Patient Medication Information: uses, side effects, how to take - Gleevec (Novartis Pharmaceuticals Canada, 100 mg)

What is a Notice of Compliance with Conditions (NOC/c)?

An NOC/c is a form of market approval granted to a product on the basis of promising evidence of clinical effectiveness following review of the submission by Health Canada.

Products approved under Health Canada’s NOC/c policy are intended for the treatment, prevention or diagnosis of a serious, life-threatening or severely debilitating illness. They have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment. In addition, they either respond to a serious unmet medical need in Canada or have demonstrated a significant improvement in the benefit/risk profile over existing therapies. Health Canada has provided access to this product on the condition that sponsors carry out additional clinical trials to verify the anticipated benefit within an agreed upon time frame.

^PrGLEEVEC*

(imatinib mesylate)

This leaflet is part III of a three-part "Product Monograph" published when GLEEVEC* was approved for sale in Canada and is designed specifically for Consumers. This leaflet is a summary and will not tell you everything about GLEEVEC*. Contact your doctor or pharmacist if you have any questions about the drug.

Read all of this leaflet carefully before you start using GLEEVEC*

Keep this leaflet. You may need to read it again.

This medicine has been prescribed only for you. Do not give it to anybody else or use it for any other illnesses.

ABOUT THIS MEDICATION

What the medication is used for:

GLEEVEC* is indicated for the treatment of adult and pediatric patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase.
GLEEVEC* is also indicated for the treatment of adult patients with chronic myeloid leukemia (CML) in blast crisis, accelerated phase or in chronic phase (after failure of interferon-alpha therapy).

Leukemia is a cancer of white blood cells. (normal white cells usually help the body to fight infection). Chronic myeloid leukemia is a form of leukemia in which certain abnormal white cells, named myeloid cells, start growing out of control.

GLEEVEC* is also indicated for use as a single agent for induction phase therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

GLEEVEC*, for use in the treatment of adult and pediatric patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+CML) in chronic phase, also for use in the treatment of adult patients with unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST), has been approved with conditions, pending the results of studies to verify its clinical benefit.

For more information, patients are advised to contact their health care provider.

GLEEVEC* has received an approval for use in the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in blast crisis, accelerated phase or chronic phase (after failure of interferon-alpha therapy); for use as a single agent for induction phase therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); in adult patients with relapsed or refractory Ph+ ALL as single agent; in adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements; in adult patients with aggressive sub-types of systemic mastocytosis (ASM and SM-AHNMD¹) without the D816V c-Kit mutation. If c-Kit mutational status in patients with ASM or SM-AHNMD¹is not known or unavailable, treatment with GLEEVEC* may be considered if there is no satisfactory response to other therapies; adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) with FIP1L1-PDGFRα rearrangement; and in adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP).

GLEEVEC* is also indicated for the treatment of adult patients with relapsed or refractory Ph+ ALL as single agent.

Acute lymphoblastic leukemia is a form of leukemia in which certain abnormal white cells named lymphoblasts start growing out of control.

GLEEVEC* is also indicated for the treatment of adult
patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.

MDS/MPD diseases are a group of blood diseases in which some blood cells start growing out of control.

GLEEVEC* is also indicated for the treatment of adult
patients with aggressive sub-types of systemic mastocytosis (ASM and SM-AHNMD¹) without the D816V c-Kit mutation. If c-Kit mutational status in patients with ASM or SM-AHNMD¹is not known or unavailable, treatment with GLEEVEC* may be considered if there is no satisfactory response to other therapies.
¹ASM: Aggressive systemic mastocytosis; SM-AHNMD: Systemic mastocytosis with an associated clonal hematological non-mast-cell disorder.

ASM is a cancer in which certain blood cells (named “mast” cells) start growing out of control.

GLEEVEC* is also indicated for the treatment of
adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) with FIP1L1-PDGFRα rearrangement.

HES and/or CEL are blood diseases in which some blood cells (named “eosinophils”) start growing out of control.

GLEEVEC* is also indicated for the treatment of
adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP).

DFSP is a cancer of the tissue beneath the skin in which some cells start growing out of control.

GLEEVEC* is also indicated for the treatment of
adult patients with unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST).

GIST is a cancer of the gastrointestinal system (stomach and the bowels). It arises from uncontrolled cell growth of the supporting tissue of this system.

What it does:

GLEEVEC* specifically targets the activity of certain enzymes called tyrosine kinases that play an important role within certain cancer cells.

GLEEVEC* inhibits the growth of abnormal white blood cells by blocking an enzyme involved in the development of certain cancers such as Ph+CML and Ph+ALL.

GLEEVEC* inhibits the uncontrolled growth cells of the supportive tissues involved in the development of cancers of the gastrointestinal system (stomach and the bowels).

When it should not be used:

If you are allergic (hypersensitive) to imatinib mesylate or any of the other ingredients of GLEEVEC* listed under section What the important nonmedicinal ingredients are.

What the medicinal ingredient is:

GLEEVEC* contains an active ingredient called imatinib mesylate.

What the important nonmedicinal ingredients are:

GLEEVEC* (imatinib mesylate) 100 mg tablets : Each tablet contains 100 mg of imatinib (as mesylate) and the following inactive ingredients: Cellulose (microcrystalline), crospovidone, colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate. The coating contains ferric oxide (red), ferric oxide (yellow), hydroxypropyl methylcellulose, polyethylene glycol, and talc.

GLEEVEC* (imatinib mesylate) 400 mg tablets : Each tablet contains 400 mg of imatinib (as mesylate) and the following inactive ingredients: Cellulose (microcrystalline), crospovidone, colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate. The coating contains ferric oxide (red), ferric oxide (yellow), hydroxypropyl methylcellulose, polyethylene glycol, and talc.

What dosage forms it comes in:

GLEEVEC* is supplied as a tablet.

GLEEVEC* (imatinib mesylate) 100 mg tablets GLEEVEC* (imatinib mesylate) 400 mg tablets

WARNINGS AND PRECAUTIONS

Before you (or your child) take GLEEVEC* talk to your doctor or pharmacist:

if you have or ever have had a liver, kidney or heart
problem,
if you are or plan to get pregnant. Women who might
get pregnant are advised to use an effective method of birth control while taking GLEEVEC*,
if you are breast-feeding,
if you had your thyroid removed and are receiving
treatment with a thyroid hormone such as levothyroxine.

While taking GLEEVEC*, if you feel dizzy or if you have blurred vision, do not drive a vehicle or operate any tools or machinery.

Use in children

There is no experience with the use of GLEEVEC* in children under 2 years of age.

INTERACTIONS WITH THIS MEDICATION

Inform your doctor or pharmacist before or while taking GLEEVEC* if you are taking or have recently taken any other medicines, even those not prescribed by a doctor or natural health products, including nonprescription drugs.

Drugs that interact with GLEEVEC* include:

some medicines used to treat infections such as
ketoconazole, itraconazole, erythromycine, or clarithromycin,
- some medicines used to treat epilepsy such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, fosphenytoin, or primidone,
- some medicines used to treat high cholesterol such as simvastatin,
- some medicines used to treat mental disorders such as pimozide,
- some medicines used to treat high bood pressure or heart disorders such as calcium channel blockers or metoprolol,
- rifampicin, a medicine used to treat tuberculosis
- St. John’s Wort - a herbal product used to treat depression and other conditions (also known as Hypericum Perforatum),
- dexamethasone, an anti-inflammatory medicine,
- cyclosporine, an immunosuppressant medicine,
- acetaminophen, a medicine used to relieve the pain or to reduce fever,
- warfarin, a medicine used to treat blood coagulation disorders (such as blood clots or thromboses).

You should also tell your doctor if you are already taking GLEEVEC* and you are prescribed a new medicine you have not previously taken during GLEEVEC* treatment.

In addition, do not drink grapefruit juice while you are being treated with GLEEVEC*.

PROPER USE OF THIS MEDICATION

How to take GLEEVEC*

Adults

Usual adult dose:

400 mg/day in newly diagnosed CML or Chronic phase CML.
600 mg/day in accelerated phase and blast crisis
CML.
400 mg/day or 600 mg/day for GIST.
600 mg/day for Ph+ALL.

For CML and GIST, your doctor may prescribe a higher or lower dose depending on how you respond to treatment. If a dose of 800 mg is administered, it should be taken as 400 mg twice a day, in the morning and in the evening.

If you are being treated for MDS/MPD: the starting dose in adult patients with
myelodysplastic/myeloproliferative diseases is 400 mg/day.

Serious Warnings and Precautions

GLEEVEC* should only be prescribed to you (or your child) by a doctor who is experienced in the use of anti-cancer drugs. Serious and/or common side effects that may occur with GLEEVEC* include:

Severe heart failure and decrease in the amount of
blood pumped by the heart,
Serious bleeding,
Fluid retention.
If you are being treated for ASM: the starting dose
in adult patients with aggressive sub-types systemic mastocytosis (ASM and SM-AHNMD) without the D816V c-Kit mutation or with c-Kit mutational status unknown is 400 mg, to be taken once a day. For patients with ASM or SM-AHNMD associated with eosinophilia, the starting dose is 100 mg once a day.
If you are being treated for HES/CEL: the usual
starting dose in adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) is 100 mg to be taken once a day.
For ASM/SM-AHNMD and HES/CEL patients receiving 100 mg/day, your doctor may decide to increase the dose to 400 mg once a day depending on how you respond to treatment.
If you are being treated for DFSP: the starting dose
is 800 mg/day, to be taken as 400 mg twice a day, in the morning and in the evening.

Children

The doctor will tell you how many tablets of GLEEVEC* to give your child. The amount of GLEEVEC* given, will depend on your child’s condition, and also his or her body weight and height.

Usual dose for children (2 years of age and older): 340 mg/m²body surface area/day, rounded up to the nearest 100 mg and not to exceed 600 mg/day.

The treatment can either be given to your child as a once-daily dose or alternatively the daily dose can be split into two administrations (one in the morning and one in the evening).

GLEEVEC* should be taken during a meal and with a large glass of water. Avoid drinking grapefruit juice while being treated with GLEEVEC*. Swallow the tablet whole. The 400 mg tablet can be broken in half.

If you (or your child) cannot swallow the tablet(s), you can place them in water or apple juice, use 200 mL for 400 mg tablet or 50 mL for 100 mg tablet. Stir with a spoon to completely disintegrate the tablet(s), then drink the whole content immediately. Rinse the container with water or apple juice and drink it to make sure no trace of disintegrated tablet(s) is left.

When and how long to take GLEEVEC*

Your doctor will determine when you will be given GLEEVEC* and for how long you should receive it. Do not

exceed the recommended dosage and make sure you take GLEEVEC* for as long as prescribed.

What if you miss a dose

If you forget to take a dose of GLEEVEC*, take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and go back to your regular dosage schedule. Do not double doses.

Overdose

If you think you may have taken more GLEEVEC* than you should (overdosage is known or suspected), contact your doctor or the nearest poison control center immediately. You may require medical attention.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Possible side effects

Very common side effects that can occur during treatment with GLEEVEC* are weight gain, headache, nausea, vomiting, diarrhea, indigestion, rash, muscle spasms and cramps, pain in the muscles and bones, joint swelling and joint pain.

Other possible side effects of GLEEVEC* are anorexia, depression, dizziness, taste disturbance, numbness of the hands or feet, difficulty sleeping, red eye (conjunctivitis), blurred vision, increased tear production, chest pain on deep breathing (pleurisy), nose bleeds, abdominal pain or distension, gas (flatulence), constipation, dry mouth, itching, dry skin, unusual hair loss or thinning, night sweats, fatigue, weakness, and increased muscle tension, hypersensitivity (allergies).

In pediatric patients, higher frequencies of the following blood levels were observed compared to adult patients:

low blood levels of calcium, sugar, phosphates, albumin protein and sodium,

-high blood levels of sugar.

Your doctor will tell if your blood tests results changed abnormally.

Abnormal thyroid hormone levels (hypothyroidism) were observed in patients whose thyroid has been removed and who are receiving treatment with a thyroid hormone such as levothyroxine.

Your doctor will tell you if your thyroid hormone levels changed abnormally.

Tell your doctor if you experience any of the events listed above.

If you notice any other side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

	SERIOUS SIDE EFFECTS, HOW OFTEN THEY
	HAPPEN AND WHAT TO DO ABOUT THEM
Symptom / effect			Talk with your doctor or pharmacist
			Only if severe	In all cases
Common		rapid weight gain, swelling, of extremities (calves, ankles), generalised swelling such as swelling of the face (signs of water retention).		√
		weakness, spontaneous bleeding or bruising, frequent infections with signs such as fever, severe chills, sore throat, mouth ulcers. Treatment with GLEEVEC* may reduce the number of white cells in your blood, which may lead to infection (signs of thrombocytopenia, neutropenia, pancitopenia¹).		√
Uncommon		crushing, chest pain, irregular heart rhythm (sign of heart disorders such as heart failure, cardiac tamponade², pericarditis²)		√
		Nausea, loss of appetite, light-coloured urine or yellowing of your skin or eyes go yellow (sign of liver disorders such as hepatic necrosis³).		√
		skin shows unusual peeling		√
		severe painful swelling of an extremity.		√
		vomit blood, find blood in your stools or urine, have black stools or have severe abdominal pain (signs of gastrointestinal hemorrhage).		√
Rare		severe abdominal pain (a sign of intestinal obstruction).		√

	SERIOUS SIDE EFFECTS, HOW OFTEN THEY HAPPEN AND WHAT TO DO ABOUT THEM
cough, or difficulty breathing (such as acute respiratory failure⁴), painful breathing. skin shows blistering. pain in your hips or have difficulty walking (such as avascular necrosis/hip osteonecrosis).			Talk with your doctor or pharmacist
					√
					√
					√
		Light-headedness, dizziness or fainting (signs of anaphylactic shock)		√
		Severe headache (signs of nervous system disorders)		√
		Sudden vision impairment (sudden change in your eyesight)		√

¹Pancytopenia was uncommonly observed.

²Cardiac tamponade and pericarditis were rarely observed. ³hepatic necrosis was rarely observed.

⁴acute respiratory failure was uncommonly observed.

This is not a complete list of side effects. If you have any unexpected effects after receiving GLEEVEC*, contact your doctor or pharmacist

HOW TO STORE GLEEVEC*

Keep GLEEVEC* out of the reach and sight of children.

Store GLEEVEC* at room temperature (15- 30°C). Protect tablets from moisture.
Store GLEEVEC* in the original package.
Do not use GLEEVEC* after the expiry date shown on the box.
Do not use any GLEEVEC* pack that is damaged or shows signs of tampering.

REPORTING SUSPECTED SIDE EFFECTS

To monitor drug safety, Health Canada collects information on serious and unexpected effects of drugs. If you suspect you have had a serious or unexpected reaction to this drug you may notify Health Canada by:

toll-free telephone: 866-234-2345

toll-free fax 866-678-6789

By email: cadrmp@hc-sc.gc.ca

By regular mail:

National AR Centre

Marketed Health Products Safety and Effectiveness

Information Division

Marketed Health Products Directorate Tunney’s Pasture, AL 0701C

Ottawa ON K1A 0K9

NOTE: Before contacting Health Canada, you should contact your physician or pharmacist.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found at:

http://www.novartis.ca
or by contacting the sponsor, Novartis
Pharmaceuticals Canada Inc., at: 1-800-363-8883
Pharmaceuticals Canada Inc.
385 Bouchard Blvd.
Dorval, Québec, H9S 1A9
Last revised: January 9, 2008.
^PrGLEEVEC* is a registered trademark

Rx or OTC	Prescription (Rx)?
DIN	02244725
Schedule(s)	PRESCRIPTION
Active ingredient(s)	Imatinib (imatinib mesylate) 100 MG
Dosage form(s)	Capsule
Route(s) of administration	Oral
Drug class (WHO ATC)	L Antineoplastic and immunomodulating agents L01 Antineoplastic agents L01E Protein kinase inhibitors, antineoplastic and immunomodulating agents L01EA BCR-ABL tyrosine kinase inhibitors L01EA01 Imatinib
Company	NOVARTIS PHARMACEUTICALS CANADA INC
Current status	Cancelled Post Market
Current status date	September 24, 2008

Gleevec (Novartis Pharmaceuticals Canada, 100 mg): Uses, Side Effects and Dosage