all trans beta Retinoic acid/Tretinoin is a naturally-occurring acid of retinol. Tretinoin binds to and activates retinoic acid receptors (RARs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, and inhibition of tumorigenesis. This agent also inhibits telomerase, resulting in telomere shortening and eventual apoptosis of some tumor cell types. The oral form of tretinoin has teratogenic and embryotoxic properties.
Isotretinoin is a vitamin A derivative used in the treatment of severe acne and some forms of skin, head and neck cancer. Isotretinoin, like many retinoids, can lead to increase in serum aminotransferase levels, but, unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver injury with jaundice.
Another Name of Tretinoin
- Acide retinoique
- all trans Retinoic acid
- all trans-Retinoic acid
- all-(E)-Retinoic acid
- all-trans-beta-Retinoic acid
- all-trans-Retinoic acid
- all-trans-Vitamin A acid
- all-trans-Vitamin A1 acid
- beta-Retinoic acid
- Retinoic acid
- Retionic acid
- trans-Retinoic acid
- Tretin M
- Vitamin A acid
Although the precise mechanism(s) of action of tretinoin has not been fully elucidated, it is known that the drug is not a cytolytic agent. Tretinoin induces cellular differentiation and decreases the proliferation of acute promyelocytic leukemia (APL) cells. The PML/RAR-a fusion protein resulting from the chromosomal translocation appears to block myeloid differentiation at the promyelocyte stage, possibly by complexing and inactivating wild-type PML or by inhibiting the normal retinoic acid signaling pathway. In patients with APL who achieve a complete remission with tretinoin therapy, the drug causes an initial maturation of the primitive promyelocytes derived from the cellular leukemic clone followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells. Observations supporting cellular differentiation effects as a mechanism of tretinoin include the absence of bone marrow hypoplasia during induction, the appearance of immunophenotypically unique “intermediate cells” expressing both mature and immature cell surface antigens, and the presence of both Auer rods and the translocation in morphologically mature granulocytes until a late stage of induction. The mechanism by which the population of malignant cells is eliminated is not fully understood but appears to involve apoptosis (programmed cell death). Following induction therapy, the PML/RAR-a fusion protein can be detected in the majority of patients, suggesting that tretinoin alone does not eradicate the leukemic clone.
Indications of Tretinoin
Antineoplastic Agents Keratolytic Agents
- Isotretinoin is a vitamin A derivative used in the treatment of severe acne and some forms of skin, head and neck cancer.
- Tretinoin gel and cream are indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established.
- Tretinoin is used topically as a 0.05 or 0.1% cream for palliative therapy to improve dermatologic changes (e.g., fine wrinkling, mottled hyperpigmentation, roughness) associated with photodamage.
- Tretinoin has been used topically for the treatment of flat warts. The drug also has been used with topical fluorouracil for the temporary, initial combination therapy of multiple actinic (solar) keratoses on areas other than the head and neck (e.g., hands, arms).
- In concentrations of 0.1-0.3%, tretinoin has been used topically for the treatment of other skin conditions such as psoriasis, ichthyosis congenital, ichthyosis Vulgaris, lamellar ichthyosis, keratosis palmaris et plantaris, epidermolytic hyperkeratosis, senile comedones, senile keratosis, keratosis follicularis (Darier’s disease), and basal cell carcinomas.
- Acne Vulgaris
- FAB classification M3 Acute promyelocytic leukemia
- Solar Lentigines
- Facial fine wrinkling
- Moderate Melasma
- Mottled hyperpigmentation
- Severe Melasma
- Severe, recalcitrant Cystic acne
- Tactile roughness of facial skin
- Photoaging of the Skin
- Necrobiosis Lipoidica Diabeticorum
- Lichen Sclerosus
- For the topical treatment of acne vulgaris, flat warts and other skin conditions (psoriasis, ichthyosis congenital, ichthyosis Vulgaris, lamellar ichthyosis, keratosis palmaris et plantaris, epidermolytic hyperkeratosis, senile comedones, senile keratosis, keratosis follicularis (Darier’s disease), and basal cell carcinomas.);
- For palliative therapy to improve fine wrinkling, mottled hyperpigmentation, roughness associated with photodamage.
- Tretinoin is used to induce remission in people with acute promyelocytic leukemia who have a mutation translocation 160 and/or the presence of the PML/RARα gene) and who don’t respond to anthracyclines or can’t take that class of drug.
Contraindications Of Tretinoin
- glucose-6-phosphate dehydrogenase (G6PD) deficiency
- deficiency of the blood enzyme cytochrome b5 reductase
- significant anemia
- liver problems
- Anemia from Pyruvate Kinase and G6PD Deficiencies
- Absolute contraindications to the use of dapsone are prior hypersensitivity to dapsone or its derivatives including agranulocytosis and hypersensitivity syndrome. Deaths from agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported with dapsone administration.
- Relative contraindications to the use of dapsone include allergy to sulfonamide antibiotics, significant cardiopulmonary disease, significant liver or renal function impairment, or pre-existing peripheral neuropathy.
- For the treatment of women who are pregnant, dapsone is a category C drug. Therefore, it should be used with caution only if benefits outweigh risks.
- According to the American Academy of Pediatrics, dapsone is listed as a “maternal medication usually compatible with breastfeeding.
- Allergies to tretinoin
Dosage of Tretinoin
Strengths: 0.05%; 0.025%; 0.02%; 0.1%; 0.04%; 0.01%; 0.06%; 0.08%; cream 0.1%; cream 0.05%; cream 0.025%; gel 0.025%; gel 0.01%; 0.0375%; 0.075%
- Recommended dose: Apply a thin layer to the entire affected area once a day at bedtime
- Recommended dose: Apply a pea-sized amount to the entire affected area once a day at bedtime
- Duration of therapy: 48 weeks (0.05% cream/emollient cream) and 52 weeks (0.02% cream)
Pediatric Dose for Acne
12 years and older
- Recommended dose: Apply a thin layer to the affected area once a day at bedtime
Side Effects Of Tretinoin
- itching, dryness, redness, scaling, or peeling of the skin
- Burning, itching, stinging, scaling, or redness of the skin
- chapping or slight peeling of the skin (mild)
- darkening of the skin
- lightening of normal skin color
- lightening of treated areas of dark skin
- redness of skin (mild)
- unusual dryness of skin (mild)
- unusually warm skin (mild)
- numbing or tingling sensation in the hands or feet
- signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities)
- signs of infections (e.g., fever or chills, sore throat)
- signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
- unusual tiredness or weakness
- Back, leg, or stomach pains
- bluish fingernails, lips, or skin
- difficult breathing
- loss of appetite
- pale skin
- skin rash
- unusual tiredness or weakness
Hematologic: Hemolytic anemia, methemoglobinemia, leukopenia, and agranulocytosis
Cutaneous hypersensitivity reactions: Mebilliform eruption, exfoliative erythroderma, drug-induced lupus erythematosus, and toxic epidermal necrolysis
Neurologic: Peripheral neuropathy, predominantly motor loss
Psychiatric: Psychosis and insomnia
Eyes: Blurred vision
Ear, nose, and throat: Tinnitus and vertigo
Pulmonary: Pulmonary Eosinophilia
Hepatic: Hepatitis, dapsone syndrome, cholestatic jaundice, and hypoalbuminemia without proteinuria
Gastrointestinal: Nausea, vomiting, abdominal pain, anorexia, and pancreatitis
Renal: Nephrotic syndrome, albuminur
- signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
- signs of infection (fever, severe chills, sore throat, mouth ulcers)
- signs of an allergic reaction (e.g., rash, hives, swelling of the lips or face, difficulty breathing)
- severe vomiting
- signs of methemoglobinemia (e.g., headache, fatigue, dizziness, shortness of breath, grey or bluish skin colour, especially of lips, mouth and nail beds)
- signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
- Itching, dryness, redness, scaling, or peeling of the skin, or loss of hair
- mood or other mental changes
- numbness, tingling, pain, burning, or weakness in hands or feet
- sore throat
- unusual bleeding or bruising
- yellow eyes or skin
- blurred vision
- fast heartbeat
- loss of appetite
- nausea or vomiting
- skin rash or itch
- trouble sleeping
Drug Interaction of all trans beta Retinoic acid
There may be an interaction between tretinoin and any of the following
- aminolevulinic acid
- aminolevulinic acid topical
- benzoyl peroxide topical
- benzoyl peroxide
- medications that increase the skin’s sensitivity to sunlight (e.g., isotretinoin, sulfamethoxazole, trimethoprim, minocycline, ciprofloxacin)
- medicated or abrasive soaps and cleansers
- other skin-applied medications
- methyl aminolevulinate topical
- resorcinol topical
- salicylic acid topical
- sulfur topical
- other topical medications to treat acne
- products with high concentrations of alcohol, astringents, spices, or lime
- skin preparations containing sulfur, resorcinol, or salicylic acid
- soaps and cosmetics with a strong drying effect
If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:
- stop taking one of the medications,
- change one of the medications to another,
- change how you are taking one or both of the medications, or
- leave everything as is.
Pregnancy Category of all trans beta Retinoic acid
FDA Pregnancy Category – C
This medication is not recommended for use during pregnancy. Women who may become pregnant should use an effective method of birth control while they are using this medication. If you become pregnant while using this medication, stop using it immediately and contact your doctor.
It is not known if tretinoin passes into breast milk. If you are a breast-feeding mother and are using this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of using this medication have not been established for children less than 12 years of age. Topical tretinoin is not recommended for this age group.
What form(s) does this medication come in?
Each gram of cream contains 0.01% tretinoin in a bland, hydrophilic base. Nonmedicinal ingredients: butylated hydroxytoluene, isopropyl myristate, polyoxyl (40) stearate, purified water, sorbic acid, stearic acid, stearyl alcohol, and xanthan gum.
Each gram of cream contains 0.025% tretinoin in a bland, hydrophilic base. Nonmedicinal ingredients: butylated hydroxytoluene, isopropyl myristate, polyoxyl (40) stearate, purified water, sorbic acid, stearic acid, stearyl alcohol, and xanthan gum.
Each gram of cream contains 0.05% tretinoin in a bland, hydrophilic base. Nonmedicinal ingredients: butylated hydroxytoluene, isopropyl myristate, polyoxyl (40) stearate, purified water, sorbic acid, stearic acid, stearyl alcohol, and xanthan gum.
Each gram of cream contains 0.1% tretinoin in a bland, hydrophilic base. Nonmedicinal ingredients: butylated hydroxytoluene, isopropyl myristate, polyoxyl (40) stearate, purified water, sorbic acid, stearic acid, stearyl alcohol, and xanthan gum.
Each gram of gel contains 0.01% tretinoin. Nonmedicinal ingredients: butylated hydroxytoluene, undenatured ethanol, and hydroxypropyl cellulose.
Each gram of gel contains 0.025% tretinoin. Nonmedicinal ingredients: butylated hydroxytoluene, undenatured ethanol, and hydroxypropyl cellulose.
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