Summary
Commonly reported side effects of tretinoin include: pleural effusion, dyspnea, edema, fever, hypotension, leukocytosis, weight gain, headache, hypercholesterolemia, hypertriglyceridemia, increased liver enzymes, nausea, visual disturbance, and vomiting. Other side effects include: pulmonary infiltrates. Continue reading for a comprehensive list of adverse effects.
Applies to tretinoin: oral capsule liquid filled.
Warning
Oral route (Capsule, Liquid Filled)
Patients with acute promyelocytic leukemia (APL) can have severe adverse reactions to tretinoin. Tretinoin should therefore be administered only to patients with APL under the strict supervision of a physician who is experienced in the management of patients with acute leukemia and in a facility with laboratory and supportive services sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity, including respiratory compromise. Use of tretinoin requires a favorable risk benefit profile.Retinoic Acid-APL Syndrome: Patients treated with tretinoin have experienced retinoic acid-APL (RA-APL) syndrome characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural and pericardial effusions, edema, and hepatic, renal, and multi-organ failure. RA-APL has been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multi-organ failure. RA-APL may occur during the first month of treatment, with some cases reported following the first dose of tretinoin. High-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality. At the first signs of RA-APL (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg IV administered every 12 hours for 3 days or until the resolution of symptoms) should be immediately initiated, irrespective of the leukocyte count. The majority of patients do not require termination of tretinoin therapy during treatment of the RA-APL syndrome. However, in cases of moderate and severe RA-APL, consider temporary interruption of therapy.Leukocytosis at Presentation and Rapidly Evolving Leukocytosis During Tretinoin Treatment: Rapidly evolving leukocytosis may occur with therapy. Patients who present with high WBC at diagnosis (greater than 5x10(9)/L) have an increased risk of a further rapid increase in WBC counts. Rapidly evolving leukocytosis is associated with a higher risk of life-threatening complications. If signs and symptoms of the RA-APL syndrome are present together with leukocytosis, treatment with high-dose steroids should be initiated immediately. Some investigators routinely add chemotherapy to tretinoin treatment in the case of patients presenting with a WBC count of greater than 5x10(9)/L or in the case of a rapid increase in WBC count for patients leukopenic at start of treatment, and have reported a lower incidence of the RA-APL syndrome. Consideration could be given to adding full-dose chemotherapy (including an anthracycline if not contraindicated) to the tretinoin therapy on day 1 or 2 for patients presenting with a WBC count of greater than 5x10(9)/L, or immediately, for patients presenting with a WBC count of less than 5x10(9)/L, if the WBC count reaches greater than or equal to 6x10(9)/L by day 5, or greater than or equal to 10x10(9)/L by day 10, or greater than or equal to 15x10(9)/L by day 28.Teratogenic Effects. There is a high risk that a severely deformed infant will result if tretinoin is administered during pregnancy. If, nonetheless, it is determined that tretinoin represents the best available treatment for a pregnant woman or a woman of childbearing potential, it must be assured that the patient has received full information and warnings of the risk to the fetus if she were to be pregnant and of the risk of possible contraception failure and has been instructed in the need to use two reliable forms of contraception simultaneously during therapy and for 1 month following discontinuation of therapy, and has acknowledged her understanding of the need for using dual contraception, unless abstinence in the chosen method. Within 1 week prior to the institution of tretinoin therapy, the patient should have blood or urine collected for a serum or urine pregnancy test with a sensitivity of at least 50 million international units/mL. When possible, tretinoin therapy should be delayed until a negative result from this test is obtained. When a delay is not possible, the patient should be placed on 2 reliable forms of contraception. Pregnancy testing and contraception counseling should be repeated monthly throughout treatment.
Serious side effects of Tretinoin
Along with its needed effects, tretinoin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking tretinoin:
More common
- Black, tarry stools
- bleeding
- blistering
- bloody stools
- bone pain
- burning
- coldness
- difficulty in moving
- discomfort or pain in chest
- enlarged heart
- feeling of pressure
- fever
- hives
- infection
- inflammation
- joint pain
- lumps
- numbness
- paleness of skin
- rash
- redness
- scaring
- seizures
- shortness of breath, troubled breathing, tightness in chest, or wheezing
- soreness
- stinging
- sweating increased
- swelling
- swollen joints
- tenderness
- tingling
- ulceration
- unusual tiredness or weakness
- vomiting of blood or material that looks like coffee grounds
- warmness at site
- weight gain (occurring together with any of the other symptoms listed before)
Less common
- Blue lips and fingernails
- convulsions (seizures)
- difficulty in speaking, slow speech, or inability to speak
- faintness
- feeling of heaviness in chest
- headache (severe)
- inability to move arms, legs, or muscles of the face
- nausea and vomiting (occurring together with a headache)
- no blood pressure or pulse
- pain in back or left arm
- painful, red lumps under the skin, mostly on the legs
- prominent superficial veins over affected area
- stopping of heart
- unconsciousness
- vision problems (occurring together with a headache)
- warmth
Check with your doctor as soon as possible if any of the following side effects occur while taking tretinoin:
More common
- Any change in vision (not occurring with a headache)
- coughing, sneezing, sore throat, and stuffy or runny nose
- cracked lips
- crusting, redness, pain, or sores in mouth or nose
- decreased urination
- earache or feeling of fullness in the ear
- increase or decrease in blood pressure
- irregular heartbeat
- mental depression
- pain in stomach, side, abdomen or back
- pain and swelling in leg or foot
- skin rash
- swelling of abdomen (stomach area)
- swelling of face, fingers, hands, feet, or lower legs
Less common
- Bone swelling
- cramping or pain in stomach (severe)
- difficult or painful urination
- drowsiness (very severe and continuing)
- hallucinations (seeing, hearing, or feeling things that are not there)
- hearing loss
- heartburn, indigestion, or nausea (severe and continuing)
- mood, mental, or personality changes
- pain in lower back or side
- swollen area that feels sore and tender
- yellow eyes or skin
Other side effects of Tretinoin
Some side effects of tretinoin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
- Acid or sour stomach
- agitation
- anxiety
- belching
- blurred vision
- bloating
- burning, crawling, or tingling feeling in the skin
- chills
- confusion
- constipation
- darkened urine
- diarrhea
- dizziness
- dryness of skin, mouth, or nose
- fast heartbeat
- flushing
- general feeling of discomfort or illness
- hair loss
- headache (mild and not occurring together with other side effects)
- indigestion
- irritability
- itching of skin
- loss of appetite
- mood or mental changes
- muscle pain
- nausea and vomiting (not occurring together with a headache)
- shivering
- trouble sleeping
- weakness
- weight loss
Less common
- Anxiety and restlessness (occurring together)
- clumsiness or unsteadiness when walking
- difficulty sleeping
- disorientation
- forgetfulness
- frequent urination
- lethargy
- lightheadedness
- low body temperature
- redness, soreness or itching skin
- sores, welting or blisters
- sores on genitals
- swelling of feet or lower legs
- thirst
- trembling, sometimes with a flapping movement
- weak or feeble pulse
- weakness in legs
For Healthcare Professionals
Applies to tretinoin: compounding powder, oral capsule.
General
-The most frequent undesirable effects of this drug are consistent with signs of hypervitaminosis A syndrome (as for other retinoids).
-APL patients treated with this drug may experience a potentially fatal syndrome characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural and pericardial effusions, edema, and hepatic, renal, and multi-organ failure. This syndrome is sometimes accompanied by impaired myocardial contractility and episodic hypotension with or without concomitant leukocytosis.[Ref]
Other
Very common (10% or more): Fever (83%), malaise (66%), peripheral edema (52%), earache/feeling of fullness in the ears (23%), edema (29%), shivering (63%), hearing impaired, chills, weakness, fatigue, chest pain
Common (1% to 10%): Face edema, hypothermia, hearing loss and other unspecified auricular disorders
Uncommon (0.1% to 1%): Irreversible hearing loss
Frequency not reported: Histamine level increased, teratogenicity[Ref]
Hematologic
Very common (10% or more): Hemorrhage (60%), disseminated intravascular coagulation (26%)
Frequency not reported: Thrombocytosis, leukocytosis, basophilia[Ref]
Hepatic
Very common (10% or more): Transaminases increased
Common (1% to 10%): Hepatosplenomegaly, hepatitis, unspecified liver disorder[Ref]
Dermatologic
Very common (10% or more): Skin/mucous membrane dryness (77%), rash (54%), pruritus (20%), increased sweating (20%), alopecia (14%), skin changes (14%), erythema, hyperhidrosis
Frequency not reported: Erythema nodosum, acute febrile neutrophilic dermatosis (Sweet's syndrome)[Ref]
Musculoskeletal
Very common (10% or more): Bone pain (77%), myalgia (14%)
Common (1% to 10%): Bone inflammation, flank pain
Frequency not reported: Myositis[Ref]
Gastrointestinal
Very common (10% or more): Nausea/vomiting (57%), GI hemorrhage (34%), abdominal pain (31%), mucositis (26%), diarrhea (23%), constipation (17%), dyspepsia (14%), abdominal distension (11%)
Common (1% to 10%): Ascites, ulcer
Frequency not reported: Organomegaly, pancreatitis[Ref]
Ocular
Very common (10% or more): Visual disturbances/ocular disorders (17%), conjunctival disorders
Common (1% to 10%): Changed visual acuity, visual field defects[Ref]
Local
Very common (10% or more): Injection site reactions (17%)[Ref]
Respiratory
Very common (10% or more): Upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), expiratory wheezing (14%), respiratory failure, nasal dryness, asthma
Common (1% to 10%): Lower respiratory tract disorders, pulmonary infiltration, pulmonary edema, larynx edema, unspecified pulmonary disease[Ref]
Cardiovascular
Very common (10% or more): Arrhythmia (23%), flushing (23%), hypotension (14%), hypertension (11%), phlebitis (11%)
Common (1% to 10%): Pallor, lymph disorders, cardiac failure, cardiac arrest, myocardial infarction, enlarged heart, heart murmur, ischemia, stroke, myocarditis, pericarditis, pulmonary hypertension, secondary cardiomyopathy
Frequency not reported: Arterial thrombosis, venous thrombosis involving various sites (e.g., cerebrovascular accident, renal infarct), vasculitis[Ref]
Nervous system
Very common (10% or more): Headache (86%), dizziness (20%), paresthesias (17%), intracranial pressure increased, pseudotumor cerebri
Common (1% to 10%): Cerebral hemorrhage, intracranial hypertension, abnormal gait, agnosia, aphasia, asterixis, cerebellar edema, cerebellar disorders, convulsions, coma, CNS depression, dysarthria, encephalopathy, facial paralysis, hemiplegia, hyporeflexia, hypotaxia, no light reflex, neurologic reaction, spinal cord disorder, tremor, leg weakness, unconsciousness, slow speech
Frequency not reported: Cerebrovascular accident[Ref]
Genitourinary
Common (1% to 10%): Dysuria, micturition frequency, enlarged prostate
Frequency not reported: Genital ulceration[Ref]
Metabolic
Very common (10% or more): Anorexia (17%), weight loss (17%), decreased appetite, weight gain (23%), blood triglyceride increased, blood creatinine increased, blood cholesterol increased
Common (1% to 10%): Fluid imbalance, acidosis
Frequency not reported: Hypercalcemia[Ref]
Psychiatric
Very common (10% or more): Anxiety (17%), insomnia (14%), depression (14%), confusion (11%)
Common (1% to 10%): Agitation, hallucination, dementia, forgetfulness, somnolence[Ref]
Renal
Very common (10% or more): Renal insufficiency (11%)
Frequency not reported: Renal infarct[Ref]
