Drug information of Tretinoin

Tretinoin

فارسی

Tretinoin , also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol).

Mechanism of effect

Tretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone.

Retinoid, induces differentiation and decreased proliferation of APL cells; produces an initial maturation of promyelocytes, followed by a repopulation of the bone marrow and peripheral blood by normal polyclonal hematopoietic cells in patients achieving complete remission

Pharmacodynamic

Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation .

Pharmacokinetics

  • Peak plasma time: 1-2 hours
  • Peak plasma concentration: 347 ng/mL
  • Protein bound: 95%
  • Metabolized by hepatic cytochrome 450
  • Metabolites: 13-cis retinoic acid, 4-oxo trans retinoic acid, 4-oxo cis retinoic acid, 4-oxo trans retinoic acid glucuronide
  • Half-life: 0.5-2 hours
  • Excretion: urine 63%; feces 30%

Dosage

Adult

Acute Promyelocytic Leukemia

Remission Induction

  • 45 mg/m²/day PO divided q12hr 
  • Discontinue 30 days after complete remission or 90 days after start of treatment (whichever comes first)

Remission Induction In Combination with an Anthracycline

  • 45 mg/m²/day PO divided q12hr 
  • Discontinue 30 days after complete remission or 90 days after start of treatment (whichever comes first)

Pediatric

Acute promyelocytic leukemia

Remission Induction

  • 45 mg/m²/day PO divided q12hr 
  • Discontinue 30 days after remission or 90 days after start of treatment (whichever comes first)

Remission Induction with an Anthracycline

  • 25 mg/m²/day PO divided q12hr until complete remission or 90 days

Drug contraindications

hypersensitivity to this drug

Alerts

Microdosed progesterone oral contraception (“minipill”) may not be adequate for contraception during tretinoin therapy

Pseudotumor cerebri associated with retinoids, especially in pediatric patients; dizziness or severe headache may be symptoms

Up to 60% incidence of hypercholesterolemia and/or hypertriglyceridemia; reversible upon completion of treatment

Elevated liver function tests may occur in 50-60% of patients during treatment

Increased risk of thrombosis during first month of treatment

Do not coadminister with other retinoids or in combination with vitamin A because symptoms of hypervitaminosis A

Black Box Warnings

Administration: Administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to diagnose and manage complications

Teratogenic effects: High risk of severe infant deformity if administered during pregnancy; if treatment with tretinoin is required in women of childbearing potential, 2 reliable forms of contraception should be used during, and for 1 month after, therapy; if it is determined that tretinoin represents the best available treatment for a pregnant woman, patients should be informed of the risk to the fetus

Retinoic acide-APL syndrome: About 25% of patients with APL treated with tretinoin experience a syndrome called the retinoic acid-APL syndrome, which can be fatal and is characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural or pericardial effusions, edema, and hepatic, renal, and/or multiorgan failure; this syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension; management has not been defined rigorously, but high-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality

Rapidly evolving leukocytosis: About 40% of patients will develop rapidly evolving leukocytosis; those who present with high WBC at diagnosis (ie, >5 x10^9/L) have an increased risk; if signs and symptoms of the RA-APL syndrome are present together with leukocytosis, treatment with high-dose steroids should be initiated immediately

Points of recommendation

  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how tretinoin (systemic) affects you.
  • This medicine may cause high cholesterol and triglyceride levels. Talk with the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
  • Blood clots have happened with tretinoin (systemic). Tell your doctor if you have ever had a blood clot. Talk with your doctor.
  • Raised pressure in the brain has happened with tretinoin (systemic). This can cause long lasting loss of eyesight and sometimes death. Call your doctor right away if you have a bad headache, dizziness, upset stomach or throwing up, or seizures. Call your doctor right away if you have weakness on 1 side of the body, trouble speaking or thinking, change in balance, or change in eyesight.
  • Do not use progestin-only birth control pills (minipills). They may not work well. Talk with your doctor.
  • If you are a woman and you miss a period, have unprotected sex, or think that your birth control has not worked, call your doctor right away.
  • Swallow whole. Do not chew, break, or crush.
  • To gain the most benefit, do not miss doses.
  • Keep taking tretinoin (systemic) as you have been told by your doctor or other health care provider, even if you feel well.
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Pregnancy level

D

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