Tacrolimus 1mg 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
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 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.
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 by your pharmacist. If you have questions about disposing of your medication, ask 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 return to 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 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.
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 by your pharmacist. If you have questions about disposing of your medication, ask 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 return to your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take tacrolimus exactly as prescribed, usually twice a day, at the same time each day, on an empty stomach (1 hour before or 2-3 hours after food).
- Do not skip doses or change your dose without talking to your doctor.
- Do not eat grapefruit or drink grapefruit juice while taking this medication, as it can dangerously increase drug levels.
- Avoid St. John's Wort, as it can decrease drug levels.
- Avoid live vaccines (e.g., MMR, chickenpox) while on tacrolimus. Discuss all vaccinations with your transplant team.
- Practice good hygiene (frequent hand washing) and avoid contact with sick people to reduce the risk of infection.
- Use sun protection (sunscreen, protective clothing) as tacrolimus can increase your risk of skin cancer.
- Report any new symptoms or side effects to your doctor immediately.
- Carry identification stating you are taking an immunosuppressant.
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, patient weight, and therapeutic drug monitoring (trough levels).
Condition-Specific Dosing:
kidney_transplant_initial:
Oral: 0.2 mg/kg/day in 2 divided doses, starting 24 hours after transplant. IV: 0.03-0.05 mg/kg/day as continuous infusion.
liver_transplant_initial:
Oral: 0.1-0.15 mg/kg/day in 2 divided doses, starting 6-12 hours after transplant. IV: 0.03-0.05 mg/kg/day as continuous infusion.
heart_transplant_initial:
Oral: 0.075 mg/kg/day in 2 divided doses, starting 6-12 hours after transplant. IV: 0.01-0.02 mg/kg/day as continuous infusion.
maintenance:
Adjust dose to achieve target trough concentrations (typically 5-20 ng/mL depending on time post-transplant and organ type).
Pediatric Dosing
Neonatal:
Not established for routine use, but used off-label with careful monitoring. Dosing is highly individualized.
Infant:
Oral: 0.15-0.2 mg/kg/day in 2 divided doses (liver transplant). Doses often higher per kg than adults due to faster metabolism.
Child:
Oral: 0.15-0.2 mg/kg/day in 2 divided doses (liver transplant). Doses often higher per kg than adults due to faster metabolism.
Adolescent:
Oral: 0.15-0.2 mg/kg/day in 2 divided doses (liver transplant). Doses often higher per kg than adults due to faster metabolism.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment, but monitor tacrolimus trough levels and renal function closely.
Moderate:
No specific dose adjustment, but monitor tacrolimus trough levels and renal function closely.
Severe:
No specific dose adjustment, but monitor tacrolimus trough levels and renal function closely. Tacrolimus is not significantly removed by dialysis.
Dialysis:
Not significantly dialyzable. No supplemental dose needed post-dialysis. Monitor trough levels.
Hepatic Impairment:
Mild:
Consider lower initial doses (e.g., 50% of standard dose) and monitor trough levels closely.
Moderate:
Consider lower initial doses (e.g., 50% of standard dose) and monitor trough levels closely.
Severe:
Consider lower initial doses (e.g., 50% of standard dose) and monitor trough levels closely. May require significant dose reduction.
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), thereby inhibiting its translocation into the nucleus. This ultimately blocks the transcription of early T-cell activation genes, such as interleukin-2 (IL-2), and other cytokines (IL-3, IL-4, IL-5, GM-CSF, TNF-alpha), leading to the inhibition of T-lymphocyte activation and proliferation.
Pharmacokinetics
Absorption:
Bioavailability:
Oral bioavailability is low and variable (approximately 20-25% in adults, ranging from 4-89%).
Tmax:
Approximately 1-3 hours (oral capsule).
FoodEffect:
Food, especially high-fat meals, significantly decreases the rate and extent of absorption (AUC and Cmax can decrease by 27% and 50% respectively). Should be taken consistently on an empty stomach (1 hour before or 2-3 hours after meals).
Distribution:
Vd:
Approximately 0.85-1.9 L/kg (adults).
ProteinBinding:
Highly protein bound (approximately 98.8-99%), primarily to albumin and alpha-1-acid glycoprotein. Also extensively distributed into red blood cells (RBCs), with a blood-to-plasma ratio of 20:1 to 35:1.
CnssPenetration:
Limited, but neurotoxicity can occur, suggesting some CNS penetration.
Elimination:
HalfLife:
Approximately 12-18 hours (adults, blood half-life). Highly variable.
Clearance:
Approximately 0.04-0.08 L/hr/kg (adults).
ExcretionRoute:
Primarily fecal (92.6%), with a small amount excreted in urine (2.3%).
Unchanged:
Less than 1% of the dose is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Immunosuppressive effects are observed within hours to days, reflected by achievement of therapeutic trough levels.
PeakEffect:
Achieved when stable therapeutic trough concentrations are maintained.
DurationOfAction:
Dependent on maintaining therapeutic trough concentrations; effects persist as long as drug levels are adequate.
Safety & Warnings
BLACK BOX WARNING
Increased risk of developing serious infections and malignancies (e.g., lymphoma, skin cancer) due to immunosuppression. Increased mortality in female liver transplant patients with a high body mass index (BMI) at the time of transplant. Cases of QT prolongation and Torsade de Pointes have been reported. Post-transplant lymphoproliferative disorder (PTLD), associated with Epstein-Barr Virus (EBV), has been reported.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. 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 changes, 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 extreme fatigue and weakness.
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 Symptoms: Shakiness, difficulty moving, unexplained bruising or bleeding, or abnormal sensations such as burning, numbness, or tingling.
Pale Skin: Unusual paleness of the skin.
Progressive Multifocal Leukoencephalopathy (PML): A rare and potentially life-threatening brain condition that may cause disability or death. Seek medical help immediately if you experience confusion, memory problems, depression, changes in behavior, uneven strength, speech or thinking difficulties, balance changes, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially life-threatening brain condition that may 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 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 immediately if you experience confusion, extreme fatigue, bruising, bleeding, dark urine, yellow skin or eyes, pale skin, changes in urine output, vision changes, uneven strength, speech or thinking difficulties, balance changes, or fever.
Other Side Effects
Most people do not experience significant side effects, but some may occur. 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, fatigue, 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 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.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. 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 changes, 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 extreme fatigue and weakness.
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 Symptoms: Shakiness, difficulty moving, unexplained bruising or bleeding, or abnormal sensations such as burning, numbness, or tingling.
Pale Skin: Unusual paleness of the skin.
Progressive Multifocal Leukoencephalopathy (PML): A rare and potentially life-threatening brain condition that may cause disability or death. Seek medical help immediately if you experience confusion, memory problems, depression, changes in behavior, uneven strength, speech or thinking difficulties, balance changes, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially life-threatening brain condition that may 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 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 immediately if you experience confusion, extreme fatigue, bruising, bleeding, dark urine, yellow skin or eyes, pale skin, changes in urine output, vision changes, uneven strength, speech or thinking difficulties, balance changes, or fever.
Other Side Effects
Most people do not experience significant side effects, but some may occur. 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, fatigue, 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 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, body aches, painful urination, new pain or swelling.
- Signs of kidney problems: swelling in your ankles or feet, decreased urination, unusual weight gain.
- Signs of nerve problems: tremors (shaking), numbness or tingling, headache, confusion, seizures, vision changes.
- Signs of high blood sugar: increased thirst, increased urination, increased hunger, unexplained weight loss.
- Signs of high blood pressure: severe headache, dizziness, blurred vision.
- Severe nausea, vomiting, or diarrhea.
- Unusual bruising or bleeding.
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 condition known as long QT on an electrocardiogram (ECG).
If you are currently taking cyclosporine or sirolimus, as these medications may interact with this drug.
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 pregnancy occurs while taking this drug, notify your doctor immediately.
If you are breastfeeding or plan to breastfeed, as it is crucial to determine the safety of this medication during lactation.
This list is not exhaustive, and it is vital to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems, to your doctor and pharmacist. This will help ensure your safety while taking this medication. Never start, stop, or modify the dosage of any medication without first consulting your doctor to confirm it is safe to do so.
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 condition known as long QT on an electrocardiogram (ECG).
If you are currently taking cyclosporine or sirolimus, as these medications may interact with this drug.
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 pregnancy occurs while taking this drug, notify your doctor immediately.
If you are breastfeeding or plan to breastfeed, as it is crucial to determine the safety of this medication during lactation.
This list is not exhaustive, and it is vital to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems, to your doctor and pharmacist. This will help ensure your safety while taking this medication. Never start, stop, or modify the dosage of any medication without first consulting your doctor to confirm it is safe to do so.
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, as ordered by your doctor. Many medications can interact with this drug, 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 monitoring is vital, as this medication can cause high blood pressure. Follow your doctor's instructions for checking your blood pressure. This medication can also lead to high blood sugar levels, including the development or worsening of diabetes. Monitor your blood sugar levels as directed by your doctor, and report any signs of high blood sugar, such as confusion, drowsiness, unusual 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 your doctor before receiving any vaccines, as some vaccines may increase the risk of infection or reduce their effectiveness when used with this medication.
Prolonged use of this medication may increase the risk of skin cancer. To minimize this risk, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear. Furthermore, 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 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 individuals who have infections, colds, or flu. Regular blood tests and other laboratory evaluations are crucial, as ordered by your doctor. Many medications can interact with this drug, 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 monitoring is vital, as this medication can cause high blood pressure. Follow your doctor's instructions for checking your blood pressure. This medication can also lead to high blood sugar levels, including the development or worsening of diabetes. Monitor your blood sugar levels as directed by your doctor, and report any signs of high blood sugar, such as confusion, drowsiness, unusual 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 your doctor before receiving any vaccines, as some vaccines may increase the risk of infection or reduce their effectiveness when used with this medication.
Prolonged use of this medication may increase the risk of skin cancer. To minimize this risk, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear. Furthermore, 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 this with your doctor before initiating treatment with this medication.
Overdose Information
Overdose Symptoms:
- Severe kidney problems (e.g., acute renal failure)
- Severe neurotoxicity (e.g., seizures, encephalopathy)
- Severe gastrointestinal upset
- Markedly elevated tacrolimus blood levels
What to Do:
There is no specific antidote for tacrolimus overdose. Treatment is supportive. Contact your local poison control center (e.g., 1-800-222-1222) or seek immediate medical attention.
Drug Interactions
Contraindicated Interactions
- Live vaccines (e.g., measles, mumps, rubella, varicella, yellow fever, rotavirus, BCG, oral typhoid) due to risk of disseminated infection.
- Concomitant use with Pimecrolimus or Sirolimus (topical) on the same area of skin.
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, ritonavir, cobicistat): Significantly increase tacrolimus levels, leading to toxicity. Requires substantial dose reduction of tacrolimus and close monitoring.
- Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort): Significantly decrease tacrolimus levels, leading to rejection. Requires substantial dose increase of tacrolimus and close monitoring.
- Nephrotoxic agents (e.g., NSAIDs, aminoglycosides, amphotericin B, cyclosporine, ACE inhibitors, ARBs): Increased risk of nephrotoxicity.
- Potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene) and potassium supplements: Increased risk of hyperkalemia.
- Grapefruit or grapefruit juice: Inhibits CYP3A4, increasing tacrolimus levels.
- Vaccines (inactivated): May have a diminished response.
Moderate Interactions
- Moderate CYP3A4 inhibitors/inducers (e.g., diltiazem, verapamil, fluconazole, erythromycin, aprepitant, efavirenz): May alter tacrolimus levels, requiring dose adjustment and monitoring.
- Drugs affecting gastric pH (e.g., antacids, H2 blockers, PPIs): May affect tacrolimus absorption (though less significant than food effect).
- Drugs causing QT prolongation: Potential additive effect (rare).
Minor Interactions
- Not typically categorized as minor due to narrow therapeutic index; all interactions are potentially significant.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline hematologic parameters and monitor for potential adverse effects like anemia, leukopenia, or thrombocytopenia.
Timing: Prior to initiation of therapy.
Renal Function (SCr, 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, ALP, bilirubin)
Rationale: To establish baseline liver function and monitor for potential hepatotoxicity.
Timing: Prior to initiation of therapy.
Electrolytes (Potassium, Magnesium, Phosphate)
Rationale: To establish baseline levels and monitor for tacrolimus-induced electrolyte disturbances (e.g., hyperkalemia, hypomagnesemia, hypophosphatemia).
Timing: Prior to initiation of therapy.
Blood Glucose
Rationale: To establish baseline glucose levels and monitor for new-onset diabetes after transplant (NODAT).
Timing: Prior to initiation of therapy.
Blood Pressure
Rationale: To establish baseline and monitor for hypertension.
Timing: Prior to initiation of therapy.
Routine Monitoring
Tacrolimus Whole Blood Trough Levels
Frequency: Initially 2-3 times per week until stable, then at least weekly for the first month, then every 1-3 months or as clinically indicated.
Target: Highly variable based on organ, time post-transplant, and concomitant immunosuppression (e.g., 5-20 ng/mL for kidney/liver, 8-12 ng/mL for heart, early post-transplant often higher).
Action Threshold: Levels outside target range; adjust dose to maintain therapeutic levels and minimize toxicity.
Renal Function (SCr, BUN, eGFR)
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Stable or improving from baseline.
Action Threshold: Significant increase in SCr or decrease in eGFR; consider dose adjustment, rule out other causes.
Liver Function Tests (ALT, AST, ALP, bilirubin)
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Stable or improving from baseline.
Action Threshold: Significant elevation; consider dose adjustment, rule out other causes.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Within normal limits (e.g., K 3.5-5.0 mEq/L, Mg 1.5-2.5 mg/dL).
Action Threshold: Hyperkalemia, hypomagnesemia, hypophosphatemia; supplement or adjust dose.
Blood Glucose
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Fasting glucose <100 mg/dL, HbA1c <6.5%.
Action Threshold: Persistent hyperglycemia; consider diabetes management or dose adjustment.
Blood Pressure
Frequency: At every clinic visit.
Target: <130/80 mmHg.
Action Threshold: Hypertension; initiate or adjust antihypertensive therapy.
CBC
Frequency: Monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant cytopenias; investigate and manage.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, new pain, changes in urination)
- Signs of kidney problems (decreased urine output, swelling in ankles/feet, unusual weight gain)
- Signs of neurotoxicity (headache, tremor, numbness/tingling, confusion, seizures, visual disturbances)
- Signs of hyperglycemia (increased thirst, increased urination, unexplained weight loss)
- Signs of hypertension (headache, dizziness, blurred vision)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
- Skin changes (rash, itching, skin cancer screening)
Special Patient Groups
Pregnancy
Tacrolimus is classified as Pregnancy Category C. 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 recommended.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of congenital anomalies, though data are conflicting and often confounded by underlying maternal conditions and concomitant medications.
Second Trimester:
Risk of prematurity, low birth weight, and transient neonatal hyperkalemia and renal dysfunction.
Third Trimester:
Risk of prematurity, low birth weight, and transient neonatal hyperkalemia and renal dysfunction. Close monitoring of neonatal renal function and potassium levels is crucial.
Lactation
Tacrolimus is excreted into breast milk. Due to the potential for serious adverse reactions in the nursing infant (e.g., immunosuppression, nephrotoxicity), breastfeeding is generally not recommended while taking tacrolimus.
Infant Risk:
L4 (Possibly Hazardous) - Significant amount in milk, potential for adverse effects on infant.
Pediatric Use
Pediatric patients, especially younger children, may require higher doses per kilogram than adults due to faster metabolism. Close monitoring of tacrolimus trough levels is essential to ensure therapeutic efficacy and minimize toxicity. They are also at higher risk for post-transplant lymphoproliferative disorder (PTLD), particularly EBV-seronegative children.
Geriatric Use
No specific dose adjustments are typically required based solely on age, but geriatric patients may be more susceptible to adverse effects (e.g., renal dysfunction, neurotoxicity, diabetes). Close monitoring of tacrolimus levels, renal function, and other side effects is recommended.
Clinical Information
Clinical Pearls
- Tacrolimus has a narrow therapeutic index; therapeutic drug monitoring (trough levels) is critical for safe and effective use.
- Consistency in administration (time of day, relation to food) is paramount due to variable absorption and narrow therapeutic window.
- Many drug interactions exist, particularly with CYP3A4 inhibitors and inducers. Always review concomitant medications carefully.
- Patients should be educated on the importance of adherence and signs/symptoms of infection and toxicity.
- Hyperkalemia and hypomagnesemia are common electrolyte disturbances; monitor and supplement as needed.
- New-onset diabetes after transplant (NODAT) and nephrotoxicity are significant long-term complications requiring vigilant monitoring.
- Different formulations (immediate-release capsules, extended-release capsules, extended-release tablets) are NOT interchangeable on a milligram-for-milligram basis. Patients should remain on the same formulation unless directed by a transplant specialist.
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:
Varies widely, typically $100-$500+ per 30 capsules (1mg)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (often requires prior authorization for brand, generic usually preferred).
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 your 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 medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.