Tacrolimus 5mg (five Mg)caps (bx)
WARNING: This drug may raise the chance of getting cancer like lymphoma or skin cancer. Talk with the doctor.Have your skin checked. Tell your doctor if you have any skin changes like a new wart, skin sore or reddish bump that bleeds or does not heal, or a change in the color or size of a mole.Call your doctor right away if you have a swollen gland, night sweats, shortness of breath, or weight loss without trying.This drug may raise the chance of very bad and sometimes deadly infections. Talk with the doctor.Call your doctor right away if you have any signs of infection like fever, chills, flu-like signs, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or a wound that will not heal. @ COMMON USES: It is used to keep the body from harming the organ after an organ transplant.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Immunosuppressant
Pharmacologic Class
Calcineurin Inhibitor
Pregnancy Category
Not available
FDA Approved
Apr 1994
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tacrolimus is a medicine used to prevent your body from rejecting a transplanted organ (like a kidney, liver, or heart). It works by weakening your immune system so it doesn't attack the new organ. Because it weakens your immune system, it's very important to take it exactly as prescribed and to be careful about infections.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
To establish a routine, take your medication at the same time every day. You can take it with or without food, but be consistent in how you take it each time. If you take it with food, always take it with food. If you take it on an empty stomach, always take it on an empty stomach.
When taking your medication, swallow the tablet whole. Do not chew, open, or crush it, as this can affect how the medication works.
Storing and Disposing of Your Medication
To keep your medication effective and safe, store it at room temperature in a dry place, away from the bathroom. Keep all medications in a secure location, out of the reach of children and pets.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist or healthcare provider. Instead, check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to explore drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for a missed dose.
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
To establish a routine, take your medication at the same time every day. You can take it with or without food, but be consistent in how you take it each time. If you take it with food, always take it with food. If you take it on an empty stomach, always take it on an empty stomach.
When taking your medication, swallow the tablet whole. Do not chew, open, or crush it, as this can affect how the medication works.
Storing and Disposing of Your Medication
To keep your medication effective and safe, store it at room temperature in a dry place, away from the bathroom. Keep all medications in a secure location, out of the reach of children and pets.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist or healthcare provider. Instead, check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to explore drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for a missed dose.
Lifestyle & Tips
- Take tacrolimus at the same time every day, usually twice a day, on an empty stomach (at least 1 hour before or 2 hours after food) to ensure consistent absorption. If you must take it with food, be consistent with how you take it.
- Do not crush, chew, or open the capsules. Swallow them whole.
- Do not eat grapefruit or drink grapefruit juice while taking this medication, as it can significantly increase tacrolimus levels and lead to serious side effects.
- Avoid St. John's Wort, as it can decrease tacrolimus levels and lead to organ rejection.
- Avoid live vaccines (e.g., measles, mumps, rubella, chickenpox) while on tacrolimus. Discuss all vaccinations with your transplant team.
- Practice good hygiene (frequent hand washing) and avoid contact with sick individuals to reduce the risk of infection.
- Use sun protection (sunscreen, protective clothing) as tacrolimus can increase your risk of skin cancer.
- Limit alcohol consumption as it can affect liver function and interact with the medication.
- Inform all healthcare providers, including dentists, that you are taking tacrolimus.
Available Forms & Alternatives
Available Strengths:
- Tacrolimus 1mg Capsules
- Tacrolimus 0.5mg (half Mg) Capsules
- Tacrolimus 5mg (five Mg) Capsules
- Tacrolimus 1mg Caps (bx)
- Tacrolimus 0.5mg (half Mg) Cap(bx)
- Tacrolimus 5mg (five Mg)caps (bx)
- Tacrolimus 0.03% Ointment 30gm
- Tacrolimus 0.03% Ointment 60gm
- Tacrolimus 0.03% Ointment 100gm
- Tacrolimus 0.1% Ointment 30gm
- Tacrolimus 0.1% Ointment 60gm
- Tacrolimus 0.1% Ointment 100gm
Dosing & Administration
Adult Dosing
Standard Dose:
Highly individualized based on therapeutic drug monitoring (TDM) and organ transplant type. Typically administered orally twice daily.
Dose Range:
0.075 - 0.2 mg
Condition-Specific Dosing:
kidney_transplant_initial:
0.2 mg/kg/day orally in two divided doses, initiated 24 hours post-transplant.
liver_transplant_initial:
0.1-0.15 mg/kg/day orally in two divided doses, initiated 6-12 hours post-transplant.
heart_transplant_initial:
0.075 mg/kg/day orally in two divided doses, initiated 6-12 hours post-transplant.
Pediatric Dosing
Neonatal:
Not established for routine use, but used off-label with careful monitoring.
Infant:
Dosing typically higher on a mg/kg basis than adults due to faster metabolism. Initial doses for liver transplant: 0.15-0.2 mg/kg/day orally in two divided doses.
Child:
Dosing typically higher on a mg/kg basis than adults due to faster metabolism. Initial doses for liver transplant: 0.15-0.2 mg/kg/day orally in two divided doses.
Adolescent:
Dosing typically higher on a mg/kg basis than adults due to faster metabolism. Initial doses for liver transplant: 0.15-0.2 mg/kg/day orally in two divided doses.
Dose Adjustments
Renal Impairment:
Mild:
No specific initial dose adjustment, but monitor tacrolimus trough levels closely.
Moderate:
No specific initial dose adjustment, but monitor tacrolimus trough levels closely and consider lower end of dosing range.
Severe:
No specific initial dose adjustment, but monitor tacrolimus trough levels closely and consider lower end of dosing range.
Dialysis:
Tacrolimus is not significantly dialyzable. No supplemental dose needed post-dialysis, but monitor levels closely.
Hepatic Impairment:
Mild:
Consider dose reduction (e.g., 25-50% of usual dose) and monitor tacrolimus trough levels closely.
Moderate:
Significant dose reduction (e.g., 50-75% of usual dose) is often required. Monitor tacrolimus trough levels closely.
Severe:
Significant dose reduction (e.g., 75% or more of usual dose) is often required. Monitor tacrolimus trough levels closely.
Pharmacology
Mechanism of Action
Tacrolimus is a calcineurin inhibitor. It binds to the immunophilin FKBP-12 (FK506 binding protein), forming a complex that inhibits the calcium-dependent phosphatase activity of calcineurin. This inhibition prevents the dephosphorylation of the nuclear factor of activated T-cells (NFAT), which is required for the transcription of genes encoding for various cytokines (e.g., interleukin-2, IL-3, IL-4, IL-5, GM-CSF, TNF-alpha). This ultimately inhibits T-lymphocyte activation, proliferation, and the generation of cytotoxic T-cells, thereby suppressing the immune response.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 20-25% (highly variable, range 4-89%)
Tmax:
1-3 hours
FoodEffect:
High-fat meals significantly decrease the rate and extent of absorption (AUC and Cmax can decrease by 27-80%). Grapefruit juice also inhibits metabolism and increases absorption.
Distribution:
Vd:
Approximately 30 L/kg (high volume of distribution)
ProteinBinding:
>98% (primarily to albumin and alpha-1-acid glycoprotein; also extensively binds to erythrocytes)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 12-36 hours (highly variable, depends on patient population and liver function)
Clearance:
Approximately 2.25 L/hr (adults)
ExcretionRoute:
Primarily fecal (approximately 95%), small amount in urine (approximately 2%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not acutely defined; immunosuppressive effects are achieved as therapeutic trough levels are maintained.
PeakEffect:
Achieved with stable therapeutic trough levels, typically after several days of consistent dosing.
DurationOfAction:
Dependent on sustained therapeutic drug levels; effects persist as long as drug is present above minimum effective concentration.
Safety & Warnings
BLACK BOX WARNING
Increased Risk of Infections and Malignancies: Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly skin cancer, are consequences of immunosuppression. Post-transplant lymphoproliferative disorder (PTLD), associated with Epstein-Barr Virus (EBV), has been reported in immunosuppressed organ transplant patients. Risk of neurotoxicity and nephrotoxicity. Not for use in combination with sirolimus or everolimus.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Kidney Problems: Inability to pass urine, changes in urine output, blood in the urine, or sudden weight gain.
Electrolyte Imbalance: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance problems, abnormal heartbeat, seizures, loss of appetite, or severe nausea and vomiting.
High Blood Pressure: Severe headache, dizziness, fainting, or changes in vision.
Acidosis (Too Much Acid in the Blood): Confusion, rapid breathing, rapid heartbeat, irregular heartbeat, severe stomach pain, nausea, vomiting, excessive sleepiness, shortness of breath, or feeling extremely tired or weak.
Skin Problems: Warm, red, or painful skin or sores on the body.
Chest Pain or Shortness of Breath: Chest pain or pressure, shortness of breath, sudden weight gain, or swelling in the arms or legs.
Neurological Symptoms: Shakiness, trouble moving around, unexplained bruising or bleeding, burning, numbness, or tingling sensations, or pale skin.
Progressive Multifocal Leukoencephalopathy (PML): A rare and potentially life-threatening brain condition that can cause disability or death. Seek medical help if you experience confusion, memory problems, depression, changes in behavior, weakness on one side of the body, speech or thinking difficulties, balance problems, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially life-threatening brain condition that can cause confusion, decreased alertness, vision changes, seizures, or severe headache. Seek medical help immediately if you experience any of these symptoms.
Abnormal Heartbeat (Prolonged QT Interval): This medication can increase the risk of abnormal heartbeats, which can be life-threatening.
Gastrointestinal Problems: Severe stomach pain, black, tarry, or bloody stools, vomiting blood, or coffee ground-like vomit.
Blood Problems: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), a rare and potentially life-threatening condition that can cause confusion, extreme tiredness or weakness, bruising, bleeding, dark urine, yellow skin or eyes, pale skin, changes in urine output, vision changes, weakness on one side of the body, speech or thinking difficulties, balance problems, or fever.
Other Possible Side Effects
While many people may not experience any side effects or only mild ones, it's essential to be aware of the following potential side effects:
Dizziness, tiredness, or weakness
Headache
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Heartburn
Trouble sleeping
Back pain
Joint pain
* Nose or throat irritation
If you experience any of these side effects or have concerns, contact your doctor or seek medical attention. You can also report side effects to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
While rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Kidney Problems: Inability to pass urine, changes in urine output, blood in the urine, or sudden weight gain.
Electrolyte Imbalance: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance problems, abnormal heartbeat, seizures, loss of appetite, or severe nausea and vomiting.
High Blood Pressure: Severe headache, dizziness, fainting, or changes in vision.
Acidosis (Too Much Acid in the Blood): Confusion, rapid breathing, rapid heartbeat, irregular heartbeat, severe stomach pain, nausea, vomiting, excessive sleepiness, shortness of breath, or feeling extremely tired or weak.
Skin Problems: Warm, red, or painful skin or sores on the body.
Chest Pain or Shortness of Breath: Chest pain or pressure, shortness of breath, sudden weight gain, or swelling in the arms or legs.
Neurological Symptoms: Shakiness, trouble moving around, unexplained bruising or bleeding, burning, numbness, or tingling sensations, or pale skin.
Progressive Multifocal Leukoencephalopathy (PML): A rare and potentially life-threatening brain condition that can cause disability or death. Seek medical help if you experience confusion, memory problems, depression, changes in behavior, weakness on one side of the body, speech or thinking difficulties, balance problems, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially life-threatening brain condition that can cause confusion, decreased alertness, vision changes, seizures, or severe headache. Seek medical help immediately if you experience any of these symptoms.
Abnormal Heartbeat (Prolonged QT Interval): This medication can increase the risk of abnormal heartbeats, which can be life-threatening.
Gastrointestinal Problems: Severe stomach pain, black, tarry, or bloody stools, vomiting blood, or coffee ground-like vomit.
Blood Problems: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), a rare and potentially life-threatening condition that can cause confusion, extreme tiredness or weakness, bruising, bleeding, dark urine, yellow skin or eyes, pale skin, changes in urine output, vision changes, weakness on one side of the body, speech or thinking difficulties, balance problems, or fever.
Other Possible Side Effects
While many people may not experience any side effects or only mild ones, it's essential to be aware of the following potential side effects:
Dizziness, tiredness, or weakness
Headache
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Heartburn
Trouble sleeping
Back pain
Joint pain
* Nose or throat irritation
If you experience any of these side effects or have concerns, contact your doctor or seek medical attention. You can also report side effects to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of infection: fever, chills, sore throat, cough, unusual fatigue, painful urination, new pain or swelling.
- Signs of kidney problems: swelling in your ankles or feet, decreased urination, unusual tiredness.
- Signs of liver problems: yellowing of your skin or eyes (jaundice), dark urine, pale stools, severe stomach pain, nausea, vomiting.
- Neurological problems: tremors (shaking), headache, dizziness, confusion, numbness or tingling in your hands or feet, seizures.
- High blood sugar: increased thirst, increased urination, increased hunger, blurred vision.
- High blood pressure: severe headache, blurred vision.
- Severe stomach pain, nausea, vomiting, or diarrhea.
- Unusual bruising or bleeding.
- Any new skin lesions or changes to existing moles.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have a prolonged QT interval on an electrocardiogram (ECG).
If you are currently taking cyclosporine or sirolimus.
If you or your partner are pregnant, as this medication may pose a risk to the unborn baby.
If you or your partner plan to become pregnant, discuss effective birth control methods with your doctor before starting this medication. If you or your partner become pregnant while taking this medication, notify your doctor immediately.
If you are breastfeeding or plan to breastfeed.
This medication can interact with other drugs and health conditions. Therefore, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
* Your health problems
Your doctor will help you determine whether it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have a prolonged QT interval on an electrocardiogram (ECG).
If you are currently taking cyclosporine or sirolimus.
If you or your partner are pregnant, as this medication may pose a risk to the unborn baby.
If you or your partner plan to become pregnant, discuss effective birth control methods with your doctor before starting this medication. If you or your partner become pregnant while taking this medication, notify your doctor immediately.
If you are breastfeeding or plan to breastfeed.
This medication can interact with other drugs and health conditions. Therefore, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
* Your health problems
Your doctor will help you determine whether it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. When you receive a new prescription, verify that you have the correct medication by checking it carefully. If you suspect that you have been given the wrong medication or are unsure about its appearance, contact your doctor immediately.
To minimize the risk of infection, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu. Regular blood tests and other laboratory evaluations, as directed by your doctor, are crucial to monitor your condition.
Be aware that taking other medications concurrently with this drug can affect its levels in your body, potentially increasing the risk of organ rejection or side effects. If you are taking other medications, consult your doctor to determine if more frequent blood tests are necessary.
If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, discuss this with your doctor. Additionally, avoid consuming grapefruit and grapefruit juice while taking this medication.
Regular blood pressure checks, as advised by your doctor, are important because this medication can cause high blood pressure. Similarly, monitor your blood sugar levels, as this medication can lead to high blood sugar, including the development or worsening of diabetes. Report any signs of high blood sugar, such as confusion, drowsiness, unusual thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath, to your doctor.
Ensure you are up to date with all recommended vaccinations before starting treatment with this medication. Consult your doctor before receiving any vaccines, as some vaccines may not be effective or may increase the risk of infection when taken with this medication.
Prolonged use of this medication may increase the risk of skin cancer. To reduce this risk, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear that provide sun protection.
This medication may also affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before initiating treatment with this medication.
To minimize the risk of infection, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu. Regular blood tests and other laboratory evaluations, as directed by your doctor, are crucial to monitor your condition.
Be aware that taking other medications concurrently with this drug can affect its levels in your body, potentially increasing the risk of organ rejection or side effects. If you are taking other medications, consult your doctor to determine if more frequent blood tests are necessary.
If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, discuss this with your doctor. Additionally, avoid consuming grapefruit and grapefruit juice while taking this medication.
Regular blood pressure checks, as advised by your doctor, are important because this medication can cause high blood pressure. Similarly, monitor your blood sugar levels, as this medication can lead to high blood sugar, including the development or worsening of diabetes. Report any signs of high blood sugar, such as confusion, drowsiness, unusual thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath, to your doctor.
Ensure you are up to date with all recommended vaccinations before starting treatment with this medication. Consult your doctor before receiving any vaccines, as some vaccines may not be effective or may increase the risk of infection when taken with this medication.
Prolonged use of this medication may increase the risk of skin cancer. To reduce this risk, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear that provide sun protection.
This medication may also affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before initiating treatment with this medication.
Overdose Information
Overdose Symptoms:
- Severe kidney problems (e.g., acute kidney injury)
- Severe neurological symptoms (e.g., seizures, severe tremor, confusion)
- Severe gastrointestinal upset (e.g., nausea, vomiting, diarrhea)
- Liver dysfunction
What to Do:
There is no specific antidote for tacrolimus overdose. Treatment is supportive. Contact a poison control center immediately or seek emergency medical attention. Call 1-800-222-1222.
Drug Interactions
Contraindicated Interactions
- Live attenuated vaccines (e.g., measles, mumps, rubella, varicella, yellow fever, rotavirus, BCG, oral typhoid)
- Pimecrolimus, Sirolimus, Everolimus (concomitant use may increase risk of adverse effects, especially nephrotoxicity and neurotoxicity)
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, erythromycin, telithromycin, ritonavir, cobicistat, nelfinavir, indinavir, saquinavir, boceprevir, telaprevir, grapefruit juice) - significantly increase tacrolimus levels, requiring substantial dose reduction.
- Strong CYP3A4 inducers (e.g., rifampin, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's Wort) - significantly decrease tacrolimus levels, requiring substantial dose increase.
- Nephrotoxic agents (e.g., aminoglycosides, amphotericin B, NSAIDs, cyclosporine) - increased risk of nephrotoxicity.
- Potassium-sparing diuretics, ACE inhibitors, ARBs - increased risk of hyperkalemia.
- Vaccines (inactivated) - may have reduced efficacy due to immunosuppression.
Moderate Interactions
- Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, fluconazole, amiodarone, cimetidine, metronidazole, omeprazole, ranitidine) - may increase tacrolimus levels.
- Moderate CYP3A4 inducers (e.g., efavirenz, etravirine, modafinil) - may decrease tacrolimus levels.
- Statins (e.g., atorvastatin, simvastatin) - increased risk of myopathy/rhabdomyolysis due to CYP3A4 inhibition.
- Oral contraceptives - may affect tacrolimus levels and vice versa.
- Cannabidiol (CBD) - potential for increased tacrolimus levels via CYP3A4 inhibition.
Minor Interactions
- Antacids (aluminum/magnesium hydroxide) - may reduce tacrolimus absorption if co-administered.
- Cholestyramine - may reduce tacrolimus absorption.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic parameters and monitor for potential myelosuppression (anemia, leukopenia, thrombocytopenia).
Timing: Prior to initiation of therapy.
Renal Function Tests (Serum Creatinine, BUN, eGFR)
Rationale: To establish baseline kidney function and monitor for tacrolimus-induced nephrotoxicity.
Timing: Prior to initiation of therapy.
Liver Function Tests (ALT, AST, Bilirubin, Alkaline Phosphatase)
Rationale: To establish baseline liver function and monitor for hepatotoxicity.
Timing: Prior to initiation of therapy.
Electrolytes (Potassium, Magnesium)
Rationale: To establish baseline levels and monitor for hyperkalemia and hypomagnesemia, common side effects.
Timing: Prior to initiation of therapy.
Blood Pressure
Rationale: To establish baseline and monitor for hypertension.
Timing: Prior to initiation of therapy.
Blood Glucose (Fasting or HbA1c)
Rationale: To establish baseline and monitor for new-onset diabetes after transplant (NODAT).
Timing: Prior to initiation of therapy.
Lipid Profile (Total Cholesterol, LDL, HDL, Triglycerides)
Rationale: To establish baseline and monitor for dyslipidemia.
Timing: Prior to initiation of therapy.
Routine Monitoring
Tacrolimus Whole Blood Trough Levels (C0)
Frequency: Initially daily or every other day until stable, then 2-3 times per week, then weekly, then every 1-3 months depending on post-transplant phase and stability.
Target: Highly variable based on organ type, time post-transplant, and concomitant immunosuppression (e.g., Kidney: 5-15 ng/mL early, 3-7 ng/mL maintenance; Liver: 8-20 ng/mL early, 5-15 ng/mL maintenance; Heart: 8-12 ng/mL early, 5-10 ng/mL maintenance).
Action Threshold: Levels outside target range require dose adjustment and re-monitoring. Levels >20 ng/mL often associated with increased toxicity.
Renal Function Tests (Serum Creatinine, BUN, eGFR)
Frequency: Initially daily or every other day, then 2-3 times per week, then weekly, then every 1-3 months.
Target: Stable baseline values; monitor for increasing trends.
Action Threshold: Significant increase in creatinine (>25% from baseline or above upper limit of normal) may indicate nephrotoxicity or rejection, requiring investigation and potential dose adjustment.
Electrolytes (Potassium, Magnesium)
Frequency: Initially daily or every other day, then 2-3 times per week, then weekly, then every 1-3 months.
Target: Potassium: 3.5-5.0 mEq/L; Magnesium: 1.5-2.5 mg/dL.
Action Threshold: Hyperkalemia (>5.5 mEq/L) or hypomagnesemia (<1.5 mg/dL) requiring intervention.
Blood Pressure
Frequency: Daily initially, then regularly at clinic visits.
Target: <130/80 mmHg (or as per target for transplant patients).
Action Threshold: Sustained hypertension requiring antihypertensive therapy.
Blood Glucose
Frequency: Weekly initially, then monthly or as clinically indicated.
Target: Fasting glucose <126 mg/dL; HbA1c <6.5%.
Action Threshold: Persistent hyperglycemia or diagnosis of NODAT requiring antidiabetic medication.
CBC with differential
Frequency: Weekly initially, then monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant leukopenia (<3,000/mm³), anemia (Hgb <10 g/dL), or thrombocytopenia (<100,000/mm³) requiring investigation or dose adjustment.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, new pain)
- Signs of kidney dysfunction (decreased urine output, swelling in legs/ankles, fatigue)
- Signs of liver dysfunction (yellowing of skin/eyes, dark urine, abdominal pain, nausea/vomiting)
- Neurological symptoms (tremor, headache, seizures, confusion, paresthesias)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
- Cardiovascular symptoms (chest pain, shortness of breath, palpitations)
- Signs of new-onset diabetes (increased thirst, frequent urination, unexplained weight loss)
- Skin changes (rash, new moles, skin lesions)
Special Patient Groups
Pregnancy
Tacrolimus can cause fetal harm when administered to a pregnant woman. It crosses the placenta. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Close monitoring of tacrolimus levels and fetal development is essential.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of congenital malformations, though data are mixed. Close monitoring of tacrolimus levels is crucial due to potential pharmacokinetic changes.
Second Trimester:
Risk of neonatal complications such as hyperkalemia, renal dysfunction, and premature birth. Close monitoring of tacrolimus levels and fetal growth.
Third Trimester:
Increased risk of neonatal complications including hyperkalemia, renal dysfunction, and premature birth. Close monitoring of tacrolimus levels and fetal growth. Consider lower tacrolimus trough levels if clinically appropriate.
Lactation
Tacrolimus is excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant (e.g., nephrotoxicity, immunosuppression), breastfeeding is not recommended during tacrolimus therapy.
Infant Risk:
High (L4 - Possibly Hazardous)
Pediatric Use
Pediatric patients generally require higher doses on a mg/kg basis compared to adults due to faster drug clearance. Close therapeutic drug monitoring is essential to maintain target trough levels and minimize toxicity. Increased risk of post-transplant lymphoproliferative disorder (PTLD), especially in EBV-seronegative children.
Geriatric Use
No specific dose adjustments are generally required based solely on age. However, elderly patients may have age-related decreases in renal or hepatic function, or more comorbidities, which may necessitate careful dose titration and closer monitoring for adverse effects and drug interactions.
Clinical Information
Clinical Pearls
- Tacrolimus has a narrow therapeutic index; therapeutic drug monitoring (TDM) of whole blood trough levels is critical for safe and effective use.
- Absorption is highly variable and affected by food; consistent administration (e.g., always on an empty stomach) is crucial.
- Numerous significant drug interactions, especially with CYP3A4 inhibitors and inducers, necessitate careful medication reconciliation and dose adjustments.
- Common side effects include nephrotoxicity, neurotoxicity (tremor, headache), hypertension, hyperglycemia (new-onset diabetes), hyperkalemia, and gastrointestinal disturbances.
- Patients are at increased risk for infections and malignancies due to immunosuppression; emphasize infection prevention and sun protection.
- Different formulations (capsules, extended-release capsules) are not interchangeable on a mg-to-mg basis; patients should remain on the same formulation.
Alternative Therapies
- Cyclosporine (another calcineurin inhibitor)
- Sirolimus (mTOR inhibitor)
- Everolimus (mTOR inhibitor)
- Mycophenolate mofetil (MMF)
- Azathioprine
- Corticosteroids (e.g., prednisone)
- Belatacept (co-stimulation blocker)
Cost & Coverage
Average Cost:
Varies widely, typically $100-$500+ per 30 capsules (5mg)
Generic Available:
Yes
Insurance Coverage:
Tier 3 (Non-preferred Brand) or Tier 1/2 (Generic) for most commercial and Medicare Part D plans. Requires prior authorization for brand name.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to facilitate prompt and effective treatment.