Tacrolimus 0.5mg (half Mg) Capsules
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
Category C
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 be careful about infections.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
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.
Swallow your medication whole, without chewing, opening, or crushing it.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications in a safe location, out of the reach of children and pets.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about how to dispose of your medication, consult your pharmacist. You may also want to check if there are 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 dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
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.
Swallow your medication whole, without chewing, opening, or crushing it.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications in a safe location, out of the reach of children and pets.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about how to dispose of your medication, consult your pharmacist. You may also want to check if there are 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 dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take tacrolimus at the same time every day, usually twice a day, on an empty stomach (1 hour before or 2-3 hours after a meal) to ensure consistent absorption. Do not take with food.
- Do not crush, chew, or open capsules. Swallow them whole.
- Do not eat grapefruit or drink grapefruit juice while taking tacrolimus, as it can significantly increase drug levels and lead to serious side effects.
- Avoid St. John's Wort, as it can decrease drug levels and lead to organ rejection.
- Avoid live vaccines (e.g., measles, mumps, rubella, varicella, rotavirus, yellow fever) while on tacrolimus due to weakened immune system. Consult your doctor about all vaccinations.
- Practice good hygiene (frequent hand washing) and avoid contact with sick individuals to reduce the risk of infection.
- Protect yourself from the sun (wear protective clothing, use sunscreen) as tacrolimus can increase your risk of skin cancer.
- Report any signs of infection (fever, chills, sore throat, unusual fatigue) or other new or worsening symptoms to your healthcare provider immediately.
- Do not stop taking tacrolimus or change your dose without consulting your transplant team, as this can lead to organ rejection.
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 indication and therapeutic drug monitoring (TDM). Typical initial oral doses for transplant: Liver: 0.1-0.15 mg/kg/day in 2 divided doses; Kidney: 0.2 mg/kg/day in 2 divided doses; Heart: 0.075 mg/kg/day in 2 divided doses. Doses are adjusted to achieve target trough levels.
Dose Range:
0.075 - 0.2 mg
Condition-Specific Dosing:
Liver Transplant:
Initial oral dose 0.1-0.15 mg/kg/day in 2 divided doses. Adjust to target trough levels (e.g., 5-20 ng/mL initially, then 5-15 ng/mL).
Kidney Transplant:
Initial oral dose 0.2 mg/kg/day in 2 divided doses. Adjust to target trough levels (e.g., 5-20 ng/mL initially, then 5-15 ng/mL).
Heart Transplant:
Initial oral dose 0.075 mg/kg/day in 2 divided doses. Adjust to target trough levels (e.g., 10-20 ng/mL initially, then 5-15 ng/mL).
Ulcerative Colitis (off-label):
Typically 0.1 mg/kg/day in 2 divided doses, adjusted to trough levels (e.g., 10-15 ng/mL).
Pediatric Dosing
Neonatal:
Not established for routine use; specific protocols for congenital anomalies may exist.
Infant:
Dosing is individualized based on weight and indication. Higher doses per kg may be required due to faster clearance. Initial oral doses for liver transplant: 0.15-0.2 mg/kg/day in 2 divided doses. Adjust to target trough levels.
Child:
Dosing is individualized based on weight and indication. Higher doses per kg may be required due to faster clearance. Initial oral doses for liver transplant: 0.15-0.2 mg/kg/day in 2 divided doses. Adjust to target trough levels.
Adolescent:
Dosing is individualized based on weight and indication. Initial oral doses similar to adult doses, but may require higher mg/kg doses due to faster clearance. Adjust to target trough levels.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment required, but monitor renal function closely due to potential nephrotoxicity.
Moderate:
No specific dose adjustment required, but monitor renal function closely and adjust dose to maintain target trough levels while minimizing nephrotoxicity.
Severe:
No specific dose adjustment required, but monitor renal function closely and adjust dose to maintain target trough levels while minimizing nephrotoxicity. Consider lower end of target trough range.
Dialysis:
Tacrolimus is not significantly dialyzable. No specific supplemental dose needed after dialysis. Monitor trough levels.
Hepatic Impairment:
Mild:
Consider lower initial doses (e.g., 25-33% reduction) and monitor trough levels closely.
Moderate:
Significant dose reduction (e.g., 33-50% reduction) is typically required. Monitor trough levels closely and adjust accordingly.
Severe:
Significant dose reduction (e.g., 50% or more reduction) is typically required. Monitor trough levels closely and adjust accordingly. Use with extreme caution.
Pharmacology
Mechanism of Action
Tacrolimus is a calcineurin inhibitor. It binds to the immunophilin FKBP-12 (FK506 binding protein), forming a complex that inhibits calcineurin, a phosphatase. This inhibition prevents the dephosphorylation of nuclear factor of activated T-cells (NFAT), which is essential for the transcription of genes encoding various cytokines (e.g., IL-2, IL-3, IL-4, IL-5, GM-CSF, TNF-alpha). By blocking cytokine production, tacrolimus inhibits T-lymphocyte activation, proliferation, and differentiation, thereby suppressing the immune response.
Pharmacokinetics
Absorption:
Bioavailability:
Oral bioavailability is low and variable (approximately 20-25%, ranging from 4-89%).
Tmax:
Approximately 1-3 hours (for immediate-release capsules).
FoodEffect:
Food, especially high-fat meals, significantly decreases the rate and extent of absorption (AUC and Cmax can decrease by up to 70%). Should be taken consistently on an empty stomach (1 hour before or 2-3 hours after meals).
Distribution:
Vd:
High (approximately 0.85-1.9 L/kg).
ProteinBinding:
Extensive (approximately 98.8-99%), primarily to albumin and alpha-1-acid glycoprotein. Also extensively binds to erythrocytes.
CnssPenetration:
Limited, but can cause neurotoxicity.
Elimination:
HalfLife:
Variable, typically 12-18 hours (range 4-40 hours) in healthy volunteers; longer in liver transplant patients (up to 35 hours).
Clearance:
Approximately 0.04-0.08 L/hr/kg.
ExcretionRoute:
Primarily fecal (approximately 92.5%), with a small amount excreted renally (approximately 2.2%).
Unchanged:
Less than 1% of the dose is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Immunosuppressive effects begin within hours to days, but clinical efficacy requires achieving stable therapeutic trough concentrations.
PeakEffect:
Achieved once stable therapeutic trough concentrations are maintained, typically within 2-3 days of consistent dosing.
DurationOfAction:
Related to the half-life and maintenance of therapeutic trough levels; effects persist as long as drug levels are within the therapeutic range.
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 of the skin, due to immunosuppression. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe tacrolimus. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information essential for the safe use of the drug and for monitoring patients for signs and symptoms of infection and malignancy.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although 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 significant 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 or 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.
Cardiovascular Issues: Chest pain or pressure, shortness of breath, significant weight gain, or swelling in the arms or legs.
Neurological Problems: Shakiness, difficulty moving, unexplained bruising or bleeding, burning, numbness, or tingling sensations, or pale skin.
Progressive Multifocal Leukoencephalopathy (PML): A rare and potentially fatal brain condition. 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. Seek medical help if you experience confusion, decreased alertness, vision changes, loss of vision, seizures, or severe headache.
Abnormal Heartbeat (Prolonged QT Interval): This medication may increase the risk of other potentially life-threatening abnormal heartbeats.
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. Seek medical help if you experience 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
Most people do not experience severe side effects, but it is essential to be aware of the potential risks. If you experience any of the following side effects, contact your doctor or seek medical attention if they bother you or do not go away:
Dizziness, tiredness, or weakness
Headache
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Heartburn
Sleep disturbances
Back pain
Joint pain
* Nose or throat irritation
This is not an exhaustive list of potential side effects. If you have concerns or questions, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although 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 significant 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 or 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.
Cardiovascular Issues: Chest pain or pressure, shortness of breath, significant weight gain, or swelling in the arms or legs.
Neurological Problems: Shakiness, difficulty moving, unexplained bruising or bleeding, burning, numbness, or tingling sensations, or pale skin.
Progressive Multifocal Leukoencephalopathy (PML): A rare and potentially fatal brain condition. 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. Seek medical help if you experience confusion, decreased alertness, vision changes, loss of vision, seizures, or severe headache.
Abnormal Heartbeat (Prolonged QT Interval): This medication may increase the risk of other potentially life-threatening abnormal heartbeats.
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. Seek medical help if you experience 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
Most people do not experience severe side effects, but it is essential to be aware of the potential risks. If you experience any of the following side effects, contact your doctor or seek medical attention if they bother you or do not go away:
Dizziness, tiredness, or weakness
Headache
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Heartburn
Sleep disturbances
Back pain
Joint pain
* Nose or throat irritation
This is not an exhaustive list of potential side effects. If you have concerns or questions, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of infection: fever, chills, sore throat, cough, flu-like symptoms, unusual pain, burning with urination.
- Signs of kidney problems: swelling in ankles/feet, decreased urine output, unusual fatigue.
- Signs of liver problems: yellowing of skin/eyes (jaundice), dark urine, pale stools, severe nausea/vomiting, abdominal pain.
- Signs of neurotoxicity: severe headache, tremor, numbness/tingling, confusion, seizures, visual disturbances.
- Signs of high blood sugar: increased thirst, increased urination, increased hunger, fatigue, blurred vision.
- Signs of high blood pressure: severe headache, dizziness, blurred vision.
- Severe diarrhea, nausea, or vomiting.
- Unusual bleeding or bruising.
- New skin lesions or changes in 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 drug, 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 drugs and health conditions. Do not initiate, stop, or adjust the dosage 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 drug, 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 drugs and health conditions. Do not initiate, stop, or adjust the dosage 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 individuals who have infections, colds, or flu.
Regular blood tests and other laboratory evaluations are crucial while taking this medication, as ordered by your doctor. Many other medications can interact with this drug, potentially increasing the risk of organ rejection or side effects. If you are taking other medications, consult with 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 to avoid potential interactions.
Avoid consuming grapefruit and grapefruit juice while taking this medication.
There is a risk of developing high blood pressure while taking this medication. Adhere to your doctor's recommendations for monitoring your blood pressure.
This medication may also cause high blood sugar levels, including the development of new-onset diabetes or worsening of existing diabetes. Monitor your blood sugar levels as instructed by your doctor, and report any symptoms of high blood sugar, such as confusion, drowsiness, increased thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
Ensure that you are up to date with all recommended vaccinations before starting treatment with this medication. Consult with 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 exposure to sunlight, sunlamps, and tanning beds may increase the risk of skin cancer while taking this medication. Protect yourself from the sun by using sunscreen, wearing protective clothing, and eyewear.
This medication may affect fertility, potentially leading to difficulty conceiving or fathering a child. If you plan to become pregnant or father a child, discuss the potential risks and consequences 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 individuals who have infections, colds, or flu.
Regular blood tests and other laboratory evaluations are crucial while taking this medication, as ordered by your doctor. Many other medications can interact with this drug, potentially increasing the risk of organ rejection or side effects. If you are taking other medications, consult with 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 to avoid potential interactions.
Avoid consuming grapefruit and grapefruit juice while taking this medication.
There is a risk of developing high blood pressure while taking this medication. Adhere to your doctor's recommendations for monitoring your blood pressure.
This medication may also cause high blood sugar levels, including the development of new-onset diabetes or worsening of existing diabetes. Monitor your blood sugar levels as instructed by your doctor, and report any symptoms of high blood sugar, such as confusion, drowsiness, increased thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
Ensure that you are up to date with all recommended vaccinations before starting treatment with this medication. Consult with 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 exposure to sunlight, sunlamps, and tanning beds may increase the risk of skin cancer while taking this medication. Protect yourself from the sun by using sunscreen, wearing protective clothing, and eyewear.
This medication may affect fertility, potentially leading to difficulty conceiving or fathering a child. If you plan to become pregnant or father a child, discuss the potential risks and consequences with your doctor before initiating treatment with this medication.
Overdose Information
Overdose Symptoms:
- Severe tremor
- Headache
- Nausea
- Vomiting
- Abdominal pain
- Kidney dysfunction (elevated creatinine)
- Neurotoxicity (seizures, confusion)
- Hypertension
What to Do:
There is no specific antidote for tacrolimus overdose. Treatment is supportive. Induce emesis or gastric lavage may be beneficial if performed soon after ingestion. Hemodialysis is not effective due to high protein binding and extensive erythrocyte binding. Contact a poison control center immediately (Call 1-800-222-1222 in the US).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Pimecrolimus, Sirolimus, Everolimus (concurrent use may increase risk of nephrotoxicity or other adverse effects, especially with sirolimus/everolimus due to similar MOA and potential for additive toxicity)
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, ritonavir, cobicistat, grapefruit juice) - significantly increase tacrolimus levels, leading to toxicity.
- Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort) - significantly decrease tacrolimus levels, leading to rejection.
- Nephrotoxic agents (e.g., NSAIDs, aminoglycosides, amphotericin B, cyclosporine, ACE inhibitors, ARBs) - increased risk of nephrotoxicity.
- Potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene) - increased risk of hyperkalemia.
- Vaccines (attenuated live vaccines) - risk of infection due to immunosuppression.
Moderate Interactions
- Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, fluconazole, erythromycin) - may increase tacrolimus levels.
- Moderate CYP3A4 inducers (e.g., efavirenz, etravirine) - may decrease tacrolimus levels.
- Drugs affecting gastric pH (e.g., antacids, H2 blockers, PPIs) - may affect tacrolimus absorption (though less significant than food effect).
- Magnesium-containing antacids - may increase tacrolimus levels (mechanism unclear, possibly absorption).
Minor Interactions
- Not typically categorized as minor due to narrow therapeutic index and critical nature of drug levels. All interactions are generally considered significant.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic parameters and monitor for potential myelosuppression.
Timing: Prior to initiation
Renal Function (SCr, BUN, eGFR)
Rationale: To establish baseline kidney function and monitor for nephrotoxicity.
Timing: Prior to initiation
Liver Function Tests (ALT, AST, ALP, bilirubin)
Rationale: To establish baseline liver function and monitor for hepatotoxicity.
Timing: Prior to initiation
Electrolytes (Potassium, Magnesium, Phosphate)
Rationale: To establish baseline levels and monitor for hyperkalemia, hypomagnesemia, hypophosphatemia.
Timing: Prior to initiation
Blood Glucose (Fasting or HbA1c)
Rationale: To establish baseline glucose levels and monitor for new-onset diabetes after transplant (NODAT).
Timing: Prior to initiation
Blood Pressure
Rationale: To establish baseline and monitor for hypertension.
Timing: Prior to initiation
Tacrolimus Whole Blood Trough Level (C0)
Rationale: To establish initial therapeutic range and guide dose adjustments.
Timing: Within 24-48 hours of first dose, or prior to 2nd dose if once daily.
Routine Monitoring
Tacrolimus Whole Blood Trough Level (C0)
Frequency: Initially 2-3 times per week until stable, then weekly for first month, then every 2-4 weeks for 3 months, then monthly or as clinically indicated.
Target: Highly variable by indication, time post-transplant, and center protocol (e.g., Liver: 5-15 ng/mL; Kidney: 5-15 ng/mL; Heart: 8-15 ng/mL).
Action Threshold: Levels outside target range require dose adjustment and re-monitoring.
Renal Function (SCr, BUN, eGFR)
Frequency: Weekly for first month, then every 2-4 weeks, then monthly or as clinically indicated.
Target: Stable baseline or within acceptable limits for transplant patients.
Action Threshold: Significant increase in SCr (>25% from baseline or >0.3 mg/dL acute rise) may indicate nephrotoxicity or other issues.
Liver Function Tests (ALT, AST, ALP, bilirubin)
Frequency: Weekly for first month, then every 2-4 weeks, then monthly or as clinically indicated.
Target: Within normal limits or stable baseline.
Action Threshold: Significant elevation may indicate hepatotoxicity or other issues.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Weekly for first month, then every 2-4 weeks, then monthly or as clinically indicated.
Target: Potassium: 3.5-5.0 mEq/L; Magnesium: 1.5-2.5 mg/dL; Phosphate: 2.5-4.5 mg/dL.
Action Threshold: Hyperkalemia (>5.5 mEq/L), hypomagnesemia (<1.5 mg/dL), hypophosphatemia (<2.5 mg/dL).
Blood Glucose (Fasting or HbA1c)
Frequency: Weekly for first month, then every 2-4 weeks, then monthly or as clinically indicated.
Target: Fasting glucose <126 mg/dL; HbA1c <6.5%.
Action Threshold: Persistent hyperglycemia (>126 mg/dL fasting) or HbA1c >6.5%.
Blood Pressure
Frequency: At every clinic visit, or daily if unstable.
Target: <130/80 mmHg (or per transplant center guidelines).
Action Threshold: Sustained hypertension (>140/90 mmHg).
CBC with differential
Frequency: Monthly for first 3-6 months, then every 3-6 months or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant leukopenia, thrombocytopenia, or anemia.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, new pain, cough, dysuria)
- Signs of kidney problems (decreased urine output, swelling in legs/ankles, unusual fatigue, nausea)
- Signs of liver problems (yellowing of skin/eyes, dark urine, pale stools, severe nausea/vomiting, abdominal pain)
- Signs of neurotoxicity (headache, tremor, numbness/tingling, confusion, seizures, visual disturbances)
- Signs of hyperglycemia (increased thirst, increased urination, increased hunger, fatigue, blurred vision)
- Signs of hypertension (headache, dizziness, blurred vision)
- Gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain)
- Hair loss
- Skin changes (rash, itching, increased sun sensitivity)
- Muscle weakness or pain
Special Patient Groups
Pregnancy
Tacrolimus crosses the placenta. While it is associated with some risks (e.g., premature birth, low birth weight, transient hyperkalemia, renal dysfunction in the neonate), it is often continued during pregnancy in transplant recipients due to the high risk of organ rejection if discontinued. The benefits of preventing rejection generally outweigh the risks to the fetus. Close monitoring of tacrolimus levels, maternal renal function, and fetal growth is essential.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of congenital malformations, though data are conflicting and overall risk appears low compared to other immunosuppressants. Close monitoring is advised.
Second Trimester:
Risk of premature birth and low birth weight. Fetal growth should be monitored.
Third Trimester:
Risk of premature birth, low birth weight, and transient neonatal hyperkalemia and renal dysfunction. Neonatal monitoring for these effects is recommended.
Lactation
Tacrolimus is excreted into breast milk. While the amount transferred is small, the potential for serious adverse effects in the infant (e.g., immunosuppression, nephrotoxicity) exists. The decision to breastfeed should consider the importance of the drug to the mother, the potential for adverse effects in the infant, and the availability of alternative therapies. Some experts suggest that breastfeeding may be acceptable with careful monitoring of the infant for adverse effects and tacrolimus levels in the infant, but generally, caution is advised.
Infant Risk:
L3 (Moderate risk) - Potential for immunosuppression, nephrotoxicity, and other adverse effects in the infant. Monitor infant for signs of infection, renal dysfunction, and growth.
Pediatric Use
Pediatric patients, especially younger children, generally require higher doses per kilogram than adults due to faster drug clearance. Dosing is highly individualized based on weight, age, and target trough levels. Close monitoring of tacrolimus levels and adverse effects is crucial.
Geriatric Use
No specific dose adjustments are typically required based solely on age. However, geriatric patients may have age-related decreases in renal or hepatic function, increased comorbidities, and polypharmacy, which can influence tacrolimus pharmacokinetics and increase the risk of adverse effects. Close monitoring of renal function, electrolytes, and tacrolimus levels is recommended.
Clinical Information
Clinical Pearls
- Tacrolimus has a narrow therapeutic index; small changes in dose or drug interactions can lead to significant changes in drug levels and clinical outcomes (rejection or toxicity).
- Always take tacrolimus consistently with respect to food (preferably on an empty stomach) to minimize variability in absorption.
- Therapeutic drug monitoring (TDM) of whole blood trough levels is essential for safe and effective use. Levels are highly individualized.
- Patients should be educated on the importance of adherence and the critical nature of reporting any missed doses or changes in medication regimen.
- Grapefruit and St. John's Wort are absolute contraindications due to significant drug interactions.
- Tacrolimus can cause new-onset diabetes after transplant (NODAT) and nephrotoxicity; close monitoring of blood glucose and renal function is vital.
- Tremor and headache are common side effects, especially at higher trough levels.
- Immunosuppression increases the risk of opportunistic infections and malignancies; patients need lifelong screening and education on prevention.
Alternative Therapies
- Cyclosporine (another calcineurin inhibitor)
- Sirolimus (mTOR inhibitor)
- Everolimus (mTOR inhibitor)
- Mycophenolate mofetil/sodium (antiproliferative agent)
- Azathioprine (antiproliferative agent)
- Belatacept (co-stimulation blocker)
- Corticosteroids (e.g., prednisone)
Cost & Coverage
Average Cost:
$100 - $300 per 30 capsules (0.5mg)
Generic Available:
Yes
Insurance Coverage:
Tier 3 or Tier 4 (Specialty Drug)
General Drug Facts
If your symptoms or health issues persist or worsen, it is 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 it's a good idea 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 taken, the amount, and the time it happened.