Tretinoin

Tretinoin is a cancer medication used to treat acute promyelocytic leukemia (a type of blood cancer).

Tretinoin is available under the following different brand names: Vesanoid.

Dosage Forms and Strengths

Capsule

• 10 mg

Dosing Consideraations – Should be Given as Follows:

Acute Promyelocytic Leukemia

For use in patients with APL classification M3, which is characterized by the presence of t(15;17) translocation and/or the presence of the PML/RAR-alpha gene, who are refractory to, or have relapsed from, anthracycline chemotherapy, as well as for use in patients for whom anthracycline-based chemotherapy is contraindicated

Remission Induction

• Adult and pediatric: 45 mg/m²/day orally divided every 12 hours
• Discontinue 30 days after complete remission or 90 days after start of treatment (whichever comes first)

Remission Induction In Combination with an Anthracycline

• Adult: 45 mg/m²/day orally divided every 12 hours
• Adult: Discontinue 30 days after complete remission or 90 days after start of treatment (whichever comes first)
• Pediatric: 25 mg/m²/day orally divided every 12 hours until complete remission or 90 days

Consolidation Therapy (Off-label)

• Adult: Intermediate and high risk patients: 45 mg/m² orally divided every 12 hours for 15 days/month for 3 months
• Pediatric: Intermediate and high risk patients: 25 mg/m² orally divided every 12 hours for 15 days/month for 3 months

Maintenance of Remission (Off-label)

• Adult: 45 mg/m²/day orally divided every 12 hours for 15 days every 3 months for 2 years
• Pediatric: 25 mg/m²/day orally divided every 12 hours for 15 days every 3 months for 2 years

Dosing Adjustment (Toxicity)

APL differentiation syndrome: 10 mg dexamethasone intravenous (IV) every 12 hours for 3-5 days; consider interrupting tretinoin until resolution of hypoxia

Liver function tests greater than 5 times upper limit of normal: Consider withholding treatment temporarily

Patient Monitoring

Monitor complete blood counts (CBC), coagulation, liver function tests, serum lipids

Common Side effects of Tretinoin include:

• Headache
• Fever
• Bone pain
• Dry mucous membranes
• Feeling unwell (malaise)
• Upper respiratory infection
• Shivering
• Shortness of breath
• Hemorrhage/Bleeding
• Elevated liver function tests
• High levels of fat in the blood (hyperlipidemia)
• Infections
• Nausea and vomiting
• Rash or itching
• Swelling of extremities
• Increased white blood cells
• Pain
• Abdominal pain
• Disseminated intravascular coagulation (DIC)
• Respiratory insufficiency
• Mucositis
• Gastrointestinal (GI) disorder
• Retinoic acid-APL syndrome
• Earache
• Diarrhea
• Fluid around the lungs (pleural effusion)
• Dizziness
• Itching
• Sweating
• Anxiety
• Numbness and tingling
• Constipation
• Vision changes or problems
• Indigestion
• Rales
• Depression
• Insomnia
• Hair loss
• Thinning hair
• Skin changes
• Confusion
• Bloating
• Renal insufficiency
• Heart failure
• Cardiac arrest
• Pale skin (pallor)
• Cardiomyopathy
• Myocarditis
• Stroke
• Heart murmur
• Facial swelling (edema)
• Intracranial hypertension
• Hypotaxia
• Seizure
• Drowsiness
• Facial paralysis
• Spinal cord disorder
• Light reflex absent
• Ulcer
• Cellulitis
• Hepatosplenomegaly
• Painful urination
• Enlarged prostate
• Ascites
• Hepatitis
• Tremor
• Bone inflammation
• Hearing loss
• Weakness
• Tiredness
• Dry mouth or nose
• Dry skin
• Other skin changes
• White patches or sores inside your mouth or on your lips
• Increased sweating

Less common side effects of tretinoin include:

• Arterial thrombosis
• High blood calcium levels (hypercalcemia)
• Myositis
• Pancreatitis
• Low platelet levels (thrombocytosis)
• Venous thrombosis
• Irreversible hearing loss
• Genital ulceration

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe Interactions of tretinoin include:
  • doxycycline
  • minocycline
  • tetracycline
• Tretinoin has serious interactions with at least 26 different drugs.
• Moderate Interactions of tretinoin include:
  • dichlorphenamide
  • ketoconazole
  • methotrexate
  • mifepristone
  • teriflunomide
  • tobramycin inhaled
  • tranexamic acid oral
• Mild Interactions of tretinoin include:
  • benazepril

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

• Administration: Administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to diagnose and manage complications.
• Teratogenic effects: High risk of severe infant deformity if administered during pregnancy; if treatment with tretinoin is required in women of childbearing potential, 2 reliable forms of contraception should be used during, and for 1 month after, therapy; if it is determined that tretinoin represents the best available treatment for a pregnant woman, patients should be informed of the risk to the fetus.
• Retinoic acid-APL syndrome: About 25% of patients with APL treated with tretinoin experience a syndrome called the retinoic acid-APL syndrome, which can be fatal and is characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural or pericardial effusions, edema, and hepatic, renal, and/or multi-organ failure; this syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension; management has not been defined rigorously, but high-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality.
• Rapidly evolving leukocytosis: About 40% of patients will develop rapidly evolving leukocytosis; those who present with high WBC at diagnosis (i.e., greater than 5 x10^9/L) have an increased risk; if signs and symptoms of the RA-APL syndrome are present together with leukocytosis, treatment with high-dose steroids should be initiated immediately.
• This medication contains tretinoin. Do not take Vesanoid if you are allergic to tretinoin or any ingredients contained in this drug.
• Keep out of reach of children
• In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Hypersensitivity to retinoids, parabens, or formulation components

Effects of Drug Abuse

• No information available

Short-Term Effects

• Increased risk of blood clots (thrombosis) during first month of treatment
• See "What Are Side Effects Associated with Using Tretinoin?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Tretinoin?"

Cautions

• Teratogenic and embryotoxic in animal studies and is expected to cause fetal harm in pregnant women; effective contraception must be used by all females of childbearing potential during and for 1 month after discontinuation
• Microdosed progesterone oral contraception (“minipill”) may not be adequate for contraception during tretinoin therapy
• Patients without the t(15;17) translocation genetic marker should be considered for alternative treatment
• Retinoic acid-APL syndrome, which can be fatal, has been reported
• Leukocytosis may occur
• Pseudotumor cerebri associated with retinoids, especially in pediatric patients; dizziness or severe headache may be symptoms
• Up to 60% incidence of hypercholesterolemia and/or hypertriglyceridemia; reversible upon completion of treatment
• Elevated liver function tests may occur in 50-60% of patients during treatment
• Increased risk of blood clots (thrombosis) during first month of treatment
• Do not co-administer with other retinoids or in combination with vitamin A because symptoms of hypervitaminosis A

Pregnancy and Lactation

• Use systemic tretinoin during pregnancy only in LIFE-THREATENING emergencies when no safer drug is available
• There is positive evidence of human fetal risk
• It is unknown if tretinoin is excreted in breast milk; do not breastfeed, because of the potential for serious adverse reactions in infants