encorafenib

Trade Name:

Braftovi®

Appearance:

beige and white capsule

Monograph Name:

encorafenib

Monograph Body:

Drug Monograph

A - Drug Name

encorafenib

COMMON TRADE NAME(S): Braftovi®

B - Mechanism of Action and Pharmacokinetics

Encorafenib is an oral, small molecule kinase inhibitor that specifically targets BRAF V600E. BRAF mutations can result in constitutively activated BRAF kinases that may stimulate tumour cell growth. By inhibiting BRAF, encorafenib interferes with the MAPK signalling pathway that regulates the proliferation and survival of cancer cells. In vitro, encorafenib exhibits activity against BRAF V600 E, D, and K mutations, and targets wild-type BRAF and CRAF.

Absorption

Bioavailability

At least 86%

Effects with food

Administration with a high-fat, high-calorie meal ↓ Cmax by 36% but no effect on AUC.
Food does not appear to have clinically meaningful effects.

T max

2 hours

Time to reach steady state

15 days

Distribution

PPB

86%

Metabolism

Encorafenib is metabolized primarily through CYP3A4 N-dealkylation.

Elimination

Half-life

3.5 hours

Feces

47% (5% unchanged)

Urine

47% (2% unchanged)

C - Indications and Status

Health Canada Approvals:

Melanoma
Colorectal cancer (CRC)

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

D - Adverse Effects

Emetogenic Potential:

Low – No routine prophylaxis; PRN recommended

The following adverse events were reported in > 10% of patients with metastatic CRC treated with encorafenib in combination with cetuximab versus either irinotecan and cetuximab or FOLFIRI and cetuximab in a randomized Phase 3 study. It also includes severe or life-threatening adverse effects from other sources. Adverse effects reported with encorafenib in combination with binimetinib for melanoma are denoted with "^".

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	QT interval prolonged (3%)	E
	Tachycardia (6%)	E
	Venous thromboembolism (6%)	E
Dermatological	Hand-foot syndrome (4%)	E
	Other (14%) (melanocytic nevus)	E
	Photosensitivity (4%) ^	E
	Rash, pruritus (29%)	E
Gastrointestinal	Abdominal pain (30%) (4% severe)	E
	Anorexia (27%)	E
	Constipation (15%)	E
	Diarrhea (33%)	E
	Nausea, vomiting (34%)	I E
General	Fatigue (51%) (7% severe)	E
	Fever (18%) (4% severe) ^
Hematological	Hemorrhage (19%) (2% severe)	E
Hepatobiliary	↑ LFTs (<5%) (severe)	E
	Pancreatitis (1%)	E
Hypersensitivity	Hypersensitivity (1%)	I E
Metabolic / Endocrine	Abnormal electrolyte(s) (19%) (↓ Mg, K, Na)	E
	Hyperglycemia (13%) (5% severe) ^	E
Musculoskeletal	Musculoskeletal pain (27%)	E
Neoplastic	Secondary malignancy (1%) (cutaneous or non-cutaneous)	D L
Nervous System	Headache (20%)	E
	Insomnia (13%)	E
	Other (1%) (facial paresis) ^	E
	Peripheral neuropathy (12%)	E
Ophthalmic	Retinal detachment (20%) ^	E
	Uveitis (4%) ^	E
	Visual disorders (6%)	E
Renal	Nephrotoxicity (2%)	E
Respiratory	Dyspnea (11%)	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 encorafenib include fatigue, nausea, vomiting, abdominal pain, rash acneiform, anorexia, rash, pruritus, headache, constipation, musculoskeletal pain and skin hyperpigmentation.

When used as a single agent, encorafenib is associated with an increased risk of certain adverse reactions including: hand-foot syndrome, hyperkeratosis, dry skin, erythema, rash, alopecia, pruritus, arthralgia, myopathy, back pain, dysgeusia, and acneiform dermatitis. Grade 3 or 4 dermatologic adverse reactions occurred in 21% of patients receiving single agent encorafenib compared to 2% of patients receiving the combination of encorafenib and binimetinib.

Based on its mechanism of action, encorafenib may promote malignancies associated with RAS activation through mutation or other pathways. New primary malignancies, cutaneous (e.g., cuSCC/KA) and non-cutaneous, have been observed in patients treated with BRAF inhibitors and can occur with encorafenib.

Fatal cerebral hemorrhage has been reported in patients with new or progressive brain metastases on combination treatment with binimetinib while fatal gastrointestinal hemorrhage has been reported in patients on combination treatment with cetuximab.

Uveitis, including iritis and iridocyclitis, has been observed in patients on combination treatment with binimetinib for melanoma.

Encorafenib has been associated with serious cardiovascular adverse effects. In clinical trials, dose-dependent QTc prolongation occurred in 0.7% and 3.2% of patients who received encorafenib in combination with binimetinib and cetuximab, respectively. Venous thromboembolism, including pulmonary embolism, has also occurred while on combination treatment.

E - Dosing

Refer to protocol by which the patient is being treated.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

BRAF V600 or V600E mutation should be confirmed by a validated test prior to starting encorafenib.

Correct electrolyte imbalances prior to and during treatment.

A dermatologic evaluation should be performed prior to initiating treatment.

Adults:

Various dosing and schedules are used depending on the indication. Refer to the product monograph or related regimen monographs for details.

Melanoma (in combination with binimetinib):

Oral: 450 mg Daily

Colorectal Cancer (in combination with cetuximab):

Oral: 300 mg Daily

Table 1 - Encorafenib Dose with CYP3A4 Inhibitors

Refer to Interactions Section for details on dosing modifications with CYP 3A4 inhibitors.

Planned Dose (mg daily)	*Encorafenib Dose (mg daily)**
Planned Dose (mg daily)	with Strong CYP3A4 inhibitor	with Moderate CYP3A4 inhibitor
450	150	225
300	75	150
225	75	75
150	75^	75

*Resume previous dose after the inhibitor has been discontinued for 3 to 5 half-lives.

^Monitor patients for adverse reactions and use clinical judgment; encorafenib exposure at 75mg daily (with a strong CYP3A4 inhibitor) is expected to be similar to the exposure at the 225mg daily dose (in the absence of a CYP3A4 inhibitor).

Dosage with Toxicity:

Table 2 - Dose Levels

Dose Level	Encorafenib Dose (mg daily)
Dose Level	Melanoma	Colorectal Cancer
0	450	300
-1	300	225
-2	225	150
-3	Discontinue	Discontinue

Table 3 - Dose Modifications

Also refer to the binimetinib, cetuximab and panitumumab product monographs for dose modifications of these drugs.

Toxicity / Severity		Action^#
Non-cutaneous malignancy		Discontinue if RAS mutation-positive.
Any new or worsening visual disturbance		Refer to ophthalmologist.
Uveitis	Grade 1 not responding to ocular therapy	Hold encorafenib for up to 6 weeks. If improves to Grade < 1, resume at same dose.
	Grade 2 not responding to ocular therapy	Hold encorafenib for up to 6 weeks. If improves to Grade < 1, resume at 1 dose level ↓.
	Grade 3
	Grade 4	Discontinue.
QT Prolongation	QTcF > 500 ms AND ≤ 60 ms increase from baseline	Hold until QTcF < 500 ms, then resume at 1 dose level ↓. If > 1 recurrence, discontinue.
QT Prolongation	QTcF > 500 ms AND > 60 ms increase from baseline	Discontinue.
Increase in AST or ALT	Grade 2, without improvement for 2 weeks	Hold until Grade < 1 or baseline. Resume at same dose.
Increase in AST or ALT	Grade 3 or 4	See Other Adverse Reactions below.
Hand-foot Syndrome	Grade 2, without improvement for 2 weeks	Hold until < Grade 1. Resume at same dose for first occurrence. Resume at same dose or with 1 dose level ↓ if recurrent.
Hand-foot Syndrome	Grade 3	Hold until < Grade 1. Resume with 1 dose level ↓.
Other Dermatologic Reactions*	Grade 2, without improvement for 2 weeks	Hold until Grade < 1. Resume at same dose.
	Grade 3	Hold until Grade < 1. Resume at same dose for first occurrence. Resume at 1 dose level ↓ if recurrent.
	Grade 4	Discontinue.
Other Adverse Reactions* (including hemorrhage)	Grade 2, recurrent	Hold for up to 4 weeks. If improves to Grade < 1 or baseline, resume at 1 dose level ↓. Discontinue if no improvement.
	Grade 3, 1st occurrence
	Grade 3, recurrent	Consider discontinuing.
	Grade 4, 1st occurrence	Discontinue OR Hold for up to 4 weeks. If improves to Grade < 1 or baseline, resume at 1 dose level ↓. Discontinue if no improvement.
	Grade 4, recurrent	Discontinue.

^#Encorafenib, when given in combination, may require dose reductions or discontinuation if other drugs are held or discontinued. Refer to the regimen monographs for more information.

*Excluding new primary cutaneous malignancies, other ocular events, ILD/pneumonitis, cardiac dysfunction, CPK elevation, rhabdomyolysis, and VTE.

Dosage with Hepatic Impairment:

For increased AST/ALT during treatment, refer to dose modifications table above.

Hepatic Impairment	Encorafenib Starting Dose
Mild (Child-Pugh Class A)	300 mg Daily
Moderate (Child-Pugh Class B)	No data available.
Severe (Child-Pugh Class C)	No data available.

Dosage with Renal Impairment:

Creatinine Clearance (mL/min)	Encorafenib Starting Dose
> 30	No dose adjustment recommended
< 30	No data available.

Dosage in the elderly:

No dose adjustment required for patients > 65 years. No clinically relevant differences in the safety or effectiveness were observed in patients > 65 years compared to younger patients on combination treatment with binimetinib. There is insufficient data with the use of encorafenib and cetuximab in patients > 65 years or older to assess differences in efficacy or safety compared to younger patients.

Dosage based on gender:

Sex does not have a clinically meaningful effect on the pharmacokinetics of encorafenib.

Children:

The safety and effectiveness of encorafenib in children < 18 years have not been established.

F - Administration Guidelines

Administer encorafenib with or without food.
Capsules should be swallowed whole with water. Do not crush, dissolve, or open capsules.
Grapefruit, starfruit, Seville oranges, their juices or products should be avoided during encorafenib treatment.
If a dose is missed, patient may take within 12 hours of the missed dose. If more than 12 hours has elapsed from the missed dose, the dose should be skipped and taken at the next scheduled time. Extra capsules should not be taken to make up for a missed dose.
Do not take an additional dose if vomiting occurs after taking encorafenib.
Store at 15 - 30°C in the original bottle. Protect from moisture and do not remove the desiccant.

G - Special Precautions

Contraindications:

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

Other Warnings/Precautions:

Patients must have a validated test to confirm BRAF V600/E mutation before treatment; paradoxical activation of MAP-kinase signaling may occur when BRAF wild-type cells are exposed to BRAF inhibitors, such as encorafenib.
Exercise caution in patients with diabetes or with risk factors for QT prolongation, including known long QT syndromes, bradyarrhythmias, heart failure, and taking other QT prolonging agents.
Patients were excluded from clinical trials if they have a history of Gilbert’s syndrome, abnormal LVEF, prolonged QTc (>480 ms), uncontrolled hypertension, and history or current evidence of retinal vein occlusion. Consider benefits vs risks of using encorafenib in these patients.
Use caution when driving or operating a vehicle or potentially dangerous machinery as vision problems have been reported.

Other Drug Properties:

Carcinogenicity:
New primary malignancies, cutaneous and non-cutaneous, have been observed in patients treated with BRAF inhibitors and can occur with encorafenib.

Pregnancy and Lactation:

Genotoxicity: No
Embryotoxicity: Yes
Fetotoxicity: Yes

Encorafenib is not recommended for use in pregnancy. Adequate non-hormonal contraception should be used by patients and their partners during treatment, and for at least 2 weeks after the last dose.
Excretion into breast milk: Unknown

Breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose
Fertility effects: Probable

No fertility data in humans. Adverse effects on male reproductive organs have been seen in animals.

H - Interactions

Encorafenib is metabolized mainly by CYP3A4, with lesser contribution from CYP2C19 and CYP2D6, and is a substrate of P-gp in vitro.

In vitro, encorafenib is a reversible inhibitor of UGT1A1, CYP1A2, CYP2B6, CYP2C8/9, CYP2D6, and CYP3A, a time-dependent inhibitor of CYP3A4, and an inhibitor of P-gp, OCT1, OCT2, and OAT1, and OAT3.

Encorafenib is a strong inducer of CYP3A4 at steady-state, and also induced CYP1A2, CYP2B6, and CYP2C9 in vitro.

Coadministration with sensitive CYP2C19, CYP2B6, or CYP2C9 substrates may result in increased toxicity or decreased efficacy of these agents.

Coadministration of encorafenib (UGT1A1 inhibitor) with binimetinib (UGT1A1 substrate) had no effect on binimetinib exposure. Coadministration of encorafenib with cetuximab had no clinically relevant effect on pharmacokinetics.

Coadministration of a proton pump inhibitor (i.e., rabeprazole) had no effect on encorafenib exposure.

AGENT	EFFECT	MECHANISM	MANAGEMENT
Strong CYP3A4 inhibitors (e.g., itraconazole, posaconazole, clarithromycin, ritonavir)	↑ encorafenib exposure (↑ AUC 3-fold and ↑ Cmax by 68% with posaconazole)	↓ metabolism of encorafenib	Avoid if possible. Reduce encorafenib dose if used in combination. See Table 1 in Dosing section.
Moderate CYP3A4 (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil, fruit or juice from grapefruit, Seville oranges or starfruit)	↑ encorafenib exposure (↑ AUC 2-fold and ↑ Cmax by 45% with diltiazem)	↓ metabolism of encorafenib	Avoid if possible. Reduce encorafenib dose if used in combination. See Table 1 in Dosing section.
Strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort)	↓ encorafenib exposure	↑ metabolism of encorafenib	Avoid concomitant use.
Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil)	↓ encorafenib exposure	↑ metabolism of encorafenib	Avoid concomitant use. If unavoidable, no change in encorafenib dose when used in combination.
CYP3A4 substrates (e.g., hormonal contraceptives, atorvastatin, midazolam)	↓ AUC and Cmax of substrate	Encorafenib is an inducer of CYP3A4.	Avoid concomitant use with substrates where a minimal decrease in concentration may lead to therapeutic failure. If coadministration of a sensitive substrate cannot be avoided, adjust substrate dose based on its product monograph recommendations.
CYP1A2 substrates (e.g., caffeine)	↑ risk of toxicity	Encorafenib is a reversible inhibitor of CYP1A2.	Caution, monitor for substrate toxicity.
Drugs that prolong QT Interval (e.g., amiodarone, furosemide)	↑ risk of toxicity	Additive	Avoid concomitant use with QT/QTc prolonging agent.
OATP1B1, OATP1B3 or BCRP substrates (e.g., rosuvastatin)	↑ substrate exposure (↑ AUC 1.6-fold and ↑ Cmax 2.7-fold of rosuvastatin)	Encorafenib is an inhibitor of OATP1B1, OATP1B3 and/or BCRP.	Caution, monitor for substrate toxicity. Consider dose adjustment of substrate.

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.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
Liver function tests	Baseline, monthly, and as clinically indicated
Renal function tests and electrolytes, including potassium and magnesium	Baseline, monthly, and as clinically indicated
CBC	Baseline, and as clinically indicated
Skin examination for any new cutaneous malignancies	Baseline, every 2 months during treatment, and continue for up to 6 months after the last dose
ECG (especially in patients at risk for QT prolongation)	Baseline and as clinically indicated
Clinical toxicity assessment for bleeding, thromboembolism, hypersensitivity, fatigue, hyperglycemia, new primary non-cutaneous malignancies, rash, ocular, and GI effects	At each visit

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

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

encorafenib - In combination with cetuximab or panitumumab in previously treated BRAF V600E-mutated metastatic colorectal cancer, according to clinical criteria
encorafenib - For the treatment of patients with locally advanced unresectable or metastatic melanoma with a BRAF V600 mutation, according to clinical criteria.

K - References

Heinzerling L, Eigentler TK, Fluck M, et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. ESMO Open. 2019 May 23;4(3):e000491.

Hesketh, P. et al. Antiemetics: ASCO Guideline Update. Journal of Clinical Oncology 2020 38:24, 2782-2797.

Kopetz, S. et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. N Engl J Med 2019.

Product Monograph: Braftovi® (encorafenib). Pfizer Canada ULC. February 23, 2024.

Proietti I. et al. BRAF Inhibitors: Molecular Targeting and Immunomodulatory Actions. Cancers (Basel). 2020 Jul 7;12(7):1823.

Summary of Product Characteristics: Braftovi. Pierre Fabre Limited. September 14, 2022.

April 2024 Modified Interactions section

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:

encorafenib (patient)

Info Sheet Introduction:

For treating certain types of melanoma (skin cancer) or colorectal cancer. It is usually given together with another medication.

Info Sheet Date: Wednesday, June 7, 2023 Info Sheet body:

Medication Information Sheet

encorafenib (en koe RAF e nib)

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: Braftovi®

Appearance:

beige and white capsule

What is this medication for?

For treating certain types of melanoma (skin cancer) or colorectal cancer. It is usually given together with another medication.

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 heart beat),
liver problems,
eye problems (such as uveitis),
diabetes or high blood sugar, 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.

You will have a blood test to check for hepatitis B before starting treatment. See the Hepatitis B and Cancer Medications pamphlet for more information.

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 2 weeks after your last dose (if you are female) or 1 week after your last dose (if you are male).
This medication may make hormonal birth control, such as birth control pills, less effective (not work as well). Talk to your health care team about the best birth control options for you.
Do not breastfeed while on this medication and for at least 2 weeks after your last dose.

How is this medication given?

This medication is usually taken once a day. Talk to your health care team about how and when to take your medication.
Swallow the capsules whole with a glass of water, with or without food.
Do not eat or drink grapefruit, starfruit, Seville oranges or their juices (or products that contain these) while taking this drug. They may increase the amount of drug in your blood and increase side effects.
If you forget to take a dose of your encorafenib:
- If it has been less than 12 hours from the missed dose, take the dose as usual. Then take your next dose at the normal scheduled time.
- If it has been longer than 12 hours, do not take the dose. Take your next dose at the normal scheduled time. Do not take extra (double up) to make up for the missed dose.
If you vomit (throw up) after taking your medication, do not take an additional dose to make up for the vomited dose.
If you take too much of your medication by accident, or if you think a child or a pet may have swallowed your medication, you must call the Ontario Poison Control Center right away at: 1-800-268-9017.

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 cannabis/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.

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 talk to your health care team about your risk of getting other cancers and heart problems after this treatment.
DO protect your skin from the sun. Wear a long sleeved shirt, long pants and a hat. Apply sunscreen with UVA and UVB protection and an SPF of at least 30. Your skin may be more sensitive to the sun and you could develop a bad sunburn or rash more easily.

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.
DO NOT eat or drink grapefruit, starfruit, Seville oranges or their juices (or products that contain these) while taking this drug. They may increase the amount of drug in your blood and increase side effects.
DO NOT drive, operate machinery or do any tasks that need you to be alert if you feel drowsy or have problems with your vision.

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.

How to safely touch oral anti-cancer medications

If you are a patient:

Wash your hands before and after touching your oral anti-cancer medication.
Swallow each pill whole. Do not crush or chew your pills.

If you are a caregiver:

Wear nitrile or latex gloves when touching tablets, capsules or liquids.
Wash your hands before putting on your gloves and after taking them off, even if your skin did not touch the oral anti-cancer medication.
Throw out your gloves after each use. Do not re-use gloves.
Do not touch oral anti-cancer medications if you are pregnant or breastfeeding.

What to do if oral anti-cancer medication gets on your skin or in your eyes

If medication gets on your skin:

Wash your skin with a lot of soap and water.
If your skin gets red or irritated, talk to your health care team.

If medication gets in your eyes:

Rinse your eyes with running water right away. Keep water flowing over your open eyes for at least 15 minutes.

What are the side effects of this medication?

The following table lists side effects that you may have when getting encorafenib. The table is set up to list the most common side effects first and the least common last. Encorafenib is usually given along with other medications to treat cancer. Some of the side effects listed below may be due to those other medications.

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 encorafenib.

Very Common Side Effects (50 or more out of 100 people)
Fatigue 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.

Very Common Side Effects (50 or more out of 100 people)

Side effects and what to do

When to contact health care team

Fatigue

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
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.
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).
Rash; dry, itchy skin (May be severe) What to look for? You may have cracked, rough, flaking or peeling areas of the skin. Your skin may look red and feel warm, like a sunburn. Your skin may itch, burn, sting or feel very tender when touched. Rarely, you may have tingling or swelling of the skin on the palms of your hands and the bottoms of your feet. This is called hand-foot syndrome. It can become painful or numb. What to do? To prevent and treat dry skin: Use fragrance-free skin moisturizer. Protect your skin from the sun and the cold. Use sunscreen with UVA and UVB protection and a SPF of at least 30. Avoid perfumed products and lotions that contain alcohol. Drink 6 to 8 cups of non-alcoholic, non-caffeinated liquids each day, unless your health care team has told you to drink more or less. If you have hand-foot syndrome: Do not do activities that cause rubbing or pressure on your skin, like heavy-duty washing, gripping tools, typing, playing musical instruments, and driving. Wear loose, comfortable footwear and clothes. Rest and try to keep off your feet. Do not let your hands and feet get too hot. Rash may be severe in some rare cases and cause your skin to blister or peel. If this happens, get emergency medical help right away.	Talk to your health care team if it does not improve or if it is severe.
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.
Headache; mild joint, muscle pain or cramps What to look for? A 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.

Less Common Side Effects (10 to 24 out of 100 people)
Side effects and what to do	When to contact health care team
Too much or too little salt in your body (May be severe) 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.
Unusual bleeding or bruising (May be severe) 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 What to do? Check with your healthcare team before you go to the dentist or if you have a surgery planned. 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. 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, you MUST get emergency medical help right away.
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.
High blood sugar What to look for? You may feel thirsty. You may pee more often than usual. You may feel tired or sleepy. What to do? Your health care team may do a blood test to check your blood sugar level. You may be told to change your diet or given medication to lower your blood sugar. If you have diabetes, check your blood sugar regularly. Your health care team may ask you to check it more often than usual.	Contact your health care team as soon as possible (office hours).
Trouble Sleeping Your medications may cause trouble sleeping. It may get better once your body gets used to the medication or when your treatment ends. What to look for? You may find it hard to fall asleep or stay asleep. How well you sleep may change over your treatment. For example, you may have several nights of poor sleep followed by a night of better sleep. You may wake up too early or not feel well-rested after a night's sleep. You may feel tired or sleepy during the day. What to do? Talk to your health care team if it does not improve or if it is severe	Talk to your health care team if it does not improve or if it is severe.
Neuropathy (Tingling, numb toes or fingers) What to look for? Numbness or tingling of your fingers and toes may happen after starting your treatment. It can also happen to other parts of your body. Sometimes it can be painful and feel like a burning sensation, which may be severe. What to do? Talk to your health care team if you have symptoms of neuropathy. Numbness and tingling may slowly get better after your treatment ends. In rare cases, it may continue long after treatment ends. If you continue to have bothersome symptoms, talk to your health care team for advice.	Talk to your health care team, especially if you have trouble doing tasks like doing up buttons, writing, moving, or if you have severe pain or numbness.

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:

Yellowish skin or eyes, or pain on the right side of your belly
Irregular heartbeat, shortness of breath, chest pain or fainting spells
Coughing, problems breathing, or coughing up blood
Trouble seeing, speaking, or using your arms and legs
New swelling in your hands, ankles, feet or other areas of your body
Pain, swelling and hardening of the vein in an arm or leg
Eye redness, irritation, pain, tearing, sensitivity to light, or blurred vision
Pain in your lower back
Changes in urination (peeing) such as less urine than usual or unusually dark pee
Itchiness, rash, swollen lips, face or tongue, chest and throat tightness
Pain in the centre of your belly that may spread to your back

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:

____________________________________________________________________________

April 2023 New patient information sheet

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):

encorafenib patient.pdf Info Sheet (French):

encorafnib pour le patient.pdf Monograph:

encorafenib.pdf Funding Program: Exceptional Access Program Funding Instance:

encorafenib - In combination with cetuximab or panitumumab in previously treated BRAF V600E-mutated metastatic colorectal cancer, according to clinical criteria
encorafenib - For the treatment of patients with locally advanced unresectable or metastatic melanoma with a BRAF V600 mutation, according to clinical criteria.

Phonetic Spelling:

en koe RAF e nib

Cancer Type: Gastrointestinal Colorectal Small bowel and appendix Skin Melanoma Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Monday, April 15, 2024 Universal Date: 2024-04-15 00:00:00 AddThis: Title URL: encorafenib Drug Display Status: Active Revision Summary:
Drug Monograph: Modified Interactions section