1] Comment on this article. This review aims to study the current evidence on topical tretinoin for photoaging treatment. Methods: A systematic search of the literature was. Topical tretinoin gel and cream FDA approved for: Topical application for treatment of acne vulgaris[1] Comment on this article. Original Article. Topical Tretinoin (Retinoic Acid) Therapy for Hyperpigmented Lesions Caused by Inflammation of the Skin in Black Patients. Topical % tretinoin cream improves the hyperpigmentation associated with photoaging in Caucasian persons. Next article in issue. Recommended articles. Non-necessary Non-necessary. Retinoic acid syndrome: a review. RAR-alpha and -beta has presented in associated with APL and squamous cell malignancies, respectively.Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Athina L. Yoham ; Damian Casadesus. Authors Athina L. Yoham 1 ; Damian Casadesus 2. Tretinoin is a valuable medication in treating mild, moderate, and severe acne that can be used topically or systemically. Tretinoin is also used systemically in the management of acute promyelocytic leukemia APL.
Tretinoin is a vitamin A derivate in the retinoids class of medications. This activity outlines and reviews the indications, actions, and contraindications of tretinoin as a valuable agent in treating acne vulgaris and APL management and therapy. This activity will highlight the mechanism of action, adverse event profile, and other key factors such as off-label uses, including some indications of APL, pre-malignant and malignant skin conditions, and other common skin conditions such as psoriasis, dosing of both oral and topical treatment options, monitoring of both topical and oral tretinoin use i.
Objectives: Explain the importance of monitoring for patients on tretinoin therapy, including target triglyceride and liver function concentrations. Summarize the risks associated with initiating tretinoin treatment along with key patient counseling points. Identify the most common adverse events associated with tretinoin treatment. Outline the importance of how collaboration and coordination among the interprofessional team can enhance patient care when dosing and monitoring tretinoin to improve patient outcomes for patients receiving topical anti-acne and palliative for photoaging and oral antineoplastic tretinoin.
Access free multiple choice questions on this topic. Tretinoin is a generic name for a medication derivative of vitamin A retinol , also commonly known as all-trans retinoic acid ATRA. Tretinoin can be given systemically or topically for various indications. The exact mechanism by which topical tretinoin functions are not completely understood, but current evidence suggests mediation through binding of retinoic acid receptors RARs alpha, beta, and gamma along with retinoid X receptors RXRs by blocking inflammatory mediators.
By doing this, the production of procollagen increases to augment collagen type I and III formations. RAR-gamma effects are associated with mucocutaneous tissues and bone. Tretinoin's effectiveness as an acne medication is because of its ability to modify the abnormal follicular formation that comes from excessive keratinization of epithelial cells.
Tretinoin promotes cornified cell detachment and enhances shedding. Tretinoin increases mitotic activity, thereby increasing loosely-adherent corneocytes turnover. By doing so, the comedo contents can be expelled, with a reduction of microcomedo precursor lesion of acne vulgaris. RAR-alpha and -beta has presented in associated with APL and squamous cell malignancies, respectively.
Retinoic acid binds to retinoic acid receptor alpha, a member of the steroid-thyroid hormone receptor superfamily. Again, like topical tretinoin, the exact mechanism of systemic tretinoin is unclear but is hypothesized to include the following:.
Systemic tretinoin produces complete remission by inducing an initial primitive promyelocyte maturation followed by bone marrow and peripheral blood repopulation occurring by normal, polyclonal hematopoietic cells. For the treatment of APL, the administration is typical with a meal; capsules are not to be opened or crushed.
According to the FDA drug labeled guidelines of orally administered tretinoin, most patients will experience drug-related toxicity, such as headaches, weakness, fever, and fatigue. Interruption of therapy is rarely required as these adverse effects are rarely permanent or irreversible. According to FDA labeled drug guidelines, contraindications include patients with evidence of hypersensitivity to tretinoin or any of its components.
If administered during pregnancy, there is a significantly high risk of fetal loss and malformations, including the musculoskeletal system, thymus, central nervous system, external ear, eye, great vessel abnormalities, a cleft palate, facial dysmorphia, and parathyroid hormone deficiency. In all females undergoing tretinoin therapy, effective contraception must be used throughout treatment then continued for one month following discontinuation. Even if the patient has a history of infertility or menopause, contraception must be used, the patient has undergone a hysterectomy.
Two 2 reliable forms of contraception are the recommendation to be used simultaneously, even in patients who have a history of infertility or menopause.
Abstinence may also be a chosen method of contraception. Patients who have undergone hysterectomy do not need a form of contraception. Discussion of continuing or terminating the pregnancy should occur between patient and physician if there is contraception during treatment.
In patients who lack genetic markers t 15;17 translocation, alternative treatment options should be considered. Oral tretinoin is also contraindicated during breastfeeding, pregnancy during the first trimester caution if pregnancy in the second or third trimester , caution in females of reproductive potential, caution in pediatric patients.
Patients with acute promyelocytic leukemia APL should be under strict supervision by an APL experienced physician, facility as well as supportive services to monitor drug tolerance and toxicity properly as there can be severe adverse reactions to taking oral tretinoin. Monitor for hypersensitivity, photosensitivity, and any other skin irritation or allergies. Monitor APL for side effects including major, life-threatening side effects such as retinoic acid RA-APL syndrome and leukocytosis and response to treatment.
Monthly follow-ups visits are required. Fasting lipid checks are recommended weekly or biweekly to monitor lipid response, but this is relative to the individual's health. Asymptomatic, young patients without a personal or significant family history of dyslipidemia or diabetes mellitus require less frequent laboratory draws mentioned above.
Clinical assessment of the following areas is necessary to assess for treatment response and adverse effects:. Monthly follow-up visits are typical to fulfill the requirements of the iPLEDGE program a program to eliminate fetal exposure to isotretinoin.
Due to tretinoin teratogenicity, women of childbearing potential are recommended the use two dependable forms of contraception while on oral tretinoin therapy for APL and one month following discontinuation of treatment; monitoring for pregnancy and contraception counseling repeated monthly while on medication. Delay of treatment should occur until obtaining a negative pregnancy result. If treatment cannot be delayed in the case of APL treatment , the patient should use two forms of contraception.
Symptoms of overdose with topical tretinoin use may include excessive redness, peeling, and discomfort. Symptoms of overdose with oral tretinoin include the following: cracked and sore lips, redness, headache, flushing, stomach pain, dizziness, loss of coordination.
Case Report: year-old overdosed on mg of ingested tretinoin in a suicide attempt and developed nothing besides some non-bloody diarrhea, which received treatment with hydration and activated charcoal. If liver enzymes increase to more than three times over baseline, the recommendation is to discontinue isotretinoin. ATRA initiation should be immediate once APL is suspected, especially if the diagnosis supports genetic or molecular data.
If molecular or genetic data do not support the diagnosis, then ATRA should no longer be given. Before tretinoin prescription and eventual use, pregnancy status should be negative through a urine pregnancy test before eventual prescribing and use of tretinoin; this is due to the routine use of urine pregnancy tests, complications such as fetal malformations, and risk of fetal loss. It is still unknown as to whether oral tretinoin appears in breast milk, but because of potentially serious adverse effects that may take place in breastfed infants, breastfeeding should be strongly discouraged.
Swift identification of RA-APL syndrome, an unpredictable but frequent complication, includes symptoms such as dyspnea, fever, weight gain, pleural and pericardial effusions, acute respiratory distress, pulmonary infiltrates on chest x-ray, edema, and multi-organ failure. After resolved, treatment may continue.
Sunscreen is a requirement for all patients on tretinoins, as there is an increased risk of photosensitivity. Encourage avoidance of exposure to sunlight or tanning beds. Patients should be encouraged to wear protective clothing and use sunscreen recommended SPF 15 or higher according to the tretinoin drug label when they are outdoors, even on a cloudy day.
Advise patients to avoid using skin products that may cause skin irritation and dryness, such as harsh soaps, shampoos, hair coloring chemicals, hair removers, or skin products that contain alcohol, spices, astringents, or lime.
The healthcare team, e. This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. Help Accessibility Careers. StatPearls [Internet]. Search term. Tretinoin Athina L. Author Information Authors Athina L. Affiliations 1 University of Miami. Continuing Education Activity Tretinoin is a valuable medication in treating mild, moderate, and severe acne that can be used topically or systemically.
Indications Tretinoin is a generic name for a medication derivative of vitamin A retinol , also commonly known as all-trans retinoic acid ATRA.
Adjunctive palliative treatment of photoaging: Fine facial wrinkles [2]. Facial mottled hyperpigmentation i. In acute promyelocytic leukemia APL , patients with refractory disease for remission induction who have previously relapsed from anthracycline chemotherapy or those who have a contraindication to anthracycline-based therapy [3].
Moderate to severe and cystic acne [7] [8] [9]. Acute promyelocytic leukemia APL patients during the consolidation phase of treatment with combination chemotherapy [10] [11] In adults with APL, tretinoin, in combination with arsenic trioxide, supports tretinoin as a part of the consolidation phase of treatment [12].
Acute promyelocytic leukemia patients during the maintenance phase of therapy in intermediate- and high-risk patients on combination chemotherapy [13] [14] Combination chemotherapy in pediatrics with APL supports tretinoin use as part of the maintenance phase of treatment [15].
Treatment of pre-malignant and malignant skin conditions in high-risk patients diagnosed with actinic keratosis, basal, and squamous cell carcinoma [16] [17] [18] [19]. Ichthyosis congenita, ichthyosis vulgaris, lamellar ichthyosis [22]. The combination of minoxidil with topical tretinoin may show increased hair growth due to increased penetrating ability.
Mechanism of Action The exact mechanism by which topical tretinoin functions are not completely understood, but current evidence suggests mediation through binding of retinoic acid receptors RARs alpha, beta, and gamma along with retinoid X receptors RXRs by blocking inflammatory mediators.
Again, like topical tretinoin, the exact mechanism of systemic tretinoin is unclear but is hypothesized to include the following: Apoptosis and degradation of PML-RAR alpha protein occur by both caspase-mediated cleavage and proteasome-dependent degradation;. Administration Topical Tretinoin Topical administration of tretinoin includes applying a thin layer once daily, before bedtime, to the skin where lesions are present.
Patients need to keep the medication away from eyes, mouth, nasal creases, and mucous membranes. Dosages vary amongst different brands. A commonly used topical tretinoin consisting of 0. Tretinoin has also been sublingually administered by squeezing the contents from the capsule beneath the tongue as well as through enteric and nasogastric tubes.
ATRA must be used in combination with other medications i. Nursing mothers should discontinue nursing before starting oral tretinoin, as nursing infants have potentially serious adverse effects. Patients should take a missed dose as soon as possible unless it is time for the next dose, at which point it's recommended to skip the missed dose and proceed with the regular schedule of medication; patients should not take a doubled dose.
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