TRET-i-noyn

Therapeutic Classification: antineoplastics

Pharmacologic Classification: retinoids

• Induction of remission in acute promyelocytic leukemia in patients who cannot receive anthracyclines due to lack of response, intolerance, or the presence of a contraindication.

• Causes maturation of promyelocytes derived from the leukemic clone.

• Repopulation with normal hematopoietic cells in patients who achieve remission.

Absorption: Well absorbed following oral administration.

Distribution: Crosses the placenta; remainder of distribution unknown.

Protein Binding: >95%.

Metabolism/Excretion: Metabolized by the liver; metabolites are renally excreted.

Half-life: 0.5–2 hr.

(complete remission)

Contraindicated in:

• Hypersensitivity to tretinoin or parabens
• OB: Lactation: Pregnancy or lactation.

Use Cautiously in:

• OB: Women of childbearing potential.

EENT: altered visual acuity, ocular disorders, visual disturbances, visual field defects, earache, hearing loss.

Resp: asthma, laryngeal edema.

CV: CARDIAC FAILURE, MI, STROKE, arrhythmias, chest discomfort, edema, hypertension, hypotension, peripheral edema, phlebitis.

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, ↑ sweating, pallor, pruritus, rash, skin changes.

F and E: acidosis, fluid imbalance.

Hemat: disseminated intravascular coagulation, hemorrhage, leukocytosis.

Metab: weight gain, weight loss.

MS: bone inflammation, bone pain, flank pain, myalgia.

Neuro: paresthesias, SEIZURES, anxiety, confusion, depression, dizziness, fatigue, headache, insomnia, malaise, pseudotumor cerebri, weakness, agitation, cerebral hemorrhage, hallucinations, intracranial hypertension.
Misc: fever, infections, pain, hypothermia, retinoic acid–acute promyelocytic leukemia syndrome, shivering.

Drug-Drug:

• Rifampin, corticosteroids, phenobarbital, and pentobarbital↑ metabolism and may ↓ effectiveness.
• Cimetidine, cyclosporine, diltiazem, erythromycin, ketoconazole, and verapamil↓ metabolism and may ↑ effects.

Drug-Natural Products:

• St. John's wort may ↑ metabolism and ↓ effectiveness.

Drug-Food:

• Absorption is ↑ by food.

• PO (Adults): 45 mg/m²/day in 2 divided doses; treatment should be continued for 30 days after a complete remission has been achieved or for a total of 90 days, whichever is first.

(Generic available)

• Capsules: 10 mg;

• Monitor patient for retinoic acid–acute promyelocytic leukemia (RA-APL) syndrome (bone pain, discomfort or pain in chest, dyspnea, chest tightness, wheezing, weight gain, pulmonary infiltrates, pleural and/or pericardial effusions). May result in impaired myocardial contractility, hypotension, hypoxemia, and death due to multiorgan failure. Risk is increased if leukocytosis occurs during therapy Treatment with high-dose corticosteroids (dexamethasone 10 mg IV every 12 hr for 3 days or until symptoms resolve) should be started at first sign of RA-APL syndrome. Discontinuation of tretinoin therapy is usually not necessary.

• Monitor WBC frequently during therapy; may cause rapidly progressing leukocytosis. If WBC reaches 6 × 10/liter by Day 5, 10 × 10/liter by Day 10, or 15 × 10/liter by Day 28 of tretinoin therapy, immediate institution of full-dose chemotherapy, including an anthracycline if not contraindicated, may decrease risk of RA-APL syndrome and should be considered.
  • Monitor hepatic function tests frequently during therapy. Temporarily discontinue tretinoin therapy if levels are >5 times normal.
  • Monitor cholesterol and triglyceride concentrations frequently during therapy. May cause elevated levels.

• High Alert:Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order and dose calculations. Tretinoin should be administered only under the supervision of a physician experienced in management of patients with acute leukemia, with monitoring facilities and supportive services available. Do not confuse tretinoin with isotretinoin.
• Following remission with tretinoin, standard consolidation or maintenance chemotherapy should be administered, unless contraindicated.
• PO: Administer daily doses with food at evenly spaced intervals.

• Instruct patient to take tretinoin with food as directed, for the full course of therapy, despite expected side effects (fever, headache, tiredness, weakness). Take missed doses as soon as possible; if just before next dose, consult with health care professional prior to taking dose.
• Instruct patient to notify health care professional immediately if symptoms of RA-APL, pseudotumor cerebri (severe headache, nausea and vomiting, papilledema, vision problems), bronchial asthma, cardiac failure, convulsions, laryngeal edema, MI, or stroke occur.

• Induction of remission in patients with acute promyelocytic leukemia.

• Acute pain (Adverse Reactions).