What Advagraf is used for and how to use it
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Advagraf - Consumer Medicine Information

Manufacture: Astellas
Country: Canada
Condition: Kidney Transplant (Renal Transplant), Liver Transplant (Organ Transplant)
Class: Immunosuppressive agents
Form: Capsules
Ingredients: tacrolimus, ethylcellulose, hypromellose, magnesium stearate, lactose, sodium lauryl sulfate, gelatin, titanium dioxide and ferric oxide

Advagraf

tacrolimus extended release capsules

About this Medication

What the medication is used for

Advagraf is the brand name for tacrolimus extended release capsules. Advagraf helps to prevent your body from rejecting a kidney or liver transplant. Advagraf is used concomitantly with adrenal corticosteroids (liver and kidney) and mycophenolate mofetil (kidney).

What it does

Your body's immune system is your defence system. Immunity is the way your body protects itself from infections and other foreign material. When you receive a transplant, your immune system recognizes the transplanted organ as foreign and will try to reject it. Advagraf is an anti-rejection drug that helps your body accept your transplanted organ.

When it should not be used

Do not take Advagraf if you are allergic to any of the ingredients in Advagraf (see “What the nonmedicinal ingredients are”).

What the medicinal ingredient is

Tacrolimus.

What the nonmedicinal ingredients are

Ethylcellulose, hypromellose, magnesium stearate, lactose, sodium lauryl sulfate, gelatin, titanium dioxide and ferric oxide.

What dosage forms it comes in

Advagraf is available in an extended release capsule, once a day. Each capsule contains 0.5 mg, 1 mg, 3 mg or 5 mg of tacrolimus.

The 0.5 mg capsule has a light yellow cap and an orange body. The capsule is imprinted in red with “647” on the capsule body and “0.5 mg” on capsule cap.

The 1 mg capsule has a white cap and an orange body. The capsule is imprinted in red with “677” on the capsule body and “1 mg” on capsule cap.

The 3 mg capsule has an orange cap and an orange body. The capsule is imprinted in red with “637” on the capsule body and “3 mg” on capsule cap.

The 5 mg capsule has a greyish red cap and an orange body. The capsule is imprinted in red with “687” on the capsule body and “5 mg” on capsule cap.

Warnings and Precautions

Advagraf should be prescribed by doctors experienced in the use of immunosuppressive drugs and management of organ transplants. Advagraf suppresses your body's immune system. As a result, it may increase your chances of getting infections and some kinds of cancer, including skin and lymph gland cancer (lymphoma). Wear protective clothing and use a sunscreen with a high sun protection factor (SPF ≥30) to limit exposure to sunlight and UV light. However, getting cancer from taking an anti-rejection medicine is not common.

BEFORE you use Advagraf, be sure that you are taking the correct dose and correct formulation of tacrolimus (Advagraf, tacrolimus extended release capsules) and you have told your doctor the following:

  • If you have taken Prograf, Advagraf or tacrolimus before and had a bad, unusual or allergic reaction
  • About all other medicines or treatments you use, including any products you buy off the shelf such as over-the-counter drugs and herbal or home remedies
  • If you have heart problems: congenital or acquired QT prolongation
  • About all other health conditions, including kidney and/or liver problems, you have now, or have had in the past
  • If you are pregnant, plan to become pregnant, or are breastfeeding a baby. Advagraf may cause fetal abnormalities and malformations. Pregnancy should be avoided while taking Advagraf because its effect on pregnancy or on an unborn baby is not known. You must use a reliable method of birth control before, during your treatment and for 6 weeks after stopping your treatment with Advagraf. Advagraf has been found in human breastmilk. Breast-feeding is not recommended while taking Advagraf. It is important to notify your doctor right away if you become pregnant or father a child while taking Advagraf. It is recommended that you do not take Advagraf if you are, or become, pregnant. However, never stop taking Advagraf without first consulting your doctor
  • If you have a rare hereditary disease of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption, as this product contains lactose

Advagraf may cause new onset diabetes in kidney transplant patients. Your doctor may order tests to monitor your blood glucose levels.

Interactions with this Medication

Some medicines and even some foods can affect how well Advagraf works. After you start taking Advagraf:

  • Be sure to tell your transplant team, family doctor, dentist, pharmacist and any other health care professional treating you the names of all the medicines you are taking. This is the only way that your health care team can help prevent drug interactions that could be serious. Make sure you know if you are to stop, or continue, other drugs you had been taking
  • Always check with your transplant team before you start taking any new medicine, or any products you buy off the shelf such as over-the-counter drugs, herbal or nutritional supplements, especially St. John's Wort (Hypericum perforatum), Schisandra sphenanthera extracts, vitamins or home remedies
  • While you are taking Advagraf, do not get any vaccinations without your transplant team's approval. The vaccination may not work as well as it should or may result in serious side effects
  • A high intake of potassium should be avoided during Advagraf treatment
  • Do not eat or drink any product that contains grapefruit or grapefruit juice in combination with your medicine unless your transplant team approves

Advagraf blood levels can be affected by other medicines you take, and blood levels of other medicines can be affected by taking Advagraf, which may require an increase or decrease in the Advagraf dose. In particular, you should tell your doctor if you have recently taken medicines such as:

  • Antacids: magnesium aluminum hydrochloride
  • Antiarrhythmic: amiodarone
  • Antifungals: clotrimazole, fluconazole, ketoconazole, itraconazole, voriconazole
  • Calcium channel blockers: diltiazem nicardipine, nifedipine, verapamil
  • Gastrointestinal prokinetic agents: cisapride*, metoclopramide
  • Macrolide antibiotics: erythromycin, clarithromycin, troleandomycin
  • Proton pump inhibitor: lansoprazole, omeprazole
  • Other drugs: bromocriptine, cimetidine, chloramphenicol, cyclosporine, danazol, ethinyl estradiol, methylprednisolone, nefazodone
  • Protease inhibitors: boceprevir, nelfinavir, ritonavir, saquinavir, telaprevir
  • Anticonvulsants: carbamazepine, phenobarbital, phenytoin
  • Anti-infectives: rifampin, rifabutin, capsofungin
  • Calcineurin inhibitor: sirolimus
  • Potassium sparing diuretics
  • Herbal preparations: St. John's Wort (Hypericum perforatum), Schisandra sphenanthera extracts

*drugs no longer marketed in Canada.

Proper Use of this Medication

Advagraf can protect your new kidney or liver only if you take the medicine correctly.

Your new organ needs around-the-clock protection so your body does not reject it. The success of your transplant depends a great deal upon how well you help Advagraf do its job. Here is what you need to do.

Take Advagraf exactly as prescribed

Your transplant team will tell you what dose to take and how to take it. It is important to take Advagraf capsules exactly as told by your transplant team. Your transplant team may adjust your dose until they find what works best for you. Never change your dose on your own. Never stop taking Advagraf even if you are feeling well. However, if you feel poorly on Advagraf, discuss this with your transplant team.

Take Advagraf once-a-day, in the morning

Try to pick a time that will be easy for you. Do not vary the time. You must take Advagraf at the same time every day. If you decide to take Advagraf at 7:00 a.m., take it at this same time every day. This will make sure you always have enough medicine in your body to give your new organ the around-the-clock protection it needs.

Take Advagraf the same way each day

Most people are directed to take Advagraf on an empty stomach, 2 hours before or after a meal. However, some people prefer to take Advagraf with food to help reduce possible stomach upset. Whether you take Advagraf with or without food, it is important to take Advagraf the same way every day. For example, if you take Advagraf with food, you should always take it with food. Do not change the way you take this medicine without telling your transplant team, since this could change the amount of protection you get from Advagraf.

Take your full dose of medication, every day

It is important to take your dose exactly as prescribed by your doctor. If you miss even one dose, your new kidney could lose the protection it needs against rejection by your body.

If you travel and change time zones, be sure to ask your transplant team how to adjust your dosage schedule so your new organ does not lose its protection.

Take the same tacrolimus medicine every time

Make sure that you receive the same tacrolimus medicine (the brand name of the medicine should always be the same) every time you collect your prescription, unless your transplant specialist has agreed to change to a different tacrolimus medicine. This medicine should be taken once a day. If the appearance of this medicine is not the same as usual, or if dosage instructions have changed, or if the brand name is different, speak to your doctor or pharmacist as soon as possible to make sure that you have the right medicine.

Plan ahead so that you do not run out of Advagraf

Make sure you have your prescription for Advagraf refilled and at home before you need it. Circle the date on a calendar when you need to order your refill. Allow extra time if you receive your medicines through the mail.

When having a blood test to measure Advagraf

On the days you are going to have a blood test to measure the amount of Advagraf in your body, your transplant team will ask you not to take your dose until after the blood sample is taken.

Missed dose

If a dose of Advagraf is missed, the dose may be taken up to 14 hours after the scheduled time without risk of overexposure (i.e., for a missed 8:00 am dose, take by 10:00 pm). Beyond the 14-hour time frame, you should wait until the usual scheduled time the following morning to take the next regular daily dose.

Do not double dose.

Overdose

In case of drug overdose, contact a healthcare practitioner (e.g. doctor), hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Side Effects and what to do about them

Like other medicines, Advagraf may cause side effects in some people. If you think that you are having side effects, talk to your doctor right away. DO NOT stop taking Advagraf on your own.

  • Because Advagraf decreases the function of your immune system you may be more likely to get an infection. Tell your doctor right away about any cold or flu-like symptoms (such as fever or sore throat), any mouth sores or burning discomfort with urination.
  • Be sure to tell your doctor right away if you notice any of these symptoms, and especially if they continue, bother you in any way, or seem to increase in intensity:
    • diarrhea, nausea, constipation, vomiting, loss of appetite, stomach pain
    • headache, tremors, convulsions, tiredness or fatigue, difficulty sleeping, nightmares
    • urinary tract infection, weakness
    • decreased or increased urine volumes, kidney or liver problems
    • diabetes/increased blood sugar, swelling or tingling in your hands and feet
    • palpitations, abnormal heart rhythms, chest pain, high blood pressure
    • fever, back pain, changes in mood or emotions, difficulty in breathing
    • headache, seizures, visual disturbances or altered mental state, which could be symptoms of posterior encephalopathy syndrome (PRES)
    • progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, changes in thinking, memory and orientation, confusion, personality changes, which could be symptoms of a rare brain infection called progressive multifocal leukoencephalopathy (PML)
  • Immunosuppressive drugs including Advagraf may also increase your chances of developing certain types of cancer. The following are possible warning signs of cancer and should be reported to your doctor as soon as possible:
    • any sore that does not heal
    • unusual bleeding or discharge
    • the appearance of a lump or thickened areas in your breast or anywhere else on your body
    • unexplained stomach upset or any trouble with swallowing
    • any noticeable change in a wart or a mole
    • a nagging cough or hoarseness
    • night sweats
    • persistent and severe headaches
    • swollen lymph nodes
    • a change in your bowel or bladder habits
  • Cases of pure red cell aplasia (PRCA- bone marrow stops producing red blood cells) have occurred in patients taking tacrolimus. Contact your doctor immediately if you suffer symptoms such as fatigue, malaise, weakness, dizziness, fainting, shortness of breath, rapid heartbeat, pallor (paleness of skin), pale stool
  • Cases of gastrointestinal perforation (hole in the stomach or intestine) have occurred in patients taking tacrolimus. If you suffer symptoms such as severe abdominal pain, burning pain, nausea, vomiting and later possibly chills or fever, get medical attention immediately.

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate or extended release tacrolimus oral formulations, have been observed. This has led to serious adverse events, including graft rejection, or other side effects which could be a consequence of either under- or over-exposure to tacrolimus. You should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist.

It is important to regularly tell your doctor how you are feeling and if you have developed any new symptoms while taking Advagraf.

Serious Side Effects, How Often They Happen and what to do about them

Symptom / effect Talk with your doctor or pharmacist Stop taking drug and call your doctor or pharmacist
Only if severe In all cases
Common
Infection (urinary tract, sinusitis, gastroenteritis, influenza, upper respiratory tract)
Early signs of high blood sugar or diabetes: more thirsty than usual, have to urinate more often, have blurred vision or seem to get confused.
Decreased or increased urine volumes, dark coloured urine which may be a sign of kidney problems
Unknown*
Posterior Encephalopathy Syndrome (PRES) with symptoms such as headache, seizures, visual disturbances or altered mental state

*Unable to determine frequency since this is a post-marketing event

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

How to Store it

Keep Advagraf out of the reach and away from children. A child who accidentally takes Advagraf may be seriously harmed. All drugs should be kept in a locked drawer or cupboard if there are children who may accidentally take your drugs. Should anyone accidentally or mistakenly take Advagraf, contact your physician immediately.

Store Advagraf in a dry area at room temperature (25°C) in the container or package that was dispensed by your pharmacist. Do not let the medicine get colder than 15°C or hotter than 30°C.

For instance, do not leave Advagraf in the glove compartment of your car in the summer or winter. Do not keep Advagraf capsules in a hot or moist place such as the medicine cabinet in the bathroom or near the stove or sink in the kitchen.

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, the Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect Canada web site at
www.healthcanada.gc.ca/medeffect.

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

More Information

If you have additional questions or would like to talk with someone to explain something you are worried about, ask your doctor, nurse or pharmacist. They are your best resource for guidance and information.

This document plus the full product monograph, prepared for health professionals can be found at:
http://www.astellas.ca/
or by contacting the sponsor, Astellas Pharma Canada, Inc., at:
1-888-338-1824