Astagraf XL 0.5mg Capsule
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.In one study of patients who used this drug after a liver transplant, a larger number of deaths happened in females. This drug is not for use after a liver transplant. @ 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
Jul 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Astagraf XL is a medicine used to prevent your body from rejecting a transplanted organ (like a kidney or liver). It works by lowering your body's immune response, which helps your body accept the new organ. It's a very important medicine that you'll need to take every day, usually once a day, to keep your new organ healthy.
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 well.
Take your medication at the same time every day.
It's best to take it in the morning on an empty stomach, either at least 1 hour before or at least 2 hours after breakfast.
Swallow the medication whole with a glass of water. Do not chew, break, or crush it.
If you have trouble swallowing, consult with your doctor for guidance.
Storing and Disposing of Your Medication
To ensure your medication remains effective and safe:
Store it at room temperature in a dry place, avoiding the bathroom.
Keep all medications in a secure 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.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to 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.
If it has been 14 hours or more since the missed dose, skip the missed dose and resume your regular dosing schedule.
Do not take two doses at the same time or take extra doses to make up for the missed one.
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 well.
Take your medication at the same time every day.
It's best to take it in the morning on an empty stomach, either at least 1 hour before or at least 2 hours after breakfast.
Swallow the medication whole with a glass of water. Do not chew, break, or crush it.
If you have trouble swallowing, consult with your doctor for guidance.
Storing and Disposing of Your Medication
To ensure your medication remains effective and safe:
Store it at room temperature in a dry place, avoiding the bathroom.
Keep all medications in a secure 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.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to 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.
If it has been 14 hours or more since the missed dose, skip the missed dose and resume your regular dosing schedule.
Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Astagraf XL consistently once daily, preferably in the morning, on an empty stomach (at least 1 hour before or 2 hours after a meal).
- Do not crush, chew, or open the capsules. Swallow them whole.
- Do not switch between Astagraf XL and other tacrolimus formulations (e.g., Prograf, Envarsus XR) without your doctor's guidance, as doses are not interchangeable.
- Avoid grapefruit and grapefruit juice, as they can significantly increase tacrolimus levels and lead to serious side effects.
- Avoid St. John's Wort, as it can decrease tacrolimus levels and lead to organ rejection.
- Limit sun exposure and use protective clothing and sunscreen, as tacrolimus increases your risk of skin cancer.
- Avoid live vaccines (e.g., measles, mumps, rubella, varicella, rotavirus, yellow fever) while taking this medication.
- Report any signs of infection (fever, chills, sore throat, unusual fatigue) immediately to your doctor.
- Maintain good hygiene to reduce infection risk.
- Adhere strictly to your medication schedule and never miss a dose without consulting your transplant team.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose based on transplant type and patient weight, adjusted to achieve target trough levels.
Condition-Specific Dosing:
Kidney Transplant (de novo):
Initial oral dose of 0.15 mg/kg/day once daily. Administer first dose no sooner than 24 hours after transplantation.
Liver Transplant (de novo):
Initial oral dose of 0.15 mg/kg/day once daily. Administer first dose no sooner than 6 hours after transplantation.
Conversion from immediate-release tacrolimus:
Administer Astagraf XL once daily at a dose that is 80% of the total daily dose of immediate-release tacrolimus.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established for Astagraf XL. Immediate-release tacrolimus is used in pediatric patients, with dosing adjusted by weight and trough levels.
Adolescent:
Not established for Astagraf XL. Immediate-release tacrolimus is used in pediatric patients, with dosing adjusted by weight and trough levels.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor tacrolimus trough concentrations and renal function closely.
Moderate:
No specific dose adjustment recommended, but monitor tacrolimus trough concentrations and renal function closely.
Severe:
No specific dose adjustment recommended, but monitor tacrolimus trough concentrations and renal function closely.
Dialysis:
Tacrolimus is not dialyzable. No specific dose adjustment for patients on dialysis, but monitor tacrolimus trough concentrations and renal function closely.
Hepatic Impairment:
Mild:
Consider lower initial doses (e.g., 0.1 mg/kg/day) and/or lower target trough concentrations. Monitor tacrolimus trough concentrations closely.
Moderate:
Consider lower initial doses (e.g., 0.1 mg/kg/day) and/or lower target trough concentrations. Monitor tacrolimus trough concentrations closely.
Severe:
Consider lower initial doses (e.g., 0.1 mg/kg/day) and/or lower target trough concentrations. Monitor tacrolimus trough concentrations closely.
Pharmacology
Mechanism of Action
Tacrolimus is a calcineurin inhibitor. It binds to the immunophilin FKBP-12 (FK506 binding protein), forming a complex that inhibits calcineurin, a phosphatase. This inhibition prevents the dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), thereby blocking the transcription of early T-cell activation genes, such as interleukin-2 (IL-2). This ultimately inhibits T-lymphocyte activation and proliferation, suppressing the immune response.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 20-25% (highly variable, 4-89%)
Tmax:
Approximately 2-4 hours
FoodEffect:
Food (especially high-fat meals) significantly decreases the rate and extent of absorption. Astagraf XL should be taken consistently on an empty stomach (at least 1 hour before or 2 hours after a meal).
Distribution:
Vd:
Approximately 0.85-1.9 L/kg
ProteinBinding:
Approximately 98.8% (primarily to albumin and alpha-1-acid glycoprotein)
CnssPenetration:
Limited, but can cause neurotoxicity
Elimination:
HalfLife:
Approximately 25-30 hours (for Astagraf XL, due to extended release formulation)
Clearance:
Approximately 0.04-0.08 L/hr/kg
ExcretionRoute:
Primarily fecal (92.6%), with a small amount excreted renally (2.3%)
Unchanged:
Less than 1% excreted unchanged in urine
Pharmacodynamics
OnsetOfAction:
Immunosuppressive effects begin shortly after administration, but clinical efficacy is assessed by achieving target trough levels.
PeakEffect:
Not directly applicable as effect is related to sustained trough levels.
DurationOfAction:
24 hours (due to extended-release formulation, allowing once-daily dosing)
Safety & Warnings
BLACK BOX WARNING
Increased Risk of Infection and the Development of Malignancies: Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly of the skin, are consequences of immunosuppression. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Astagraf XL. 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 requisite for the follow-up of the patient. Post-transplant diabetes mellitus and nephrotoxicity are also associated with tacrolimus use.
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, uneven strength, speech or thinking difficulties, balance problems, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially fatal 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 condition may increase the risk of other potentially fatal 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 fatal 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, uneven strength, speech or thinking difficulties, balance problems, or fever.
Other Possible Side Effects
Most people do not experience severe 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, 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 possible side effects. If you have questions or concerns, 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, uneven strength, speech or thinking difficulties, balance problems, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially fatal 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 condition may increase the risk of other potentially fatal 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 fatal 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, uneven strength, speech or thinking difficulties, balance problems, or fever.
Other Possible Side Effects
Most people do not experience severe 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, 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 possible side effects. If you have questions or concerns, 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, pain or burning during urination, skin rash, redness or swelling.
- Signs of kidney problems: swelling in your ankles or feet, decreased urination, unusual tiredness.
- Signs of liver problems: yellowing of skin or eyes (jaundice), dark urine, pale stools, severe nausea or vomiting, abdominal pain.
- Neurological problems: headache, tremor (shaking), numbness or tingling, confusion, seizures, vision changes.
- High blood sugar: increased thirst, increased urination, increased hunger, unexplained weight loss.
- High blood pressure: severe headache, blurred vision.
- Signs of malignancy: new lumps or growths, changes in moles, persistent cough, unexplained weight loss.
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 harm 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, as the safety of this medication during breastfeeding is not established.
This list is not exhaustive, and it is crucial to inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you have. This will help ensure your safety while taking this medication. Never start, stop, or change the dose 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 harm 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, as the safety of this medication during breastfeeding is not established.
This list is not exhaustive, and it is crucial to inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you have. This will help ensure your safety while taking this medication. Never start, stop, or change the dose 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 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.
Monitor your blood pressure regularly, as this medication can cause high blood pressure. Your doctor will advise you on the frequency of blood pressure checks.
This medication can also cause high blood sugar levels, including new-onset or worsening diabetes. Check your blood sugar levels as directed by your doctor, and report any signs of high blood sugar, such as confusion, drowsiness, increased thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
Refrain from drinking alcohol while taking this medication.
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 can 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 this with your doctor before starting 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.
Monitor your blood pressure regularly, as this medication can cause high blood pressure. Your doctor will advise you on the frequency of blood pressure checks.
This medication can also cause high blood sugar levels, including new-onset or worsening diabetes. Check your blood sugar levels as directed by your doctor, and report any signs of high blood sugar, such as confusion, drowsiness, increased thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
Refrain from drinking alcohol while taking this medication.
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 can 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 this with your doctor before starting treatment with this medication.
Overdose Information
Overdose Symptoms:
- Severe tremor
- Headache
- Nausea
- Vomiting
- Abdominal pain
- Kidney dysfunction (elevated creatinine)
- Neurotoxicity (seizures, confusion)
- Cardiac effects (QT prolongation)
What to Do:
There is no specific antidote for tacrolimus overdose. Treatment is supportive. Contact your doctor or emergency services immediately. Call 1-800-222-1222 (Poison Control Center).
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Nefazodone (strong CYP3A4 inhibitor)
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, nelfinavir, indinavir, saquinavir, grapefruit juice) - significantly increase tacrolimus levels, leading to toxicity.
- Strong CYP3A4 inducers (e.g., rifampin, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's Wort) - significantly decrease tacrolimus levels, leading to rejection.
- Nephrotoxic agents (e.g., aminoglycosides, amphotericin B, NSAIDs, cyclosporine) - increased risk of nephrotoxicity.
- Potassium-sparing diuretics, ACE inhibitors, ARBs - increased risk of hyperkalemia.
- Vaccines (reduced efficacy of vaccines, especially live attenuated vaccines).
Moderate Interactions
- Moderate CYP3A4 inhibitors/inducers (e.g., diltiazem, verapamil, fluconazole, erythromycin, cimetidine, omeprazole, metoclopramide, aprepitant, bosentan, efavirenz, etravirine, modafinil, prednisone) - require close monitoring and potential dose adjustment.
- Drugs that affect gastric pH (e.g., antacids, H2 blockers, PPIs) - may affect tacrolimus absorption (less significant for extended-release).
- Drugs that prolong QT interval (e.g., amiodarone, quinidine, sotalol, macrolides, fluoroquinolones) - tacrolimus can prolong QT interval.
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic parameters and monitor for anemia, leukopenia, or thrombocytopenia.
Timing: Prior to initiation
Renal Function (serum creatinine, BUN, GFR)
Rationale: To establish baseline kidney function and monitor for nephrotoxicity.
Timing: Prior to initiation
Liver Function Tests (ALT, AST, bilirubin, alkaline phosphatase)
Rationale: To establish baseline liver function and monitor for hepatotoxicity.
Timing: Prior to initiation
Electrolytes (potassium, magnesium, phosphorus)
Rationale: To establish baseline levels and monitor for hyperkalemia, hypomagnesemia, hypophosphatemia.
Timing: Prior to initiation
Blood Glucose (fasting)
Rationale: To establish baseline 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
ECG
Rationale: To establish baseline and monitor for QT prolongation.
Timing: Prior to initiation (especially if risk factors for QT prolongation)
Routine Monitoring
Tacrolimus Whole Blood Trough Concentrations
Frequency: Initially 2-3 times per week until stable, then at least weekly for the first month, then every 1-2 months or as clinically indicated.
Target: Varies by transplant type, time post-transplant, and concomitant immunosuppression (e.g., 5-15 ng/mL for kidney/liver, 8-20 ng/mL early post-transplant, lower long-term).
Action Threshold: Levels outside target range require dose adjustment and re-monitoring.
Renal Function (serum creatinine, BUN)
Frequency: At least weekly for the first month, then every 1-2 months or as clinically indicated.
Target: Within patient's baseline or acceptable post-transplant range.
Action Threshold: Significant increase (e.g., >25% above baseline) may indicate nephrotoxicity; requires investigation and potential dose adjustment.
Electrolytes (potassium, magnesium, phosphorus)
Frequency: At least weekly for the first month, then every 1-2 months or as clinically indicated.
Target: Potassium 3.5-5.0 mEq/L, Magnesium 1.5-2.5 mg/dL, Phosphorus 2.5-4.5 mg/dL.
Action Threshold: Hyperkalemia, hypomagnesemia, hypophosphatemia require intervention.
Blood Glucose (fasting)
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: <100 mg/dL (fasting).
Action Threshold: Persistent hyperglycemia requires management for NODAT.
Blood Pressure
Frequency: Regularly (e.g., daily in inpatient, at each clinic visit).
Target: <130/80 mmHg (or as per transplant center protocol).
Action Threshold: Hypertension requires management.
CBC with differential
Frequency: Weekly for the first month, then monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant leukopenia, anemia, or thrombocytopenia requires investigation.
Liver Function Tests
Frequency: Monthly or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant elevation requires investigation.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, new pain)
- Signs of malignancy (new lumps, persistent cough, unexplained weight loss, changes in skin lesions)
- Neurological symptoms (headache, tremor, seizures, confusion, paresthesias, visual disturbances)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
- Cardiovascular symptoms (chest pain, palpitations, swelling, shortness of breath)
- Renal dysfunction symptoms (decreased urine output, swelling, fatigue)
- Symptoms of diabetes (increased thirst, increased urination, unexplained weight loss)
Special Patient Groups
Pregnancy
Tacrolimus crosses the placenta. Use during pregnancy should only be considered if the potential benefit justifies the potential risk to the fetus. There is an increased risk of premature birth, low birth weight, and neonatal hyperkalemia and renal dysfunction. Close monitoring of tacrolimus levels and fetal development is essential.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of congenital malformations, though data are conflicting and overall risk appears low compared to other immunosuppressants.
Second Trimester:
Risk of premature birth, low birth weight, and neonatal complications.
Third Trimester:
Risk of premature birth, low birth weight, and neonatal complications, including hyperkalemia and renal dysfunction in the neonate.
Lactation
Tacrolimus is excreted into breast milk. Due to the potential for serious adverse reactions in the breastfed infant (e.g., nephrotoxicity, immunosuppression), breastfeeding is not recommended during tacrolimus therapy.
Infant Risk:
L4 (Possibly Hazardous) - Significant amount in milk, potential for adverse effects on infant.
Pediatric Use
Safety and efficacy of Astagraf XL have not been established in pediatric patients. Immediate-release tacrolimus is used in pediatric transplant recipients, with dosing adjusted based on weight and target trough levels. Pediatric patients may require higher doses on a mg/kg basis due to faster metabolism.
Geriatric Use
No specific dose adjustment is generally required based on age alone. However, elderly patients may have reduced renal or hepatic function, which could necessitate dose adjustments. Monitor tacrolimus levels and renal/hepatic function closely in this population.
Clinical Information
Clinical Pearls
- Astagraf XL is a once-daily formulation of tacrolimus, which can improve adherence compared to twice-daily immediate-release formulations.
- Consistency in administration (e.g., always with or without food, always at the same time of day) is crucial due to variable absorption and narrow therapeutic index.
- Patients converting from immediate-release tacrolimus (Prograf) to Astagraf XL should receive 80% of their total daily immediate-release dose as the once-daily Astagraf XL dose.
- Therapeutic drug monitoring (TDM) of tacrolimus trough levels is essential for safe and effective use, guiding dose adjustments to balance efficacy and toxicity.
- Tacrolimus has a narrow therapeutic index; even small changes in dose or concomitant medications can lead to significant changes in blood levels.
- Educate patients thoroughly about drug interactions, especially with grapefruit juice and St. John's Wort, and the importance of reporting all medications and supplements.
- Be vigilant for signs of nephrotoxicity, neurotoxicity, and new-onset diabetes after transplant (NODAT), which are common side effects.
- Immunosuppression increases the risk of infections (opportunistic, viral, bacterial, fungal) and malignancies (especially skin cancer and post-transplant lymphoproliferative disorder - PTLD).
Alternative Therapies
- mTOR inhibitors (e.g., sirolimus, everolimus)
- Antiproliferative agents (e.g., mycophenolate mofetil, azathioprine)
- Corticosteroids (e.g., prednisone)
- Induction agents (e.g., basiliximab, alemtuzumab, antithymocyte globulin)
Cost & Coverage
Average Cost:
Varies widely, typically several hundred to over a thousand USD per 30 capsules (0.5mg)
Generic Available:
Yes
Insurance Coverage:
Tier 3 or Specialty Tier (requires prior authorization, often covered for transplant patients)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which provides crucial information about its safe and effective use. It is vital to read this guide carefully when you first receive your medication and again each time your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to consult with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information about the overdose, including the name of the medication, the amount taken, and the time it occurred.
This medication is accompanied by a Medication Guide, which provides crucial information about its safe and effective use. It is vital to read this guide carefully when you first receive your medication and again each time your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to consult with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information about the overdose, including the name of the medication, the amount taken, and the time it occurred.