Dosing and uses of Vesanoid (tretinoin)
Adult dosage forms and strengths
capsule
- 10mg
Remission Induction
condition
- Acute promyelocytic leukemia
dose
- 45 mg/sq.meter/day PO divided BID
- Discontinue 30 days after complete remission or 90 days after start of treatment (whichever comes first)
description
- For use in patients with APL classification M3, which is characterized by the presence of t(15;17) translocation and/or the presence of the PML/RAR-alpha gene, who are refractory to, or have relapsed from, anthracycline chemotherapy, as well as for use in patients for whom anthracycline-based chemotherapy is contraindicated
Post Consolidation & Maintenance (Off-label)
condition
- Acute promyelocytic leukemia
dose
- 45-200 mg/sq.meter/day PO divided BID-TID
- Regimens and duration vary, such as daily until complete remission or after 90 days; 15 days/month x3 months; and 15 days q3months for 2 years
Patient Monitoring
Monitor CBC, coagulation, liver function tests, serum lipids
Pediatric dosage forms and strengths
capsule
- 10mg
Remission Induction
condition
- Acute promyelocytic leukemia
dose
- Limited clinical data for children 1-16 years old: 45 mg/sq.meter/day PO divided BID
- Discontinue 30 days after remission or 90 days after start of treatment (whichever comes first)
description
- For use in patients with APL classification M3, which is characterized by the presence of t(15;17) translocation and/or the presence of the PML/RAR-alpha gene, who are refractory to, or have relapsed from, anthracycline chemotherapy, as well as in patients in whom anthracycline-based chemotherapy is contraindicated
Patient Monitoring
Monitor CBC, coagulation, liver function tests, serum lipids
Vesanoid (tretinoin) adverse (side) effects
>10%
Headache (86%)
Fever (83%)
Bone pain (77%)
Dry mucous membranes (77%)
Malaise (67%)
URI (63%)
Shivering (60%)
Dyspnea (60%)
Hemorrhage (60%)
Elevated liver function tests (50-60%)
Hyperlipidemia (60%)
Infections (58%)
Nausea and vomiting (57%)
Rash (54%)
Peripheral edema (52%)
Leukocytosis (40%)
Pain (37%)
Abdominal pain (31%)
DIC (26%)
Respiratory insufficiency (26%)
Mucositis (26%)
GI disorder (26%)
Retinoic acid-APL syndrome (25%)
Ear ache (23%)
Diarrhea (23%)
Pleural effusion (20%)
Dizziness (20%)
Pruritus (20%)
Sweating (20%)
Anxiety (17%)
Paresthesia (17%)
Constipation (17%)
Vision changes (17%)
Dyspepsia (14%)
Rales (14%)
Depression (14%)
Insomnia (14%)
Alopecia (14%)
Skin changes (14%)
Confusion (11%)
Abdominal distention (11%)
Renal insufficiency (11%)
1-10% (selected)
Cardiac failure
Pseudotumor cerebri
Ulcer
Warnings
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
Contraindications
Hypersensitivity to retinoids and parabens
Cautions
Teratogenic and embryotoxic in animal studies and is expected to cause fetal harm in pregnant women; effective contraception must be used by all females of childbearing potential during and for 1 month after discontinuation (see Black box warnings)
Microdosed progesterone oral contraception (“minipill”) may not be adequate for contraception during tretinoin therapy
Patients without the t(15;17) translocation genetic marker should be considered for alternative treatment
Retinoic acid-APL syndrome, which can be fatal, has been reported (see Black box warnings)
Leukocytosis may occur (see Black box warnings)
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
Pregnancy and lactation
Pregnancy category: D (systemic)
Lactation: Unknown if excreted in breast milk; do not breast-feed, because of potential for serious adverse reactions in infant
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Vesanoid (tretinoin)
Mechanism of action
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
Absorption
Bioavailability: 50%
Peak plasma time: 1-2 hours
Peak plasma concentration: 347 ng/mL
Distribution
Protein bound: 95%
Metabolism
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
Elimination
Half-life: 0.5-2 hours
Excretion: urine 63%; feces 31%
