Tacrolimus 1mg 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
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 aware of signs of infection.
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 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.
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.
When you no longer need your medication or it has expired, dispose of it properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist. Check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to check if there are any 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 return to your regular 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, 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.
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.
When you no longer need your medication or it has expired, dispose of it properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist. Check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to check if there are any 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 return to your regular 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 each day, consistently, either with or without food, but always the same way (e.g., always with food or always without food) to ensure consistent absorption. Avoid high-fat meals if taking with food, as they can reduce absorption.
- Do not eat grapefruit or drink grapefruit juice while taking tacrolimus, as it can significantly increase drug levels and lead to 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, chickenpox) while on tacrolimus, as your immune system is suppressed and you could get the infection. Discuss all vaccinations with your doctor.
- 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.
- Regularly monitor your blood pressure and blood sugar as instructed by your doctor.
- 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 therapeutic drug monitoring (TDM) of whole blood trough levels. Initial dosing varies by organ transplant type and formulation (e.g., for liver transplant, immediate-release capsules typically 0.1-0.15 mg/kg/day orally divided every 12 hours).
Dose Range:
0.05 - 0.3 mg
Condition-Specific Dosing:
liver_transplant_initial:
0.1-0.15 mg/kg/day orally divided every 12 hours
kidney_transplant_initial:
0.2 mg/kg/day orally divided every 12 hours
heart_transplant_initial:
0.075 mg/kg/day orally divided every 12 hours
Pediatric Dosing
Neonatal:
Not established for routine use, but used off-label with careful monitoring.
Infant:
Dosing is generally higher on a mg/kg basis than adults due to faster metabolism. Initial doses typically 0.15-0.2 mg/kg/day orally divided every 12 hours for liver transplant.
Child:
Dosing is generally higher on a mg/kg basis than adults due to faster metabolism. Initial doses typically 0.15-0.2 mg/kg/day orally divided every 12 hours for liver transplant.
Adolescent:
Dosing is generally higher on a mg/kg basis than adults due to faster metabolism. Initial doses typically 0.15-0.2 mg/kg/day orally divided every 12 hours for liver transplant.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment required, but monitor tacrolimus trough levels and renal function closely.
Moderate:
No specific dose adjustment required, but monitor tacrolimus trough levels and renal function closely.
Severe:
No specific dose adjustment required, but monitor tacrolimus trough levels and renal function closely. Consider lower end of dosing range.
Dialysis:
Tacrolimus is highly protein-bound and not significantly removed by hemodialysis. No supplemental dose needed after dialysis, but monitor levels.
Hepatic Impairment:
Mild:
Consider dose reduction (e.g., 25% reduction) and monitor tacrolimus trough levels closely.
Moderate:
Dose reduction is generally required (e.g., 30-50% reduction). Monitor tacrolimus trough levels closely.
Severe:
Significant dose reduction is required (e.g., 50% or more). Monitor tacrolimus trough levels closely and frequently.
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 (NF-AT), which is required for its translocation into the nucleus. Consequently, the transcription of early T-cell activation genes, such as interleukin-2 (IL-2), IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, is inhibited, leading to a reduction in T-lymphocyte proliferation and cytokine production.
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% and 73% respectively). Grapefruit juice also affects absorption.
Distribution:
Vd:
Approximately 0.85-1.9 L/kg (high volume of distribution)
ProteinBinding:
Approximately 99% (primarily to albumin and alpha-1-acid glycoprotein; also extensively partitions into red blood cells)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 12-18 hours (range 4-40 hours, varies with patient population and liver function)
Clearance:
Approximately 0.04-0.08 L/hr/kg
ExcretionRoute:
Primarily fecal (approximately 95%), small amount in urine (approximately 2%)
Unchanged:
Less than 1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not directly applicable; immunosuppressive effects are achieved once therapeutic trough levels are maintained.
PeakEffect:
Achieved once stable therapeutic trough levels are maintained, typically within 2-3 days of consistent dosing.
DurationOfAction:
Dependent on maintaining therapeutic trough levels; effects persist as long as drug is present at effective concentrations.
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, have been reported in immunosuppressed patients. Increased Mortality in Female Liver Transplant Patients with Astagraf XL: Increased mortality in female liver transplant patients receiving Astagraf XL. Not for use in female liver transplant patients. Not Interchangeable: Tacrolimus extended-release capsules (Astagraf XL and Envarsus XR) and tacrolimus immediate-release capsules (Prograf) are not interchangeable. Under- or over-exposure may result from switching between tacrolimus products. Monitor tacrolimus whole blood trough concentrations and adjust dosage when converting from one tacrolimus product to another.
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 reactions: 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 imbalances: 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, sudden weight gain, or swelling in the arms or legs.
Neurological problems: Shakiness, trouble moving around, unexplained bruising or bleeding, burning, numbness, or tingling sensations, or pale skin.
Progressive multifocal leukoencephalopathy (PML): A rare and potentially deadly brain condition that can cause 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 deadly brain condition that can cause confusion, decreased alertness, vision changes, seizures, or severe headache.
Abnormal heart rhythms: This medication can cause a prolonged QT interval, which may increase the risk of other potentially life-threatening abnormal heart rhythms.
Gastrointestinal problems: Severe stomach pain, black, tarry, or bloody stools, vomiting blood, or coffee ground-like vomit.
Blood disorders: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), which 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
Most people taking this medication do not experience severe side effects. However, some may occur. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
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
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, 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 reactions: 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 imbalances: 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, sudden weight gain, or swelling in the arms or legs.
Neurological problems: Shakiness, trouble moving around, unexplained bruising or bleeding, burning, numbness, or tingling sensations, or pale skin.
Progressive multifocal leukoencephalopathy (PML): A rare and potentially deadly brain condition that can cause 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 deadly brain condition that can cause confusion, decreased alertness, vision changes, seizures, or severe headache.
Abnormal heart rhythms: This medication can cause a prolonged QT interval, which may increase the risk of other potentially life-threatening abnormal heart rhythms.
Gastrointestinal problems: Severe stomach pain, black, tarry, or bloody stools, vomiting blood, or coffee ground-like vomit.
Blood disorders: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), which 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
Most people taking this medication do not experience severe side effects. However, some may occur. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
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
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, 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, unusual fatigue, painful urination, skin sores.
- Signs of kidney problems: swelling in your ankles or feet, decreased urination, unusual weight gain.
- Signs of nervous system problems: tremors (shaking), headache, confusion, numbness or tingling, seizures.
- Signs of high blood sugar: increased thirst, increased urination, unexplained weight loss.
- Signs of high blood pressure: severe headache, blurred vision.
- Severe nausea, vomiting, or diarrhea.
- Yellowing of the skin or eyes (jaundice), dark urine, pale stools (signs of liver problems).
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, vitamins, or supplements you are using
* Your existing 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 consulting your doctor first.
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, vitamins, or supplements you are using
* Your existing 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 consulting your doctor first.
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 vital 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 exposure to sunlight, sunlamps, and tanning beds increases the risk of skin cancer when taking this medication. Protect yourself from the sun by using sunscreen, wearing protective clothing, and eyewear. Furthermore, this medication may 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.
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 vital 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 exposure to sunlight, sunlamps, and tanning beds increases the risk of skin cancer when taking this medication. Protect yourself from the sun by using sunscreen, wearing protective clothing, and eyewear. Furthermore, this medication may 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.
Overdose Information
Overdose Symptoms:
- Severe kidney problems (e.g., acute kidney injury)
- Severe neurotoxicity (e.g., seizures, severe tremor, encephalopathy)
- Severe gastrointestinal disturbances (e.g., nausea, vomiting, diarrhea)
- Severe hypertension
- Hyperkalemia
What to Do:
There is no specific antidote for tacrolimus overdose. Treatment is supportive. Contact a poison control center immediately (1-800-222-1222) or seek emergency medical attention. Hemodialysis is not effective in removing tacrolimus due to its high protein binding and extensive red blood cell partitioning.
Drug Interactions
Contraindicated Interactions
- Live attenuated vaccines (e.g., measles, mumps, rubella, varicella, rotavirus, yellow fever, BCG, oral typhoid)
- Concomitant use with other tacrolimus formulations (e.g., Astagraf XL, Envarsus XR) due to different pharmacokinetic profiles and risk of over/under-immunosuppression.
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, erythromycin, telithromycin, ritonavir, cobicistat, nefazodone, delavirdine, indinavir, nelfinavir, saquinavir): Significantly increase tacrolimus levels, leading to toxicity.
- Strong CYP3A4 inducers (e.g., rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, St. John's Wort): Significantly decrease tacrolimus levels, leading to rejection.
- Nephrotoxic agents (e.g., aminoglycosides, amphotericin B, NSAIDs, cyclosporine, ganciclovir, cidofovir, foscarnet): Increased risk of nephrotoxicity.
- Potassium-sparing diuretics, ACE inhibitors, ARBs: Increased risk of hyperkalemia.
- Sirolimus, Everolimus: Increased risk of nephrotoxicity and other adverse effects.
Moderate Interactions
- Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, fluconazole, amiodarone, cimetidine, ranitidine, grapefruit juice): May increase tacrolimus levels.
- Moderate CYP3A4 inducers (e.g., efavirenz, etravirine, modafinil): May decrease tacrolimus levels.
- Vaccines (inactivated): Reduced immune response to vaccines.
- Magnesium-containing antacids: May reduce tacrolimus absorption.
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic parameters and monitor for leukopenia, anemia, or thrombocytopenia.
Timing: Prior to initiation
Renal Function (Serum Creatinine, BUN, eGFR)
Rationale: To establish baseline renal function and monitor for tacrolimus-induced nephrotoxicity.
Timing: Prior to initiation
Liver Function Tests (ALT, AST, Bilirubin, Alkaline Phosphatase)
Rationale: To establish baseline hepatic function and monitor for tacrolimus-induced hepatotoxicity.
Timing: Prior to initiation
Electrolytes (Potassium, Magnesium, Phosphate)
Rationale: To establish baseline levels and monitor for hyperkalemia, hypomagnesemia, and hypophosphatemia.
Timing: Prior to initiation
Blood Pressure
Rationale: To establish baseline and monitor for hypertension.
Timing: Prior to initiation
Blood Glucose
Rationale: To establish baseline and monitor for new-onset diabetes after transplant (NODAT).
Timing: Prior to initiation
Lipid Profile
Rationale: To establish baseline and monitor for dyslipidemia.
Timing: Prior to initiation
Routine Monitoring
Whole Blood Tacrolimus Trough Levels
Frequency: Initially daily or every other day until stable, then 2-3 times per week, then weekly, then monthly or as clinically indicated.
Target: Highly variable based on organ type, post-transplant period, and concomitant immunosuppression (e.g., liver: 5-15 ng/mL; kidney: 5-12 ng/mL; heart: 8-15 ng/mL).
Action Threshold: Levels outside target range require dose adjustment and re-monitoring.
Renal Function (Serum Creatinine, BUN)
Frequency: Initially daily or every other day, then weekly, then monthly or as clinically indicated.
Target: Within patient's baseline or acceptable post-transplant range.
Action Threshold: Significant increase (e.g., >25% from baseline or rising trend) may indicate nephrotoxicity or rejection, requiring investigation and potential dose adjustment.
Electrolytes (Potassium, Magnesium)
Frequency: Initially daily or every other day, then weekly, then monthly or as clinically indicated.
Target: Potassium: 3.5-5.0 mEq/L; Magnesium: 1.5-2.5 mg/dL.
Action Threshold: Hyperkalemia (>5.0 mEq/L) or hypomagnesemia (<1.5 mg/dL) require intervention and potential dose adjustment.
Blood Pressure
Frequency: Daily initially, then weekly, then monthly or as clinically indicated.
Target: <130/80 mmHg (or as per clinical guidelines).
Action Threshold: Sustained hypertension requires antihypertensive therapy.
Blood Glucose
Frequency: Weekly initially, then monthly or as clinically indicated.
Target: Fasting <100 mg/dL; HbA1c <6.5%.
Action Threshold: Persistent hyperglycemia requires management for NODAT.
CBC with differential
Frequency: Weekly initially, then monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant leukopenia, anemia, or thrombocytopenia may require dose adjustment or investigation for infection/malignancy.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, cough, painful urination)
- Signs of nephrotoxicity (decreased urine output, swelling in ankles/feet, weight gain)
- Signs of neurotoxicity (tremor, headache, confusion, seizures, paresthesias)
- Signs of hyperglycemia (increased thirst, increased urination, unexplained weight loss)
- Signs of hypertension (headache, dizziness, blurred vision)
- Gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal pain)
- Skin changes (rash, itching)
- Muscle weakness or pain
Special Patient Groups
Pregnancy
Tacrolimus crosses the placenta. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is an increased risk of adverse pregnancy outcomes, including premature birth, low birth weight, and congenital anomalies (e.g., cardiac, renal). Close monitoring of tacrolimus trough levels is essential during pregnancy, as dosage adjustments may be required.
Trimester-Specific Risks:
First Trimester:
Potential for congenital anomalies, though data are mixed. Close monitoring and risk-benefit assessment.
Second Trimester:
Risk of premature birth, low birth weight, and potential for renal dysfunction in the neonate.
Third Trimester:
Risk of premature birth, low birth weight, and potential for neonatal hyperkalemia, renal dysfunction, and transient hyperglycemia.
Lactation
Tacrolimus is excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant (e.g., immunosuppression, nephrotoxicity, neurotoxicity), 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 metabolism. Therapeutic drug monitoring is crucial to maintain appropriate trough levels. They are at similar risks for adverse effects as adults, including infections, malignancies, and nephrotoxicity.
Geriatric Use
No specific dose adjustment is generally required based solely on age. However, geriatric patients may have age-related decline in renal or hepatic function, which could necessitate dose adjustments. Close monitoring of tacrolimus trough levels, renal function, and adverse effects is recommended.
Clinical Information
Clinical Pearls
- Therapeutic Drug Monitoring (TDM) is essential: Tacrolimus has a narrow therapeutic index, and trough levels must be monitored closely to balance efficacy (preventing rejection) and toxicity (e.g., nephrotoxicity, neurotoxicity).
- Formulation-specific dosing: Immediate-release (Prograf) and extended-release (Astagraf XL, Envarsus XR) formulations are NOT interchangeable. Switching requires careful monitoring and dose adjustment.
- Food effect: Consistent administration (always with food or always without food) is crucial due to variable absorption with food. High-fat meals significantly reduce absorption.
- Drug interactions: Tacrolimus is a CYP3A4 substrate, leading to numerous significant drug interactions with inhibitors (increasing levels) and inducers (decreasing levels). Always review concomitant medications.
- Nephrotoxicity and Neurotoxicity: These are common and dose-limiting side effects. Monitor renal function and neurological symptoms closely.
- Hyperkalemia and Hypomagnesemia: Common electrolyte disturbances; monitor and supplement as needed.
- New-onset diabetes after transplant (NODAT): Tacrolimus can induce or worsen diabetes; monitor blood glucose regularly.
- Immunosuppression risks: Patients are at increased risk for infections (bacterial, viral, fungal, opportunistic) and malignancies (especially skin cancer and post-transplant lymphoproliferative disorder - PTLD).
Alternative Therapies
- Cyclosporine (another calcineurin inhibitor)
- Sirolimus (mTOR inhibitor)
- Everolimus (mTOR inhibitor)
- Mycophenolate Mofetil (antimetabolite)
- Azathioprine (antimetabolite)
- Belatacept (selective T-cell costimulation blocker)
- Corticosteroids (e.g., Prednisone)
Cost & Coverage
Average Cost:
$100 - $500+ per 30 capsules (1mg)
Generic Available:
Yes
Insurance Coverage:
Tier 3 (Non-preferred Brand) or Tier 1/2 (Generic) for most insurance plans. Often requires prior authorization and is covered under pharmacy or medical benefit for transplant patients.
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. If you have any questions or concerns about this medication, don't hesitate to discuss them with 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 detailed information about the overdose, including the medication taken, the amount, and the time it occurred.