Tretinoin, a natural vitamin A metabolite, is an anti-cancer drug used in the treatment of acute promyelocytic leukemia (APL).
Tretinoin is given to APL patients with the goal of bringing on a remission. The drug is being investigated as a treatment for skin cancer, and it is also available in an acne cream commonly called Retin-A.
Tretinoin causes abnormal leukemia cells in the blood to mature into normal cells (granulocytes). The exact mechanism of action is not known. In clinical trials 72-94% of APL patients experienced a complete remission when taking this drug. Tretinoin can be used to induce remission and to maintain remission.
The recommended dosage for adults with APL is 45 milligrams per square meter taken by mouth as two evenly divided doses. The physician will calculate the specific dose for each patient. The drug should be discontinued 30 days after remission or 90 days after treatment begins, whichever comes first.
Patients who are hypersensitive to vitamin A or other retinoids should not take this drug. People should avoid tretinoin if they are sensitive to parabens, a preservative used in the drug's capsule. Pregnant or breastfeeding women should not take tretinoin. Women of child-bearing age should take a pregnancy test to assure that they are not pregnant prior to starting this drug.
Tretinoin has a number of side effects. Patients should discuss the risk of complications with their physician. Some side effects resemble symptoms that are common in APL patients. All side effects should be reported to a patient's doctor.
Side effects that are more commonly reported include headache, fever , dry skin and mucous membranes, bone pain , rash, itching , inflamed lips, sweating, nausea and vomiting , abdominal pain, diarrhea , constipation, indigestion, bloating, irregular heart beat, visual disturbances, earache, hair loss (alopecia ), skin changes, vision changes, and bone inflammation.
Hemorrhage is a life-threatening complication. Blood coagulation studies are done while the patient is taking the drug to monitor the risk of hemorrhage. Hepatitis is another life-threatening side effect. Liver function tests can be abnormal in 50-60% of patients taking the drug. Liver function is monitored periodically while a person is taking the drug.
Also, approximately one quarter of patients taking tretinoin develop retinoic-acid-APL (RA-APL) syndrome. Symptoms include fever, weight gain, difficulty breathing, and other respiratory disorders. Some patients have cardiac changes and low blood pressure as part of this syndrome. The syndrome can occur two days after treatment begins or three to four weeks later. Symptoms must be reported to the patient's physician immediately so that treatment can begin. In rare cases this syndrome is fatal. Most patients do not need to stop taking tretinoin if the syndrome develops.
Approximately 40% of patients taking tretinoin develop high white blood cell counts (leukocytosis). If the number of white blood cells increases rapidly there is a higher chance of developing life-threatening complications. White blood cell counts are monitored during treatment. As many as 60% of patients taking tretinoin develop increased cholesterol and triglyceride levels. The levels drop when the medication is stopped. Cholesterol and triglyceride levels are monitored while the drug is being taken.
Tretinoin has other side effects that may impact the heart, skin, digestive tract, lungs, central nervous system, and other parts of the body. Patients should report all unusual symptoms to the doctor immediately.
Tretinoin interacts with:
- Cimetidine (antipeptic ulcer drug)
- Cyclosporine (immunosuppressant)
- Dilitiazem (heart medication)
- Erythromycin (antibiotic)
- Glucocorticoids (steroids)
- Ketoconazole (antifungal)
- Phenobarbital (sedative/hypnotic)
- Pentobarbital (sedative/hypnotic)
- Rifampicin (an antituberculosis drug)
- Verapamil (heart medication)
See Also Acute myelocytic leukemia; Antineoplastic agents
Rhonda Cloos, R.N.
—White blood cell. Leukocytosis is an excess number of white blood cells, and is seen in conditions such as infection and leukemia.
—A product of metabolism.
—Natural or artificial compound that is similar to vitamin A.