romidepsin

Trade Name:

Istodax®

Appearance:

clear, colourless liquid

Monograph Name:

romidepsin

Monograph Body:

Drug Monograph

A - Drug Name

romidepsin

COMMON TRADE NAME(S): Istodax®

DO NOT initiate romidepsin treatment in new patients. It is only available through the Restricted Access Program to registered patients currently receiving treatment with this drug.

Refer to Health Canada’s health professional risk communication.

Contact Bristol-Myers Squibb’s medical information at 1-866-463-6267 or medical.canada@bms.com for more information on the Restricted Access Program.

B - Mechanism of Action and Pharmacokinetics

Romidepsin, initially isolated from Chromobacterium violaceum, is a bicyclic peptide inhibitor of Class I histone deacetylases. Accumulation of acetylated histones induces cell cycle arrest and apoptosis in some cancer cell lines, although the exact mechanism of its anticancer effect is not clear. Romidepsin is a prodrug and requires reduction of disulfide bonds for activation.

Distribution

Rapid distribution into many tissue and organ systems. Accumulates into human hepatocytes via an unknown uptake mechanism.

PPB

92-94%, mainly to alpha-1 acid glycoprotein

Cross blood brain barrier?

Very low

Metabolism

Active metabolites

Yes

Elimination

Multiphasic elimination; mainly eliminated through bile with excretion into feces. No accumulation was observed after repeat dosing.

Half-life

3.7 hours

Feces

96% (animal studies)

Urine

< 20%, with < 5% parent drug (animal studies)

C - Indications and Status

DO NOT initiate romidepsin treatment in new patients. It is only available through the Restricted Access Program to registered patients currently receiving treatment with this drug. Romidepsin will be withdrawn from the Canadian market once the last patient completes treatment.

The Phase 3 confirmatory study failed to demonstrate romidepsin, in combination with chemotherapy, was more effective than chemotherapy alone at delaying the progression of peripheral T-cell lymphoma (PTCL). However, there is no evidence of new safety issues with romidepsin monotherapy.

Refer to Health Canada’s health professional risk communication.

Contact Bristol-Myers Squibb’s medical information at 1-866-463-6267 or medical.canada@bms.com for more information on the Restricted Access Program.

Health Canada Conditional Approvals
(pending the result of studies to verify the drug’s clinical benefit. Patients should be advised of the nature of the marketing authorization granted.)

peripheral T-cell lymphoma (PTCL)

Refer to the product monograph for a full list of approved indications.

D - Adverse Effects

Emetogenic Potential:

Low

Extravasation Potential: Minimal

The following adverse effects were reported in ≥ 5% of patients with PTCL treated with romidepsin in the pivotal single-arm clinical trial. Severe, life-threatening and post-marketing adverse effects are also included.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arterial/venous thromboembolism (4%)	E
	Hypotension (8%)	I E
	QT interval prolonged (rare)	E
	Tachycardia (10%)	E
Dermatological	Rash (9%)	E
Gastrointestinal	Abdominal pain (14%)	E
	Anorexia, weight loss (28%)	E
	Constipation (30%)	E
	Diarrhea (36%)	E
	Dyspepsia (8%)	E
	Mucositis (11%)	E
	Nausea, vomiting (59%)	I
General	Edema (10%)	E
	Fatigue (55%) (8% severe)	E
Hematological	Myelosuppression ± infection, bleeding (41%) (including opportunistic infections/viral reactivation; 24% severe)	E
Hepatobiliary	↑ LFTs (29%) (2% severe)	E
Hypersensitivity	Hypersensitivity (rare)	I
Metabolic / Endocrine	Abnormal electrolyte(s) (11%) (↓ K, ↓ Mg)	E
	Tumor lysis syndrome (2%)	I
Musculoskeletal	Musculoskeletal pain (9%)	E
Nervous System	Anxiety (7%)	E
	Depression (5%)	D
	Dizziness (8%)	E
	Dysgeusia (21%)	E
	Headache (15%)	E
	Insomnia (7%)	E
Respiratory	Cough, dyspnea (18%)	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)

The most common side effects for romidepsin include nausea/vomiting , fatigue, myelosuppression ± infection/bleeding, diarrhea, constipation, ↑ LFTs, anorexia/weight loss, dysgeusia, cough/dyspnea and headache.

Gastrointestinal adverse effects such as nausea, vomiting, constipation and diarrhea were generally mild to moderate.

Serious or fatal infections (including opportunistic infections) have been observed during treatment and within 30 days after treatment. Patients with a history of bone marrow involvement or prior treatment with monoclonal antibodies directed against lymphocyte antigens may have high risk of infections. Viral reactivation (hepatitis B, CMV, EBV) has been described.

E - Dosing

Refer to protocol by which patient is being treated.

Plasma potassium and magnesium levels should be within normal range before each romidepsin administration.

Do not treat if QTc > 480 ms.

Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.

Consider prophylaxis in patients at increased risk for opportunistic infections or reactivation of hepatitis B, cytomegalovirus and Epstein-Barr virus infections.

Adults:

Q 28 day cycle:

Intravenous: 14 mg/m² Days 1, 8, 15

Dosage with Toxicity:

Dose Level	*Romidepsin Dose (mg/m²)**
0	14
-1	10
-2	Discontinue

*Do not re-escalate reduced doses.

Toxicity	Action
Grade 2 or 3 non-hematological/organ	Hold; Restart at same dose level. If grade 3 toxicity recurs, hold then ↓ 1 dose level. If grade 3 toxicity recurs after dose reduction, discontinue.
Grade 4 non-hematological/organ	Hold*; Restart by ↓ 1 dose level. If grade 4 toxicity recurs after dose reduction, discontinue.
Grade 3 or 4 ANC or platelets	Hold*; Restart at same dose level.
Grade 4 febrile neutropenia or thrombocytopenia requiring platelet transfusion	Hold*; Restart by ↓ 1 dose level.

*Do not retreat until platelets ≥ 75 x 10⁹/L, ANC ≥ 1.5 x 10⁹/L, non-hematological/organ toxicities recover to ≤ grade 1 or baseline.

Dosage with Hepatic Impairment:

Patients with hepatic impairment have a higher risk of adverse effects. Romidepsin clearance decreases with severity of hepatic impairment.

Bilirubin		AST	Romidepsin Starting Dose
≤ ULN	and	> ULN	No dose adjustment required
1 to 1.5 x ULN	and	any	No dose adjustment required
> 1.5 to 3 x ULN	and	any	↓ by 50%
> 3 x ULN	and	any	Not recommended for use

Dosage with Renal Impairment:

Not formally studied. Population pharmacokinetic analysis suggested that renal impairment was not expected to affect drug exposure significantly.

Creatinine Clearance (mL/min)	Romidepsin Dose
> 50-80	No change
30-50	No change
< 30	No change
ESRD	Caution (no data)

Dosage in the elderly:

No overall differences in safety or efficacy were observed between elderly and younger patients; however, elderly patients are at higher risk of toxicity and may require dose modifications.

Dosage based on ethnicity:

Race did not appear to affect romidepsin pharmacokinetics.

Children:

Safety and efficacy have not been established in patients < 18 years of age.

F - Administration Guidelines

Reconstitute romidepsin using the supplied diluent. Refer to the product monograph for instructions.
Add the required dose into 500 mL 0.9% Sodium Chloride (NS).
Infuse IV over 4 hours.
Missed doses should be administered as soon as possible, unless it is within 5 days of the next scheduled dose.
Diluted solution is compatible with PVC, ethylene vinyl acetate (EVA), polyethylene (PE) infusion bags as well as glass bottles.
Store unopened vial and diluent together at room temperature (15 to 30^oC).

G - Special Precautions

Contraindications:

Patients who have hypersensitivity to this drug or any of its components

Other Warnings/Precautions:

Patients with a significant cardiac history were excluded from clinical trials; exercise extreme caution in these patients
Use with caution in patients who are at risk of experiencing torsade de points or QT prolongation, including female patients, age ≥ 65 years, congenital long QT syndrome, cardiac disease, history of arrhythmias, electrolyte disturbances, bradycardia, acute neurological events, diabetes, on concomitant antiarrhythmics or drugs that prolong QT, or autonomic neuropathy.
Use with caution in patients with advanced stage disease and/or high tumour burden due to the risk of tumour lysis syndrome.
Use with caution in patients with compromised bone marrow (disease, or heavily pretreated) due to the risk of infection.
Patients should avoid driving, operating dangerous machinery or performing tasks that require alertness if experiencing fatigue and dizziness.

Other Drug Properties:

Carcinogenicity: Unknown

Pregnancy and Lactation:

Fetotoxicity: Yes

Romidepsin is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 8 weeks after the last dose (in females) and for at least 1 month after the last dose (in males). Estrogen-containing contraceptives should not be used (refer to interactions).
Embryotoxicity: Yes
Teratogenicity: Yes
Mutagenicity: No
Clastogenicity: No
Excretion into breast milk: Unknown

Breastfeeding is not recommended during treatment.
Fertility effects: Yes
These effects may be irreversible.

H - Interactions

Romidepsin is metabolized by CYP3A4; it does not significantly inhibit or induce CYP450 substrates, but is susceptible to drug interactions from CYP3A4 inhibitors/inducers. Minor metabolism occurs via CYP3A5, 1A1, 2B6, and 2C19, but substrates of these enzymes are unlikely to affect romidepsin.

Romidepsin is a substrate of Pgp and MRP1.

AGENT	EFFECT	MECHANISM	MANAGEMENT
CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit)	↑ romidepsin concentration and/or toxicity	↓ metabolism of romidepsin	Avoid use with strong inhibitors. Caution with moderate inhibitors; monitor for toxicity.
CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc)	↓ romidepsin concentration/efficacy (theoretical), ↑ romidepsin exposure observed with rifampin	↑ metabolism of romidepsin; rifampin may inhibit hepatic uptake that limits romidepsin access to induced CYP3A4	Avoid strong CYP3A4 inducers.
Coumarin derivatives	↑ PT and INR observed	Unknown	Caution; monitor PT and INR closely.
Estrogen containing contraceptives	↓ effectiveness of estrogen-containing contraceptives	Competition with binding to the estrogen receptors	Caution; use alternate non-estrogen contraception (e.g. condoms, IUD); monitor for estrogen deficiency in patients on hormone replacement therapy.
P-glycoprotein inhibitors (i.e. quinidine, verapamil, cyclosporine)	↑ Romidepsin concentration and/or toxicity	↓ Romidepsin elimination	Caution.
Drugs that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc)	↑ QT prolongation effect	Additive	Caution; monitor patient closely.
Drugs that disrupt electrolyte levels (i.e. loop/thiazide diuretics, laxatives, amphotericin B, high dose corticosteroids)	↑ risk of QT prolongation	Electrolyte disturbance	Avoid if possible.

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline and before each treatment
Electrolytes, including potassium and magnesium	Baseline, before each treatment and as clinically indicated
ECG	Baseline and as clinically indicated (for all patients); baseline and periodic (for patients at risk of QT prolongation)
Liver function tests	Baseline and as clinically indicated
INR and PT (for patients taking warfarin or its derivatives)	Baseline and as clinically indicated
Clinical toxicity assessment for infection (including opportunistic infections/viral reactivation), bleeding, thromboembolism, fatigue, GI effects, hypersensitivity, tumour lysis syndrome	At each visit

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

J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

Romidepsin - Relapsed or Refractory Peripheral T-Cell Lymphoma

K - References

Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 2012 Feb 20;30(6):631-6.

Health Canada’s health professional risk communication (Istodax: Restricted access program). March 20, 2023.

Product Monograph: Istodax® (romidepsin). Celgene Inc. July 25, 2019 and March 8, 2023.

Yang LPH. Romidepsin: in the treatment of T-cell lymphoma. Drugs 2011;71(11):1469-80.

March 2023 Updated Drug name and Indications sections with info on the Restricted Access Program

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.

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Info Sheet Name:

romidepsin (patient)

Info Sheet Introduction:

For treating a certain type of blood cancer called Peripheral T-cell Lymphoma (PTCL)

Info Sheet Date: Mardi, mai 25, 2021 Info Sheet body:

Medication Information Sheet

romidepsin (ROE-mi-DEP sin)

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: Istodax®

Appearance:

clear, colourless liquid

What is this medication for?

For treating a certain type of blood cancer called Peripheral T-cell Lymphoma (PTCL)

What should I do before I have this medication?

Tell your health care team if you have or had significant medical condition(s), especially if you have / had:

heart problems (including irregular or fast heartbeat),
kidney or liver problems,
electrolyte imbalances,
serious infections (such as hepatitis B, cytomegalovirus (CMV) or Epstein-Barr virus), or
any allergies.

Remember to:

Tell your health care team about all of the other medications you are taking.
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.

How will this medication affect sex, pregnancy and breastfeeding?

Talk to your health care team about:

How this medication may affect your sexual health.
How this medication may affect your ability to have a baby, if this applies to you.

This medication may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.

If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time until 8 weeks after your last treatment dose (if you are female) and 1 month after your last treatment dose (if you are male).
This medication may make hormonal birth control (such as birth control pills) that contains estrogen not work as well. Talk to your health care team about which birth control options are best for you.
Do not breastfeed while on this medication.

How is this medication given?

This drug is given through an IV (injection into a vein). Talk to your health care team about your treatment schedule.
Treatment is usually divided into cycles that are 4 weeks long. Usually you are given romidepsin on days 1, 8 and 15, followed by 13 days of rest (no treatment).
If you missed your treatment appointment, talk to your health care team to find out what to do.

To Prevent or Treat Nausea and Vomiting

You may be given medications to help prevent nausea (feeling like throwing up) and vomiting (throwing up) before they start.

These are called anti-nausea medications and include medications such asondansetron (Zofran®), granisetron (Kytril®), prochlorperazine (Stemetil®) or others.

To Prevent Tumor Lysis Syndrome (TLS)

TLS can happen when a large number of cancer cells die quickly and your body cannot get rid of them fast enough. TLS can make you very sick. Ask your health care team if you are at risk for TLS.

If you are at risk for TLS, you may be given medications before your romidepsin treatment to help prevent it.

These are called anti-uricemics (such as allopurinol), or others.

To Prevent Hepatitis B Flare Ups

If you have ever been infected with hepatitis B, there is a risk that this treatment can cause it to flare up (come back). Tell your health care team if you have had hepatitis B. You may need to take medication to prevent a hepatitis B flare-up.

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

Will this medication interact with other medications or natural health products?

This medication can interact with other medications, vitamins, foods and natural health products. Interactions can make the treatment not work as well or cause severe side effects.
Tell your health care team about all of your:
- prescription and over-the-counter (non-prescription) medications and all other drugs, such as marijuana (medical or recreational)
- natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements
Check with your health care team before starting or stopping any of them.
If you are taking a blood thinner (such as warfarin), your health care team may need extra blood tests and may change your dose.

What should I do if I feel unwell, have pain, a headache or a fever?

Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol) or ibuprofen (Advil)).
- Fever can be a sign of infection that may need treatment right away.
- If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.

How to check for fever:

Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).

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.

If you do have a fever:

Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
Ask your health care team for the Fever pamphlet for more information.

If you do not have a fever but have mild symptoms such as headache or mild pain:

Ask your health care team about the right medication for you. Acetaminophen (Tylenol®) is a safe choice for most people.
Talk to your health care team before you start taking Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or ASA (Aspirin®), as they may increase your chance of bleeding or interact with your cancer treatment.
Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.

What to DO while on this medication:

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.
DO tell your health care team about any serious infections that you have now or have had in the past.
DO consider asking someone to drive you to and from the hospital on your treatment days. You may feel drowsy or dizzy after your treatment.

What NOT to DO while on this medication:

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

What are the side effects of this medication?

The following table lists side effects that you may have when getting romidepsin. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.

Read over the side effect table so that you know what to look for and when to get help. Refer to this table if you experience any side effects while on romidepsin.

Very Common Side Effects (50 or more out of 100 people)
Side effects and what to do	When to contact health care team
Nausea and vomiting (Generally mild) What to look for? Nausea is feeling like you need to throw up. You may also feel light-headed. You may feel nausea within hours to days after your treatment. What to do? To help prevent nausea: It is easier to prevent nausea than to treat it once it happens. If you were given anti-nausea medication(s), take them as prescribed, even if you do not feel like throwing up. Drink clear liquids and have small meals. Get fresh air and rest. Do not eat spicy, fried foods or foods with a strong smell. Limit caffeine (like coffee, tea) and avoid alcohol. If you have nausea or vomiting: Take your rescue (as needed) anti-nausea medication(s) as prescribed. Ask your health care team for the Nausea & Vomiting pamphlet for more information. Talk to your health care team if: nausea lasts more than 48 hours vomiting lasts more than 24 hours or if it is severe	Talk to your healthcare team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if it is severe
Fatigue (May be severe) What to look for? Feeling of tiredness or low energy that lasts a long time and does not go away with rest or sleep. What to do? Be active. Aim to get 30 minutes of moderate exercise (you are able to talk comfortably while exercising) on most days. Check with your health care team before starting any new exercise. Pace yourself, do not rush. Put off less important activities. Rest when you need to. Ask family or friends to help you with things like housework, shopping, and child or pet care. Eat well and drink at least 6 to 8 glasses of water or other liquids every day (unless your health care team has told you to drink more or less). Avoid driving or using machinery if you are feeling tired. Ask your health care team for the Fatigue pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe

Common Side Effects (25 to 49 out of 100 people)
Side effects and what to do	When to contact health care team
Infection (May be severe) When neutrophils are low, you are at risk of getting an infection more easily. Ask your health care team for the Neutropenia (Low white blood cell count) pamphlet for more information. When your immune system is weakened, bacteria, viruses, or fungi that would not normally be harmful may cause an infection. If you have had hepatitis, you may get this infection again when the immune system is weakened. This happens rarely. What to look for? If you feel hot or unwell (for example if you have chills or a new cough), you must check your temperature to see if you have a fever. Do not take medications that treat a fever before you take your temperature (for example, Tylenol®, acetaminophen, Advil® or ibuprofen). Do not eat or drink anything hot or cold right before taking your temperature. Yellowish skin or eyes, unusually dark pee or pain on the right side of your belly (hepatitis) 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. What to do? Let your health care team know if you have had hepatitis If your health care team has told you that you have low neutrophils: Wash your hands often to prevent infection. Check with your health care team before getting any vaccines, surgeries, medical procedures or visiting your dentist. Keep a digital thermometer at home so you can easily check for a fever. If you have a fever: If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you must get emergency medical help right away.	If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you MUST get emergency medical help right away.
Low platelets in the blood (May be severe) When your platelets are low, you are at risk for bleeding and bruising. Ask your health care team for the Low Platelet Count pamphlet for more information. What to look for? Watch for signs of bleeding: bleeding from your gums unusual or heavy nosebleeds bruising easily or more than normal black coloured stools (poo) or blood in your stools (poo) coughing up red or brown coloured mucus dizziness, constant headache or changes in your vision heavy vaginal bleeding red or pink coloured urine (pee) What to do? If your health care team has told you that you have low platelets: Tell your pharmacist that your platelet count may be low before taking any prescriptions or over-the-counter medication. Check with your healthcare team before you go to the dentist. Take care of your mouth and use a soft toothbrush. Try to prevent cuts and bruises. Ask your health care team what activities are safe for you. Your treatment may have to be delayed if you have low platelets. Your health care team may recommend a blood transfusion. If you have signs of bleeding: If you have a small bleed, clean the area with soap and water or a saline (saltwater) rinse. Apply pressure for at least 10 minutes. If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away.	Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe (very heavy), you MUST get emergency help right away.
Diarrhea What to look for? Loose, watery, unformed stool (poo) that may happen days to weeks after you get your treatment. What to do? If you have diarrhea: Take anti-diarrhea medication if your health care team prescribed it or told you to take it. Do not eat foods or drinks with artificial sweetener (like chewing gum or ‘diet’ drinks), coffee and alcohol. Eat many small meals and snacks instead of 2 or 3 large meals. Drink at least 6 to 8 cups of liquids each day, unless your health care team has told you to drink more or less. Talk to your health care team if you can’t drink 6 to 8 cups of liquids each day when you have diarrhea. You may need to drink special liquids with salt and sugar, called Oral Rehydration Therapy. Talk to your health care team if your diarrhea does not improve after 24 hours of taking diarrhea medication or if you have diarrhea more than 7 times in one day. Ask your health care team for the Diarrhea pamphlet for more information.	Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day)
Constipation What to look for? Having bowel movements (going poo) less often than normal. Small hard stools (poo) that look like pellets. The need to push hard and strain to have any stool (poo) come out. Stomach ache or cramps. A bloated belly, feeling of fullness, or discomfort. Leaking of watery stools (poo). Lots of gas or burping. Nausea or vomiting. What to do? To help prevent constipation: Try to eat more fiber rich foods like fruits with skin, leafy greens and whole grains. Drink at least 6 to 8 cups of liquids each day unless your health care team has told you to drink more or less. Be Active. Exercise can help to keep you regular. If you take opioid pain medication, ask your health care team if eating more fibre is right for you. To help treat constipation: If you have not had a bowel movement in 2 to 3 days you may need to take a laxative (medication to help you poo) to help you have regular bowel movements. Ask your health care team what to do. Ask your health care team for the Constipation Pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe
Liver problems (May be severe) Your health care team may check your liver function with a blood test. The liver changes do not usually cause any symptoms. What to look for? Rarely, you may develop yellowish skin or eyes, unusually dark pee or pain on the right side of your belly. This may be severe. What to do? If you have any symptoms of liver problems, get emergency medical help right away.	Get emergency medical help right away
Low appetite What to look for? Loss of interest in food or not feeling hungry. Weight loss. What to do? Try to eat your favourite foods. Eat small meals throughout the day. You may need to take meal supplements to help keep your weight up. Talk to your health care team if you have no appetite. Ask your health care team for the Loss of Appetite pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe

Less Common Side Effects (10 to 24 out of 100 people)
Side effects and what to do	When to contact health care team
Taste changes What to look for? Food and drinks may taste different than usual. What to do? Eat foods that are easy to chew, such as scrambled eggs, pasta, soups, cooked vegetables. Taste foods at different temperatures, since the flavour may change. Try different forms of foods, like fresh, frozen or canned. Experiment with non-spicy foods, spices and seasonings.	Talk to your health care team if it does not improve or if it is severe
Cough and feeling short of breath What to look for? You may have a cough and feel short of breath. Symptoms that commonly occur with a cough are: Wheezing or a whistling breathing Runny nose Sore throat Heartburn Weight loss Fever and chills Rarely this may be severe with chest pain, trouble breathing or coughing up blood. What to do? Check your temperature to see if you have a fever. Read the above section "What should I do if I feel unwell, have pain, a headache or a fever?". If you have a fever, try to talk to your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away. If you have a severe cough with chest pain, trouble breathing or you are coughing up blood, get medical help right away.	Talk to your health care team. If you are not able to talk to your health care team for advice, and you have a fever or severe symptoms, you MUST get emergency medical help right away
Headache, mild joint, muscle pain or cramps What to look for? Mild headache New pain in your muscles or joints, muscle cramps, or feeling achy. What to do? Take pain medication (acetaminophen or opioids such as codeine, morphine, hydromorphone, oxycodone) as prescribed. Read the above section: "What should I do if I feel unwell, have pain, a headache or a fever?" before taking acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or Aspirin. These medications may hide an infection that needs treatment or they may increase your risk of bleeding. Rest often and try light exercise (such as walking) as it may help. Ask your health care team for the Pain pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe
Pains or cramps in the belly What to look for? Pain or cramps in your belly. Constipation and diarrhea can cause pain in your belly. What to do? If the pain is severe, gets worse or doesn’t go away, talk to your health care team about other possible causes.	Talk to your health care team if it does not improve or if it is severe
Mouth sores What to look for? Round, painful, white or gray sores inside your mouth that can occur on the tongue, lips, gums, or inside your cheeks. In more severe cases they may make it hard to swallow, eat or brush your teeth. They may last for 3 days or longer. What to do? To help prevent mouth sores: Take care of your mouth by gently brushing and flossing regularly. Rinse your mouth often with a homemade mouthwash. To make a homemade mouthwash, mix 1 teaspoonful of baking soda and 1 teaspoonful of salt in 4 cups (1L) of water. Do not use store-bought mouthwashes, especially those with alcohol, because they may irritate your mouth. If you have mouth sores: Avoid hot, spicy, acidic, hard or crunchy foods. Your doctor may prescribe a special mouthwash to relieve mouth sores and prevent infection. Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow. Ask your health care team for the Oral Care (Mouth Care) pamphlet for more information.	Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow
Too much or too little salt in your body What to look for? Muscle spasms, cramping, weakness, twitching, or convulsions. Irregular heartbeat, confusion or blood pressure changes. What to do? Get emergency medical help right away for severe symptoms.	Get emergency medical help right away for severe symptoms
Heart problems What to look for? You may have an irregular heartbeat, shortness of breath, chest pain or fainting spells. Swelling in your legs, ankles and belly. Sharp pain in the centre or left side of the chest (often worsens when taking a deep breath). Extreme tiredness that prevents you from exercising or doing normal activities. What to do? Get emergency medical help right away.	Get emergency medical help right away
Mild swelling What to look for? You may have mild swelling or puffiness in your arms and/or legs. Rarely, this may be severe. What to do? To help prevent swelling: Eat a low-salt diet. If you have swelling: Wear loose-fitting clothing. For swollen legs or feet, keep your feet up when sitting.	Talk to your health care team if it does not improve or if it is severe

Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:

Pain or hardening of a vein in your arm or leg,
Confusion,
Weight gain that is not normal for you,
Pain in your lower back,
Changes in urination (peeing) such as less urine that usual,
Signs of an allergy such as rash, itchiness, swollen face, lip or tongue, chest or throat tightness

Who do I contact if I have questions or need help?

My cancer health care provider is: ______________________________________________

During the day I should contact:________________________________________________

Evenings, weekends and holidays:______________________________________________

Other Notes:

____________________________________________________________________________

May 2021 Updated other name

For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.

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):

romidepsin patient.pdf Info Sheet (French):

romidepsin pour le patient.pdf Monograph:

romidepsin.pdf Funding Program: New Drug Funding Program Funding Instance:

Romidepsin - Relapsed or Refractory Peripheral T-Cell Lymphoma

Phonetic Spelling:

ROE-mi-DEP sin

Eligibility Form:

Romidepsin - Relapsed or Refractory Peripheral T-Cell Lymphoma Cancer Type: Hematologic Lymphoma - T-cell Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Mardi, mars 21, 2023 Universal Date: 2023-03-21 00:00:00 AddThis: Title URL: romidepsin Drug Display Status: Active Revision Summary:
Drug Monograph: Updated Drug name and Indications sections with info on the Restricted Access Program