Tacrolimus Extended-Release Capsule 0.5mg (Tacrolimus)

Adult dose

1. Kidney transplantation Adults: The usual initial dose is 0.20 ∼ 0.30 mg/kg body weight of tacrolimus orally once daily in the morning, followed by gradual dose reduction. The maintenance dose should be adjusted as appropriate according to symptoms, with reference to the “recommended target trough blood concentration.” 2. Liver transplantation Adults: The usual initial dose is 0.10 ∼ 0.20 mg/kg body weight of tacrolimus orally once daily in the morning, followed by gradual dose reduction. The maintenance dose should be adjusted as appropriate according to symptoms, with reference to the “recommended target trough blood concentration.” General considerations for kidney and liver transplantation The initial doses presented above are intended only as a guide. Administration of this drug should be based on clinical assessment of rejection and tolerability, together with measurement of blood concentrations in each patient (see “Recommended target trough blood concentrations” below). If clinical signs of rejection are evident, a change in the immunosuppressive regimen should be considered. Method of administration It is recommended that this drug be taken once daily in the morning. This drug should be taken immediately after removal from the blister. Patients should be instructed not to swallow the desiccant. The capsules should be swallowed with liquid (preferably water). This drug should generally be administered on an empty stomach, or 1 hour before or 2 ∼ 3 hours after a meal, to achieve maximum absorption. If the morning dose is missed, it should be taken as soon as possible on the same day. A double dose should not be taken the next morning. Recommended dose—Conversion from conventional tacrolimus formulations to this drug When a transplant patient taking a conventional tacrolimus formulation twice daily (Prograf capsules) is converted to this drug, which is taken once daily, the total daily dose should be converted at a ratio of 1 : 1 (mg : mg). This drug should be administered in the morning. Tacrolimus trough blood concentrations should be measured for 2 weeks after conversion, and the dose should be adjusted if necessary to maintain a similar systemic exposure. Dose adjustment in specific patient groups 1) Patients with hepatic impairment The dose may be reduced in patients with severe hepatic impairment to maintain trough blood concentrations within the recommended target range. 2) Patients with renal impairment Because the pharmacokinetics of tacrolimus are not affected by renal function, dose adjustment is not necessary. However, because of the potential nephrotoxicity of tacrolimus, careful monitoring of renal function is recommended (including serial serum creatinine concentrations, calculation of creatinine clearance, and monitoring of urine output). 3) Sex There is no evidence that men and women require different doses to achieve similar trough blood concentrations. 4) Elderly patients There is no evidence that dose adjustment is necessary in elderly patients. Recommended tacrolimus trough blood concentrations (whole blood trough level) for kidney and liver transplantation Several immunoassays are available for monitoring whole-blood tacrolimus concentrations (whole blood level) to optimize the dose. Comparisons between blood concentrations reported in the literature and those measured in clinical practice should be made on the basis of detailed knowledge of the assay method used. Immunoassays are currently used in clinical practice to monitor whole-blood concentrations. The relationship between tacrolimus trough blood concentration (C24) and systemic exposure (AUC0-24) is similar for this drug and conventional tacrolimus formulations, in both formulations. Tacrolimus trough blood concentrations should be monitored continuously. The trough blood concentration of this drug should be measured immediately before the next dose (approximately 24 hours after the previous dose). It is recommended that trough blood concentrations be measured frequently during the first 2 weeks after transplantation, followed by regular monitoring during the maintenance period. Trough blood concentrations should be monitored when converting from a conventional tacrolimus formulation to this drug, adjusting the dose, changing immunosuppressive therapy, or co-administering drugs that may affect whole-blood tacrolimus concentrations (see “Interactions”). The frequency of blood concentration measurements should be determined according to clinical need. Because tacrolimus has low clearance, changes in blood concentrations may take several days to become apparent after dose adjustment. According to the results of clinical trial analyses, successful outcomes were achieved in most patients when tacrolimus trough blood concentrations were maintained below 20 ng/mL. The patient’s clinical condition should be taken into account when interpreting blood concentrations. In general, initial post-transplant trough blood concentrations in clinical practice were 5 ∼ 20 ng/mL in liver transplant patients and 10 ∼ 20 ng/mL in kidney and heart transplant patients. Thereafter, during the maintenance period, trough blood concentrations were 5 ∼ 15 ng/mL in liver, kidney, and heart transplant patients.

This medication may suppress immune function, making the body more susceptible to infections; thus, it should only be used under the supervision of a physician experienced in immunosuppressive therapy. During the use of this medication, there is a risk of kidney function impairment, so regular kidney function tests should be performed, and the dosage should be adjusted according to the physician’s guidance. Potassium levels in the blood may increase, therefore it should not be taken with potassium-sparing diuretics, and periodic checks of blood potassium concentrations should be conducted. Neurological side effects such as headaches, tremors, and changes in mental state may occur, and if these symptoms arise, medical staff should be notified immediately. This medication may increase the risk of cancer, particularly skin cancer and lymphoma; regular screening is recommended. Increased risk of infection is possible, so medical personnel should be consulted immediately if any infection symptoms appear, and live vaccinations should be avoided. Do not take extended-release and immediate-release formulations together, and any changes to formulation or dosage should be supervised by a professional. This medication may induce or exacerbate diabetes, so blood sugar levels should be monitored frequently, and consultation with a doctor is recommended if any abnormalities occur. If taken with certain medications, it may affect drug concentrations, so patients should inform their doctor or pharmacist if they are taking other medications. Women who are pregnant or may become pregnant should consult with a doctor before taking this medication, and it should be avoided during breastfeeding. Elderly patients or those with compromised liver or kidney function are at higher risk for side effects from this medication, and careful observation and dosage adjustment are necessary during use. It is advisable to take this medication with sufficient water on an empty stomach and to avoid chewing or swallowing the packaging while taking the capsule. While on this medication, regular clinical tests for blood pressure, blood sugar, and kidney function should be conducted, and any abnormal symptoms should be reported to medical staff promptly. Care should be taken when driving or operating machinery due to potential visual and neurological abnormalities; if symptoms occur, activities should be limited.

Increased susceptibility to infection, lymphoma, kidney dysfunction, elevated serum creatinine, hyperkalemia, decreased urine output, hyperuricemia, chronic kidney impairment, tremors, headache, changes in motor function, changes in mental status, changes in sensory function, seizures, coma, delirium, posterior reversible encephalopathy syndrome (PRES), convulsions, visual impairment, hypertension, lymphoproliferative disorders, BK virus nephropathy, JC virus-associated progressive multifocal leukoencephalopathy (PML), CMV infection, post-transplant diabetes, pure red cell aplasia (PRCA), myocardial dysfunction, heart failure, ventricular and supraventricular arrhythmias, myocardial infarction, angina, pericardial effusion, QT interval prolongation, Torsades de pointes, acute renal failure, nephrotic syndrome, thrombotic microangiopathy, pancytopenia, thrombocytopenic purpura, agranulocytosis, hemolytic anemia, intestinal obstruction, bacterial infection, viral infection, fungal infection, parasitic infection, fever, lymphadenopathy, generalized seizures, altered consciousness, confusion, speech impairment, hemiplegia, cerebral infarction, cerebral hemorrhage, aspiration pneumonia, exacerbation of diabetes, hyperglycemia, pancreatitis, Stevens-Johnson syndrome, respiratory distress, acute respiratory distress syndrome, decreased urine output, polyuria, urinary frequency, post-void residual, glucosuria, hypomagnesemia, acidosis, hypercholesterolemia, hyperphosphatemia, hypophosphatemia, hypertriglyceridemia, hyperchloremia, hypercalcemia, hypocalcemia, hyponatremia, hypokalemia, anemia, either increased or decreased platelet count, leukopenia, leukocytosis, pruritus, hair loss, erythema, rash, tubular necrosis, hypertrophic cardiomyopathy, gynecomastia, vasodilation, decreased serum phosphate levels, pleural effusion, ascites, asthma, weight loss, flushing, generalized malaise, menorrhagia, myalgia, arthralgia, taste disturbances, aplastic anemia, cerebral infarction, toxic epidermal necrolysis (Lyell syndrome), glaucoma, ketosis, nystagmus, mania, meningitis, cholecystitis, thrombophlebitis, thrombosis, vasculitis, sensation of foreign body in the throat, pain, ocular pain, redness, excessive sweating, thirst, temperature fluctuations, optic neuropathy, fever-induced neutropenia, sleep disturbances, agitation, anxiety, confusion, depression, mood changes, feelings of happiness, dreams, abnormal thoughts, drowsiness, loss of reflex, emotional instability, hallucinations, excessive tension, lack of coordination, dystonic muscle spasms, neurotic disorders, neurological disorders, psychosis, cognitive impairment, amnesia, dizziness, encephalopathy, hemorrhagic stroke, monoplegia, nerve compression, irritability, neuralgia, flaccid paralysis, incomplete paralysis of limbs, hemiplegia, aphasia, visual impairment, amblyopia, tinnitus, cataracts, photophobia, hearing loss, ear pain, otitis media, cholangitis, cholestatic jaundice, dyspepsia, flatulence, gastrointestinal bleeding, elevated γ-GTP, gastrointestinal perforation, hepatitis, increased appetite, jaundice, liver damage, oral candidiasis, dysphagia, esophagitis, gastritis, intestinal obstruction, abnormal liver function tests, rectal disorders, stomatitis, duodenitis, intestinal gas retention, gastroesophageal reflux, gastrointestinal disorders, granulomatous hepatitis, ulcerative esophagitis, pancreatic pseudocyst, chest pain, abnormal ECG, bleeding, hypotension, tachycardia, angina, severe vascular thrombosis, orthostatic hypotension, peripheral vascular disorders, arrhythmias, atrial fibrillation, bradycardia, heart flutter, cardiac failure, loss of cardiac function, increased heart rate, syncope, thrombosis, vasodilation, hematuria, renal failure, cystitis, dysuria, hydronephrosis, pyuria, toxic nephropathy, acute renal failure, proteinuria, BK nephropathy, bladder spasms, decreased urine output, urgency incontinence, frequency, urinary incontinence, urine retention, vaginitis, acidosis, increased alkaline phosphatase, alkalosis, hyperbilirubinemia, non-healing, hyperlipidemia, hyperphosphatemia, hyperuricemia, hypocalcemia, hyponatremia, hypoalbuminemia, elevated AST, elevated ALT, decreased bicarbonate, dehydration, weight gain, edema, gout, peripheral edema, diabetes, Cushing's syndrome, coagulation disorders, petechiae, hypopigmented anemia, leukopenia, decreased platelet count, erythrocytosis, decreased prothrombin, decreased plasma iron, increased hematocrit, abnormal hemoglobin, leukocytosis, arthralgia, generalized seizures, limb spasms, myalgia, myasthenia gravis, osteoporosis, joint disorders, painful muscle spasms, reduced movement, asthma, bronchitis, increased cough, lung disease, pulmonary edema, pharyngitis, pneumonia, respiratory distress, rhinitis, sinusitis, voice changes, pneumothorax, hiccups, decreased lung function, hair loss, herpes simplex, hypertrichosis, skin disorders, sweating, acne, fungal dermatitis, skin discoloration, skin ulcers, exfoliative dermatitis, shingles, benign skin tumors, abdominal distension, abscesses, chills, hernia, peritonitis, photosensitive reactions, allergic reactions, cellulitis, influenza-like syndrome, sepsis, abdominal pain, incidental injuries, weakness, back pain, soft tissue infection, falls, sensory disturbances, temperature intolerance, ulcers, liver failure due to reactivation of hepatitis B

This medication should be stored in a tightly sealed container protected from light and in a place that avoids high humidity. The appropriate storage temperature is room temperature between 1 to 30 degrees Celsius.

Appearance

A hard capsule with a pale yellow upper part and dark brown lower part containing white or nearly white granules.

Package unit

50 capsules (10 capsules/PTP X 5)