tretinoin (ATRA)

Trade Name:

Vesanoid®

Synonym:

ATRA

All-trans Retinoic Acid

Appearance:

capsule

Monograph Name:

tretinoin (ATRA)

Monograph Body:

Drug Monograph

A - Drug Name

tretinoin (ATRA)

SYNONYM(S): ATRA; All-trans Retinoic Acid

COMMON TRADE NAME(S): Vesanoid®

B - Mechanism of Action and Pharmacokinetics

Tretinoin is an endogenous metabolite of retinol (vitamin A). It induces terminal differentiation and inhibits cell proliferation in transformed hemopoietic precursor cell lines, including human myeloid lines. Acute Promyelocytic Leukemia (APL) is associated with a specific translocation between chromosomes 15 and 17 (region of retinoic acid receptor - α). The translocation appears to inhibit differentiation and lead to carcinogenesis; tretinoin may overcome this when used in high doses. Tretinoin induces remissions in 64-100% of APL patients, with time to remission usually between 8 and 119 days of therapy (Gillis 1995). Acquired resistance during therapy is common especially with prolonged dosing (4-6 months) possibly due to induction of metabolism or increased expression of cellular retinoic acid binding proteins.

Absorption

Oral: well absorbed with 50% bioavailability.

Absorption is affected by biliary pH and fatty composition. Effect of food on tretinoin absorption is unclear but increases bioavailability of retinoids as a class. Hence, tretinoin should be administered with food.

Peak plasma concentrations are reached within 1-2 hours. Pharmacokinetics (AUC, peak plasma concentration) initially increase in a higher than dose proportional manner. Prolonged dosing leads to a significant decrease in AUC and plasma levels.

Distribution

Rapidly and extensively distributed into tissues

Cross blood brain barrier?

PPB

>95% (mainly to albumin)

Metabolism

Primarily by hepatic cytochrome P450 (e.g. CYP3A4, CYP2C8, CYP2E). Metabolites are glucuronidated and excreted in bile and urine. Tretinoin induces its own metabolism, with lower plasma level and AUC after 2-6 weeks of continuous treatment with an increase in urinary excretion of 4-oxo metabolites.

Active metabolites

Several, including 13-cis isomer

Inactive metabolites

Many

Elimination

Feces

31% within 6 days

Urine

63 % within 72 hours

Half-life

0.7 hours (range 0.5 - 2 h)

C - Indications and Status

Health Canada Approvals:

For the induction of remission in acute promyelocytic leukemia (either de novo or after relapse following cytotoxic chemotherapy). Consolidation chemotherapy should be given after complete remission.

D - Adverse Effects

Emetogenic Potential:

Minimal – No routine prophylaxis; PRN recommended

Extravasation Potential: Not applicable

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Auditory	Ear pain (23%)	E
	Hearing impaired (6%) (irreversible in <1%)	E
Cardiovascular	Arrhythmia (23%)	E
	Arterial thromboembolism (3%)	E
	Cardiotoxicity (6%)	E
	Flushing (23%)	I E
	Hypertension (11%)	E
	Hypotension (14%)	E
	Pericarditis (3%)	E D
	Tachycardia	E
	Venous thromboembolism	E
Dermatological	Alopecia (14%)	E
	Dry skin (77%) (including mucosal dryness)	E
	Erythema nodosum (rare)
	Nail disorder	E D
	Other (Sweet's syndrome- rare)	E
	Photosensitivity (rare)	I E
	Rash (54%)	E
Gastrointestinal	Abdominal distension (11%)	E
	Abdominal pain (31%)	E
	Anorexia, weight loss (17%)	E
	Constipation (17%)	E
	Diarrhea (23%)	E
	Dyspepsia (14%)	E
	Mucositis (26%)	E
	Nausea, vomiting (57%)	I E
	Weight gain (23%)	E
General	Edema (52%)	E
	Fatigue (66%)	E
	Hypothermia (3%)	I E
	Other (25%) (retinoic acid syndrome)	I E
Hematological	Basophilia (severe-rare)	E
	Disseminated intravascular coagulation (26%)	E
	Hemorrhage (60%)	E
	Leukocytosis (75%) (hyperleukocytosis)	I E
	Thrombocytosis (rare)	E
Hepatobiliary	↑ LFTs (60%)	E
	Pancreatitis (rare)	E
Infection	Infection (58%)	E
Metabolic / Endocrine	Acidosis (3%)	E
	↑ Ca (rare)	E
	Hyperlipidemia (60%) (increased cholesterol and triglycerides)	E
	Hyperuricemia	E
Musculoskeletal	Musculoskeletal pain (77%)	E
	Myositis (rare)	E
Nervous System	Anxiety (17%)	E
	Confusion (11%)	E
	Depression (14%)	E D
	Dizziness (20%)	E
	Headache (86%)	I E
	Insomnia (14%)	E
	Other (9%) (pseudotumour cerebri)	E
	Paresthesia (17%)	E
Ophthalmic	Conjunctivitis (rare)	E
	Other (17%) (visual disturbance)	E
	Photophobia (rare)	E
Renal	Nephrotoxicity (11%)	E D
Respiratory	Bronchospasm	E
	Cough, dyspnea (60%)	E
	Lung infiltrate (6%)	E
	Pleural effusion (20%)	E
Vascular	Vasculitis (rare)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

Hypervitaminosis A syndrome is seen in at least 25% of patients, with rash, dry skin and mucosa, edema, nausea, vomiting, bone pain. Headache occurring several hours after tretinoin ingestion is the most common side effect. It differs from that associated with pseudotumour cerebri in that it is often transient, mild in intensity and well-controlled with mild analgesics. Patients usually develop tolerance with continued tretinoin therapy.

Retinoic acid syndrome (RAS) occurs in 20-25% of patients, and is characterized by some or all of the following symptoms: fever, dyspnea, hypotension, bone pain, weight gain, edema, respiratory distress, pulmonary infiltrates, hyperleukocytosis, pleural or pericardial effusion, congestive heart failure, hepatic / renal failure, multi-organ failure and may be fatal. Due to the severity and poor prognosis of the syndrome once the full-blown signs have been developed, prophylaxis or early treatment with chemotherapy, corticosteroids or temporary interruption is required (section E)

Basophilia/ Hyperhistaminemia: Basophilia-associated hyperhistaminemia has been rarely reported in patients with rare basophilic variants of APL. The severity of symptoms depends on the level of plasma histamine. Severe symptoms include tachycardia, shock due to vasodilatation, gastric and duodenal ulceration. Prophylactic H₂ or H₁ antagonist has been used to prevent symptoms mediated via H₂ and H₁ receptors.

Pseudotumour cerebri syndrome: Also known as benign or idiopathic intracranial hypertension, it is characterized by signs and symptoms of intracranial hypertension without evidence of infective or space occupying lesions. Symptoms include severe headache which may be aggravated by analgesic or narcotic overuse, nausea and vomiting, papilledema, retinal hemorrhages, visual changes (e.g., intermittent visual loss), and ophthalmoplegia. Cases reported onset of symptoms from 3-17 days to 6 months of tretinoin therapy. Pseudotumour cerebri is more common in children than in adults and may be due to their increased sensitivity to the CNS effects of tretinoin. The cause and appropriate management of pseudotumour cerebri have not been established, but the risk is increased with other drugs known to cause pseudotumour cerebri such as tetracyclines. Narcotic analgesics, corticosteroids, or temporary discontinuation of tretinoin in non-responding cases may help reduce severe headache, nausea and vomiting. Diuretics (acetazolamide, furosemide) or lumbar puncture may reduce CSF pressure.

Sweet's syndrome is a hyperinflammatory reaction of neutrophil infiltration of the skin and internal organs. Symptoms include fever, painful erythematous cutaneous plaques involving the extremities and the trunk, and prominent musculoskeletal involvement (e.g., myositis, fasciitis). The onset of symptoms is about 7-34 days of tretinoin therapy. The cause of the syndrome is unknown and symptoms generally resolve within 48 hours of corticosteroid therapy.

E - Dosing

Refer to protocol by which patient is being treated. Consolidation chemotherapy should be considered after complete response to tretinoin as well as during therapy depending on white cell count.

Adults:

Oral: 45 mg/m²/day (Round dose to the nearest 10 mg) in 2 divided doses.
Continue for 30 days to a maximum of 90 days until complete remission and then give consolidation chemotherapy (anthracycline + cytarabine).

Dosage with Toxicity:

Baseline WBC x 10⁹/L		During Treatment WBC x 10⁹/L	Action
> 5	AND	At any time	Add anthracycline-based chemotherapy.
< 5	AND	≥ 6, day 1 - day 6 OR ≥ 10, day 7 – day 10 OR ≥15, day 11 – day 28	Add full-dose anthracycline-based chemotherapy

Retinoic Acid Syndrome and Toxicity:

For patients with early signs of the syndrome any time during tretinoin therapy, start dexamethasone 10 mg IV every 12 hours for at least 3 days until symptom resolution.
Consider temporary interruption of tretinoin with moderate or severe retinoic acid syndrome
Reduce dose in the event of intractable headaches

Dosage with Hepatic Impairment:

Reduced dose of 25 mg/m²/day is recommended as a precautionary measure, as studies have not been done in patients with hepatic impairment. Consider withholding tretinoin in patients with serum transaminase concentrations greater than 5 x ULN. (AHFS 2013)

Dosage with Renal Impairment:

Reduced dose of 25 mg/m²/day is recommended as a precautionary measure, as studies have not been done in patients with renal impairment.

Dosage in the elderly:

No adjustment is required.

Children:

Few studies or data are available. Same dosage as for adults. There appears to be an increased risk of pseudotumour cerebri.

F - Administration Guidelines

Oral self-administration; drug available by outpatient prescription.
Should be administered with food.
Tretinoin capsules should not be opened.
Avoid grapefruit, starfruit, Seville oranges, their juices or products during treatment.
Store at room temperature (15-30°C); protect from heat and direct light.

G - Special Precautions

Contraindications:

patients with a history of hypersensitivity reaction to tretinoin or related compounds (e.g. acitretin, isotretinoin, vitamin A)
patients taking vitamin A

Other Warnings/Precautions:

Use with caution with antifibrinolytic agents (as fatal thrombosis may occur) and with tetracyclines
Overdose may result in symptoms of hypervitaminosis A; no specific antidote is available but patients should be closely monitored.
Patients who are drowsy or who have headaches may have reduced ability to operate heavy machinery or motor vehicles.

Other Drug Properties:

Carcinogenicity: Yes

Pregnancy and Lactation:

Embryotoxicity: Yes
Teratogenicity: Yes
Tretinoin is highly teratogenic with a high risk of severe malformations; therefore, it is contraindicated in pregnancy and in women who might become pregnant during or within one month of treatment cessation. All patients of childbearing potential should use effective contraception at least 4 weeks prior to treatment, during and for at least 1 month after treatment cessation. Therapy should not begin until the second or third day of the next normal menstrual period and a pregnancy test should be negative within 2 weeks before starting treatment (Refer to product monograph for full details). Low dose progesterone contraceptives should not be used.
Lactation: Contraindicated
Fertility effects: Yes

H - Interactions

AGENT	EFFECT	MECHANISM	MANAGEMENT
Drugs inducing P450 (rifampicin, glucocorticoids, Phenobarbital, etc)	↓ blood levels of tretinoin	Induces tretinoin metabolism	Avoid concurrent therapy or use with caution
Ketoconazole and drugs inhibiting p450 (cimetidine, erythromycin, cyclosporine, etc)	↑ tretinoin AUC	Inhibits tretinoin metabolism	Avoid concurrent therapy
Progesterone (low dose)	↓ contraceptive efficacy of progestogens	Unknown	Avoid concurrent therapy; use alternative methods for contraception
Tetracyclines	May ↑ intracranial blood pressure/ pseudotumour cerebri	Additive	Avoid concurrent therapy
Vitamin A	May ↑ Tretinoin toxicity	Additive	CONTRAINDICATED
Antifibrinolytic agents (e.g. tranexamic acid, aminocaproic acid, aprotinin)	↑ risk of thrombosis	Additive	Avoid concomitant use or use with caution
Hydroxyurea	Massive cell lysis and marrow necrosis	Synergistic (tretinoin induces cells to enter S phase; hydroxyurea cytotoxic to S phase cells)	Avoid concomitant use

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
Pregnancy test in patients of childbearing potential	Baseline (within 2 weeks before treatment starts) and at each month
Renal function tests	Baseline and regular
Liver function tests	Baseline and regular
CBC & coagulation	Baseline and frequent (weekly for the first month)
Clinical toxicity assessment (including skin, headache, bleeding, infection, Retinoic Acid Syndrome).

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
Cholesterol and triglycerides	Baseline and regular

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

tretinoin (ATRA)

K - References

Gillis JC, Goa KL. Tretinoin. A review of its pharmacodynamic and pharmacokinetic properties and use in the management of acute promyelocytic leukemia. Drugs 1995; 50(5):897-923.

Koike T, Tatewaki W, Aoki A, et al. Brief report: severe symptoms of hyperhistaminemia after the treatment of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 1992;327(6):385-7.

McEvoy GK, editor. AHFS Drug Information 2013. Bethesda: American Society of Health-System Pharmacists, p. 1226-30.

Shimamoto Y, Suga K, Yamaguchi M, et al. Prophylaxis of symptoms of hyperhistaminemia after the treatment of acute promyelocytic leukemia with all-trans retinoic acid. Acta Haematol 1994;92(2):109-12. Tretinoin drug monograph. BCCA Cancer Drug Manual, February 2014.

Product monograph: Vesanoid (tretinoin). Xediton Pharmaceuticals. October 3, 2013.

Tretinoin drug monograph. BCCA Cancer Drug Manual, February 2014.

Yeh YC, Tang HF, Fang IM. Pseudotumor cerebri caused by all-trans-retinoic acid treatment for acute promyelocytic leukemia. Jpn J Ophthalmol. 2006 May-Jun;50(3):295-6.

June 2019 Updated emetic risk category.

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

tretinoin (patient)

Info Sheet Introduction:

• For treating acute promyelocytic leukemia

Info Sheet Date: Vendredi, avril 29, 2016 Info Sheet body:

Medication Information Sheet

tretinoin (ATRA) (TRET-i-noyn)

This document provides general information about your medication. It does not replace the advice of your health care professional. Always discuss your therapy with your health care professional and refer to the package insert for more details.

Other Name: Vesanoid®, All-trans retinoin acid (ATRA)

Appearance:

capsule

What is this medication for?

For treating acute promyelocytic leukemia

What should I do before I have this medication?

Tell your doctor if you have/had significant medical condition(s), such as heart, liver or kidney problems, high cholesterol or fats in the blood, or if you have any allergies.
People who have cancer or leukemia are at a higher risk of developing other cancers/leukemias or blood clots. Also, some cancer medications, such as tretinoin, may increase these risks. You should discuss these with your doctor.

How will this medication affect sex, pregnancy and breastfeeding?

Tretinoin can harm the unborn baby and must never be used in pregnant women.
Do not use tretinoin if you are pregnant. If there is ANY chance that you or your partner may become pregnant, you and your partner together must: ►Use 2 effective forms of birth control at the same time at least 4 weeks before starting treatment and while taking this drug: Keep using birth control until at least 1 month after the last dose. You must follow birth control measures carefully as directed by your doctor. Discuss with your health care team.
Tell your doctor right away if you or your partner becomes pregnant.
Do not breastfeed while on tretinoin treatment.

Effects on Fertility: Yes

Effects on Fertility: Yes

How is this medication given?

Tretinoin is usually taken twice a day, for a specific timeframe as directed by your doctor. Make sure you understand the instructions.
Swallow whole with a glass of water, with food.
Take the dose at about the same times each day.
If you miss a dose, take it as soon as possible. If it is close to your next dose, do not double the dose. Discuss with your doctor or pharmacist.

What else do I need to know while on this medication?

This medication can interact with other medications and can result in the treatment not working as well or cause severe side effects.
Make sure your health care team knows about all your medications (prescription, over-the-counter, herbals and supplements). Check with your health care team before starting or stopping any of them.
For mild aches and pain:
- You may take acetaminophen (Tylenol®) tablets. Ask your health care team about the right dose for you.
- Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or aspirin (acetylsalicylic acid, ASA), including low dose aspirin for heart conditions, may increase your chance of bleeding.
- Talk to your health care team before you start or stop these medications.
- If you feel unwell, take your temperature before taking any of these medications. They may hide a fever.
- Talk to your health care team or go to the closest emergency room right away if you have a fever. See the Fever pamphlet for more information.

Do not take any vitamins and supplements containing vitamin A as this can increase the chance of getting severe side effects. Check with your doctor or pharmacist before starting any supplements.

How should I safely store this medication?

Keep this medication in the original packaging at room temperature in a dry place, away from heat and light. Keep out of sight and reach of children and pets.
Do not throw out any unused medications at home. Bring them to your pharmacy to be thrown away safely.

What are the side effects of this medication?

The following side effects are common or severe. You may not have all of the side effects. Other side effects may occur. If you have any unusual or bothersome symptoms, discuss with your doctor.

Side effects and what to do	When to contact doctor?
More Common Side Effects

Dry lips, mouth or skin

Sip water regularly. Use lip balm and skin moisturizer several times a day.
For dry mouth, try artificial saliva or suck on hard candy/ice chips.

Contact your health care team if no improvement or if severe

Rash; sensitivity to sunlight

Stay out of the sun; wear sunblock, a hat and cover exposed skin.
Use daily moisturizer.

Contact your health care team if no improvement or if severe

Headache; mild joint, muscle pain or cramps

Headache and muscle/bone pain may slowly go away as your body gets used to the drug.
Contact your doctor immediately if headache is severe (not controlled with acetaminophen (Tylenol®)), or happens with nausea/vomiting or changes in your eye sight.

Contact your health care team if no improvement or if severe

Rapid increase of white blood cells

Your doctor may monitor your blood counts regularly.

Get emergency medical help right away

Tiredness

Rest often; take naps if needed. Move slowly when getting up.
Eat well-balanced meals and drink plenty of fluids. Light exercise may help.
If you are feeling tired, avoid driving or operating machinery

Contact your health care team if no improvement or if severe

Abnormal liver lab tests

Your doctor will monitor these regularly. Call your doctor if you have yellowish skin or eyes, or unusual dark urine.

Contact your health care team if no improvement or if severe

Unusual bleeding or bruising
(black stools, coughing up blood, purple or red dots on skin, bleeding that will not stop)

May occur in days to weeks after treatment starts.
Use a soft toothbrush. Be careful not to cut or bruise yourself.
Check with your doctor before any surgery or dental work.
Also see Low Platelets pamphlet.*

Get emergency medical help right away

Increased cholesterol or fat levels in the blood

Your doctor may monitor these regularly.

Contact your health care team if no improvement or if severe

Fever, chills, infection

You have a fever if your temperature taken in your mouth (oral temperature) is:

38.3°C (100.9°F) or higher at any time OR
38.0°C (100.4°F) or higher for at least one hour.

While you are getting chemotherapy treatments:

Keep a digital thermometer at home and take your temperature if you feel hot or unwell (for example, chills).
Avoid taking medications that treat a fever before you take your temperature (for example, Tylenol®, acetaminophen, Advil® or ibuprofen) as they may hide a fever.
Do not eat or drink anything hot or cold right before taking your temperature.
Wash your hands often.
Check with your doctor before getting any vaccines, surgeries or visiting your dentist.

If you have a fever, talk to your health care team or go to the closest emergency room.
See our Neutropenia (Low white blood cell count) pamphlet for more information.

Get emergency medical help right away

Nausea and vomiting

May occur in hours to days after treatment starts.
Drink clear fluids and avoid large meals. Get fresh air and rest.
Limit spicy, fried foods or foods with a strong smell.
Take anti-nausea drug(s) exactly as directed by your doctor. It is easier to prevent nausea than to treat it.
Contact your doctor if nausea lasts more than 48 hours or vomiting for more than 24 hours.
Also see Nausea & Vomiting pamphlet.*

Contact your health care team if no improvement or if severe

Bleeding/clotting disorder (may include bleeding from more than 1 site, bruising, signs of blood clots, kidney/liver/lung problems, fever, confusion)

Get emergency medical help right away

Mild swelling in arms and legs; puffiness

Keep your feet up when sitting. Eat a low-salt diet.
Avoid tight fitting clothing.

Contact your health care team if no improvement or if severe

Retinoic acid syndrome (group of signs and symptoms that may include fever, fluid buildup around the heart and lungs, lower ability of the lung in absorbing oxygen)

If you have any of these symptoms, contact your doctor right away.
- fever
- shortness of breath, difficulty breathing, wheezing
- unusual weight gain
- unusual or severe swelling of arms, hands, legs, ankles, feet
- pain or tightness in chest
- bone pain
- yellowing of the skin or eyes
- trouble with passing urine

Get emergency medical help right away

Side effects and what to do	When to contact doctor?
Less Common Side Effects, but may be Severe

Kidney problems
(lower back pain, body swelling, passing little or no urine, or recent unusual weight gain)

Get emergency medical help right away

Increased pressure in the brain (may include headaches with pain behind the eye/with eye movement, changes or loss in eye sight)

Get emergency medical help right away

Heart problems
(irregular heartbeat, chest pain, fainting, swelling in legs/ankles/belly, shortness of breath)

Get emergency medical help right away

Fullness/pain in the ear; hearing loss

Contact your health care team as soon as possible (office hours)

Lung problems
(increased cough, breathing problems, chest pain, coughing blood)

Get emergency medical help right away

Blockage of an artery (blood vessel) in your heart, brain, chest, belly, or limbs; this may result in stroke (sudden loss of vision, speech, or the use of your limb(s)) or heart attack (chest pain, shortness of breath), or pain in chest, belly or limb

Get emergency medical help right away

Increased calcium levels in the blood
(confusion, severe muscle weakness, seizures, irregular heartbeat)

Get emergency medical help right away

Rapid killing of cancer cells when you start treatment may lead to build up of cell waste products

If mild, this may cause gout, with joint pains, but if severe, may cause fevers, kidney failure, confusion and be life-threatening.
You MUST take the preventive medicines given by your doctor AND
Drink plenty of fluids (6-8 glasses per day) and void (urinate) frequently.

Get emergency medical help right away

Sweets syndrome

Severe rash with other symptoms, such as fever.
May include effects on other organs.

Get emergency medical help right away

Pancreas problems
(increased pain in centre of belly and may extend to the back, appetite or weight loss)

Get emergency medical help right away

Blood clot (limb pain or swelling, hardened vein in limb), may occur in lungs (sudden start of coughing, breathing problems, chest pain, coughing blood)

Get emergency medical help right away

For more links on how to manage your symptoms go to https://www.cancercareontario.ca/en/symptom-management.

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

tretinoin patient.pdf Info Sheet (French):

tretinoin pour le patient.pdf Monograph:

tretinoin ATRA.pdf Funding Program: Exceptional Access Program Funding Instance:

tretinoin (ATRA)

Phonetic Spelling:

TRET-i-noyn

Cancer Type: Hematologic Leukemia - Acute Promyelocytic (APL) Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Mardi, juin 4, 2019 Universal Date: 2019-06-04 00:00:00 AddThis: Title URL: tretinoinATRA Drug Display Status: Active Revision Summary:

Updated emetic risk category.