Tretinoin Side Effects

Medically reviewed by Drugs.com. Last updated on Jun 15, 2023.

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]