Tacrolimus (Oral)

Tacrolimus is an immunosuppressive medication administered after an allogeneic organ transplant to lower the risk of organ rejection.

Overview

Tacrolimus is used in combination with other medications to prevent the body from rejecting a transplanted organ like the liver, heart, and kidney. The drug belongs to a group of medications called immunosuppressive agents. It works by suppressing the immune system to stop the white blood cells from attempting to get rid of the transplanted organ. Tacrolimus may be used together with steroids, mycophenolate mofetil (brand name Cellcept), basiliximab (Simulect), or azathioprine (Imuran).

Tacrolimus is a very strong medication. It can cause very severe side effects, such as kidney problems. It may also suppress the body's ability to fight infections. You and your healthcare provider should talk about potential benefits and risks of this medication before using it. Tacrolimus is only available with your healthcare provider's prescription.

Conditions Treated

  • Prophylaxis of organ rejection during kidney transplant

Tacrolimus has been indicated for the prophylaxis of organ rejection in people on allogeneic kidney transplants. It is advisable that tacrolimus should be administered concomitantly with mycophenolate mofetil (MMF) or azathioprine and adrenal corticosteroids. Therapeutic drug monitoring is recommended for patients on tacrolimus.

  • Prophylaxis of organ rejection during liver transplant

Tacrolimus is indicated for the prophylaxis of organ rejection in patients on allogeneic liver transplants. It is advisable that tacrolimus be administered concomitantly with adrenal corticosteroids. Therapeutic drug monitoring is recommended for patients on tacrolimus during liver transplant.

  • Prophylaxis of organ rejection during heart transplant

Tacrolimus has been indicated for prophylaxis of organ rejection in patients on allogeneic heart transplants. It is advisable that tacrolimus be administered concomitantly with mycophenolate mofetil (MMF) or azathioprine. Therapeutic drug monitoring is recommended for all patients on tacrolimus during heart transplant.

Limitations of use

  • Tacrolimus should never be used simultaneously with cyclosporine
  • Tacrolimus injection should be considered for patients unable to take tacrolimus orally
  • Use of tacrolimus together with sirolimus is not recommended during liver transplant. The efficacy and safety of tacrolimus with sirolimus during kidney transplant is yet to be established.

Type of Medicine

  • Immunosuppressive agent

Side Effects

Along with the desired effects, tacrolimus may cause some unwanted effects. Check with your healthcare provider immediately if you experience any of the following side effects.

Most common side effects

  • Hallucinations and abnormal dreams
  • Stomach or abdominal pain
  • Convulsions (seizures)
  • Diarrhea
  • Fever and sore throat
  • Agitation
  • Frequent urination
  • Severe headache
  • Loss of energy and general body weakness
  • Shortness of breath
  • Nausea and vomiting
  • Muscle twitching and trembling
  • Flu-like symptoms
  • Loss of appetite
  • Pale skin or rashes on the skin
  • Mental depression

Less common side effects include:

  • Chest pain
  • Blurred vision
  • Profuse sweating
  • Muscle cramps
  • Increased sensitivity to pain
  • Pain or numbness in the limbs
  • Ringing in the ears
  • Blurred vision
  • Chest pain
  • Increased sensitivity to pain
  • Muscle cramps
  • Numbness or pain in the legs
  • Ringing in the ears
  • Sweating
  • Dementia
  • Enlarged heart
  • Bloating
  • Bloody urine
  • Constipation and indigestion
  • Increased thirst
  • Cough
  • Drowsiness
  • Lower back or side pain
  • Yellow eyes or skin
  • Rapid weight gain
  • Red skin lesions
  • Tender, swollen glands in the neck

Call your healthcare provider for medical advice about these side effects. You may also report the side effects to the FDA at 1-800-FDA-1088

Dosage

Tacrolimus is available in the following doses:

  • Tablet, extended release
  • Capsule
  • Capsule, extended release

Tacrolimus dosage differs from patient to patient. Follow your healthcare provider's orders or directions on the label. The following is information on the average tacrolimus dosage. If your dose is different, do not change it without the approval of your healthcare provider.

The amount of the medicine you take depends on a number of factors, including the strength of the medicine, number of daily doses, time allowed between doses. The length of time you will be on this medication depends on the medical problem for which it has been prescribed.

For tacrolimus oral dosage(capsules):

To counter heart transplant rejection

  • Adults

Dosage is based on body weight and must be set by your healthcare provider. Starting dose is usually 0.075 mg per kilogram of body weight per day. This should be divided into two doses and taken twice a day (12 hours apart). Your healthcare provider may adjust the dose as needed.

  • Children

Use and dosage must be determined by the healthcare provider

To counter kidney transplant rejection

  • Adults

Dosage is based on body weight and should be determined by your healthcare provider. The starting dose should be 0.1 to 0.2 mg per kg of body weight, divided into two doses and taken 12 hours apart. Your healthcare provider may adjust the doses as needed.

  • Children

Use and dosage should be determined by the healthcare provider

To counter liver transplant rejection

  • Adults and children aged 16 and older

Dosage is based on body weight and must be set by your healthcare provider. Starting dose is 0.1 to 0.15 mg per kg of body weight, divided into two doses and taken 12 hours apart. Your healthcare provider may adjust the doses as needed

  • Children younger than 16 years

Dosage is based on body weight and must be determined the healthcare provider. The starting dose is 0.15 to 0.2 mg per kg of body, divided into two doses and taken 1 hours apart. The healthcare provider may adjust the dosage as needed.

Oral dosage (extended release capsules):

To counter kidney transplant rejection

  • Adults and children 16 years and older

Dosage is based on body weight and must be set by your healthcare provider. The dose is usually between 0.1 to 0.2 mg per kg of body per day. It is administered as a single dose. Your healthcare provider may adjust the dosage as necessary

  • Children younger than 16 years

Use and dosage should be determined by the healthcare provider

For oral dosage form (extended-release tablets):

To counter kidney transplant rejection

  • Adults

Take one tablet daily, every morning

  • Children

Use and dosage should be determined by the healthcare provider

Proper use of tacrolimus

Take tacrolimus exactly as directed by your healthcare provider. Never take more or less of the medication, or more often than your healthcare provider directed. Using too much of the medication will increase the chance, and severity, of the side effects, while using too little may cause your body to reject the transplanted organ.

Tacrolimus comes with a Medication Guide and patient information. It is quite important to read and understand the information contained therein. Ask your healthcare provider about anything you do not understand.

Tacrolimus is administered together with other medications. Make sure you have a proper schedule of all your medications during the day. Your healthcare provider will give you a daily schedule for taking your medication.

You may take tacrolimus immediate-release capsule with or without food. But, be sure to take it the same way each time.

If you are using tacrolimus extended capsules:

  • Swallow the capsule whole with water. Do not break, chew, crush or divide the capsule
  • Take the capsule every morning, preferably on an empty stomach 1 hour before or 3 hours after breakfast
  • Do not take the capsule with alcohol or a beverage drink

If you are taking extended-release tablet:

  • Take the tablet at the same time every day (possibly in the morning)
  • Take the medication on an empty stomach
  • Swallow the tablet whole. Do not chew, crush, or divide it
  • Do not take the tablet with alcohol or a beverage drink

Do not drink grapefruit juice or eat grapefruit while on tacrolimus medication. Grapefruit and grapefruit juice will increase the levels of the medicine in your body.

Do not stop taking this medication without first informing your healthcare provider. You may be required to be on tacrolimus for the rest of your life to prevent your body from rejecting the transplanted organ.

Use only tacrolimus brand that has been prescribed by your healthcare provider as different brands do not work the same way.

Missed tacrolimus dosage

If you have missed tacrolimus and it is less than 14 hours since your regular time, take the missed dose right away. If more than 14 hours have elapsed since your regular schedule, skip the dose and resume your regular schedule the following day. Do not double dose to make up for missed dosage.

Tacrolimus overdose

Inform your healthcare as soon as possible if you suspect tacrolimus overdose. You may also report tacrolimus overdose to the Poison Control Center at 1-800-222-1222

Interactions

Since tacrolimus is metabolized primarily by CYP3A enzymes, drugs and substances known to inhibit these enzymes may increase the concentration of tacrolimus in the blood. On the other hand, medications that cause induction of CYP3A enzymes may lower the levels of tacrolimus in the blood. Thus, dosage adjustments may be necessary along with close monitoring of tacrolimus levels in the blood when the medication is co-administered with CYP3A inducers or inhibitors. In addition, patients should be monitored for adverse reactions including QT prolongation as well as changes in renal function.

Mycophenolic acid products

With a given dose of mycophenolic acid (MPA) products, exposure to MPA is higher with tacrolimus co-administration than with cyclosporine co-administration because cyclosporine, unlike tacrolimus, interrupts the enterohepatic recirculation of MPA. Healthcare providers should also be aware of the potential for increased MPA exposure after crossover from cyclosporine to tacrolimus in patients who are concomitantly receiving MPA-containing medications.

Grapefruit juice

Grapefruit inhibits CYP3A-enzymes resulting in increased levels of tacrolimus in the blood. Patients should avoid drinking grapefruit juice or eating grapefruits, while on this medication.

Protease inhibitors

Most protease inhibiting medications disrupt CYP3A enzymes and can cause a rise in tacrolimus levels in the blood. It is advisable to avoid concomitant use of nelfinavir with tacrolimus unless the benefits far outweigh the risks. Tacrolimus concentrations in the blood tend to increase when the drug is co-administered with boceprevir or telaprevir. Monitoring tacrolimus blood levels, and tacrolimus-associated adverse effects are recommended when the drug is used concomitantly with protease inhibitors like boceprevir, ritonavir, and telaprevir.

Antifungal agents

Regular monitoring of tacrolimus levels in the blood and appropriate dose adjustments is recommended when the medication is concomitantly used with antifungal drugs like Voriconazole, itraconazole, ketoconazole, and clotrimazole. These medications inhibit CY3A metabolism.

Calcium channel blockers

Calcium channel blockers like nifedipine, diltiazem, verapamil, and nicardipine inhibit CYP3A metabolism of tacrolimus and may increase tacrolimus levels in the blood. Monitoring tacrolimus levels in the blood and appropriate dosage adjustments of the drug are recommended when tacrolimus is used concomitantly with calcium channel blocking medications.

Anti-bacterial medications

Anti-bacterial medications like clarithromycin, erythromycin, and chloramphenicol inhibit CYP3A metabolism of tacrolimus and may increase the drug's concentrations in the blood. Monitoring tacrolimus levels in the blood and appropriate dosage adjustment are recommended when anti-bacterial medications are used concomitantly with tacrolimus.

Anti-mycobacterial medications

Anti-bacterial medications like rifampin and rifabutin induce CYP3A enzymes and may decrease tacrolimus concentrations in the blood. It is important that tacrolimus levels are monitored and appropriate dosage adjustments made when tacrolimus is used concomitantly with these anti-mycobacterial medications.

Anticonvulsants

Anticonvulsant medications like phenobarbital and carbamazepine induce CYP3A enzymes and may lower tacrolimus levels in the blood. It is important that the drug's level is monitored and appropriate dosage adjustment effected with tacrolimus is used concomitantly with anticonvulsants.

Besides, studies indicate that concomitant administration of tacrolimus with phenytoin may result in a rise in phenytoin plasma concentrations.

St. John's Wort (Hypericum perforatum)

St. John's Wort may induce CYP3A enzymes to result in lower tacrolimus levels in the blood. It is, therefore, important that tacrolimus concentrations in the blood is regularly monitored and appropriate dosage adjustment effected with these two medications are used concomitantly.

Gastric acid neutralizers/ suppressors

Gastric acid suppressors like omeprazole and lansoprazole, as CYP3A4 and CYP2C19, may potentially inhibit CYP3A4 metabolism of tacrolimus and thus substantially increase the drug's concentrations in the body. This is especially common in transplant patients who are poor or intermediate CYP2C19 metabolizers, as compared to those who are efficient CYP2C19 metabolizers. Cimetidine may also inhibit the CYP3A4 metabolism of tacrolimus to increase its levels in the blood.

Co-administration of tacrolimus with aluminum and magnesium hydroxide antacids may also increase tacrolimus concentrations in the blood.

Other interactions

Nefazodone, bromocriptine, metoclopramide, ethynyl, danazol, estradiol, methylprednisolone, amiodarone, and herbal products that contain schisandra sphenanthera extracts may inhibit CYP3A metabolism of tacrolimus to result in increased levels of the drug in the blood.

Use of tacrolimus with any of the following medications may increase the risk of developing side effects. If both medications have been prescribed by your doctor, there may be a need for dosage adjustment or change of how often you use one or both medicines:

  • Aluminum Carbonate, Basic
  • Aluminum Phosphate
  • Aluminum hydroxide
  • Danazol
  • Chloramphenicol
  • Dihydroxyaluminum Aminoacetate
  • Clotrimazole
  • Magnesium Carbonate
  • Magnesium Oxide
  • Magnesium Hydroxide
  • Ertapenem
  • Lansoprazole
  • Magnesium Trisilicate
  • Nifedipine
  • Metoclopramide

Tacrolimus interactions with food/alcohol/tobacco

Certain medications should never be used at or around the time of eating certain types of food to avoid interactions. Using tobacco and alcohol with certain medications may also cause interactions. Using tacrolimus with the following is not recommended:

  • Ethanol
  • Grapefruit Juice

Other medical problems

The pre-existence of certain medical conditions may affect the use of tacrolimus. Make sure to tell your healthcare provider if you suffer from, or have a family history of, any of the following conditions before using tacrolimus.

Warnings

Before using any medication, the risks associated with it must be weighed against potential benefits. This is a decision that you and your healthcare provider will have to make. For tacrolimus, the following should be considered:

Allergies

Let your doctor know if you have ever had any unusual allergic reaction to any medication, including tacrolimus. Also, tell your healthcare provider if you have any other allergies, including food, dyes, animals, or preservatives.

Pediatric

Studies have not shown any pediatric-specific complications that would limit the use of tacrolimus in children with a liver transplant. However, no studies have been performed on the relationship of age to the effects of this medication in children with heart and kidney transplants. Safety and efficacy of tacrolimus are yet to be established.

Geriatric

Studies conducted to date have not identified geriatric-specific complications that would limit the usefulness of tacrolimus in the elderly patients. However, these patients are more likely to develop liver, kidney, and heart problems, which may prompt the need for caution and dosage adjustments when on tacrolimus medication.

Management of immunosuppression

Only healthcare providers experienced in immunosuppressive therapy and management of organ transplant should prescribe tacrolimus. Patients on this medication should be managed in facilities that are fully equipped and staffed with laboratory and supportive medical resources. Healthcare providers handling maintenance therapy should have complete information requisite for following up on the patient

Lymphoma and related malignancies

Patients on immunosuppressants, including tacrolimus, are at a greater risk of developing lymphomas and other malignancies, especially of the skin. The risk is related to the duration and intensity of immunosuppression rather than use of any specific agent. Patients at risk of skin cancer should limit their exposure to sunlight and UV light by using sunscreen and protective clothing when outdoors.

Serious infections

Patients on immunosuppressants, including tacrolimus, are at increased risk of developing bacterial, fungal, protozoan, and viral infections, including opportunistic infections. These infections may result in severe, and at times fatal, outcomes. Because they suppress the immune system, immunosuppressants should be used cautiously.

Polyomavirus infection

Patients on immunosuppressants, including tacrolimus, are at increased risk of polyomavirus infection. Polyomavirus infection in transplant patients may have serious, and at times fatal, outcomes. Reduction in tacrolimus dosage should be considered when the patient has developed evidence of PML or PVAN.

New onset of diabetes after organ transplant

Tacrolimus has been shown to trigger new onset of diabetes mellitus. A new onset after an organ transplant is reversible in some patients. However, Hispanic and Black patients are at a greater risk. Thus, blood glucose levels should be closely monitored in patients on tacrolimus.

Nephrotoxicity

Tacrolimus, like other calcineurin-inhibitors, can cause acute or chronic nephrotoxicity, especially when administered in high doses. Acute nephrotoxicity is often linked to vasoconstriction of the afferent renal arteriole. It is characterized by increased serum creatinine, hyperkalemia, and reduced urine output. The condition is reversible. Patients with impaired renal function should be monitored closely and tacrolimus dosage adjusted where possible.

Neurotoxicity

Tacrolimus may cause a range of neurotoxicities, especially when administered in high doses. The most severe neurotoxicities include delirium, posterior reversible encephalopathy syndrome (PRES), and coma. Patients on tacrolimus therapy have been reported to develop PRES. Delirium and coma have been associated with high doses of tacrolimus. Necessary immunosuppressant dose adjustment is recommended if a patient develops any of these conditions during treatment.

Hyperkalemia

Hyperkalemia has been reported with tacrolimus use. Serum potassium levels should be monitored in patients on this medication. Also, careful consideration should be taken into account before administering agents associated with hyperkalemia like angiotensin receptor blockers to patients on tacrolimus.

Hypertension

Hypertension is a common adverse effect of tacrolimus. Patients on this medication may require antihypertensive therapy.

Vaccinations

The use of live vaccines should be avoided during tacrolimus treatment. These include mumps, measles, oral polio, yellow fever, intranasal influenza, BCG, TY21a Typhoid, and varicella vaccines.

Pregnancy and breastfeeding

Do not use this medication while pregnant or breastfeeding. Inform your doctor when you get pregnant while on tacrolimus.

Storage

Tacrolimus should be stored in a closed container at room temperature away from moisture, heat and direct light. Do not free the medicine. Keep out of reach of children and pets. All unused and expired medication should be disposed of appropriately.

Summary

Tacrolimus is an immunosuppressant medication that is used in combination with other medications to prevent the body from rejecting transplanted organs like the liver, kidney, or heart. The drug is can be co-administered with steroids, mycophenolate mofetil, or azathioprine. It works by suppressing the immune system to stop the white blood cells from attempting to reject the transplanted organ

Tacrolimus is available for oral administration as tablets or capsules. Inactive ingredients in the medication include hypromellose USP, lactose monohydrate NF, magnesium stearate NF, and croscarmellose sodium NF. Other ingredients include titanium dioxide USP and ferric oxide NF.

Tacrolimus is a very strong medication hence it should never be used in the absence of a qualified healthcare provider specialized in immunosuppression medications and organ transplant. The medication is only available with doctor's prescription.

Being an immunosuppressant, tacrolimus greatly affects the body's immune system. Thus, the risk of opportunistic infections such as bacterial, fungal, viral, and protozoal infections is high among patients on this medication. Patients tacrolimus are also at a high risk of developing lymphoma and other malignancies, especially of the skin. Patients on this medication are advised to use sunscreen and wear protective clothing while outdoors to protect them from UV radiation.

Some of tacrolimus' side effects can be severe. Call your healthcare provider immediately if you notice some of the drugs side effects like breathing difficulty, irregular heartbeats, mental depression and impaired vision and hearing.

Important precautions when using tacrolimus

It is important that your healthcare provider checks your progress on a regular basis to make sure that the body is responding properly to the drug. Regular blood and urine tests may be conducted to check for, and correct, unwanted effects.

Tacrolimus may increase your risk of developing skin cancer or cancer of the lymph system. As such, talk to your doctor if you have concerns about this risk.

Tacrolimus may increase your risk of developing opportunistic infections. Avoid being near sick people while you are on this medication. Clean your hands often and inform your doctor if you have any infection before starting this medication. Also, tell your healthcare provider if you have ever had an infection that is persistent or one that keeps coming back.

While on tacrolimus treatment, and immediately after stopping treatment, do not get any immunization without your healthcare provider's consent. Tacrolimus lowers the body's resistance hence the vaccine might not work well, or you might end up contracting the disease the vaccine is meant to prevent. In addition, you should avoid contact with members of your household who recently received live vaccines (like measles, polio, rubella, BCG, and flue) as the chance of passing the virus to you are quite high. Do not get into contact or share a room with them for long. Talk to your healthcare provider if you have concerns or questions about this.

Tacrolimus may increase your risk of contracting a rare, and serious, viral infection caused by the BK polyomavirus. This virus may affect your kidney's function resulting in the failure of the transplanted kidney. Contact your healthcare provider immediately if you experience any of the following symptoms: reduced frequency or amount of urine, blood in urine, persistent thirst, lower back and side pain, loss of appetite, swelling of the face and limbs, nausea, breathing difficulty, vomiting, unusual fatigue and tiredness, and rapid weight gain.

Tacrolimus may increase your risk of contracting a serious, and rare, brain infection called progressive multifocal leukoencephalopathy (PML). Call your healthcare provider as soon as possible if you notice the following symptoms: loss of vision and hearing ability, clumsiness, loss of coordination, memory loss, confusion, speaking difficulty, and weakness of the limbs.

Tacrolimus may also increase your risk of developing a stomach condition called gastrointestinal perforation. Talk to your healthcare provider if you have concerns about this risk.

Some patients may develop a serious nervous system condition upon using this medication. Inform your doctor as soon as possible when you notice the following symptoms: dizziness, blurred vision, mental depression, high blood pressure, seizures, rapid heartbeat, and persistent headache.

Do not take other medications, including over-the-counter prescriptions, supplements, vitamins, and herbal medications without the consent of your healthcare service provider.

Tacrolimus may cause a rare condition called pure red cell aplasia (PRCA). This is a rare condition where the body stops making red blood cells resulting in severe anemia. Call your healthcare provider if you develop persistent fever, pale skin, sore throat, unusual bleeding, or unusual fatigue and general weakness.

 

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Last Reviewed:
January 30, 2018
Last Updated:
April 16, 2018
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