TACROLIMUS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Prograf

In Canada?

• Prograf

Category

• Immunosuppressant

Description

Tacrolimus (ta-KROE-li-mus) belongs to a group ofmedicines known as immunosuppressive agents. It is used to lower the body'snatural immunity in patients who receive organ (for example, kidney, liver,pancreas, lung, and heart) transplants.

When a patient receives an organ transplant, the body's white blood cellswill try to get rid of (reject) the transplanted organ. Tacrolimus works bypreventing the white blood cells from getting rid of the transplanted organ.

Tacrolimus may also be used for other indications, as determined by yourdoctor.

Tacrolimus is a very strong medicine. It can cause side effects that canbe very serious, such as kidney problems. It may also reduce the body's abilityto fight infections. You and your doctor should talk about the good this medicinewill do as well as the risks of using it.

Tacrolimus is available only with your doctor's prescription, in the followingdosage forms:

Oral
• Capsules (U.S. and Canada)

Parenteral
• Injection (U.S. and Canada)

Before Using This Medicine

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

Allergies?Tell your health care professional if you have everhad any unusual or allergic reaction to tacrolimus. Also, if you will be receivingthis medicine by injection, tell your health care professional if you areallergic to any other substances, such as castor oil.

Pregnancy?Some women have become pregnant and had babies whilereceiving tacrolimus after an organ transplantation. Some of the newborn babieshad temporary kidney problems after birth. Some babies were born prematurely.

Breast-feeding?Tacrolimus passes into breast milk. There is achance that it causes the same side effects in the baby that it does in themother. It may be necessary for you to stop breast-feeding during treatment.

Children?This medicine does not cause different types of sideeffects or problems in children than it does in adults, although some sideeffects may occur more or less often than they do in adult patients.

Older adults?There is no specific information comparing the useof tacrolimus in the elderly with the use in other age groups. Tacrolimusis not expected to cause different side effects or problems in older peoplethan it does in younger adults. However, older patients may need lower dosesof tacrolimus.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takingtacrolimus, it is especially important that your health care professionalknows if you are taking any of the following:

• Amiloride or
• Spironolactone (e.g., Aldactone) or
• Triamterene (e.g., Dyrenium)?Since both tacrolimus and thesemedicines increase the amount of potassium in the body, potassium levels couldbecome too high

• Cyclosporine (e.g., Neoral)?May increase the effects of tacrolimusby increasing the amount of this medicine in the body; may cause kidney problems

• Danazol (e.g., Danocrine) or
• Erythromycin (medicine for infection) or
• Fluconazole (e.g., Diflucan) or
• Itraconazole (e.g., Sporanox) or
• Ketoconazole (e.g., Nizoral) or
• Lansoprazole (e.g., Prevacid)?May increase the effects of tacrolimusby increasing the amount of this medicine in the body

• Nelfinavir (e.g., Viracept)?May increase the amount of tacrolimusin the body; your doctor may need to lower the dose of your medicine

• Rifampin (e.g., Rifadin)?May decrease the effects of tacrolimusby decreasing the amount of this medicine in the body

Other medical problems?The presence of other medicalproblems may affect the use of tacrolimus. Make sure you tell your doctorif you have any other medical problems, especially:

• Cancer?Tacrolimus can make this condition worse.

• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)?Risk of severe disease affecting otherparts of the body

• Diabetes mellitus (sugar diabetes)?Tacrolimus can increasethe amount of sugar in the blood.

• Hepatitis or
• Kidney disease or
• Liver disease, other?Tacrolimus can have harmful effects onthe kidney in patients with these conditions; a lower dose of tacrolimus maybe needed in patients with these conditions.

• Hyperkalemia (high amount of potassium in the blood) or
• Nervous system problems?Tacrolimus can make these conditionsworse.

• Infection?Tacrolimus decreases the body's ability to fightinfection.

Proper Use of This Medicine

Take this medicine only as directed by your doctor. Do not take moreor less of it and do not take it more often than your doctor ordered. Theexact amount of medicine you need has been carefully worked out. Taking toomuch may increase the chance of side effects, while taking too little maylead to rejection of your transplanted organ.

To help you remember to take your medicine, try to get into the habit oftaking it at the same time each day. This will also help tacrolimus work betterby keeping a constant amount in the blood.

Absorption of this medicine may be changed if you change your diet. Thismedicine should be taken consistently with respect to meals. You should notchange the type or amount of food you eat unless you discuss it with yourhealth care professional.

Grapefruit and grapefruit juice may increase the effects of tacrolimusby increasing the amount of this medicine in the body. You should not eat grapefruit or drink grapefruit juice while you are takingthis medicine.

Do not stop taking this medicine without first checkingwith your doctor. You may have to take medicine for the rest of yourlife to prevent your body from rejecting the transplant.

Dosing?The dose of tacrolimus will be different fordifferent patients. Follow your doctor's orders or thedirections on the label. The following information includes only theaverage doses of tacrolimus. If your dose is different,do not change it unless your doctor tells you to do so.

The number of capsules that you take depends on the strength of the medicinein the capsule and the dose prescribed by your doctor. Also, the number of doses you take each day, the time allowed between doses, andthe length of time you take the medicine depend on the medical problem forwhich you are taking tacrolimus.

• For oral dosage form (capsules):
  • Adults, teenagers, or children?Dose is based on body weightand will be determined by your doctor.
• For injection dosage form:
  • Adults, teenagers, or children?Dose is based on body weightand will be determined by your doctor.

Missed dose?If you miss a dose of tacrolimus and remember itwithin 12 hours, take the missed dose as soon as you remember. However, ifit is almost time for the next dose, skip the missed dose, go back to yourregular dosing schedule, and check with your doctor. Do not double doses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in otherdamp places.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of reach of children.

Precautions While Using This Medicine

The effectsof tacrolimus may cause increased infections and delayed healing. Dental work,whenever possible, should be completed prior to beginning this medicine.

It is very important that your doctor check your progressat regular visits. Your doctor will want to do laboratory tests tomake sure that tacrolimus is working properly and to check for unwanted effects.

Tacrolimus may increase your risk for getting skincancer when exposed to sunlight.

• Stay out of direct sunlight especiallybetween the hours of 10:00 AM and 3:00 PM if possible.
• Wear protective clothing , including ahat. Also, wear sunglasses
• Apply a sun block product that has askin protection factor (SPF) of 15 or higher. If you have questions aboutthis, check with your health care professional.
• Apply a sunblock lipstick that has an SPF of at least 15 to protectyour lips.
• Do not use a sun lamp or a tanning bed.
• If you notice any unusual changes to your skin,check with your doctor

While you are taking tacrolimus, it is important to maintain good dentalhygiene and see a dentist regularly for teeth cleaning.

Raw oysters or other shellfish may contain bacteriathat can cause serious illness, and possibly death. This is more likely tobe a problem if these foods are eaten by patients with certain medical conditions. Even eating oysters from "clean" water or good restaurants does notguarantee that the oysters do not contain the bacteria. Symptoms of this infectioninclude sudden chills, fever, nausea, vomiting, blood poisoning, and sometimesdeath. Eating raw shellfish is not a problem for most healthy people; however,patients with the following conditions may be at greater risk: cancer, immunedisorders, organ transplantation, long-term corticosteroid use (as for asthma,arthritis, or organ transplantation), liver disease (including viral hepatitis),excess alcohol intake (2 to 3 drinks or more per day), diabetes, stomach problems(including previous stomach surgery and low stomach acid), and hemochromatosis(an iron disorder). Do not eat raw oysters or other shellfishwhile you are taking tacrolimus. Be sure oysters and shellfish are fully cooked.

While you are being treated with tacrolimus, and after you stop treatmentwith it, it is important to see your doctor about theimmunizations (vaccinations) you should receive. Do not get any immunizationswithout your doctor's approval. Tacrolimus lowers your body's resistance.For some immunizations, there is a chance you might get the infection theimmunization is meant to prevent. For other immunizations, it may be especiallyimportant to receive the immunization to prevent a disease. In addition, otherpersons living in your house should not take oral poliovirus vaccine sincethere is a chance they could pass the poliovirus on to you. Also, avoid personswho have recently taken oral poliovirus vaccine. Do not get close to them,and do not stay in the same room with them for very long. If you cannot takethese precautions, you should consider wearing a protective face mask thatcovers the nose and mouth.

Treatment with tacrolimus may also increase the chance of getting otherinfections. If you can, avoid people with colds or other infections. If youthink you are getting a cold or other infection, check with your doctor.

Tacrolimus is not available in all countries. If youare traveling to another country, be sure you will have a supply of your medicine.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Some side effects will have signs or symptoms that you can see or feel. Yourdoctor will watch for others by doing certain tests.

Also, because of the way tacrolimus acts on the body, there is a chancethat it may cause effects that may not occur until years after the medicineis used. These delayed effects may include certain types of cancer, such aslymphomas or skin cancers.

Check with your doctoror nurse immediately if any of the following side effects occur:

More common

Abdominal pain; abnormal dreams; agitation; anxiety; chills; confusion; convulsions(seizures); diarrhea; dizziness; fever and sore throat; flu-like symptoms; frequent urination; hallucinations (seeing or hearing things that are not there); headache; infection; itching; loss of appetite; loss of energy or weakness; mental depression; muscle trembling or twitching; nausea; nervousness; paleskin; shortness of breath; skin rash; swelling of feet or lower legs; tingling; trembling and shaking of hands; trouble in sleeping; unusual bleeding or bruising; unusual tiredness orweakness; vomiting

Less common

Blurred vision; chest pain; increased sensitivity to pain; musclecramps; numbness or pain in legs; ringing in ears; sweating

Rare

Enlarged heart; flushing of face orneck; general feeling of discomfort or illness; weight loss; wheezing

Incidence not determined??Observed during clinical practice with tacrolimus;estimates of frequency cannot be determined

black, tarry, stools ; blistering, peeling, looseningof skin ; bloating; bloodin urine ; blurred vision; cough; constipation ; cramping, or burning; convulsions; drowsiness; fainting ; fast, slow, or irregular heartbeat ; heartburn; increased blood pressure; increased thirst ; indigestion; irregular heartbeat ; itching ; joint or muscle pain; lightheadedness ; loss of appetite; lowerback/side pain ; nausea; pinpoint red spots on skin ; pounding or rapidpulse; recurrent fainting; red irritated eyes; red skin lesions, often witha purple center; shortness of breath; sores; stomach pain; sugar in the urine; troubled breathing ; ulcers, or white spots in mouth or on lips ; weakness; weight gain; yellow eyes or skin

This medicine may also cause the following side effects thatyour doctor will watch for:

More common

Hyperkalemia (too much potassium in the blood); hypomagnesemia (not enough magnesium in the blood); kidney problems

Less common

Hyperlipidemia (high cholesterol); hypertension (high blood pressure)

Other side effects not listed above may also occur insome patients. If you notice any other effects, check with your doctor.

Additional Information

Once a medicine has been approved for marketingfor a certain use, experience may show that it is also useful for other medicalproblems. Although not specifically included in the product labeling, tacrolimusis used in certain patients with the following medical conditions:

• Bone marrow transplantation
• Uveitis, severe, refractory (an eye condition)

For patients receiving bone marrow transplantation, tacrolimus may workby preventing the cells from the transplanted bone marrow from attacking thecells of the patient. The dose of tacrolimus for patients receiving bone marrowtransplantation is based on body weight. The usual dose is 0.12 to 0.3 mgper kg (0.05 to 0.14 mg per pound) of body weight a day for patients takingtacrolimus by mouth, and 0.04 to 0.1 mg per kg (0.018 to 0.045 mg per pound)of body weight a day for patients receiving tacrolimus by injection.

The dose of tacrolimus for patients with severe, refractory uveitis isbased on body weight. For severe, refractory uveitis, the usual dose is 0.1to 0.15 mg per kg (0.045 to 0.068 mg per pound) of body weight a day.

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.