Astagraf XL 5mg 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.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 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 aware of potential side effects like infections.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel well.
To establish a routine, 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 the medication. If you have difficulty swallowing, consult your doctor for guidance.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs available 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 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.
To establish a routine, 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 the medication. If you have difficulty swallowing, consult your doctor for guidance.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs available 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 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 once daily, consistently at the same time each day, 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.
- 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 exposure to sunlight and UV light, and wear protective clothing and sunscreen, as tacrolimus can increase your risk of skin cancer.
- Avoid live vaccines while taking Astagraf XL.
- Report any signs of infection (fever, chills, sore throat) immediately to your doctor.
- Do not stop taking Astagraf XL without consulting your doctor, as this can lead to organ rejection.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose is highly individualized based on transplant type and patient factors, typically 0.15-0.2 mg/kg/day orally once daily. Dosing is adjusted to achieve target tacrolimus whole blood trough concentrations.
Dose Range:
0.15 - 0.2 mg
Condition-Specific Dosing:
kidney_transplant_prophylaxis:
Initial dose 0.2 mg/kg/day orally once daily.
liver_transplant_prophylaxis:
Initial dose 0.15-0.2 mg/kg/day orally once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Dosing for liver transplant: Initial dose 0.15-0.2 mg/kg/day orally once daily. Adjust to target trough levels.
Child:
Dosing for liver transplant: Initial dose 0.15-0.2 mg/kg/day orally once daily. Adjust to target trough levels.
Adolescent:
Dosing for liver transplant: Initial dose 0.15-0.2 mg/kg/day orally once daily. Adjust to target trough levels.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor tacrolimus trough levels and renal function closely.
Moderate:
No specific dose adjustment recommended, but monitor tacrolimus trough levels and renal function closely.
Severe:
No specific dose adjustment recommended, but monitor tacrolimus trough levels and renal function closely. Consider lower initial doses.
Dialysis:
Tacrolimus is not significantly dialyzable. No specific dose adjustment for patients on dialysis, but monitor tacrolimus trough levels closely.
Hepatic Impairment:
Mild:
Consider lower initial doses and/or dose reductions. Monitor tacrolimus trough levels closely.
Moderate:
Consider lower initial doses and/or dose reductions (e.g., 50% of standard dose). Monitor tacrolimus trough levels closely.
Severe:
Consider lower initial doses and/or dose reductions (e.g., 50% or more of standard dose). Monitor tacrolimus trough levels closely.
Pharmacology
Mechanism of Action
Tacrolimus is a calcineurin inhibitor. It binds to the immunophilin FKBP-12 (FK506 binding protein), forming a complex that inhibits calcineurin, a calcium-dependent phosphatase. This inhibition prevents the dephosphorylation of the nuclear factor of activated T-cells (NF-AT), thereby inhibiting its translocation into the nucleus. As a result, 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 suppressed. This leads to the inhibition of T-lymphocyte activation, proliferation, and the generation of cytotoxic T-cells, thus preventing transplant rejection.
Pharmacokinetics
Absorption:
Bioavailability:
4-28% (highly variable)
Tmax:
6-12 hours
FoodEffect:
Food, especially high-fat meals, significantly decreases the rate and extent of tacrolimus 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 98.8-99% (primarily to albumin and alpha-1-acid glycoprotein, also extensively to erythrocytes)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 25-38 hours (for Astagraf XL)
Clearance:
Approximately 0.04-0.08 L/hr/kg
ExcretionRoute:
Primarily fecal (approximately 92%), with a small amount excreted in urine (approximately 2%).
Unchanged:
Less than 1% of the dose is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Not directly applicable for chronic immunosuppression; therapeutic effects are achieved once steady-state trough levels are maintained.
PeakEffect:
Not directly applicable; efficacy is related to maintaining target trough concentrations.
DurationOfAction:
Related to the half-life and consistent maintenance of therapeutic trough levels.
Safety & Warnings
BLACK BOX WARNING
Increased Risk of Infections and Malignancies: Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression. Increased Mortality in Female Liver Transplant Patients: Increased mortality in female liver transplant patients when converted from tacrolimus immediate-release to Astagraf XL. Not approved for use in heart or lung transplant. Neurotoxicity and Nephrotoxicity: Tacrolimus can cause neurotoxicity and nephrotoxicity. Post-transplant Diabetes Mellitus: Tacrolimus can cause new-onset diabetes mellitus after transplant (NODAT).
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.
Chest Pain or Shortness of Breath: Chest pain or pressure, shortness of breath, significant 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 disability. Seek medical help if you experience confusion, memory problems, depression, changes in behavior, weakness on one side of the body, speech or thinking difficulties, balance problems, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially deadly brain condition. Seek medical help if you experience confusion, decreased alertness, vision changes, loss of vision, seizures, or severe headache.
Abnormal Heartbeat (Prolonged QT Interval): This medication can 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 but potentially deadly condition. Seek medical help if you experience confusion, extreme tiredness or weakness, bruising, bleeding, dark urine, yellow skin or eyes, pale skin, changes in urine output, vision changes, weakness on one side of the body, speech or thinking difficulties, balance problems, or fever.
Other Possible Side Effects
Most people do not experience 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, tiredness, or weakness
Headache
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Heartburn
Trouble sleeping
Back pain
Joint pain
* Nose or throat irritation
Reporting Side Effects
If you have questions about side effects or want to report any side effects, contact your doctor or the FDA at 1-800-332-1088 or visit 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.
Chest Pain or Shortness of Breath: Chest pain or pressure, shortness of breath, significant 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 disability. Seek medical help if you experience confusion, memory problems, depression, changes in behavior, weakness on one side of the body, speech or thinking difficulties, balance problems, or vision changes.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially deadly brain condition. Seek medical help if you experience confusion, decreased alertness, vision changes, loss of vision, seizures, or severe headache.
Abnormal Heartbeat (Prolonged QT Interval): This medication can 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 but potentially deadly condition. Seek medical help if you experience confusion, extreme tiredness or weakness, bruising, bleeding, dark urine, yellow skin or eyes, pale skin, changes in urine output, vision changes, weakness on one side of the body, speech or thinking difficulties, balance problems, or fever.
Other Possible Side Effects
Most people do not experience 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, tiredness, or weakness
Headache
Constipation, diarrhea, stomach pain, nausea, vomiting, or decreased appetite
Heartburn
Trouble sleeping
Back pain
Joint pain
* Nose or throat irritation
Reporting Side Effects
If you have questions about side effects or want to report any side effects, contact your doctor or the FDA at 1-800-332-1088 or visit https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, body aches, flu-like symptoms (signs of infection)
- Unusual bleeding or bruising
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Swelling in your hands, ankles, or feet
- Decreased urination
- Severe headache, confusion, seizures, numbness or tingling in hands/feet
- Tremors or shaking
- Increased thirst or urination (signs of high blood sugar)
- New skin lesions or changes in existing moles
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have a 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 it is crucial to determine the safety of this medication for your baby.
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 you have. Your doctor and pharmacist need this information to ensure it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have a 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 it is crucial to determine the safety of this medication for your baby.
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 you have. Your doctor and pharmacist need this information to ensure it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. When you receive a new prescription, verify that you have the correct medication by checking it carefully. If you suspect that you have been given the wrong medication or are unsure about its appearance, contact your doctor immediately.
To minimize the risk of infection, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu. Regular blood tests and other laboratory evaluations, as directed by your doctor, are crucial to monitor your condition.
Be aware that taking other medications concurrently with this drug can affect its levels in your body, potentially increasing the risk of organ rejection or side effects. If you are taking other medications, consult your doctor to determine if more frequent blood tests are necessary.
If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, discuss this with your doctor. Additionally, avoid consuming grapefruit and grapefruit juice while taking this medication.
Regular blood pressure checks, as advised by your doctor, are important because this medication can cause high blood pressure. Furthermore, this drug may 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.
It is recommended to avoid alcohol consumption while taking this medication. If you are not up to date with all recommended vaccinations, consult your doctor, as you may need to receive certain vaccines before starting treatment with this drug. Before getting any vaccinations, discuss this with your doctor, 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 when taking this medication. Protect yourself from the sun by using sunscreen, wearing protective clothing, and eyewear. Additionally, 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 with this drug.
To minimize the risk of infection, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu. Regular blood tests and other laboratory evaluations, as directed by your doctor, are crucial to monitor your condition.
Be aware that taking other medications concurrently with this drug can affect its levels in your body, potentially increasing the risk of organ rejection or side effects. If you are taking other medications, consult your doctor to determine if more frequent blood tests are necessary.
If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, discuss this with your doctor. Additionally, avoid consuming grapefruit and grapefruit juice while taking this medication.
Regular blood pressure checks, as advised by your doctor, are important because this medication can cause high blood pressure. Furthermore, this drug may 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.
It is recommended to avoid alcohol consumption while taking this medication. If you are not up to date with all recommended vaccinations, consult your doctor, as you may need to receive certain vaccines before starting treatment with this drug. Before getting any vaccinations, discuss this with your doctor, 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 when taking this medication. Protect yourself from the sun by using sunscreen, wearing protective clothing, and eyewear. Additionally, 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 with this drug.
Overdose Information
Overdose Symptoms:
- Severe kidney problems (e.g., acute renal failure)
- Neurotoxicity (e.g., severe tremor, headache, seizures, encephalopathy)
- Liver dysfunction
- Gastrointestinal disturbances
What to Do:
There is no specific antidote for tacrolimus overdose. Treatment is supportive. Contact a poison control center immediately (Call 1-800-222-1222 in the US). Hemodialysis is not effective in removing tacrolimus due to its high protein binding and extensive distribution.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Nelfinavir (strong CYP3A4 inhibitor, significantly increases tacrolimus levels)
- Ritonavir (strong CYP3A4 inhibitor, significantly increases tacrolimus levels)
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, cobicistat, grapefruit juice) - significantly increase tacrolimus levels, leading to toxicity.
- Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort) - significantly decrease tacrolimus levels, leading to rejection.
- Nephrotoxic agents (e.g., NSAIDs, aminoglycosides, amphotericin B, cyclosporine) - increase risk of nephrotoxicity.
- Potassium-sparing diuretics, ACE inhibitors, ARBs - increased risk of hyperkalemia.
- Vaccines (attenuated live vaccines) - risk of disseminated infection.
Moderate Interactions
- Moderate CYP3A4 inhibitors/inducers (e.g., diltiazem, verapamil, fluconazole, erythromycin, cimetidine, phenobarbital, efavirenz) - may alter tacrolimus levels, requiring monitoring.
- Drugs that affect gastric pH (e.g., antacids, H2 blockers, PPIs) - may affect tacrolimus absorption (less significant for extended-release).
- Mycophenolate mofetil - may affect tacrolimus levels (and vice versa) due to shared enterohepatic recirculation.
Minor Interactions
- Not specifically categorized as minor for tacrolimus; most interactions are clinically significant due to narrow therapeutic index.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC)
Rationale: To establish baseline hematologic parameters and monitor for potential myelosuppression.
Timing: Prior to initiation of therapy
Renal Function (Serum Creatinine, BUN, eGFR)
Rationale: To establish baseline kidney function and monitor for tacrolimus-induced nephrotoxicity.
Timing: Prior to initiation of therapy
Liver Function Tests (ALT, AST, 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 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
Tacrolimus Whole Blood Trough Concentration
Rationale: To establish initial therapeutic range and guide dose adjustments.
Timing: Within 24-48 hours of first dose, or as per protocol
Routine Monitoring
Tacrolimus Whole Blood Trough Concentration
Frequency: Initially 2-3 times per week, then weekly, then less frequently (e.g., monthly) once stable. More frequently with dose changes, drug interactions, or changes in clinical status.
Target: Highly variable based on transplant type, time post-transplant, and concomitant immunosuppression (e.g., 5-15 ng/mL for kidney/liver, 8-20 ng/mL early post-transplant). Refer to institutional protocols.
Action Threshold: Levels outside target range, signs of toxicity or rejection.
Renal Function (Serum Creatinine, BUN, eGFR)
Frequency: Weekly initially, then monthly once stable, or as clinically indicated.
Target: Stable baseline, within normal limits or acceptable post-transplant range.
Action Threshold: Significant increase in creatinine, decrease in eGFR.
Liver Function Tests (ALT, AST, ALP, Bilirubin)
Frequency: Weekly initially, then monthly once stable, or as clinically indicated.
Target: Within normal limits or acceptable post-transplant range.
Action Threshold: Significant elevation of liver enzymes or bilirubin.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Weekly initially, then monthly once stable, or as clinically indicated.
Target: Potassium: 3.5-5.0 mEq/L; Magnesium: 1.5-2.5 mg/dL; Phosphate: 2.5-4.5 mg/dL.
Action Threshold: Hyperkalemia, hypomagnesemia, hypophosphatemia.
Blood Glucose
Frequency: Weekly initially, then monthly once stable, or as clinically indicated.
Target: Fasting glucose <100 mg/dL, HbA1c <6.5%.
Action Threshold: Hyperglycemia, signs of new-onset diabetes.
Blood Pressure
Frequency: At each clinic visit, or more frequently if unstable.
Target: <130/80 mmHg (or as per transplant guidelines).
Action Threshold: Hypertension.
Complete Blood Count (CBC)
Frequency: Weekly initially, then monthly once stable, or as clinically indicated.
Target: Within normal limits.
Action Threshold: Leukopenia, anemia, thrombocytopenia.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue, new pain)
- Signs of kidney problems (decreased urine output, swelling in legs/ankles, unusual weight gain)
- Signs of nerve problems (tremor, headache, confusion, seizures, numbness/tingling)
- Signs of liver problems (yellowing of skin/eyes, dark urine, severe stomach pain)
- Signs of high blood sugar (increased thirst, increased urination, blurred vision)
- Signs of high blood pressure (headache, dizziness, blurred vision)
- Gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain)
- Skin changes (rash, increased sensitivity to sun, new moles or skin lesions)
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 and low birth weight. Neonates exposed in utero may experience hyperkalemia and renal dysfunction.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of congenital malformations, though data are conflicting and overall risk appears low.
Second Trimester:
Risk of premature birth, low birth weight, and neonatal complications.
Third Trimester:
Risk of premature birth, low birth weight, and neonatal complications (e.g., hyperkalemia, renal dysfunction).
Lactation
Tacrolimus is excreted into human breast milk. Due to the potential for serious adverse reactions in the breastfed infant (e.g., nephrotoxicity, immunosuppression), breastfeeding is not recommended during treatment with Astagraf XL.
Infant Risk:
High (L4 - Possibly Hazardous)
Pediatric Use
Astagraf XL is approved for the prophylaxis of organ rejection in pediatric liver transplant patients. Dosing is weight-based and requires careful monitoring of tacrolimus trough levels due to potential differences in pharmacokinetics compared to adults. Pediatric patients may require higher doses on a mg/kg basis.
Geriatric Use
No specific dose adjustment is generally required based on age alone. However, elderly patients may have reduced renal or hepatic function, or more comorbidities, which may necessitate closer monitoring of tacrolimus levels and adverse effects. Start at the lower end of the dosing range and titrate carefully.
Clinical Information
Clinical Pearls
- Astagraf XL is an extended-release formulation of tacrolimus and is taken once daily. It is NOT interchangeable on a milligram-to-milligram basis with immediate-release tacrolimus (Prograf) or other extended-release formulations (e.g., Envarsus XR). Switching formulations requires careful monitoring and dose adjustment.
- Always administer Astagraf XL consistently on an empty stomach (1 hour before or 2 hours after a meal) to minimize variability in absorption.
- Therapeutic drug monitoring (TDM) of tacrolimus whole blood trough concentrations is crucial due to its narrow therapeutic index and high pharmacokinetic variability. Target ranges vary based on transplant type, time post-transplant, and concomitant immunosuppression.
- Patients should be educated about the importance of strict adherence to the dosing schedule and avoiding missed doses, which can lead to organ rejection.
- Counsel patients to avoid grapefruit and St. John's Wort due to significant drug interactions.
- Monitor for common side effects such as tremor, headache, hypertension, hyperglycemia, nephrotoxicity, and gastrointestinal disturbances.
- Immunosuppression increases the risk of infections and malignancies; patients should be vigilant for symptoms and practice sun protection.
Alternative Therapies
- Cyclosporine (another calcineurin inhibitor)
- Sirolimus (mTOR inhibitor)
- Everolimus (mTOR inhibitor)
- Mycophenolate mofetil (antimetabolite)
- Azathioprine (antimetabolite)
- Belatacept (co-stimulation blocker)
- Corticosteroids (e.g., prednisone)
Cost & Coverage
Average Cost:
Highly variable, typically several hundred to over a thousand USD per 30 capsules
Generic Available:
Yes
Insurance Coverage:
Tier 3 or 4 (Specialty Drug)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides important information. Please read this guide carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.