osimertinib

Trade Name:

Tagrisso®

Appearance:

tablet

in various strengths, shapes and colours

Monograph Name:

osimertinib

Monograph Body:

Drug Monograph

A - Drug Name

osimertinib

COMMON TRADE NAME(S): Tagrisso®

B - Mechanism of Action and Pharmacokinetics

Osimertinib is an irreversible inhibitor of both Epidermal Growth Factor Receptor (EGFR) with activity in clinically relevant sensitizing mutations as well as T790M.

Absorption

Bioavailability

70%

Peak plasma levels

median t_max of 6 (3-24) hours

Effects with food

Food does not alter osimertinib bioavailability to a clinically significant extent. The drug may be taken with or without food.

Time to reach steady state

15 days

Distribution

Extensive tissue distribution

PPB

94.7%

Cross blood brain barrier?

Brain penetration and activity in the CNS have been observed in animal studies.

Metabolism

Main enzymes involved

CYP3A4 and CYP3A5

Active metabolites

yes (10% of osimertinib exposure at steady state)

Inactive metabolites

yes

Elimination

Feces

68% (~1% unchanged)

Urine

14% (~1% unchanged)

Half-life

44 hours

C - Indications and Status

Health Canada Approvals:

Non-small cell lung cancer

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

D - Adverse Effects

Emetogenic Potential:

Minimal – No routine prophylaxis; PRN recommended

Extravasation Potential: Not applicable

The following table lists adverse effects that occurred in previously untreated patients, or previously treated patients (marked with #), in phase III trials treated with osimertinib. Adverse events from other trial data or severe / post-marketing events may also be included.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Cardiotoxicity (3%)	E D
	QT interval prolonged (1%) (> 500 msec)	E
	Venous thromboembolism (1%)	E D
Dermatological	Dry skin (36%)	E
	Erythema multiforme (rare)	E
	Nail disorder (35%)	E D
	Rash, pruritus (58%) (1% severe)	E
	Stevens-Johnson syndrome (rare)	E
	Toxic epidermal necrolysis (rare)	E
Gastrointestinal	Anorexia (18%) #	E
	Constipation (14%) #	E
	Diarrhea (58%) (2% severe)	E
	Mucositis (31%)	E
	Nausea, vomiting (16%) #	E
General	Fatigue (16%) #	E
Hematological	Myelosuppression ± infection, bleeding (6%) (severe)	E
	Other - Aplastic anemia (rare)	E
Hepatobiliary	↑ LFTs (1%) (severe) #	E
Musculoskeletal	Musculoskeletal pain (10%) #	E
Nervous System	Headache (10%) #	E
Ophthalmic	Conjunctivitis (8%) # (related to ocular surface events)	E
	Keratitis (<1%)	E
Renal	Creatinine increased (9%)	E
Respiratory	Cough, dyspnea (17%) #	E
	Epistaxis (6%) #	E
	Other (bronchiolitis obliterans organizing pneumonia; rare)	E
	Pneumonitis (4%)	E D
Vascular	Vasculitis (cutaneous; 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)

The most common side effects for osimertinib include diarrhea, rash, pruritus, dry skin, nail disorder, mucositis, anorexia, cough, dyspnea, fatigue, nausea, vomiting and constipation.

Skin effects observed with osimertinib have mainly been mild in nature, including rash, dry skin pruritus and nail effects. Regular application of moisturizers to skin and nails, practice of good hand hygiene, and keeping hands dry help prevent and control skin and nail adverse effects. Rare, post-marketing case reports of erythema multiforme, toxic epidermal necrolysis, or non-fatal Stevens-Johnson syndrome have been reported with osimertinib.

QTc interval prolongation has been observed and may lead to an increased risk of ventricular arrhythmias, including Torsade de pointes, although no QT-associated arrhythmias were reported in clinical trials. A pharmacokinetic/ pharmacodynamic analysis with osimertinib predicted a concentration-dependent increase in QTc prolongation.

Left ventricular dysfunction has been reported. Across clinical trials, 3% of patients had decreases in LVEF ≥ 10% and drops in LVEF to below 50%. Three percent of patients reported cardiomyopathy events, including 1 case of fatal congestive heart failure.

Interstitial lung disease (ILD) and/or pneumonitis were reported in 4% of patients with a median onset of about 3 months, and may be fatal. Patients with a history of or active ILD, or those with radiation pneumonitis requiring steroids were excluded from clinical trials.

Ocular surface events (i.e. conjunctivitis, blepharitis and dry eye) were usually mild and rarely required dose modification. Keratitis has been rarely reported.

E - Dosing

Refer to protocol by which 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.

A validated test is required to identify EGFR mutation-positive status prior to adjuvant or first-line locally advanced/metastatic NSCLC treatment.

A validated test is required to confirm EGFR T790M mutation-positive status prior to treatment of NSCLC that has progressed on or after EGFR TKI.

Electrolyte abnormalities should be corrected prior to treatment.

Adults:

Oral: 80 mg Daily

Dosage with Toxicity:

Dose Level	Osimertinib Dose (mg/day)
0	80
-1	40
-2	Discontinue

Toxicity	Dose Modification
ILD/pneumonitis	Hold and investigate. Discontinue permanently if confirmed.
Asymptomatic LVEF < 50% and absolute decrease of 10% from baseline	Hold for up to 4 weeks. If recovery to baseline, restart. If no recovery to baseline, discontinue permanently.
QTc interval > 500 msec on at least 2 separate ECGs	Hold until QTc interval is < 481 msec or recovery to baseline if baseline is ≥ 481 msec. Then restart at 1 dose level ↓.
QTc interval prolonged with signs/symptoms of serious arrhythmia (e.g. Torsade de pointes, polymorphic VT) OR Symptomatic congestive heart failure	Discontinue permanently.
Signs & symptoms suggestive of keratitis	Refer promptly to an ophthalmology specialist. For ≥ grade 3 toxicity, also refer to action below.
Signs and symptoms suggestive of aplastic anemia	Hold if suspected; discontinue if confirmed.
Signs and symptoms of Stevens-Johnson syndrome, Toxic epidermal necrolysis	Hold if suspected; discontinue if confirmed.
Signs and symptoms of erythema multiforme	Hold if suspected; consider discontinuing if confirmed. (Discontinue for erythema multiforme major.)
Other ≥ grade 3 toxicity	Hold for up to 3 weeks. If recovery to ≤ grade 2, restart at the same dose or at 1 dose level ↓. If no recovery, discontinue permanently.

Dosage with Hepatic Impairment:

Hepatic Impairment

Osimertinib Dose

Mild (total bilirubin ≤ ULN and AST > ULN OR total bilirubin 1-1.5 x ULN and any AST) or

Moderate (total bilirubin 1.5 to 3 x ULN and any AST)

No dosage adjustment required.

Severe

No data; use with caution.

Dosage with Renal Impairment:

Renal Impairment (Creatinine Clearance)	Osimertinib Dose
Mild to moderate (30 to <60 mL/min)	No dosage adjustment required.
Severe (15 to < 30 mL/min)	No dosage adjustment required. Use with caution.
End-stage renal disease (<15 mL/min) or dialysis	No data.

Dosage in the elderly:

No dosage adjustment is required.

No overall differences in efficacy or predicted steady state exposure of osimertinib were observed between patients ≥ 65 years of age and younger patients.

Patients ≥ 65 years of age experienced more ≥ Grade 3 adverse reactions compared to younger patients and had more reported adverse reactions that led to drug dose interruptions or reductions.

Dosage based on ethnicity:

No dosage adjustment required due to ethnicity.

In clinical trials, the incidence of ILD was higher in Japanese patients compared to other Asian and non-Asian patients.

Children:

Safety and efficacy are not established in children under 18 years.

F - Administration Guidelines

Osimertinib may be taken orally with or without food at the same time each day.
The tablet should be swallowed whole with water and not crushed, split or chewed.
If a dose is missed, it may be taken within 12 hours. If there are less than 12 hours until the next dose, the missed dose should be skipped and the next dose should be taken at the scheduled time.
If the patient has difficulty swallowing, the tablet may be dispersed in 50 ml of non-carbonated water (room temperature) and swallowed immediately. An additional 50 ml of water should be added to capture drug residue and immediately swallowed. No other liquids should be added.
For nasogastric administration, the tablet may be dispersed in 15 mL of noncarbonated water; using an additional 15 mL of water for residue rinses. The 30 mL of liquid should be administered within 30 minutes via the nasogastric tube and flush appropriately as per the nasogastric tube manufacturer’s instructions.
Store tablets at room temperature (15-30^oC).

G - Special Precautions

Contraindications:

Patients who are hypersensitive to this drug or to ingredients in the formulation or component in the container

Other Warnings/Precautions:

Not recommended in patients with congenital long QT syndrome or those taking other medications know to prolong QTc
Patients at risk for prolonged QTc such as those with cardiac disease, history of arrhythmias, electrolyte disturbances or conditions leading to electrolyte disturbances, bradycardia, acute neurological events, diabetes mellitus and autonomic neuropathy should be monitored closely and electrolyte abnormalities corrected prior to treatment.
Patients with abnormal LVEF, significant cardiac history, significant rhythm and conduction abnormalities, or resting QTc > 470 msec were excluded from clinical trials.
Exercise caution in patients with cardiac risk factors and those with conditions that can affect LVEF.
Patients with a history of ILD/pneumonitis, evidence of clinically active ILD or those with radiation pneumonitis requiring steroids were excluded from clinical trials.
Ocular events have been reported. Contact lens use is a risk factor for ocular toxicity, including keratitis. Caution should be used when driving or operating machinery in patients who experience visual disturbances.

Other Drug Properties:

Carcinogenicity: Unknown

Carcinogenicity studies have not been performed.

Pregnancy and Lactation:

Embryotoxicity: Yes
Fetotoxicity: Yes

Osimertinib is not recommended for use in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for at least 2 months after the last dose.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for at least 4 months after the last dose.
Excretion into breast milk: Unknown

Breastfeeding is not recommended.
Fertility effects: Documented in animals

H - Interactions

Osimertinib is metabolized primarily by CYP3A4/5. It does not inhibit P-gp, OAT1, OAT3, OATP1B1, OATP1B3, MATE1, MATE2K and OCT2.

Strong CYP3A4 inhibitors decreased the osimertinib maximum plasma concentration (Cmax) by approximately 20% and increased the area under the curve (AUC) by approximately 24%. Given the inter-patient variability of 46% in the osimertinib exposure in the population PK analysis, this change of 24% is not clinically significant.

Clinical pharmacokinetic interactions with CYP3A4 substrates are unlikely.

There are no interactions with gastric pH modifying agents.

AGENT	EFFECT	MECHANISM	MANAGEMENT
Strong CYP3A4 inducers (i.e. phenytoin, rifampin, carbamazepine, St. John’s Wort, etc)	↓ osimertinib concentration and/or efficacy (e.g. rifampin ↓ osimertinib exposure by 78%)	↑ metabolism of osimertinib	Avoid. If coadministration is unavoidable, closely monitor therapy and increase osimertinib dose to 160mg daily during concurrent use. Continue this dose for 3 weeks after discontinuation of the strong CYP3A4 inducer. Then, resume osimertinib dose at 80mg daily.
Moderate CYP3A4 inducers (i.e. bosentan, efavirenz, etravirine, phenobarbital, primidone)	↓ osimertinib concentration and/or efficacy	↑ metabolism of osimertinib	Monitor therapy if co-administered. No dose adjustments required.
BCRP and P-gp substrates (e.g. certain HMG-CoA reductase inhibitors, digoxin, fexofenadine, dabigatran)	↑ substrate concentration and/or toxicity	osimertinib is a competitive inhibitor of BCRP	Monitor closely when co-administered with substrates with narrow therapeutic indices.
Drugs that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc)	↑ risk of QT prolongation and arrhythmias	Additive	Avoid if possible; closely monitor if co-administered
Drugs that disrupt electrolyte levels (i.e. loop/thiazide diuretics, laxatives, amphotericin B, high dose corticosteroids)	↑ risk of QT prolongation and arrhythmias	Additive	Avoid if possible; closely monitor if co-administered

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
CBC	Baseline, at each visit, and as clinically indicated
Liver function tests	Baseline, at each visit, and as clinically indicated
Renal function tests	Baseline and at each visit; more frequent in patients with severe renal impairment
Electrolytes (calcium, potassium and magnesium), especially in patients at risk of electrolyte abnormalities	Baseline, at each visit, and as clinically indicated
ECG	Baseline and as clinically indicated
LVEF; in patients with cardiac risk factors or those who develop cardiac signs/symptoms during treatment	Baseline, during treatment* and as clinically indicated
Clinical toxicity assessment for GI, skin, and respiratory effects, signs and symptoms of CHF, thromboembolism and ocular effects	At each visit

*LVEF was monitored every 12 weeks while on treatment in some clinical trials

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

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

osimertinib - For the treatment of locally advanced (not amenable to curative therapies) or metastatic non-small cell lung cancer (NSCLC) according to clinical criteria
osimertinib - For adjuvant therapy after tumour resection in patients with stage IB-IIIA (AJCC 7th edition, or equivalent) NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858 R) substitution mutations

K - References

Lacouture ME, Sibaud V, Gerber PA, et al. Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines. Ann Oncol 2021 Feb;32(2):157-70.

Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, et al.; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-40.

Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018 Jan 11;378(2):113-25.

Prescribing information: Tagrisso (osimertinib). AstraZeneca Pharmaceuticals (USA), May 2023.

Product monograph: Tagrisso (osimertinib). AstraZeneca Canada Ltd., March 2023.

Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med . 2020 Oct 29;383(18):1711-23.

December 2023 Modified Adverse effects, Dose modifications, Special precautions, Pregnancy/lactation, Interactions, and Monitoring sections

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.

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Info Sheet Name:

osimertinib (patient)

Info Sheet Introduction:

For treating certain types of non-small cell lung cancer (NSCLC)

Info Sheet Date: Tuesday, January 16, 2024 Info Sheet body:

Medication Information Sheet

osimertinib (OH sim ER ti 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: Tagrisso

Appearance:

tablet

in various strengths, shapes and colours

What is this medication for?

For treating certain types of non-small cell lung cancer (NSCLC)

What should I do before I have this medication?

Tell your health care team if you have or had significant medical condition(s) such as:
- heart problems, including irregular heartbeat
- liver, kidney or lung problems,
- dehydration or if you suffer from severe vomiting or eating disorders,
- problems with electrolytes (salts) in your blood,
- a history of fainting,
- a history of eye problems or if you wear contact lenses,
- 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 you may become pregnant, you and your partner together must use 2 effective forms of birth control at the same time until at least 2 months after your last dose. Talk to your health care team about which birth control options are best for you.
If you are a patient that can get somebody pregnant, you and your partner together must use 2 effective forms of birth control at the same time until at least 4 months after your last dose. 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 medication is usually taken once a day by mouth. Talk to your health care team about how and when to take your medication.
Swallow whole with a glass of water, with or without food.
Do not crush or chew the tablets.
If you have difficulty swallowing tablets, talk to your health care team about another method to take this medication.
If you miss a dose, take it if it is within 12 hours from the missed dose, otherwise skip and take your next dose as scheduled. Do not double the dose to make up for the forgotten one.
If you vomit (throw up) after taking your medication, talk to your health care team about what to do.
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 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.

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 drive or use any tools or machines if you feel dizzy or get any symptoms that affect your eyesight, ability to concentrate or react.

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 taking osimertinib. 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 taking osimertinib.

Side effects and what to do	When to contact doctor?
Very Common Side Effects (50 or more out of 100 people)

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.

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.

Rash may be severe in some rare cases and cause your skin to blister or peel, or marks may appear as "bulls-eyes". If any of these symptoms happen, get emergency medical help right away.

Talk to your health care team if it does not improve or if it is severe.

Side effects and what to do	When to contact doctor?
Common Side Effects (25 to 49 out of 100 people)

Nail changes

What to look for?

You may have changes in nail colour, pain or tenderness, swelling of cuticles, or loosening of nails.
Nails will slowly return to normal after treatment ends.

What to do?

Moisturize your nails and cuticles.
Do not use nail polish and fake fingernails until your nails have gone back to normal.
Wear gloves when doing house chores or gardening.

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.

Side effects and what to do	When to contact doctor?
Less Common Side Effects (10 to 24 out of 100 people)

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.

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.

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.

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.
Take your anti-nausea medication(s) 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.

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.

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.

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:

Irregular heartbeat, shortness of breath, fainting or swelling in your legs, ankles and belly
Pain, swelling or hardening of the vein in your arm or leg
Blurred vision or eye pain, eye swelling and redness, watery eyes, vision changes, and sensitivity to light
Breathing problems or coughing up blood
New unusual weight gain, or passing very little or no pee
Yellowish skin or eyes, unusually dark pee or pain on the right side of your belly
Bleeding from your gums, unusual nosebleeds, bruising easily or more than normal, or blood in your urine (pee) or stools (poo)
Pain, redness or swelling of vein, or red or purple patches on your skin, or a rash that does not turn white when pressed

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:

____________________________________________________________________________

December 2023 Updated 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):

osimertinib patient.pdf Info Sheet (French):

osimertinib pour le patient.pdf Monograph:

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

osimertinib - For the treatment of locally advanced (not amenable to curative therapies) or metastatic non-small cell lung cancer (NSCLC) according to clinical criteria
osimertinib - For adjuvant therapy after tumour resection in patients with stage IB-IIIA (AJCC 7th edition, or equivalent) NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858 R) substitution mutations

Phonetic Spelling:

OH sim ER ti nib

Cancer Type: Lung Non-Small Cell Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Thursday, December 21, 2023 Universal Date: 2024-01-16 00:00:00 AddThis: Title URL: osimertinib Drug Display Status: Active Revision Summary:
Drug Monograph: Modified Adverse effects, Dose modifications, Special precautions, Pregnancy/lactation, Interactions, and Monitoring sections
Patient Info Sheet EN: Updated information sheet
Patient Info Sheet FR: Updated/revised information sheet (Fiche d’information mise à jour/révisée)