Rapalobel Tablet 1 mg (Sirolimus)

Adult dose

This medicine is administered orally once daily. To minimize variability in exposure to this medicine, it should be administered consistently either with food or on an empty stomach. Do not crush, chew, or cut this medicine. 1. Usual dosage in kidney transplant patients The initial dose of this medicine should be administered as soon as possible after transplantation. It is recommended that this medicine be administered 4 hours after oral cyclosporine solution and/or cyclosporine capsules. Therapeutic drug monitoring is recommended for all patients receiving this medicine. Because this medicine has a long half-life, frequent dose adjustments based on concentrations measured under non-steady-state conditions may result in overdosage or underdosage. Once the maintenance dose of this medicine has been adjusted, maintain that dose for at least 7~14 days before readjusting the dose based on blood concentration monitoring. The following equation may be used for dose adjustment in most patients: New dose of this medicine = Current dose X (Target blood concentration / Current blood concentration) If a substantial increase in the trough blood concentration of this medicine is desired, a loading dose should also be considered in addition to the new maintenance dose: Loading dose of this medicine = 3 X (New maintenance dose - Current maintenance dose) The maximum daily dose of this medicine should not exceed 40mg. If administration of the loading dose would cause the scheduled daily dose to exceed 40mg, the loading dose should be administered over 2 days. The trough concentration of this medicine should be monitored at least 3-4 days after administration of the loading dose. In clinical trials in patients at low to moderate immunologic risk, 2mg of this medicine was shown to be clinically equivalent to 2mg of sirolimus oral solution; therefore, the oral solution and tablets may be substituted for one another. However, it is not known whether the oral solution and tablets are clinically equivalent at doses greater than 2mg. 2. Kidney transplant patients at low to moderate immunologic risk This medicine in combination with cyclosporine: Initially, this medicine is recommended for use in combination with cyclosporine and corticosteroids. New kidney transplant recipients should receive a loading dose 3 times the maintenance dose. For kidney transplant patients, an initial loading dose of 6mg/day and a maintenance dose of 2mg/day are recommended. Maintain sirolimus concentrations within the target range through therapeutic drug monitoring. Administration of this medicine after withdrawal of cyclosporine: Patients withdrawing from cyclosporine for the first time should be receiving this medicine in combination with cyclosporine. Withdrawal of cyclosporine is recommended 2~4 months after transplantation. At 2-4 months after transplantation, cyclosporine should be gradually discontinued over 4-8 weeks, and the dose of this medicine should be adjusted to achieve a trough blood concentration of 16-24ng/mL (chromatographic method) during the first year after transplantation. Thereafter, the target blood concentration of this medicine should be 12-20 ng/mL (chromatographic method). Cyclosporine inhibits the metabolism and transport of this medicine; therefore, if the dose of this medicine is not increased when cyclosporine is discontinued, its concentration will decrease. When cyclosporine is not administered, the dose of this medicine needs to be increased approximately 4-fold because there is no pharmacokinetic interaction (requiring an approximately 2-fold increase) and the need for immunosuppression increases (requiring an approximately 2-fold increase). 3. Kidney transplant patients at high immunologic risk For patients at high immunologic risk, combination therapy with cyclosporine and corticosteroids is recommended for 12 months after transplantation. The safety and efficacy of administering this combination therapy for more than 1 year in patients at high immunologic risk have not been studied. Therefore, based on the patient's clinical status, a change in immunosuppressive therapy after the first 12 months following transplantation should be considered. Patients receiving this medicine in combination with cyclosporine should receive a loading dose of 15mg on the day of transplantation. Starting on day 2, a maintenance dose of 5mg should be administered. Measure the trough concentration on days 5-7 of treatment and adjust subsequent doses of this medicine to achieve a trough blood concentration of 10-15ng/mL (chromatographic method). The initial dose of cyclosporine should be 7mg/kg/day in divided doses, and the dose should continue to be adjusted until the target whole-blood trough concentration is reached. The target whole-blood trough concentration is 200-300ng/mL through day 14, 150-200ng/mL from day 15 through week 26, and 100-150ng/mL from week 27 through week 52. Prednisolone should be administered at a dose of at least 5mg/day. Antibody induction therapy may be used. 4. Dosage in patients with lymphangioleiomyomatosis The initial dose of this medicine in patients with lymphangioleiomyomatosis is 2 mg once daily. The whole-blood trough concentration of this medicine should be measured on days 10-20, and the concentration should be maintained within 5-15 ng/mL through dose adjustment. The following equation may be used for dose adjustment in most patients: New dose of this medicine=Current doseX(Target blood concentration/Current blood concentration). Because this medicine has a long half-life, frequent dose adjustments based on concentrations measured under non-steady-state conditions may result in overdosage or underdosage. Once the maintenance dose of this medicine has been adjusted, maintain that dose for at least 7-14 days before readjusting the dose based on blood concentration monitoring. Once a stable dose has been established, therapeutic drug monitoring should be performed at least once every 3 months. 5. Dose adjustment For patients with hepatic impairment, a maintenance dose of approximately 2/3 of the dose used in patients with normal hepatic function is recommended for those with mild to moderate hepatic impairment. For patients with severe hepatic impairment, a maintenance dose of approximately 1/2 of the dose used in patients with normal hepatic function is recommended. No adjustment of the loading dose is necessary. No dose adjustment is required for patients with renal impairment. 6. Therapeutic drug monitoring (see 4. General precautions, 12) ‘Differences in the trough concentrations of this medicine reported with chromatographic and immunoassay methods’ under Precautions for use) Dose adjustment of this medicine should not be based solely on therapeutic drug monitoring. Clinical symptoms/signs, biopsy findings, and laboratory factors should also be considered. In patients receiving concentration-guided dosing with this medicine, the whole-blood trough concentration of this medicine should be monitored. Monitoring is particularly necessary in patients who may have altered drug metabolism, patients with hepatic impairment, patients receiving concomitant potent CYP3A4 and/or P-glycoprotein (P-gp) inducers or inhibitors, and/or when the cyclosporine dose changes substantially or treatment is discontinued.

Child dose

For patients aged 13 years and older who weigh less than 40kg, adjust based on body surface area to an initial loading dose of up to 3mg/m2/day and a maintenance dose of up to 1mg/m2/day.

This medication suppresses the immune system, making it easier to become infected, and there may be an increased risk of malignant tumors, especially lymphomas or skin lymphomas. Safety and efficacy of this medication have not been sufficiently established in liver or lung transplant patients. In patients who have just undergone liver transplantation, using this medication with other immunosuppressants can increase mortality and the risk of serious complications such as hepatic artery thrombosis. During the use of this medication, special attention should be paid to infection symptoms, as severe infections can be life-threatening. This medication may affect liver function, thus patients with liver impairment require dosage adjustments and regular liver function tests. Blood levels of this medication may interact with other drugs, so caution is needed when taken with certain antifungals, antibiotics, calcium channel blockers, etc. This medication can raise blood cholesterol and triglyceride levels; therefore, patients with hyperlipidemia should periodically check lipid levels before and after treatment. Renal function may also be affected, so regular kidney function tests must be conducted, and appropriate measures should be taken if renal function deteriorates. During pregnancy, it may harm the fetus, so women who are planning to become pregnant or are pregnant should avoid taking this medication and should use effective contraception while taking it. During treatment, live vaccinations should be avoided, and consult with healthcare professionals, as vaccine efficacy may be diminished. Adverse reactions may include blood abnormalities, gastrointestinal issues, skin rashes, difficulty breathing, hypertension, etc., and if any abnormal symptoms occur, inform medical staff immediately. Safety for children and the elderly has not been fully evaluated, so special care is required. This medication can cause skin irritation if it comes into direct contact, so if contact occurs, wash thoroughly with soap and water. Patients should undergo regular examinations at a specialized medical institution while taking this medication, and follow their doctor's instructions regarding usage.

Increased susceptibility to infections, lymphoma, malignant tumors, lymphoma of the skin, opportunistic infections, sepsis, fatal infections, hepatic artery thrombosis, bronchial anastomotic dehiscence, thrombocytopenia, anemia, leukopenia, hemolytic uremic syndrome, neutropenia, pancytopenia, thrombotic thrombocytopenic purpura, tachycardia, pericardial effusion, abdominal pain, constipation, diarrhea, nausea, pancreatitis, stomatitis, ascites, healing disorders, edema, peripheral edema, fever, pain, hypersensitivity, angioedema, anaphylactic reactions, anaphylactoid reactions, pneumonia, fungal infections, viral infections, bacterial infections, herpes simplex, urinary tract infections, pyelonephritis, cytomegalovirus infection, shingles, mycobacterial infections, Epstein-Barr virus infection, abnormal liver function tests, elevated serum creatinine, increased serum lactate dehydrogenase, hypokalemia, hypophosphatemia, hyperlipidemia, hypercholesterolemia, hyperglycemia, hypertriglyceridemia, fluid retention, diabetes mellitus, arthralgia, osteonecrosis, squamous cell carcinoma of the skin, basal cell carcinoma, malignant melanoma, post-transplant lymphoproliferative disease, neuroendocrine carcinoma of the skin, headache, reversible posterior leukoencephalopathy syndrome, proteinuria, nephrotic syndrome, focal segmental glomerulosclerosis, menstrual disorders, amenorrhea, menorrhagia, ovarian cysts, pulmonary embolism, interstitial pneumonia, pleural effusion, epistaxis, pulmonary hemorrhage, pulmonary alveolar proteinosis, rash, acne, exfoliative dermatitis, hypersensitivity vasculitis, hypertension, lymphorrhea, venous thrombosis, deep vein thrombosis, lymphedema, asthenia, abdominal distension, chills, cold symptoms, hernia, malaise, atrial fibrillation, congestive heart failure, hemorrhage, hypervolemia, hypotension, palpitations, peripheral vascular disorders, orthostatic hypotension, syncope, vasodilation, dyspepsia, vomiting, anorexia, dysphagia, belching, esophagitis, gastric distension, gingival overgrowth, intestinal obstruction, oral moniliasis, Cushing's syndrome, petechiae, leukocytosis, lymphadenopathy, erythrocytosis, hyperkalemia, weight gain, acidosis, elevated BUN, increased creatine phosphokinase, dehydration, hypercalcemia, hypocalcemia, hyperphosphatemia, hypoglycemia, hypomagnesemia, hyponatremia, weight loss, arthrosis, leg cramps, myalgia, osteoporosis, rigidity, tremors, anxiety, confusion, depression, dizziness, emotional instability, hypertonia, sensory impairment, hypotonus, insomnia, neuropathy, paresthesia, drowsiness, dyspnea, asthma, atelectasis, increased cough, hypoxemia, pulmonary edema, fungal dermatitis, hirsutism, pruritus, skin hypertrophy, skin ulcers, sweating, abnormal vision, cataracts, hearing loss, tinnitus, dysuria, hematuria, hydronephrosis, erectile dysfunction, renal colic, tubular necrosis, nocturia, oliguria, pyuria, testicular disorders, toxin-induced nephropathy, frequency of urination, urinary incontinence, urinary retention, polyuria, localized reactions to surgery, stomatitis, rhinopharyngitis, chest pain, upper respiratory infections, dizziness, muscle pain, hypercholesterolemia, constipation, elevated serum cholesterol, postoperative pain, hyperglycemia, azotemia, transplant rejection, pneumonia, bowel obstruction, increased susceptibility to infections, fractures, agranulocytosis, abscess, cholangitis, cystitis, vesicoureteral reflux, ascites, hyperplasia of the parathyroid glands, contact dermatitis, polyomavirus infection, dyspnea, increased plasma osmolality, exacerbation of angina, cholangitis, renal artery occlusion, dental caries

This medication should be stored in a tightly sealed container to prevent exposure to air and light, avoiding direct sunlight and stored at room temperature, preferably between 20 to 25 degrees Celsius.

Appearance

White or nearly white triangular tablet

Package unit

100 tablets (10 tablets/PTP x 10)