Doxorubicin Hydrochloride Injection (Novopharm): Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

DOXORUBICIN HYDROCHLORIDE INJECTION is used alone and in combination with other anti-cancer medication to produce regression of tumor in several cancer conditions.

For the treatment of superficial bladder tumor, DOXORUBICIN HYDROCHLORIDE INJECTION is administered directly in the bladder.

What it does:

DOXORUBICIN HYDROCHLORIDE INJECTION is a chemotherapy drug, often used in combination with other drugs to kill cancer cells. Most chemotherapy agents (including DOXORUBICIN HYDROCHLORIDE INJECTION) work by killing rapidly dividing cells, such as cancer cells. This action can affect normal cells as well.

When it should not be used:

For intravenous administration:

• Allergy to DOXORUBICIN

  HYDROCHLORIDE INJECTION or to any ingredient in the formulation or component of the container;

• Allergy to other anthracyclines or

  anthracenediones such as epirubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone or mitomycin C;

• Persistent low blood cell count
• (myelosuppression);
• Severe liver disease;
• Severe heart disease;
• Recent heart attack;

• Severe irregular heartbeat;

  • History of severe cardiac disease;
  • Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines and anthracenediones. Accumulation of anthracyclines doses may be harmful for your heart.

For intravesical administration:

• hematuria;
• Urinary tract infections;
• Inflammation of the bladder.

What the medicinal ingredient is:

Doxorubicin hydrochloride.

What the important non-medicinal ingredients are:

Sodium Chloride USP,

Water for Injection USP and

Hydrochloric Acid NF for pH adjustment.

What dosage form it comes in:

DOXORUBICIN HYDROCHLORIDE INJECTION 2 mg/mL (doxorubicin hydrochloride injection) is available in 10 mg (5mL), 50 mg (25mL) and 200 mg (100mL) contained in glass vials.

WARNINGS AND PRECAUTIONS

BEFORE you use DOXORUBICIN

HYDROCHLORIDE INJECTION talk to your doctor or pharmacist if:

• you have low blood cell counts;
• you have a liver disease;
• you have a heart disease, recent heart attack or irregular heartbeat;

• you are taking other drugs (including calcium channel blockers) or have been previously treated with DOXORUBICIN

  HYDROCHLORIDE INJECTION or other anti-cancer drugs;

• you are pregnant, breast-feeding or planning to become pregnant.

As DOXORUBICIN HYDROCHLORIDE INJECTION may be harmful to an unborn child, women should be advised to avoid becoming pregnant. Effective contraceptive methods should be used.

As DOXORUBICIN HYDROCHLORIDE INJECTION may cause fertility impairment and damage chromosomes in sperm. Men undergoing treatment with DOXORUBICIN

HYDROCHLORIDE INJECTION, should use effective contraceptive methods.

INTERACTIONS WITH THIS MEDICATION

Combination chemotherapy regimens that contain other agents with similar action may lead to additive toxicity, especially with regard to bone

marrow/hematologic, gastrointestinal, and cardiac effects.

Administration of live vaccines to immunosuppressed patients including those undergoing cytotoxic chemotherapy should be avoided.

Drug interactions with DOXORUBICIN HYDROCHLORIDE INJECTION and the following drugs have been reported in the literature:

• Paclitaxel;
• Phenobarbital;
• Phenytoin;
• Streptozocin;
• Cyclophosphamide;
• 6-mercaptopurine;
• Actinomycin-D.

PROPER USE OF THIS MEDICATION

How is DOXORUBICIN HYDROCHLORIDE INJECTION given?

You may receive DOXORUBICIN

HYDROCHLORIDE INJECTION through a vein in the arm (“intravenously” or “IV”) by your doctor or nurse, usually in the hospital, outpatient department or clinic.

If you are getting many injections over several weeks or months, for your convenience, your doctor may insert a catheter (thin tube) or port into a large vein in your body that is placed there as long as it is needed. Medicines get injected through the catheter or port rather than directly into a vein.

Depending on your medical condition, you may also receive DOXORUBICIN HYDROCHLORIDE INJECTION by instillation into your bladder through a catheter inserted into the urinary natural tract.

Is treatment with DOXORUBICIN

HYDROCHLORIDE INJECTION painful? It is unusual to feel pain during the injection, however, if you do feel pain or burning, you should immediately tell your nurse or doctor. Although usually painless, instillation of DOXORUBICIN HYDROCHLORIDE INJECTION into the bladder can cause you to feel discomfort. Your doctor or nurse can suggest ways to prevent or relieve your discomfort.

How much time does it take to get a treatment with DOXORUBICIN HYDROCHLORIDE INJECTION?

It usually takes about 3-10 minutes to inject DOXORUBICIN HYDROCHLORIDE INJECTION. However, you may get other medicines before or after DOXORUBICIN HYDROCHLORIDE INJECTION, so your entire treatment may last an hour or longer.

If you are administered DOXORUBICIN HYDROCHLORIDE INJECTION by instillation into your bladder, the solution should generally be retained in your bladder for 1-2 hours prior to voiding.

How long will I need treatment?

Your doctor will determine the length of your treatment based on your medical condition, your treatment goals, the medicines you receive, and how your body responds to those medicines.

Chemotherapy is usually given in cycles that include rest periods between treatments. The rest periods give your body a chance to build healthy new cells and regain your strength before your next treatment. DOXORUBICIN HYDROCHLORIDE INJECTION is usually given in treatment cycles of 21 days or 28 days. You may receive 1 dose of DOXORUBICIN HYDROCHLORIDE INJECTION every 3 or 4 weeks (on Day 1 of the cycle). Alternately, you may also receive DOXORUBICIN HYDROCHLORIDE INJECTION instilled into your bladder weekly for 4 weeks and then monthly. Your treatment cycle will depend on your medical condition and the other chemotherapy medicines you are getting.

Will I be able to work?

Some people work full time, while others work part time or wait until their chemotherapy treatments are finished. It depends on the type of job you have and the side effects you experience.

Is it okay to become pregnant or nurse a baby? No. DOXORUBICIN HYDROCHLORIDE INJECTION can be harmful to an unborn child. If there is any possibility that you may become pregnant, ask your doctor about using birth control to prevent pregnancy during your treatment with DOXORUBICIN HYDROCHLORIDE INJECTION. Tell your doctor right away if you become pregnant during treatment. If you have been nursing, you should stop before starting treatment with DOXORUBICIN HYDROCHLORIDE INJECTION. Ask your baby’s doctor to recommend a formula that would be best for your baby.

What should men consider when taking DOXORUBICIN HYDROCHLORIDE INJECTION?

Men undergoing treatment with doxorubicin should use effective contraceptive methods.

Your first treatment: what to expect There will be tests

Before you get your first treatment, your doctor will probably order blood tests to check your blood count (white blood cells, red blood cells, and platelets), heart and liver function tests, X-rays or other tests. These “baseline” tests show your current condition, and will be compared to future test results.

You may get one or more medicines

Before your first treatment, you and your doctor will discuss all of the medicines you will receive during the treatment session. In addition to DOXORUBICIN HYDROCHLORIDE INJECTION, you may get other intravenous (IV) medicines, such as a medicine to prevent nausea, and other chemotherapy medicines. You can also ask your doctor about possible side effects and what to do if you experience any of these side effects.

Receiving your treatment

If you are getting your treatment at a clinic or a hospital, there is usually a comfortable treatment room where you can relax while you are getting your medicines.

Your nurse may insert a very thin plastic tube into your vein, which allows fluid to drip into your vein from a plastic bag. If you are getting a medicine to prevent nausea, you will probably take that medicine first. Then you will get the rest of your IV medicines

• including DOXORUBICIN HYDROCHLORIDE INJECTION - one at a time.

If DOXORUBICIN HYDROCHLORIDE INJECTION is administered by instillation into your bladder, your nurse or your doctor may insert a catheter (a very thin plastic tube) into your bladder through the urinary tract. After instillation of the product, the catheter is retained intravesically for 1 to 2 hours and you will be rotated to ensure that the vesical mucosa will be in contact with the medicine. To avoid dilution with urine, you should be instructed not to drink any fluid in the 12 hours prior to instillation and to void at the end of the instillation so, your urine will be handled safely.

What happens after treatment?

After you have completed all your chemotherapy treatments, your doctor will check you regularly to make sure the cancer has not returned.

Overdosage:

Due to the cumulative cardiac-toxicity of doxorubicin, which means that the accumulation of doses with anthracyclines may be harmful to your heart, it is important that you let your doctor know if you have been previously treated with

DOXORUBICIN HYDROCHLORIDE INJECTION or other anticancer drugs in order for your doctor to ensure the maximum cumulative dose has not been reached.

In the event of overdosage, contact your doctor, hospital emergency department, or regional Poison Control Centre immediately.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Hearing about all of the side effects from chemotherapy may seem overwhelming. But many people go through chemotherapy with very mild or few side effects.

Other people, who are more sensitive to chemotherapy, may have many side effects - but they can usually be controlled. Everyone reacts in a different way to chemotherapy.

Because DOXORUBICIN HYDROCHLORIDE INJECTION is also given with other chemotherapy medicines, it is sometimes hard to know which medicine is causing a particular side effect. If you are having a problem with side effects, call your doctor or nurse. They can suggest medicines or other ways to prevent or relieve your discomfort. Do not skip doses or make changes in your treatment on your own.

Why do side effects occur?

Chemotherapy medicines work by killing the fastest growing cells in the body, which include cancer cells and some normal cells. Normal cells that grow very rapidly are in your bone marrow, lining of the mouth, stomach, and hair follicles. These fast-growing cells can be affected by the chemotherapy medicines too, sometimes causing side effects such as low white blood cell count, low red blood cell count (anemia), nausea and vomiting, mouth sores, rash, itch and hair loss. These side effects usually disappear after treatment ends. Before your next cycle of chemotherapy, your white blood cell count normally increases and new cells grow back. After your chemotherapy is completely finished, your hair will begin to grow back.

Hair loss

Hair loss is common in chemotherapy with DOXORUBICIN HYDROCHLORIDE INJECTION. However, the hair loss is temporary, and your hair usually starts to grow back within 2 or 3 months after you’ve finished your treatments.

Infection

A week or two after a chemotherapy cycle, your white blood cell count may be low. This is the most dangerous time for getting an infection. White blood cells defend your body against infections. When there are very few white blood cells, there may not be enough to fight off an infection. It’s important to know the signs of infection so that you can get treatment before the infection becomes serious. The signs of infection include:

• Fever over 38°C (100°F);
• Chills or sweating;
• Sore throat or coughing;

• Redness or swelling around a cut, wound or a

  catheter site;

• A burning feeling when you urinate;
• Unusual vaginal itching or discharge.

Your doctor may prescribe oral antibiotics to help prevent infection during chemotherapy. Your doctor may also give you a medicine to help increase the number of your white blood cells. If there is evidence of an infection, your doctor may need to admit you to the hospital for a short period of time to receive intravenous antibiotics.

If you have signs of an infection, call your doctor right away. Waiting too long (even a few hours) can lead to a serious illness.

The following tips can help you prevent infections.

• Wash your hands often. Use lotion afterwards to

  prevent your skin from becoming dry and cracked;

• Bathe or shower every 1 to 2 days;

• Be careful not to cut yourself when you use a

  knife, scissors, razor or other sharp objects;

• Stay away from people who are sick;

• Have someone else clean cat litter boxes, bird

  cages or fish tanks;

• Eat well-balanced meals.

Nausea and vomiting

The amount of nausea and vomiting varies widely from person to person. Some have mild nausea and vomiting, while others may have severe nausea and vomiting for a short time after treatment. Nausea and vomiting may start right after a chemotherapy treatment or several hours later. Your doctor can give you medicine to prevent nausea or reduce its severity. If you’ve been treated with a medicine for nausea, but still feel sick to your stomach or you vomit, tell your doctor. There are other medicines your doctor can give you that may work better for you. You can also try drinking clear fluids (water, diluted soft drinks, apple juice, and broth) or sucking on

popsicles and ice chips. Here are some tips that may help reduce nausea.

• Eat small meals or snacks throughout the day instead of 2 or 3 large meals;
• Eat foods that are cold or at room temperature;
• Cut out foods that are fried, spicy, fatty or sweet;
• Stay away from odours that may bother you such as cooking smells, cigarette smoke, car exhaust or perfume;
• Sit upright in a chair after eating - don’t lie flat for at least 2 hours;
• Wear loose-fitting clothes, especially around the waist;
• Suck on ice, mints or sour candy (but avoid sour candy if you have mouth sores);
• Eat something light a few hours before your chemotherapy treatment.

Fatigue

Feeling tired - or fatigued - is one of the most common side effects of chemotherapy. Many other factors such as stress, diet, sleeping patterns, and your age can also cause fatigue. For some, fatigue may start to improve 2 to 3 months after you complete your chemotherapy treatments. Here’s how you can help reduce fatigue.

• Plan your activities. Allow rest between periods of activity.
• List all of the things you have to do, and number them in order of importance. Only do the things on your list that must get done. Leave the other tasks for another day.
• Ask family and friends to help you with driving, housework or other tasks. For example, ask your friend to pick up a few things for you the next time she goes to the supermarket.
• Eat a well-balanced diet.
• Do light exercise regularly.

Anemia

Chemotherapy medicines affect the bone marrow, which is where red blood cells are formed. Red blood cells carry oxygen to the muscles and other tissues in your body. When there are too few red blood cells, your muscles, and other body tissues can’t get enough oxygen to do their work, and you feel exhausted. If your red blood cell count drops very low, you may also feel weak or dizzy, or may have shortness of breath. These are all symptoms of anemia. If you have these symptoms, tell your doctor or nurse. Your doctor may give you medicine to treat anemia that is caused by chemotherapy. Do not start taking iron tablets on your own, they may not work for anemia caused by chemotherapy medicines and can make your nausea worse.

Mouth sores

Chemotherapy medicines may cause sores in your mouth and throat about a week or two after a chemotherapy treatment. It’s important to keep your mouth clean during the time you’re having chemotherapy because mouth sores can be a source of infection. Be sure to brush your teeth after each meal with a soft toothbrush. You should also see your dentist before you start chemotherapy to have your teeth cleaned and to take care of any dental work you might need. Mouth sores can be painful, but there are a few things you can do to relieve the pain and prevent further irritation.

• Talk to your doctor about medicines you can use

  to relieve painful mouth sores. There are anesthetic lozenges and sprays you can use to numb the sores before you eat.

• Eat your food cold or at room temperature.

  Eating warm or hot food can irritate your mouth sores.

• Cook your food until it’s soft and tender.

• Eat soft, smooth foods such as applesauce,

  bananas, cooked cereals, scrambled eggs, yogurt, noodles, macaroni and cheese, mashed potatoes, cottage cheese, custards, puddings, milk shakes and ice cream You can also make foods smoother and easier to eat by pureeing them in a blender. Some people enjoy eating baby food as the pureed fruits are tasty, easy to store, and ready to eat.

• Cut out spicy or acidic foods (citrus fruits or

  tomatoes) or rough, coarse foods that can irritate mouth sores such as toast and raw vegetables.

• Use a straw to drink liquids. Rinse your mouth

  with water to remove pieces of food that may get stuck in the mouth sore.

• Avoid mouthwashes that contain alcohol,

  smoking cigarettes or drinking alcoholic beverages (beer, wine, and hard liquor).

Colouration of Urine: You can expect to see red colouration of your urine for 1 to 2 days after administration during active therapy.

At site of injection:

Severe adverse events such as local tissue necrosis due to extravasation with intravenous injection might be observed. If you start to have pain, redness, or swelling where the IV is given tell your doctor or nurse right away.

You may also experience:

• Abdominal pain;
• Allergy to light;
• Weight gain.

This is not a complete list of side effects. For any unexpected effects while taking DOXORUBICIN HYDROCHLORIDE INJECTION, contact your doctor or pharmacist.

HOW TO STORE IT

DOXORUBICIN HYDROCHLORIDE INJECTION 2 mg/mL shall be stored under refrigeration (2-8ºC), protected from light and retained in carton until time of use. Discard unused solution.

REPORTING SUSPECTED SIDE EFFECTS

To monitor drug safety, Health Canada through the Canada Vigilance Program 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 Canada Vigilance:

By toll-free telephone: 866-234-2345

By toll-free fax 866-678-6789

Online: www.healthcanada.gc.ca/medeffect By email: CanadaVigilance@hc-sc.gc.ca

By regular mail:

Canada Vigilance National Office

Marketed Health Products Safety and Effectiveness Information Bureau

Marketed Health Products Directorate

Health Products and Food Branch

Health Canada

Tunney’s Pasture, AL 0701C

Ottawa ON K1A 0K9

NOTE: Should you require information related to the management of the side effect, please contact your health care provider before notifying Canada Vigilance. The Canada Vigilance Program does not provide medical advice.

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

1-800-268-4127 ext. 5005 (English);

1-877-777-9117 (French)

or druginfo@novopharm.com

Novopharm Limited

30 Novopharm Court

Toronto, Ontario

Canada, M1B 2K9

Last revised: July 18, 2008