AdvaGrap Capsule 0.5 mg (Tacrolimus Hydrate)

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 appropriately 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 appropriately 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 for guidance only. 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. Take this drug immediately after removing it from the blister. Instruct patients not to swallow the desiccant. Swallow the capsules with liquid (preferably water). This drug should generally be taken on an empty stomach, either 1 hour before a meal or 2 ∼ 3 hours after a meal, to achieve maximum absorption. If the morning dose is missed, take it as soon as possible on the same day. Do not take a double dose the next morning. Recommended dose—Conversion from conventional tacrolimus formulations to this drug When a transplant patient who has been taking a conventional tacrolimus formulation (Prograf capsules) twice daily is switched to this once-daily drug, convert the total daily dose at a ratio of 1 : 1 (mg : mg). This drug should be taken in the morning. Measure tacrolimus trough blood concentrations for 2 weeks after the switch and adjust the dose if necessary to maintain 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 No dose adjustment is necessary because the pharmacokinetics of tacrolimus are not affected by renal function. 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 in kidney and liver transplantation (Whole blood trough level) Several immunoassay methods are available for monitoring tacrolimus whole blood levels to optimize the dose. Comparisons between blood concentrations reported in the literature and those measured in clinical practice should be made with detailed knowledge of the assay method used. Immunoassay methods 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. 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). Frequent measurement of trough blood concentrations is recommended during the first 2 weeks after transplantation, followed by regular monitoring during the maintenance period. Trough blood concentrations should be monitored when switching from a conventional tacrolimus formulation to this drug, adjusting the dose, changing immunosuppressive therapy, or coadministering drugs that may affect tacrolimus whole blood concentrations (see ‘Interactions’). The frequency of blood concentration measurements should be based on clinical need. Because tacrolimus has low clearance, changes in blood concentrations may take several days to appear after a dose adjustment. Analysis of clinical trial results indicates that 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, during the early post-transplant period in clinical practice, trough blood concentrations were 5 ∼ 20 ng/mL in liver transplant patients and 10 ∼ 20 ng/mL in kidney and heart transplant patients. During the subsequent maintenance period, trough blood concentrations were 5 ∼ 15 ng/mL in liver, kidney, and heart transplant patients.

This medication is an immunosuppressant and may weaken resistance to infections. Therefore, it should be administered under the management of a specialist experienced in immunosuppressants, and the patient should undergo regular examinations and monitoring by healthcare professionals. This medication can affect kidney function, so kidney function tests should be done frequently, and dosage adjustments or temporary discontinuation may be necessary if kidney function deteriorates. Additionally, metabolic abnormalities such as hyperkalemia, hypertension, and hyperglycemia may occur during the course of treatment, so blood pressure, blood glucose, and blood potassium levels should be monitored regularly. Neurological side effects may include headaches, tremors, and seizures, and in severe cases, symptoms of encephalopathy may appear, so the healthcare provider should be informed immediately if symptoms occur. This medication may increase the risk of malignant tumor occurrence when combined with other immunosuppressants, so caution is required. In particular, this medication should not be used with ciclosporin, as the nephrotoxicity may worsen with concomitant use. Concurrent use with potassium-sparing diuretics should be avoided due to an increased risk of hyperkalemia. It should only be administered during pregnancy when absolutely necessary, and pregnant women should carefully manage blood glucose and blood pressure. The risk of infection increases while taking this medication, so if there are any symptoms of infection, the healthcare provider should be informed immediately. Furthermore, this medication can cause changes in vision or neurological symptoms, so if any unusual signs occur, prompt medical attention from an ophthalmologist or neurologist is necessary. Elderly patients or those with impaired liver or kidney function may require dosage adjustments and regular tests. It is recommended to take the medication at least 1 hour before meals or in a fasting state 2 to 3 hours after meals with sufficient water, and to be cautious not to chew or swallow the packaging when taking the capsules. Finally, this medication can interact with various drugs, so it is essential to inform the healthcare provider if other medications are being taken.

Increased sensitivity to infections, possibility of lymphoma development, nephrotoxicity, acute kidney injury, increased serum creatinine, hyperkalemia, decreased urea excretion, hyperuricemia, chronic kidney disease, tremors, headaches, changes in motor function, alterations in mental state, changes in sensory function, seizures, coma, confusion, posterior reversible encephalopathy syndrome (PRES), fever, lymphoproliferative disorders, malignant tumors, BK virus-associated nephropathy, JC virus-related PML, CMV infection, post-transplant diabetes, pure red cell aplasia, gastrointestinal perforation, QT interval prolongation, Torsades de Pointes, thrombotic microangiopathy, cardiac dysfunction, heart failure, ventricular and supraventricular arrhythmias, myocardial infarction, angina pectoris, pericardial effusion, pancytopenia, thrombocytopenic purpura, agranulocytosis, hemolytic anemia, intestinal obstruction, bacterial infection, viral infection, fungal infection, protozoan infection, reversible posterior encephalopathy syndrome, generalized seizures, altered consciousness, delirium, speech impairment, visual impairment, hemiplegia, cerebral infarction, intracerebral hemorrhage, pneumonia due to aspiration, exacerbation of diabetes, hyperglycemia, pancreatitis, Stevens-Johnson syndrome, dyspnea, acute respiratory distress syndrome, decreased urine output, polyuria, urinary frequency, residual urine sensation, glucosuria, hypomagnesemia, acidosis, hypercholesterolemia, hyperphosphatemia, hypophosphatemia, hypertriglyceridemia, hyperchloremia, hypercalcemia, hypocalcemia, hyponatremia, hypokalemia, tachycardia, palpitations, increased blood pressure, decreased blood pressure, bradycardia, ataxia, hallucinations, sensory disturbances, anxiety, delirium, insomnia, paresthesia, eyelid twitching, limb rigidity, paralysis, drowsiness, stupor, clouding of consciousness, localized sensory loss, nonsensical speech, depression, excitement, sleep disturbances, agitation, worry, confusion, euphoria, euphoria, dreams, abnormal thoughts, loss of reflexes, emotional instability, hypertonia, dyskinesia, neurotic tremors, neurological disorders, psychosis, inability to think, amnesia, encephalopathy, hemorrhagic stroke, hemiparesis, nerve compression, irritability, neuralgia, flaccid paralysis, incomplete limb paralysis, sensory processing disorder, aphasia, visual impairment, amblyopia, tinnitus, cataracts, photophobia, hearing loss, ear pain, otitis media, cholangitis, cholestatic jaundice, dyspepsia, flatulence, gastrointestinal bleeding, increased γ-GTP, hepatitis, increased appetite, jaundice, liver damage, oral candidiasis, dysphagia, esophagitis, gastritis, intestinal obstruction, abnormal liver function tests, rectal disorders, stomatitis, duodenitis, pneumatosis intestinalis, gastroesophageal reflux disease, gastrointestinal disorders, granulomatous hepatitis, esophageal ulceration, pseudocyst of the pancreas, chest pain, abnormal ECG, bleeding, hypotension, angina, severe vascular inflammation, orthostatic hypotension, peripheral vascular disorders, arrhythmias, atrial fibrillation, bradyarrhythmia, cardiac flutter, cardiac failure, heart failure, increased heart rate, syncope, thrombosis, vasodilation, hematuria, renal failure, cystitis, dysuria, hydronephrosis, renal cortical necrosis, nocturia, pyuria, toxic nephropathy, acute renal failure, proteinuria, BK nephropathy, bladder spasms, decreased urine output, urgency incontinence, anemia, increases or decreases in platelet count, leukopenia, leukocytosis, lymphocytopenia, pruritus, alopecia, erythema, rash, tubular necrosis, hypertrophic cardiomyopathy, gynecomastia, vasodilation, decreased phosphate concentration in the blood, pleural effusion, ascites, asthma, fever, weight loss, flushing, generalized malaise, menorrhagia, myalgia, arthralgia, dysgeusia, aplastic anemia, cerebral infarction, colitis, toxic epidermal necrolysis, glaucoma, ketosis, nystagmus, mania, meningitis, hyperpyrexia, thrombotic venous inflammation, thrombosis, vasculitis, sensation of foreign body in the throat, pain, ocular pain, erythema, excessive sweating, thirst, fluctuations in body temperature, optic neuropathy, febrile neutropenia

This medication should be stored in a tightly sealed container that blocks light and kept away from humid areas. The appropriate storage temperature is room temperature between 1 degree and 30 degrees.

Appearance

A hard capsule with the upper half in light yellow and the lower half in orange containing a white powder

Package unit

50 capsules (10 capsules/PTP X 5) / box