Tretinoin

Tretinoin oral capsule helps induce remission in acute promyelocytic leukemia (APL, APML) patients. Use of this medication needs to be administered and monitored by an experienced doctor in a well-equipped hospital due to its possible adverse side effects.

Overview

Tretinoin oral capsule is an anti-cancer (also known as antineoplastic or cytotoxic) treatment. It is used for induction of remission in acute promyelocytic leukemia (APL, APML) patients. It is known for its drug brand name Vesanoid®.

Tretinoin is administered orally (in capsule form) to treat acute promyelocytic leukemia (or APL, APML). It is used to induce remission of APL only. It should not be used until 30 days after complete remission is documented or 90 days after its initial use, whichever happens first.

Tretinoin is a type of medicine that forms part of the group called retinoids (RET-i-noyds), which are similar to Vitamin A. The medicine is used to treat a type of leukemia (acute promyelocytic leukemia [APL]). Use of Tretinoin may lead to severe side effects and should be administered with caution. Talk to the doctor about the possible side effects and the risks associated with this medicine. This is a prescription drug which is not available over-the-counter.

Condition Treated:

  • Acute promyelocytic leukemia (or APL, APML)

Type of Medicine:

  • Retinoids

Side Effects:

Not all patients will experience side effects from using Tretinoin. Often, the side effects can be predicted particularly when it comes to seriousness, onset and for how long it will be. The side effects will go away once treatment is completed. The side effects are manageable, especially if dealt with early on. There are ways to prevent or reduce the possible side effects of Tretinoin. There is no known relationship between the presence of side effects or its severity on how effective Tretinoin is in treating the patient.

These side effects are noted in almost 30% of the patients using Tretinoin:

  • Retinoid toxicity symptoms: fever, pain in head, dry mouth and nose, dry skin, bone ache, nauseous, rashes, sores in the mouth, itchiness, perspiring profusely, changes in eyesight.
  • Symptoms similar to flu such chills and general body weakness or malaise
  • Bleeding
  • Rapid increase of white blood cells
  • Infections
  • Edema in ankle and feet
  • Dyspnea or shortness of breathing
  • Joint, bone, and chest pains
  • Pain in abdomen
  • Cholesterol levels changes
  • Liver function test changes

Less common side effects noted in 10-29% of patients:

  • Weight gain
  • Irregularity in beating of heart of arrhythmia
  • Temporary redness of face or neck or flushing
  • Loss of appetite
  • Pain in ear
  • Constipation
  • Diarrhea
  • Feeling dizzy
  • Tingling or numbing in extremities
  • Nervousness
  • Sleeplessness
  • Heartburn
  • Fluid in the lungs
  • Hypotension or lowering of blood pressure
  • Depression
  • Myalgia or muscle aches
  • Hypertension or high blood pressure
  • Feeling dazed or confused
  • Changes in skin
  • Loss of hair

A severe side effect of Tretinoin is called the APL differentiation syndrome. This can be prevented by vigilant monitoring and immediate medical attention. It can be treated with a high dosage of steroids. The patient should inform the doctor right away if he or she notices certain symptoms upon the administration of the initial dose or during the first month of treatment.

The patient should contact the doctor immediately if he or she experiences fever that reaches 100.4ºF and chills. These are signs of a possible infection which need to be treated right away to prevent further complications.

Dosage

This medicine is available in capsule, liquid-filled form. Its drug brand name is Vesanoid. Dosage is based on different factors, such as weight, age, gender, and medications the patient is taking. Dosage differs from patient to patient. Use Tretinoin as directed by the doctor. Do not change the dosage unless specified by the doctor.

The recommended dosage is expressed in the formula = 45 mg/m2/day. This should be taken until remission is attained. The use of Tretinoin should be stopped 30 days after getting complete remission or after 90 days of taking it, whichever comes first.

If after first treatment, the t(15;17) translocation is not present, Tretinoin may need to be stopped. If its presence is not confirmed by a polymerase chain reaction test and a cytogenetics, this means the patient is not responding to Tretinoin. The medication may be discontinued and another therapy for acute myelogenous leukemia should be used.

Standard dosage for Tretinoin in oral or capsule form include:

  • Acute promyelocytic leukemia (APL):
    • For Adults - dosage computer based on body surface or size. The prescribed dosage is 45 milligrams (mg) for each square meter of surface area of the patient’s body per day. The total dosage in mg based on total body surface area is divided equally into two and administered to the patient.
    • For Children - the doctor will compute the required dosage for kids.

Tretinoin is given orally in capsule, liquid filled form. Each capsule is 10mg. It should be taken as it is. It should not be chewed, dissolved or crushed as this may impact its effectiveness. Take the medicine with food as the absorption of this medication is enhanced by doing so. Do not take it on an empty stomach.

Tretinoin also comes in topical form as a lotion usually used by patients to treat acne and certain kinds of rashes.

Take Tretinoin as prescribed by the doctor. Do not take more or less than the required dosage. Also, do not take it more frequently or for a longer time than what is directed by the doctor. Taking less than required will not produce the desired effects. Taking it more often or longer might cause overdosage, which can be fatal.

When discussing the use of Tretinoin with the doctor, the patient should disclose all kinds of medications he or she is taking whether prescription, illegal, herbal, over-the-counter, vitamins, and others. Refrain from taking aspirin, or medicines that contain aspirin while taking Tretinoin, unless the doctor allows it.

Missed Dose

The patient should take the medicine right away if he or she forgets. If it is almost time for the next dose, then he or she should skip the dose missed. Do not take twice the dosage to prevent overdosing. Call the doctor to inquire how much Tretinoin is needed for the next dose.

Drug Interactions

There are limited data on the drug interactions associated with Tretinoin. However, like any other medications, the medicine is not recommended for patients who are allergic to tretinoin, any of its ingredients, or other retinoid products.

Tretinoin, being a retinoid, may cause increase risks of pseudotumor cerebri (or benign intracranial hypertension), especially among children. Use of Tretinoin should be monitored if taken with other retinoids that are known to cause intracranial hypertension, such as tetracyclines, as this may cause a sudden increase in blood pressure.

Tretinoin is metabolized by the hepatic P450 system. If taken along with other medication that induces or inhibits the P450 system, the effects of Tretinoin might alter. Drugs that can induce hepatic P450 enzymes are the following: glucocorticoids, phenobarbital, rifampicin, and pentobarbital. Medications that inhibit hepatic P450 enzymes include cyclosporine, erythromycin, ketoconazole, verapamil, cimetidine, and diltiazem. It cannot be ascertained though if the use of Tretinoin with these medications can reduce or heighten the effectiveness of Tretinoin.

Do not take Tretinoin with vitamin A. Using both at the same time could cause or worsen hypervitaminosis A.

Patients should be cautious in taking Anti-fibrinolytic medications such as Aprotinin, Aminocaproic Acid, or Tranexamic Acid. This may cause life-threatening thrombotic complications.

Warning

Patients with acute promyelocytic leukemia (APL) should seek the help of a doctor with years of experience in administering Tretinoin to cancer patients. APL patients have a higher risk of incurring serious side effects from Tretinoin. This medication should only be taken under the strict supervision of an experienced doctor.

The patient should also stay in a hospital complete with all the facilities that he or she requires, such as laboratory and other services. This is important in order to be able to monitor the patient's reaction or tolerance to the medication. Also, in case a patient incurs adverse reaction to Tretinoin, proper services can be quickly administered, particularly in the case of problems with the respiratory system. The doctor should determine that the benefits of Tretinoin to the patient outweigh the potential life-threatening risks it might cause.

An estimated 25% of acute leukemia patients taking Tretinoin experience a symptom called retinoic acid-APL (RA-APL) syndrome. This syndrome causes severe respiratory distress, fever, edema, failure in liver, kidney, and multi-organ, shortness of breath, weight gain, and many others. These symptoms are usually observed during the first month of treatment. Some symptoms manifest upon the administration of the first dose. The patient may require intubation in the endotracheal and the use of mechanical ventilation to counter hypoxemia or low levels of oxygen in the blood.

A noted fast increase of white blood cells is observed in 40% of patients taking Tretinoin. Patient with high WBC count during diagnosis usually have a higher risk of further increasing WBC during the treatment using Tretinoin. Rapid increase of WBC count may lead to complications, which should be monitored.

Do not get vaccinated or immunized unless approved by the doctor while using Tretinoin.

Tretinoin is not safe for pregnant women. It belongs to FDA’s category D for medicines classification. Category D could be dangerous to the unborn baby. There are no studies conducted on the effects of the use of Tretinoin among pregnant women. However, some retinoids are known to induce spontaneous abortion or can cause major deformities or abnormalities to the fetus. It can also lower the baby's IQ. The patient should inform the doctor if she is pregnant so that other alternative medicine options can be explored.

For women planning to get pregnant, it is advisable to postpone pregnancy plans until it is safe to do so. Tretinoin can cause deformity in a fetus, even if the medicine is used for only a short period of time. The patient should use two kinds of contraception to prevent getting pregnant while taking Tretinoin, even if the patient is undergoing menopause or is known to be infertile. Use of contraception should be continued one month after using Tretinoin was stopped.

Women should not breastfeed while taking the medication; Tretinoin may pass in milk being fed to the infant.

Patients are advised not to drive or operate machinery when taking Tretinoin as it can cause dizziness.

Storage

Store Tretinoin in a tightly closed container. Place it at room temperature. Do not store it in areas that are too hot, moist and exposed directly to sunlight. Also, do not store it in cold, freezing temperatures.

Tretinoin can be fatal to children if ingested. Make sure it is beyond the children’s reach. Discard medicines safely especially those that are no longer used or have expired.

Summary

Tretinoin can have possible toxic effects to patients with acute promyelocytic leukemia (APL, APML). The administration of Tretinoin should be done by an experienced doctor in a well-equipped facility. This is to ensure that side effects, especially the life-threatening ones, are addressed immediately. Patients need to be closely monitored by the doctor for any adverse side effects after the initial dose or after a month of treatment. Some of the severe side effects of Tretinoin in APL patients include respiratory distress or breathlessness and rapid increase in white blood cell count or leukocytosis. Prompt attention should be given to patients who show signs of various side effects. These symptoms are treatable. In some cases, the doctor might give the patient a high dosage of steroids to contain the side effects. In cases of progressive hypoxemia, or low levels of oxygen in the blood, the patient may require additional medications or therapies to address it.

Pregnant women should take necessary precautions while taking tretinoin. Tretinoin is a Class D medication. It may cause spontaneous abortion or major deformities to the fetus. Those who plan to get pregnant should refrain from doing so while using Tretinoin. Women should take two forms of contraceptives to ensure they will not get pregnant while taking the medication or 30 days after taking Tretinoin, even if they are undergoing the menopause or have a history of infertility.

Tretinoin is used to induce remission only. It is not a therapy used for long-term or for maintenance purposes. Patients should stop using the medication 30 days after complete remission is documented, or after 90 days of treatment, whichever comes first. It is important for patients to follow doctor’s orders. Tretinoin should not be taken more than it should, as this could have fatal consequences.

Patients should report symptoms of side effects immediately to the doctor. There are ways to treat side effects or to prevent them such as dose reduction, use of alternative therapy or using tretinoin with other medications.

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Last Reviewed:
December 23, 2017
Last Updated:
December 22, 2017
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