tretinoin

(trĕt'ĭ-noin')
n.
See retinoic acid.

[T(RANS-) + RETINO(IC ACID) + -IN.]

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Key Terms: Leukocyte, Metabolite.

Definition

Tretinoin, a natural vitamin A metabolite, is an anticancer drug used in the treatment of acute promyelocytic leukemia (APL). Tretinoin is more commonly used to treat such skin disorders as acne, warts, hyperpigmentation, and reactions to sunlight.

Purpose

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.

As of 2004, tretinoin is also being investigated as a possible chemopreventive for breast cancer. The drug is thought to slow the spread of tumors and speed up the process of tumor cell self-destruction (apoptosis).

Description

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.

Recommended Dosage

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.

Precautions

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 childbearing age should take a pregnancy test to assure that they are not pregnant prior to starting this drug.

Side Effects

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 (including formation of inflammatory growths known as granulomas), 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.

In addition, 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.

Interactions

Tretinoin interacts with:

• Cimetidine (antipeptic ulcer drug)
• Cyclosporine (immunosuppressant)
• Dilitiazem (heart medication)
• Erythromycin (antibiotic)
• Glucocorticoids (steroids)
• Ketoconazole (antifungal drug)
• Phenobarbital (sedative/hypnotic)
• Pentobarbital (sedative/hypnotic)
• Rifampicin (an antituberculosis drug, also known as rifampin)
• Verapamil (heart medication)

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Acne." Section 10, Chapter 116 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Warts (Verrucae)." Section 10, Chapter 115 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L. Stang. Nurse's Drug Guide 2003. Upper Saddle River, NJ: Prentice Hall, 2003.

Periodicals

Halder, R. M., and G. M. Richards. "Topical Agents Used in the Management of Hyperpigmentation." Skin Therapy Letter 9 (June-July 2004): 1–3.

Kligman, D. E., and Z. D. Draelos. "High-Strength Tretinoin for Rapid Retinization of Photoaged Facial Skin." Dermatologic Surgery 30 (June 2004): 864–866.

Simeone, A. M., and A. M. Tari. "How Retinoids Regulate Breast Cancer Cell Proliferation and Apoptosis." Cellular and Molecular Life Sciences 61 (June 2004): 1475–1484.

Teknetsis, A., D. Ioannides, G. Vakali, et al. "Pyogenic Granulomas Following Topical Application of Tretinoin." Journal of the European Academy of Dermatology and Venereology 18 (May 2004): 337–339.

Organizations

American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000. .

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA. .

—Rhonda Cloos, R.N.; Rebecca J. Frey, PhD

A retinoid used topically for the treatment of acne and orally to treat certain types of leukaemia (see cancer). A prescription only medicine, it is available as a gel or as capsules.

Side effects:
skin preparations may cause redness, local irritation, and peeling at the start of treatment, but this should not last; they may cause changes in skin pigmentation and make the skin more sensitive to light. Side effects caused by the capsules include stomach upsets, irregular heart rhythms, flushing, headache, dry skin and mucous membranes, rash, visual impairment, hearing disturbances, confusion, dizziness, bone pain, and chest pain; the retinoic acid syndrome (including fever, breathlessness, and oedema) requires immediate treatment.

Precautions:
skin preparations should not be used on damaged or sunburnt skin, by people with eczema or a personal or family history of skin cancer, or by pregnant women. These preparations should not come into contact with the eyes, nostrils, or mouth, and exposure of treated skin to ultraviolet light (including excessive sunlight) should be avoided. Skin preparations should not be used with other topical agents (e.g. keratolytics) that may cause irritation. Capsules should not be taken by women who are pregnant or breastfeeding, and contraception must be used for one month before and during treatment and for at least one month after stopping treatment (see retinoids). They should be used with caution in people with liver or kidney disease. Blood tests to monitor concentrations of fats should be carried out during treatment; there is a risk of thrombosis during the first month of treatment.

Interactions with other drugs:

Keratolytics see Precautions above.
Tetracyclines may increase pressure in the brain and should not be used with tretinoin.

Proprietary preparations:
Retin-A (gel); Vesanoid (capsules); Aknemycin Plus (combined with erythromycin).

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a WHO-approved nonproprietary name for retinoic acid, especially for pharmacological use.

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