Astagraf XL 1mg Capsules
WARNING: This drug may raise the chance of getting cancer like lymphoma or skin cancer. Talk with the doctor.Have your skin checked. Tell your doctor if you have any skin changes like a new wart, skin sore or reddish bump that bleeds or does not heal, or a change in the color or size of a mole.Call your doctor right away if you have a swollen gland, night sweats, shortness of breath, or weight loss without trying.This drug may raise the chance of very bad and sometimes deadly infections. Talk with the doctor.Call your doctor right away if you have any signs of infection like fever, chills, flu-like signs, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or a wound that will not heal.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 called an immunosuppressant. It works by lowering your body's immune system to help prevent your body from rejecting a transplanted organ (like a kidney or liver). Because it lowers your immune system, it can also increase your risk of infections and certain cancers.
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 precisely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
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 tablet whole with a glass of water. Do not chew, break, or crush the tablet. 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 with your prescription and follow the instructions precisely. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
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 tablet whole with a glass of water. Do not chew, break, or crush the tablet. 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 exactly as prescribed, usually once daily, on an empty stomach (at least 1 hour before or 2 hours after a meal). Take it at the same time each day.
- Do not switch between different tacrolimus products (e.g., Astagraf XL, Prograf, Envarsus XR) without your doctor's explicit instruction, as they are not interchangeable and can lead to serious problems.
- Avoid grapefruit and grapefruit juice, as they can significantly increase tacrolimus levels.
- Avoid St. John's Wort, as it can significantly decrease tacrolimus levels.
- Limit sun exposure and wear protective clothing and sunscreen (SPF 30+) due to increased risk of skin cancer.
- Avoid live vaccines (e.g., MMR, varicella, rotavirus) while on this medication. Discuss all vaccinations with your doctor.
- Report any signs of infection (fever, chills, sore throat, unusual fatigue) immediately.
- Report any new lumps, skin changes, or unexplained weight loss.
- Attend all scheduled blood tests and doctor appointments to monitor drug levels and side effects.
- Maintain good hygiene to reduce infection risk.
- Inform all healthcare providers (including dentists) that you are taking Astagraf XL.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Individualized based on tacrolimus trough concentrations. Initial dose for kidney transplant: 0.15 to 0.2 mg/kg/day orally once daily. Initial dose for liver transplant: 0.1 to 0.2 mg/kg/day orally once daily.
Dose Range:
0.1 - 0.2 mg
Condition-Specific Dosing:
kidney_transplant_initial:
0.15 to 0.2 mg/kg/day once daily
liver_transplant_initial:
0.1 to 0.2 mg/kg/day once daily
maintenance:
Adjusted to achieve target trough levels (typically 5-15 ng/mL for kidney, 5-10 ng/mL for liver, depending on time post-transplant and concomitant therapy)
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (Astagraf XL is not approved for pediatric use; other tacrolimus formulations may be used with specific dosing)
Adolescent:
Not established (Astagraf XL is not approved for pediatric use; other tacrolimus formulations may be used with specific dosing)
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor tacrolimus trough levels closely.
Moderate:
No specific dose adjustment recommended, but monitor tacrolimus trough levels closely.
Severe:
No specific dose adjustment recommended, but monitor tacrolimus trough levels closely. Tacrolimus is nephrotoxic; consider lower initial doses and close monitoring.
Dialysis:
Tacrolimus is not significantly dialyzable. No specific dose adjustment for dialysis, but monitor trough levels closely.
Hepatic Impairment:
Mild:
Consider lower initial doses (e.g., 25-50% reduction) and monitor tacrolimus trough levels closely.
Moderate:
Consider lower initial doses (e.g., 25-50% reduction) and monitor tacrolimus trough levels closely.
Severe:
Consider lower initial doses (e.g., 25-50% reduction) and monitor tacrolimus trough levels closely. Patients with severe hepatic impairment may require substantial dose reductions.
Pharmacology
Mechanism of Action
Tacrolimus is a calcineurin inhibitor. It binds to the immunophilin FKBP-12 (FK506 binding protein), forming a complex that inhibits calcineurin, a phosphatase. This inhibition prevents the dephosphorylation of nuclear factor of activated T-cells (NF-AT), which is required for the transcription of genes encoding various cytokines (e.g., IL-2, IL-3, IL-4, IL-5, GM-CSF, TNF-alpha). By inhibiting cytokine production, tacrolimus prevents the activation and proliferation of T-lymphocytes, thereby suppressing the immune response and preventing organ rejection.
Pharmacokinetics
Absorption:
Bioavailability:
Highly variable (approximately 20-25% for oral capsules, but can range from 4-89%). Astagraf XL has similar bioavailability to immediate-release tacrolimus.
Tmax:
Approximately 2-4 hours (for Astagraf XL)
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 (high volume of distribution)
ProteinBinding:
Approximately 98.8% (primarily to albumin and alpha-1-acid glycoprotein, and also extensively to erythrocytes)
CnssPenetration:
Limited (low CSF concentrations, but neurotoxicity can occur)
Elimination:
HalfLife:
Approximately 25-43 hours (for Astagraf XL, highly variable)
Clearance:
Approximately 0.04-0.08 L/hr/kg (highly variable)
ExcretionRoute:
Primarily fecal (92.6%), with a small amount excreted in urine (2.3%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not directly quantifiable for immunosuppression; therapeutic effects are achieved once stable trough levels are reached.
PeakEffect:
Achieved once stable trough levels are reached, typically within several days to a week of consistent dosing.
DurationOfAction:
Related to drug levels; once-daily dosing maintains therapeutic levels over 24 hours.
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, are consequences of immunosuppression. Only physicians experienced in immunosuppressive therapy and the management of organ transplant patients should prescribe Astagraf XL. Patients receiving Astagraf XL should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information essential for the safe use of the drug and for monitoring patients. Astagraf XL is not interchangeable with other tacrolimus products. Medication errors with tacrolimus products have resulted in serious adverse events, including death. Avoid medication errors by prescribing and dispensing Astagraf XL by brand name.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 sudden 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, dizziness, fainting, or changes in vision.
Acidosis (Too Much Acid in the Blood): Confusion, rapid breathing, rapid heartbeat, irregular heartbeat, severe stomach pain, nausea, vomiting, excessive sleepiness, shortness of breath, or feeling extremely tired or weak.
Skin Problems: Warm, red, or painful skin or sores on the body.
Cardiovascular Issues: Chest pain or pressure, shortness of breath, sudden weight gain, or swelling in the arms or legs.
Neurological Problems: Shakiness, difficulty moving, unexplained bruising or bleeding, burning, numbness, or tingling sensations.
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 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 life-threatening brain condition that may cause confusion, decreased alertness, vision changes, seizures, or severe headaches. 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 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 notice any of the following symptoms, contact your doctor or seek medical help 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, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 sudden 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, dizziness, fainting, or changes in vision.
Acidosis (Too Much Acid in the Blood): Confusion, rapid breathing, rapid heartbeat, irregular heartbeat, severe stomach pain, nausea, vomiting, excessive sleepiness, shortness of breath, or feeling extremely tired or weak.
Skin Problems: Warm, red, or painful skin or sores on the body.
Cardiovascular Issues: Chest pain or pressure, shortness of breath, sudden weight gain, or swelling in the arms or legs.
Neurological Problems: Shakiness, difficulty moving, unexplained bruising or bleeding, burning, numbness, or tingling sensations.
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 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 life-threatening brain condition that may cause confusion, decreased alertness, vision changes, seizures, or severe headaches. 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 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 notice any of the following symptoms, contact your doctor or seek medical help 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:
- Fever, chills, sore throat, body aches (signs of infection)
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- Swelling in hands, ankles, or feet
- Decreased urination
- Severe headache, confusion, seizures, numbness or tingling
- Tremors or shaking
- Vision changes
- Yellowing of skin or eyes (jaundice)
- Dark urine, pale stools
- Severe nausea, vomiting, or diarrhea
- New or worsening skin lesions, moles, or lumps
- Increased thirst or urination (signs of high blood sugar)
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 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 it is crucial to determine the safety of this medication for your baby.
This list is not exhaustive, and it is vital 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 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 to avoid potential interactions.
Grapefruit and grapefruit juice should be avoided while taking this medication, as they may interact with it.
Monitor your blood pressure regularly, as prescribed by your doctor, since this medication can cause high blood pressure.
Additionally, this medication can cause high blood sugar levels, including new-onset or worsening diabetes. Check your blood sugar levels as instructed 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 consuming alcohol while taking this medication.
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 not be effective or may increase the risk of infection when taken with this medication.
Prolonged exposure to sunlight, sunlamps, and tanning beds should be avoided, as this medication may increase the risk of skin cancer. Use sunscreen, protective clothing, and eyewear to minimize sun exposure.
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 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 to avoid potential interactions.
Grapefruit and grapefruit juice should be avoided while taking this medication, as they may interact with it.
Monitor your blood pressure regularly, as prescribed by your doctor, since this medication can cause high blood pressure.
Additionally, this medication can cause high blood sugar levels, including new-onset or worsening diabetes. Check your blood sugar levels as instructed 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 consuming alcohol while taking this medication.
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 not be effective or may increase the risk of infection when taken with this medication.
Prolonged exposure to sunlight, sunlamps, and tanning beds should be avoided, as this medication may increase the risk of skin cancer. Use sunscreen, protective clothing, and eyewear to minimize sun exposure.
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 kidney problems (decreased urine, swelling)
- Severe neurological symptoms (tremor, headache, confusion, seizures)
- Liver dysfunction
- Severe gastrointestinal upset
What to Do:
Seek immediate medical attention or call a poison control center. In the US, call 1-800-222-1222. There is no specific antidote; treatment is supportive.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
- Concomitant use with Pimecrolimus or Tacrolimus topical (additive immunosuppression)
Major Interactions
- Strong CYP3A4/5 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, ritonavir, cobicistat, grapefruit juice) - significantly increase tacrolimus levels, leading to toxicity.
- Strong CYP3A4/5 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) - increased risk of nephrotoxicity.
- Potassium-sparing diuretics, ACE inhibitors, ARBs - increased risk of hyperkalemia.
- Sirolimus, Everolimus - increased risk of nephrotoxicity and other toxicities.
Moderate Interactions
- Moderate CYP3A4/5 inhibitors (e.g., diltiazem, verapamil, fluconazole, erythromycin) - may increase tacrolimus levels.
- Moderate CYP3A4/5 inducers (e.g., efavirenz, etravirine) - may decrease tacrolimus levels.
- Vaccines (non-live) - reduced efficacy of vaccines.
- Drugs that affect gastric pH (e.g., antacids, H2 blockers, PPIs) - may affect tacrolimus absorption (less significant for extended-release).
Minor Interactions
- Not typically categorized as minor due to narrow therapeutic index; all interactions should be carefully managed.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic parameters and monitor for anemia, leukopenia, thrombocytopenia.
Timing: Prior to initiation of therapy
Renal Function (SCr, BUN, eGFR)
Rationale: To establish baseline kidney function and monitor for nephrotoxicity.
Timing: Prior to initiation of therapy
Liver Function Tests (ALT, AST, ALP, bilirubin)
Rationale: To establish baseline liver function and monitor for 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 (Fasting or HbA1c)
Rationale: To establish baseline glucose control 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
Lipid Panel
Rationale: To establish baseline and monitor for dyslipidemia.
Timing: Prior to initiation of therapy
Routine Monitoring
Tacrolimus Whole Blood Trough Levels (C0)
Frequency: Initially 2-3 times per week until stable, then at least weekly for the first month, then every 2-4 weeks or as clinically indicated.
Target: Typically 5-15 ng/mL for kidney transplant (early post-transplant), 5-10 ng/mL for liver transplant (early post-transplant). Ranges vary based on time post-transplant, concomitant immunosuppression, and center protocol.
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 every 2-4 weeks or as clinically indicated.
Target: Stable and within acceptable post-transplant limits.
Action Threshold: Significant increase in SCr or decrease in eGFR; investigate for nephrotoxicity, rejection, or other causes.
Electrolytes (Potassium, Magnesium, Phosphate)
Frequency: Weekly for the first month, then every 2-4 weeks 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; supplement as needed or adjust tacrolimus dose if severe.
Blood Glucose
Frequency: Weekly for the first month, then every 2-4 weeks or as clinically indicated.
Target: Fasting glucose <126 mg/dL; HbA1c <6.5-7%.
Action Threshold: Persistent hyperglycemia; consider anti-diabetic therapy or dose adjustment.
Blood Pressure
Frequency: At each clinic visit.
Target: <130/80 mmHg (or per guideline for transplant patients).
Action Threshold: Hypertension; initiate or adjust antihypertensive therapy.
Complete Blood Count (CBC)
Frequency: Weekly for the first month, then every 2-4 weeks or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant leukopenia, anemia, or thrombocytopenia; investigate and manage.
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 (tremor, headache, confusion, seizures, paresthesias)
- Renal dysfunction (decreased urine output, swelling, fatigue)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
- Cardiovascular symptoms (chest pain, palpitations, swelling)
- Signs of diabetes (increased thirst, increased urination, unexplained weight loss)
- Skin changes (new or changing moles, 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 are reports of adverse outcomes including premature birth, low birth weight, and congenital anomalies (e.g., cardiac, renal) in infants exposed to tacrolimus in utero. Neonatal hyperkalemia and renal dysfunction have also been reported.
Trimester-Specific Risks:
First Trimester:
Potential for congenital anomalies, though data are limited and inconsistent.
Second Trimester:
Risk of premature birth, low birth weight, and potential for neonatal renal dysfunction and hyperkalemia.
Third Trimester:
Increased risk of premature birth, low birth weight, and potential for neonatal renal dysfunction and hyperkalemia. Close monitoring of tacrolimus levels and fetal growth is essential.
Lactation
Tacrolimus is excreted into human milk. Due to the potential for serious adverse reactions in the breastfed infant (e.g., immunosuppression, nephrotoxicity, neurotoxicity), breastfeeding is not recommended during treatment with Astagraf XL.
Infant Risk:
High (immunosuppression, nephrotoxicity, neurotoxicity, growth retardation)
Pediatric Use
Astagraf XL is not approved for use in pediatric patients. Other tacrolimus formulations (e.g., immediate-release) are used in pediatric transplant patients, but dosing is complex and requires careful monitoring.
Geriatric Use
No specific dose adjustments are generally required based solely on age, but elderly patients may be more susceptible to adverse effects (e.g., renal impairment, neurotoxicity, diabetes). Close monitoring of tacrolimus levels and renal function is recommended.
Clinical Information
Clinical Pearls
- Astagraf XL is a once-daily extended-release formulation of tacrolimus. It is NOT interchangeable with other tacrolimus products (e.g., Prograf, Envarsus XR) on a milligram-for-milligram basis due to different pharmacokinetic profiles. Medication errors are a significant risk.
- Always administer Astagraf XL on an empty stomach (at least 1 hour before or 2 hours after a meal) to ensure consistent absorption. Food, especially high-fat meals, can significantly reduce absorption.
- Therapeutic drug monitoring (TDM) of tacrolimus whole blood trough levels is crucial due to its narrow therapeutic index and high inter-patient variability in pharmacokinetics. Levels must be individualized.
- Tacrolimus is a potent immunosuppressant but carries significant risks of nephrotoxicity, neurotoxicity, new-onset diabetes after transplant (NODAT), hypertension, and hyperkalemia. Close monitoring of renal function, electrolytes, blood glucose, and blood pressure is essential.
- Patients should be educated about the importance of adherence, avoiding grapefruit products and St. John's Wort, and reporting any signs of infection or malignancy immediately.
- Immunosuppressed patients are at increased risk for opportunistic infections and malignancies (especially skin cancer and post-transplant lymphoproliferative disorder - PTLD). Lifelong surveillance is necessary.
Alternative Therapies
- Cyclosporine (another calcineurin inhibitor)
- Sirolimus (mTOR inhibitor)
- Everolimus (mTOR inhibitor)
- Belatacept (co-stimulation blocker)
- Mycophenolate Mofetil/Sodium (antiproliferative agent)
- Azathioprine (antiproliferative agent)
- Corticosteroids (e.g., prednisone)
Cost & Coverage
Average Cost:
Varies widely by strength and quantity (e.g., $1000 - $4000+) per 30 capsules
Generic Available:
Yes
Insurance Coverage:
Tier 4 (Specialty Drug) or higher, often requiring prior authorization and/or step therapy.
General Drug Facts
If your symptoms or health issues persist or worsen, it is 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 crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult 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 reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.