Adult Dosing

Acute Myelocytic Leukemia; remission induction

• 45 mg/m²/day PO divided bid; continue therapy for 90 days or 30 days after achieving complete remission whichever comes first

Pediatric Dosing

Acute Myelocytic Leukemia; remission induction

Child >1 yr

• 45 mg/m²/day PO divided bid; continue therapy for 90 days or 30 days after achieving complete remission whichever comes first

[Outline]

• Adult Dosing
• Pediatric Dosing

• Induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RAR gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated.

• Hypersensitivity to any of the ingredients/parabens of the product
• Pregnancy or lactation

• Tretinoin should be administered only by a physician experienced in acute leukemia treatment in adequate medical facility to manage adverse reactions/complications. Weigh potential benefits vs known adverse effects
• Retinoic acid-APL syndrome has occurred in 25% of pts; occurs within 1 month of treatment (possibly after 1st dose). It is characterized by fever, dyspnea, acute respiratory distress, weight gain, pulmonary infiltrates on x-ray, pleural and pericardial effusion, edema, and hepatic, renal, and multi-organ failure. It may also be accompanied by impaired myocardial contractility, episodic hypotension, and leukocytosis. At first sign suggestive of this syndrome, give dexamethasone 10 mg IV q12 hrs x 3 days or until symptoms resolve. Can continue tretinoin treatment in most patients, but may hold therapy if moderate to severe retinoic acid-APL syndrome
• Patients presenting with increased WBC > 5 x 10⁹/L at diagnosis are at increased risk of rapidly evolving leukocytosis associated with high risk of life-threatening complications. Start high dose steroids immediately if retinoic acid-APL syndrome signs/symptoms are present along with leukocytosis. Starting chemotherapy in patients presenting with a WBC count of >5 x 10⁹/L with baseline leukopenia or if rapid increase in WBC count on tretinoin, can reduce the incidence of retinoic acid-APL syndrome
• High risk of severe fetal deformities if administered during pregnancy. Apprise pregnant women or those of child-bearing potential of fetal risk and possible contraception failure risk. Women of reproductive potential must use 2 reliable forms of contraception during and for 1 month after discontinuation of therapy. Pregnancy test performed < 1 wk prior to starting therapy must be negative. Delay therapy until a negative result is obtained, or if unable to delay may start treatment with 2 reliable forms of contraception. Continue pregnancy testing and contraception counseling qmo during therapy

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

• Tretinoin should be administered only by a physician experienced in acute leukemia treatment in adequate medical facility to manage adverse reactions/complications. Weigh potential benefits vs known adverse effects [US Black Box Warning]
• Retinoic acid-APL syndrome characterized by fever, dyspnea, acute respiratory distress, weight gain, pulmonary infiltrates on x-ray, pleural and pericardial effusion, edema, and hepatic, renal, and multi-organ failure has been reported
• Increased risk of leucocytosis, especially in patients with increased WBC > 5 x 10⁹/L at baseline. Start high dose steroids immediately if retinoic acid-APL syndrome signs/symptoms are present along with leukocytosis
• High risk of severe fetal deformities if administered during pregnancy; advise women of reproductive potential to use 2 reliable forms of contraception during and for 1 month after discontinuation of therapy
• Pseudotumor cerebri (benign intracranial hypertension), especially in pediatric patients have been reported after administration of drug. Avoid concomitant use of other agents (eg. tetracyclines) known to cause pseudotumor cerebri/intracranial hypertension, might increase the risk of this condition. Evaluate and institute appropriate therapy after early signs and symptoms of pseudotumor cerebri including papilledema, headache, nausea and vomiting, and visual disturbances
• It may cause reversible hypercholesterolemia/hypertriglyceridemia
• Monitor LFT periodically. Withdraw therapy if test results reach >5 times the upper limit of normal values
• Closely observe for signs of respiratory compromise/leukocytosis. Maintain appropriate supportive care for APL patients during therapy as it shows significant toxic side effects
• During the first month of treatment there is a risk of thrombosis (both venous and arterial) which may involve any organ system. Caution advised when treating patients with the combination of tretinoin and anti-fibrinolytic agents
• Patients receiving tretinoin may experience dizziness, severe headache, inability to drive or operate machinery
• Frequently monitor hematologic profile, coagulation profile, liver function test results, and triglyceride and cholesterol levels
• Microdosed progesterone preparations may be an inadequate method of contraception during treatment with tretinoin
• Tretinoin must not be administered in combination with vitamin A because symptoms of hypervitaminosis A could be aggravated

Cautions: Use cautiously in

• Co-administration of anti-fibrinolytics
• Co-administration of tetracyclines
• Women of childbearing potential

Pregnancy Category:D

Breastfeeding: Unsafe.

• CNS: Seizures, anxiety, confusion, depression, dizziness, fatigue, headache, insomnia, malaise, pseudotumor cerebri, weakness, agitation, cerebral hemorrhage, hallucinations, intracranial hypertension
• EENT: Altered visual acuity, ocular disorders, visual disturbances, visual field defects, earache, hearing loss
• RESP: Asthma, laryngeal edema, pleural effusion, pulmonary infultrate
• CV: Cardiac failure, MI, stroke, arrhythmias, chest discomfort, edema, hypertension, hypotension, peripheral edema, phlebitis, acidosis, fluid imbalance, myocarditis, pericardial effusion
• GI: GI bleeding, abdominal distention, abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia, hepatosplenomegaly, mucositis, nausea, ulcer, vomiting
• GU: Renal insufficiency, acute renal failure, dysuria, enlarged prostate, renal tubular necrosis, urinary frequency
• DERM: Alopecia, cellulitis, dry skin, facial edema, flushing, increased sweating, pallor, pruritus, rash, skin changes
• HEMA: Disseminated intravascular coagulation, hemorrhage, leukocytosis, hypercholesterolemia, hypertriglyceridemia
• METABOLIC: Weight gain, weight loss
• NEURO: Paresthesias
• MISC: fever, infections, pain, hypothermia, retinoic acid–acute promyelocytic leukemia syndrome, shivering, bone inflammation, bone pain, flank pain, myalgia

• Retinoid; exact mechanism of action not known; induces differentiation and decrease proliferation of APL cells
• Well absorbed following oral administration
• Metabolized by liver
• Renally excreted (63%); feces (31%)
• Half-life: 0.5-2 hrs

US Trade Name(s)

• Only generic available

US Availability

tretinoin (generic)

• CAPS: 10 mg

Canadian Trade Name(s)

• Vesanoid

Canadian Availability

Vesanoid

• CAPS: 10 mg

UK Trade Name(s)

• Vesanoid

UK Availability

Vesanoid

• CAPS: 10 mg

Australian Trade Name(s)

• Vesanoid

Australian Availability

Vesanoid

• CAPS: 10 mg

[Outline]

Hematology/Oncology

Antineoplastics

Retinoids

Pricing data from www.DrugStore.com in U.S.A.

• Vesanoid 10 MG CAPS [Bottle] (ROCHE)
  30 mg = $808.87
  90 mg = $2302.72

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

Drug Name: Vesanoid 10 MG Oral Capsule

Ingredient(s): Tretinoin

Imprint: VESANOID;10;ROCHE

Color(s): Orange, Red

Shape: Oval

Size (mm): 10.00

Score: 1

Inactive Ingredient(s): wax, yellow / butylated hydroxyanisole / edetate disodium / soybean oil / gelatin / glycerin / ferric oxide yellow / ferric oxide red / titanium dioxide / methylparaben / propylparaben

Drug Label Author:
Hoffmann-La Roche

DEA Schedule:
Non-Scheduled