Methotrexate Injection BP (Uman Pharma): Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

Methotrexate belongs to a group of medicines known as antimetabolites. It is used in high doses to treat many types of cancers, including breast cancer, Non-Hodgkin's lymphoma and leukemia. At lower doses, it may also be used to treat psoriasis and rheumatoid arthritis.

What it does:

Methotrexate works by blocking an enzyme needed by body cells to live. This interferes with the growth of some cells, such as skin cells in psoriasis that are growing rapidly. In rheumatoid arthritis, methotrexate acts on the inflammatory cells that cause joint swelling. Methotrexate therapy is used to control psoriasis and rheumatoid arthritis but it will not cure them. In cancer, methotrexate works by blocking an enzyme process in cancer cells so that they cannot grow. Some normal cells in the body may be affected as well.

Your doctor may have prescribed methotrexate for another purpose. Ask your doctor if you have any questions about why it has been prescribed for you.

When it should not be used:

Do not take Methotrexate Injection, BP if you:

• Are allergic to any component of the drug (see What the

  important non-medicinal ingredients are). Some of the symptoms of an allergic reaction to methotrexate may include rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or troubled breathing.

• Have any blood disorders including:

  • bleeding from a lack of blood cells called platelets.
  • low iron in the blood (anemia).

• Have an immune system disorder such as AIDS

  (autoimmune deficiency syndrome) or HIV, the virus which causes AIDS.

• Have an infection.
• Have severe kidney or liver disorder.

• Suffer from alcoholism or alcoholic liver disease.

• Have a stomach ulcer.

• Have inflammation and bleeding from the rectum, with

  abdominal pain and diarrhea (ulcerative colitis).

• Are pregnant or breastfeeding.

What the medicinal ingredient is:

Methotrexate (meth-o-TREX-ate).

What the important non-medicinal ingredients are: Sodium chloride, sodium hydroxide and water for injection.

What dosage forms it comes in:

Methotrexate Injection, BP 25 mg/mL in the following presentation:

25 mg/mL

50 mg / 2 mL (no preservative) as a single use vial

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

• You should not plan to have children while taking methotrexate or for a while after stopping treatment. (Talk to your doctor for further details.)
• Use a reliable method of birth control to prevent pregnancy.

Before Using This Medicine

Before you begin treatment with methotrexate, you should talk to your doctor about the good this medicine will do as well as the risks of using it.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For methotrexate, the following should be considered:

Allergies:

• Tell your doctor if you have ever had any unusual or allergic reaction to methotrexate.

Pregnancy:

• Tell your doctor if you are pregnant or if you plan to have children. There is a good chance that this medicine may cause birth defects if either the male or female is taking it at the time of conception or if it is taken during pregnancy. Methotrexate may cause harm or even death of the fetus. Also, many cancer medicines may cause sterility, which could be permanent. Although sterility is probably rare with this medicine, the possibility should be kept in mind.
• Be sure that you have discussed this with your doctor before taking this medicine. It is best to use some kind of birth control while you are taking methotrexate. Tell your doctor right away if you think you have become pregnant while taking methotrexate.

Breast-feeding:

• Tell your doctor if you are breast-feeding or if you intend to breast-feed during treatment with this medicine. Because methotrexate may cause serious side effects, breast-feeding is generally not recommended while you are taking it.

Children:

• Newborns and other infants may be more sensitive to the

  effects of methotrexate. However, in other children it is not expected to cause different side effects or problems than it does in adults.

Older adults:

• Side effects may be more likely to occur in the elderly,

  who are usually more sensitive to the effects of methotrexate.

Other medicines:

• When you are taking methotrexate, it is important that

  your doctor know if you are taking any other prescription or nonprescription medicine. They should also be told if you have ever been treated with x-rays or cancer medicines or if you drink alcohol.

Other medical problems:

The presence of other medical problems may affect the use of methotrexate. Tell your doctor if you have any other medical problems, especially:

• Alcohol abuse (or history of)

• Chickenpox (including recent exposure) or

  Herpes zoster (shingles)

• Colitis
• Disease of the immune system
• Gout (or history of)
• Kidney stones (or history of)
• Infection
• Intestine blockage
• Kidney disease
• Liver disease
• Mouth sores or inflammation
• Stomach ulcer

Precautions while using this medicine

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

Do not drink alcohol while taking methotrexate. Alcohol can increase the chance of liver problems.

Some patients who take methotrexate may become more sensitive to sunlight than they are normally. Avoid too much sun exposure and do not use a sunlamp until you see how you react to the sun, especially if you tend to burn easily.

You should not receive certain vaccinations while taking methotrexate. Discuss this with your doctor. Avoid anyone who has had oral polio vaccine for at least six weeks. Do not get close to them or stay in the same room for very long. If this is not possible, wear a mask over your nose and mouth.

Some side effects such as dizziness and fatigue may affect the ability to drive or operate machinery. These activities should be avoided. If you have any concerns, please consult your doctor.

Methotrexate can lower the number of white blood cells in your blood temporarily, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this happens, there are certain precautions you can take, especially when your blood count is low to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Check with your doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands.
• Be careful not to cut yourself when you are using sharp objects such as scissors or a razor.
• Avoid contact sports or other situations where bruising or injury could occur.

INTERACTIONS WITH THIS MEDICATION

Tell your doctor and pharmacist what prescription and nonprescription medications you are taking. Methotrexate may interact with other medicines such as:

• acetyl salicyclic acid (ASA) and other pain killers or nonsteroidal anti-inflammatory drugs (NSAIDs)
• Some antibiotics (including penicillins and sulfonamides, and medicines to prevent malaria – pyrimethamine)
• some epilepsy treatments
• some cancer treatments
• some vaccines

• some medicines used to lower your cholesterol

  (including cholestyramine)

• azathioprine (used to prevent transplant organ

  rejection)

• cytarabine (used to treat leukemia)
• leflunomide (used to treat rheumatoid arthritis)
• mercaptopurine (used to treat leukemia)
• nitrous oxide anaesthesia
• probenicid (used to treat gout)
• retinoid medicines (used to treat acne)
• sulfonylureas (used to treat diabetes)

• sulfasalazine (used to treat Crohn's disease,

  rheumatoid arthritis and ulcerative colitis)

• theophylline (used to treat asthma)
• the vitamin folic acid
• phenytoins

It is very important to tell your doctor about all other medicines you are taking including those you buy without a prescription. You may need to receive different amounts of your medicine or you may need to

receive different medicines.

Tell any doctor that is treating you that you are taking methotrexate.

If you have not told your doctor or pharmacist about any of the above, tell them before you are given methotrexate.

PROPER USE OF THIS MEDICATION

Take methotrexate only as directed by your doctor. Do not take more or less of it, and do not take it more often than your doctor ordered. The exact amount of medicine you need has been carefully worked out. Taking too much may increase the chance of side effects, while taking too little may not improve your condition.

Methotrexate is often given together with certain other medicines. If you are using a combination of medicines, make sure that you take each one at the proper time and do not mix them. Ask your doctor or pharmacist to help you plan a way to remember to take your medicines at the right times.

While you are using methotrexate, your doctor may want you to drink extra fluids so that you will pass more urine. This will help the drug to pass from the body, and will prevent kidney problems and keep your kidneys working well.

Methotrexate commonly causes nausea and vomiting. Even if you begin to feel ill, do not stop using this medicine without first checking with your doctor. Ask your doctor for ways to lessen these effects.

If you vomit shortly after taking a dose of methotrexate, check with your doctor. You will be told whether to take the dose again or to wait until the next scheduled dose.

Usual dose:

The dose of methotrexate will be different for different patients. The dose that is used may depend on a number of things, including what the medicine is being used for, the patient's size, whether the medicine is being given by mouth or by injection, and whether or not other medicines are also being taken. If you are taking or receiving methotrexate at home, follow your doctor's orders or the directions on the label. If you have any questions about the proper dose of methotrexate, ask your doctor.

If you take too much methotrexate (overdose):

• In the event of overdosage, contact your doctor,

  hospital emergency department or regional Poison Control Centre.

• Do this even if you have no signs of discomfort.

• Always take the labeled medicine bottle with you,,

  even if it is empty.

  If you forget to take methotrexate (missed dose):

  • If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.
  • Otherwise, take it as soon as you remember, then contact your doctor for advice on when to take the next dose.
  • Do not try to make up for missed doses by taking more than one dose at a time.
  • Contact your doctor or pharmacist if you have any doubts or concerns about missed doses.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Along with their needed effects, medicines like methotrexate can sometimes cause unwanted effects. Also, because of the way these medicines act on the body, there is a chance that they might cause other unwanted effects that may not occur until months or years after the medicine is used. These delayed effects may include certain types of cancer, such as leukemia. Discuss these possible effects with your doctor.

The most common side effects include:

• Upset stomach, stomach pain, vomiting, nausea, loss of appetite, dizziness, chills and fever, diarrhea or sores on lips or mouth.
• A fall in the number of white blood cells. This may reduce your resistance to infection and increase your chances of cold sores, blood poisoning or swelling of blood vessels.

Less common side effects are:

• Headaches, hair loss, mood changes, confusion, ringing in the ears, sore eyes, skin rashes, increased sensitivity to sunlight or unexplained weight loss.
• A fall in the number of other blood cells. This may increase your chances of bruising, bleeding or tiredness.
• Damage to the lungs.
• Harm to the unborn baby.

•

Rarely and generally at higher doses for treatment of other diseases, methotrexate can cause other side effects including:

• Liver damage, kidney damage, pain or difficulty urinating, lower back or side pain, blood in urine or stools, dark urine
• Fits, blurred vision, short term blindness
• Drowsiness, weakness
• Hoarseness
• Bloody vomit, black tarry stools or pin-point red spots on the skin
• Reddening or whitening of the skin, acne, boils, itching yellow skin or eyes
• Impotence or loss of interest in sex, decreased fertility, abortion

• Diabetes, thinning of the bones, painful muscles and

  joints

More rarely, it can cause:

• Skin rash and other skin disorders.
• Cancer of lymph glands, sudden death.
• Severe allergic reactions.

This is not a complete list of side effects. For any unexpected effects while taking Methotrexate Injection BP, contact your doctor or pharmacist.

HOW TO STORE IT

To store this medicine:

• Keep out of the reach of children.

• Store it at room temperature and away from heat and

  direct light. Avoid freezing Methotrexate Injection, BP.

• Do not keep outdated medicine or medicine no longer

  needed. Be sure that any discarded medicine is out of the reach of children.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

Report online at www.healthcanada.gc.ca/medeffect Call toll-free at 1-866-234-2345

Complete a Canada Vigilance Reporting Form and:

• Fax toll-free to 1-866-678-6789, or

• Mail to: Canada Vigilance Program

  Health Canada

  Postal Locator 0701C Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^TM Canada Web site at

www.healthcanada.gc.ca/medeffect

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

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found by contacting the sponsor, Uman Pharma Inc., at:

100, boul. de l’Industrie

Candiac, QC, J5R 1J1

Tel: 1-866-296-0354

Last revised: September 2, 2009