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- Clinician Information:
Astagraf XL Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Astagraf XL (tacrolimus) Extended-Release Capsules is a macrolide immunosuppressant used with other medicines to help prevent organ rejection in people who have had a kidney transplant. Common side effects include diarrhea; constipation; nausea; swelling of the hands, ankles, or legs; tremors; or low red blood cell count (anemia). It can also make you more sensitive to sunlight.
Dosing of Astagraf XL is adjusted for each patient based on the patient's weight, clinical assessments of rejection and tolerability, and to maintain blood concentration ranges. Astagraf XL may interact with cyclosporine, azole antifungals, calcium channel blockers, antibiotics, rifampin, anticonvulsants, St. John's Wort, proton pump inhibitors, amiodarone, bromocriptine, nefazodone, metoclopramide, danazol, ethinyl estradiol, methylprednisolone, "live" vaccines, alcoholic beverages, grapefruit and grapefruit juice. Tell your doctor all medications and supplements you use and all vaccines you recently received. Talk to your doctor about taking Astagraf XL if you are pregnant or plan to become pregnant. It may harm a fetus. Astagraf XL passes into breast milk. Consult your doctor before breastfeeding.
Our Astagraf XL (tacrolimus) Extended-Release Capsules Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Astagraf XL FDA Prescribing Information: Side Effects
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
- Lymphoma and Other Malignancies [see WARNINGS AND PRECAUTIONS]
- Serious Infections [see WARNINGS AND PRECAUTIONS]
- Cytomegalovirus (CMV) Infections [see WARNINGS AND PRECAUTIONS]
- New Onset Diabetes after Transplant [see WARNINGS AND PRECAUTIONS]
- Nephrotoxicity [see WARNINGS AND PRECAUTIONS]
- Neurotoxicity [see WARNINGS AND PRECAUTIONS]
- Hyperkalemia [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Pure Red Cell Aplasia [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In addition, the clinical trials were not designed to establish comparative differences across study arms with regards to the adverse reactions discussed below.
Study 1: With Basiliximab Induction
The proportion of patients who discontinued treatment due to adverse reactions was 9% in the ASTAGRAF XL arm and 11% in the Prograf control arm through 12 months of treatment. The most common adverse reactions leading to discontinuation in ASTAGRAF XL-treated patients were related to infections or renal/urinary disorders. The most common ( ≥ 30%) adverse reactions observed in the ASTAGRAF XL group were: diarrhea, constipation, nausea, peripheral edema, tremor and anemia.
Study 2: Without Induction
The proportion of patients who discontinued treatment due to adverse reactions was 13% in the ASTAGRAF XL arm and 11% in the Prograf control arm through 12 months of treatment. The most common adverse reactions leading to discontinuation in ASTAGRAF XL-treated patients were related to infections, graft dysfunction, renal vascular/ischemic conditions and diabetes. The most common ( ≥ 30%) adverse reaction observed in the ASTAGRAF XL group was anemia.
Information on selected significant adverse reactions observed during Studies 1 and 2 are summarized below.
New Onset Diabetes After Transplant (NODAT)
New onset diabetes after transplantation (defined by the composite occurrence of ≥ 2 fasting plasma glucose values that were > 126 mg/dL at ≥ 30 days apart, insulin use for ≥ 30 consecutive days, oral hypoglycemic use for ≥ 30 consecutive days, oral hypoglycemic use for ≥ 30 consecutive days, and/or HbA1C ≥ 6.5%) is summarized in Table 2 below for Study 1 and Study 2 through one year post-transplant.
Table 2: Composite NODAT Through 1 Year
Post-Transplant in Studies 1 and 2
|Study 1||Study 2|
|Composite NODAT||58 (36)||53 (35)||105 (37)||90 (30)|
|≥ 2 Fasting Plasma Glucose Values ≥ 126 mg/dL ≥ 30 days apart||42 (26)||35 (23)||51 (18)||47 (16)|
|Insulin use ≥ 30 consecutive days||10 (6)||12 (8)||29 (10)||29 (10)|
|Oral hypoglycemic use ≥ 30 consecutive days||22 (14)||13 (9)||20 (7)||23 (8)|
|HbA1C ≥ 6.5%||31 (19)||33 (22)||48 (17)||39 (13)|
Adverse reactions of infectious etiology were reported based on clinical assessment by physicians. The causative organisms for these reactions are identified when provided by the physician. The overall number of infections, serious infections, and select infections with identified etiology reported in patients treated with ASTAGRAF XL or the control in Studies 1 and 2 are shown in Table 3.
Table 3: Overall Infections
and Select Infections by Treatment Group in Studies 1 and 2 Through One Year
|Study 1||Study 2|
|All Infections||148 (69)||146 (69)||228 (69)||216 (64)|
|Serious Infections||48 (22)||49 (23)||79 (24)||64 (19)|
|Bacterial Infections||18 (8)||25 (12)||125 (38)||137 (41)|
|Respiratory Infections||73 (34)||65 (31)||75 (23)||74 (22)|
|Cytomegalovirus Infections||21 (10)||24 (11)||38 (12)||21 (6)|
|Polyomavirus Infections||6 (3)||10 (5)||7 (2)||1 (0)|
|Gastroenteritis||16 (7)||6 (3)||16 (5)||8 (2)|
|Studies 1 and 2 were not designed to support comparative claims for ASTAGRAF XL for the adverse reactions reported in this table.|
Glomerular Filtration Rate
The estimated mean glomerular filtration rates, using the Modification of Diet in Renal Disease (MDRD) formula, by treatment group at Month 12 in the ITT population in Studies 1 and 2 are shown in Table 4.
Table 4: Estimated Glomerular
Filtration Rate (mL/min/1.73m²) by MDRD Formula at 12 Months
|Study 1||Study 2|
|Month 1 Baseline Mean (SD)||56 (20)||56 (21)||51 (19)||52 (20)|
|Month 12 LOCFa|
|Mean (Standard deviation)||58 (21)||56 (23)||52 (20)||55 (19)|
|Median (Min-Max)||56 (0, 177)||57 (0, 120)||54 (0, 116)||54 (0, 134)|
|Mean Difference XL-Prografb||+2.3 (-1.2, +5.8)||-1.8 (-4.6, +0.8)|
|a Subject's last observation carried forward (LOCF) for
missing data at Month 1; patients who died, lost the graft or were lost to
follow-up are imputed as zeroes
b Tacrolimus XL-Prograf treatment mean difference results of analysis of covariance model with Month 1 Baseline as a covariate.
The incidence of adverse reactions that occurred in ≥ 15% of ASTAGRAF XL-treated patients compared to control through one year of treatment in Studies 1 and 2 are shown in Table 5.
Table 5: Adverse Events
Occurring in ≥ 15% of ASTAGRAF XL-Treated Kidney Transplant Patients
Through One year Post Transplant in Studies 1 or 2a
|Adverse Reactions||Study 1||Study 2|
|Anemia||70 (33)||61 (29)||103 (31)||87 (26)|
|Constipation||85 (40)||68 (32)||45 (14)||60 (18)|
|Diarrhea||96 (45)||94 (44)||88 (27)||103 (31)|
|Fatigue||34 (16)||22 (10)||7 (2)||6 (2)|
|Graft Dysfunction||29 (14)||45 (21)||57 (17)||56 (17)|
|Headache||46 (22)||50 (24)||39 (12)||33 (10)|
|Hyperglycemia||34 (16)||39 (18)||61 (18)||65 (19)|
|Hyperkalemia||43 (20)||49 (23)||50 (15)||49 (15)|
|Hyperlipidemia||35 (16)||36 (17)||23 (7)||28 (8)|
|Hypertension||59 (28)||63 (30)||80 (24)||76 (23)|
|Hypomagnesemia||52 (24)||57 (27)||9 (3)||12 (4)|
|Hypophosphatemia||50 (23)||59 (28)||15 (5)||22 (7)|
|Increased Blood Creatinine||40 (19)||49 (23)||54 (16)||63 (19)|
|Insomnia||52 (24)||60 (28)||29 (9)||34 (10)|
|Leukopenia||35 (16)||33 (16)||51 (15)||37 (11)|
|Nausea||76 (36)||75 (35)||51 (15)||42 (13)|
|Peripheral Edema||76 (36)||73 (34)||38 (12)||49 (15)|
|Tremor||75 (35)||73 (34)||58 (18)||58 (17)|
|Urinary Tract Infection||34 (16)||53 (25)||7 (2)||10 (3)|
|Urinary Tract Infection (bacterial)||1 (1)||6 (3)||86 (26)||102 (30)|
|Vomiting||53 (25)||53 (25)||42 (13)||43 (13)|
|aStudies 1 and 2 were not designed to support comparative claims for ASTAGRAF XL for the adverse reactions reported in this table.|
Less Frequently Reported Adverse Reactions ( < 15%) by System Organ Class
The following adverse reactions were also reported in clinical studies of kidney transplant recipients who were treated with ASTAGRAF XL.
Cardiac Disorders: Angina pectoris, atrial fibrillation, atrial flutter, bradycardia, cardiac arrest, congestive cardiac failure, hypertrophic cardiomyopathy, myocardial ischemia, myocardial infarction, pericardial effusion, tachycardia, ventricular extrasystoles
Eye Disorders: Vision blurred, conjunctivitis
Gastrointestinal Disorders: Abdominal distension, abdominal pain, aphthous stomatitis, ascites, colitis, dyspepsia, esophagitis, flatulence, gastritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, ileus, impaired gastric emptying, pancreatitis, stomach ulcer
General Disorders and Administration Site Conditions: Anasarca, asthenia, edema
Injury, Poisoning and Procedural Complications: Fall
Investigations: Abnormal electrocardiogram T wave, increased blood lactate dehydrogenase, increased blood urea, increased hematocrit, increased hepatic enzyme, increased international normalized ratio, weight fluctuation
Metabolism and Nutrition Disorders: Anorexia, dehydration, fluid overload, hypercalcemia, hyperphosphatemia, hyperuricemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypoproteinemia, metabolic acidosis
Nervous System Disorders: Aphasia, carpal tunnel syndrome, cerebral infarction, cerebral ischemia, convulsion, dizziness, hypoesthesia, neurotoxicity, paresthesia, peripheral neuropathy, somnolence, syncope
Psychiatric Disorders: Agitation, anxiety, confusional state, depression, hallucination, mental status changes, mood swings, nightmare
Respiratory, Thoracic and Mediastinal Disorders: Acute respiratory distress syndrome, allergic rhinitis, dyspnea, emphysema, hiccups, lung infiltration, pulmonary edema, productive cough, respiratory failure
The following adverse reactions have been reported from worldwide marketing experience with tacrolimus. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: Agranulocytosis, decreased blood fibrinogen, disseminated intravascular coagulation, hemolytic uremic syndrome, prolonged activated partial thromboplastin time, pure red cell aplasia [see WARNINGS AND PRECAUTIONS], thrombotic thrombocytopenic purpura
General Disorders: Multi-organ failure
Immune disorders: Graft versus host disease (acute and chronic)
Nervous System Disorders: Coma, dysarthria, flaccid paralysis, hemiparesis, mutism, nerve compression, posterior reversible encephalopathy syndrome (PRES) [see WARNINGS AND PRECAUTIONS], progressive multifocal leukoencephalopathy (PML) sometimes fatal [see WARNINGS AND PRECAUTIONS], quadriplegia, status epilepticus
Respiratory, Thoracic and Mediastinal Disorders: Interstitial lung disease, pulmonary hypertension
Read the entire FDA prescribing information for Astagraf XL (Tacrolimus Extended-release Capsules) »
Additional Astagraf XL Information
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