tretinoin (systemic)

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >95%.

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

Half-Life: 0.5–2 hr.

Time/Action Profile ⬆ ⬇

(complete remission)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	40–50 days	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to tretinoin or parabens;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

OB: Women of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, chest discomfort, edema, hypertension, hypotension, HF, MI

Derm: ↑sweating, alopecia, cellulitis, dry skin, facial edema, flushing, pallor, pruritus, rash, skin changes

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

F and E: acidosis

GI: abdominal distention, abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia, hepatosplenomegaly, mucositis, nausea, ulcer, vomiting

GU: renal impairment, ↓fertility (men), acute renal failure, dysuria, enlarged prostate, renal tubular necrosis, urinary frequency

Hemat: bleeding, disseminated intravascular coagulation, leukocytosis, retinoic acid–acute promyelocytic leukemia (RA-APL) syndrome

Local: phlebitis

Metab: weight gain, weight loss

MS: bone pain, flank pain, myalgia

Neuro: anxiety, confusion, depression, dizziness, fatigue, headache, insomnia, malaise, paresthesias, pseudotumor cerebri, weakness, agitation, hallucinations, intracranial hypertension, SEIZURES, STROKE

Resp: asthma, laryngeal edema

Misc: fever, infection, hypothermia, shivering

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Strong CYP3A4 inhibitors, including ketoconazole, and moderate CYP3A4 inhibitors may ↑ levels and risk of toxicity; avoid concurrent use with strong CYP3A4 inhibitors.
Tetracyclines may ↑ risk of intracranial hypertension; avoid concurrent use.
Vitamin A may ↑ risk of vitamin A–related toxicity; avoid concurrent use.
Tranexamic acid, aminocaproic acid, and aprotinin may ↑ risk of thromboembolic events; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Absorption is ↑ by food.

Route/Dosage ⬆ ⬇

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 1st.

Availability ⬆ ⬇

(Generic available)

Capsules: 10 mg

Assessment ⬆ ⬇

Monitor for 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 ↑ if leukocytosis occurs during therapy. If RA-APL symptoms occur, promptly administer dexamethasone 10 mg IV every 12 hr for 3 days or until symptoms resolve. Discontinuation of tretinoin is usually not necessary.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
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 ↓ risk of RA-APL syndrome and should be considered.
- Monitor hepatic function at baseline and as clinically indicated during therapy. If levels are >5 times the upper limit of normal, temporarily discontinue tretinoin therapy until resolved.
- Monitor fasting cholesterol and triglycerides at baseline and periodically during therapy.

Implementation ⬆ ⬇

Do not confuse tretinoin with isotretinoin.
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.
Following remission with tretinoin, standard consolidation or maintenance chemotherapy should be administered unless contraindicated.
PO: Administer capsules with food at evenly spaced intervals. DNC: Swallow capsules whole with water. Do not chew, dissolve, or open capsule.

Patient/Family Teaching ⬆ ⬇

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. If vomiting occurs, omit and take next scheduled 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.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during therapy and for 1 wk after last dose. Advise patient to avoid breastfeeding during therapy and for 1 wk after last dose. May impair fertility in male patients.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇