Mechanism of Action of Tretinoin

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%
Acne

Recommended dose: Apply a thin layer to the entire affected area once a day at bedtime

Dermatoheliosis

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
More common

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
fever
loss of appetite
pale skin
skin rash
unusual tiredness or weakness

Common

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

Cardiac: Tachycardia

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)

Rare

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
dizziness
fast heartbeat
fatigue
headache
loss of appetite
nausea or vomiting
skin rash or itch
trouble sleeping

Drug Interaction of Tretinoin
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
erythromycin
isotretinoin
methoxsalen
methyl aminolevulinate topical
resorcinol topical
salicylic acid topical
sulfur topical
verteporfin
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 Tretinoin
FDA Pregnancy Category - C

Pregnancy

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.

Breast-feeding

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?

Question

Mechanism of Action of Tretinoin





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%
Acne

 	Recommended dose: Apply a thin layer to the entire affected area once a day at bedtime

Dermatoheliosis

 	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
More common

 	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
 	fever
 	loss of appetite
 	pale skin
 	skin rash
 	unusual tiredness or weakness

Common

 	
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
 	
Cardiac: Tachycardia
 	
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)

Rare

 	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
 	dizziness
 	fast heartbeat
 	fatigue
 	headache
 	loss of appetite
 	nausea or vomiting
 	skin rash or itch
 	trouble sleeping

Drug Interaction of Tretinoin
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
 	erythromycin
 	isotretinoin
 	methoxsalen
 	methyl aminolevulinate topical
 	resorcinol topical
 	salicylic acid topical
 	sulfur topical
 	verteporfin
 	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 Tretinoin
FDA Pregnancy Category - C

Pregnancy

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.

Breast-feeding

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?

Accepted Answer

Cream 0.01% 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. 0.025% 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. 0.05% Each gram of cream contains 0.05% tretinoin in a bland, hydrophilic base. Nonmedicinal ingredients: butylated hydroxytoluene, isopropyl myristate,&hellip;

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Another Name of Tretinoin

Mechanism of Action of Tretinoin

Indications of Tretinoin

Contraindications Of Tretinoin

Dosage? of Tretinoin

Acne

Dermatoheliosis

Pediatric Dose for Acne

Side Effects Of Tretinoin

Drug Interaction of Tretinoin

Pregnancy Category of Tretinoin

What form(s) does this medication come in?

References

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