Rapavel Tablets 0.5 mg (Sirolimus)

Adult dose

This medication is administered orally once daily. To minimize variability in exposure to this medication, it should be administered consistently either with food or on an empty stomach. Do not crush, chew, or split this medication. 1. Usual dosage in kidney transplant patients The initial dose of this medication should be administered as soon as possible after transplantation. It is recommended that this medication be administered 4 hours after oral cyclosporine solution and/or cyclosporine capsules. Therapeutic drug monitoring is recommended for all patients receiving this medication. Because this medication has a long half-life, frequent dose adjustments based on concentrations measured at non-steady state may result in overdosing or underdosing. Once the maintenance dose of this medication has been adjusted, maintain that dose for at least 7~14 days before readjusting the dose based on blood concentration monitoring. The following formula may be used for dose adjustments in most patients: New dose of this medication = Current dose X (Target blood concentration / Current blood concentration) If a substantial increase in the trough blood concentration of this medication is desired, a loading dose should also be considered in addition to the new maintenance dose: Loading dose of this medication = 3 X (New maintenance dose - Current maintenance dose) The maximum daily dose of this medication should not exceed 40mg. If administration of a loading dose would result in a scheduled daily dose exceeding 40mg, the loading dose should be administered over 2 days. The trough concentration of this medication should be monitored at least 3-4 days after administration of the loading dose. In clinical trials in patients at low or moderate immunologic risk, a 2mg dose of this medication was shown to be clinically equivalent to 2mg of sirolimus oral solution; therefore, substitution of the oral solution with tablets, or vice versa, is possible. However, it is not known whether the oral solution and tablets are clinically equivalent at doses higher than 2mg. 2. Kidney transplant patients at low or moderate immunologic risk This medication in combination with cyclosporine: Initially, this medication is recommended to be administered in combination with cyclosporine and corticosteroids. New kidney transplant recipients should receive a loading dose three 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 medication after cyclosporine withdrawal: Patients undergoing cyclosporine withdrawal for the first time should be receiving this medication in combination with cyclosporine. Cyclosporine withdrawal 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 medication 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 medication should be 12-20 ng/mL (chromatographic method). Cyclosporine inhibits the metabolism and transport of this medication; therefore, its concentration will decrease if its dose is not increased when cyclosporine is discontinued. When cyclosporine is not administered, the dose of this medication needs to be increased approximately 4-fold because there is no pharmacokinetic interaction (approximately 2-fold dose increase required) and the need for immunosuppression increases (approximately 2-fold dose increase required). 3. Kidney transplant patients at high immunologic risk Combination therapy with cyclosporine and corticosteroids is recommended for 12 months after transplantation in patients at high immunologic risk. The safety and efficacy of this combination therapy when administered 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 medication 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 medication 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 be adjusted continuously until the target whole-blood trough concentration is achieved. 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 medication in patients with lymphangioleiomyomatosis is 2 mg once daily. The whole-blood trough concentration of this medication should be measured on days 10-20, and the dose should be adjusted to maintain the concentration within 5-15 ng/mL. The following formula may be used for dose adjustments in most patients: New dose of this medication=Current doseX(Target blood concentration/Current blood concentration). Because this medication has a long half-life, frequent dose adjustments based on concentrations measured at non-steady state may result in overdosing or underdosing. Once the maintenance dose of this medication 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 In patients with hepatic impairment, a maintenance dose of approximately 2/3 of the dose used in patients with normal liver function is recommended for patients 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 liver function is recommended. The loading dose does not need to be changed. No dose adjustment is required in patients with renal impairment. 6. Therapeutic drug monitoring (see Precautions for Use, 4. General Precautions, 12) ‘Differences in the trough concentrations of this medication reported by chromatographic and immunoassay methods’) Dose adjustment of this medication should not be based solely on therapeutic drug monitoring. Clinical symptoms/signs, biopsy findings, and laboratory parameters should also be taken into account. Patients receiving blood concentration-guided therapy with this medication should have their whole-blood trough concentration 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 and inhibitors, and/or when the cyclosporine dose changes substantially or cyclosporine is discontinued.

Child dose

For patients aged 13 years and older who weigh less than 40 kg, adjust the initial loading dose to 3mg/m2/day and the maintenance dose to up to 1mg/m2/day based on body surface area. Patients receiving blood concentration-guided therapy with this medicine should have the trough concentration of this medicine in whole blood monitored. Monitoring is particularly necessary for patients aged 13 years and older who weigh less than 40 kg.

This medication is an immunosuppressant and can make patients more susceptible to infections. Therefore, if any symptoms of infection arise, it is essential to consult a physician immediately. This medication may increase the risk of malignancies such as lymphoma, particularly skin lymphoma, necessitating regular skin examinations and medical evaluations. The use of this medication is not recommended for patients who have received liver or lung transplants, and particular caution is required, especially for those who have recently undergone a liver transplant, as severe side effects may occur. When used in combination with other immunosuppressants, side effects such as renal function deterioration, thrombosis, and increased risk of infection may occur, so it should be taken strictly as prescribed by a doctor. Regular blood tests and liver function tests are required, and any unusual symptoms should be reported to a physician immediately. During the use of this medication, UV exposure should be minimized, and sunscreen should be used to reduce the risk of skin cancer. Blood lipid levels (cholesterol, triglycerides) may increase, so dietary adjustments and lipid-lowering medications may be necessary. Many medications can interact with this one, so if you are taking other medications, be sure to inform your doctor or pharmacist. If you are pregnant or planning to become pregnant, you must consult your physician before using this medication, and effective contraception should be used during treatment. If you are breastfeeding, this medication may be excreted in breast milk, so breastfeeding should be halted or you should consult your physician. Severe side effects may occur in case of overdose, so it is crucial to adhere strictly to the prescribed dosage, and if overdose is suspected, visit a medical institution immediately. This medication is not absorbed through the skin; however, if it comes into direct contact with skin or eyes, it should be washed immediately with soap and water, and the eyes should be rinsed thoroughly with clean water. Store this medication in a closed container out of reach of children, avoiding direct sunlight, and keep it in a dry place at a temperature of 20-25 degrees Celsius.

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, pneumonia, fungal infection, viral infection, bacterial infection, herpes simplex, urinary tract infection, sepsis, pyelonephritis, cytomegalovirus infection, herpes zoster, mycobacterial infection, Epstein-Barr virus infection, abnormal liver function tests, increased serum creatinine, increased serum lactate dehydrogenase, hypokalemia, hypophosphatemia, hyperlipidemia, hyperglycemia, hypertriglyceridemia, fluid retention, diabetes mellitus, arthralgia, osteonecrosis, squamous cell carcinoma, basal cell carcinoma, lymphoma, malignant melanoma, post-transplant lymphoproliferative disorder, neuroendocrine carcinoma, headache, reversible posterior leukoencephalopathy syndrome, proteinuria, nephrotic syndrome, focal segmental glomerulosclerosis, menstrual disorders, ovarian cysts, pulmonary embolism, interstitial pneumonia, pleural effusion, epistaxis, pulmonary hemorrhage, alveolar proteinosis, rash, acne, exfoliative dermatitis, hypersensitivity vasculitis, hypertension, venous thrombosis, lymphedema, asthenia, abdominal distension, chills, cold symptoms, hernia, malaise, atrial fibrillation, congestive heart failure, hemorrhage, hypervolemia, hypotension, palpitations, peripheral vascular disorder, orthostatic hypotension, syncope, vasodilation, dyspepsia, vomiting, loss of appetite, dysphagia, belching, esophagitis, gastric distention, gingival hyperplasia, intestinal obstruction, oral moniliasis, Cushing's syndrome, diabetes, petechiae, leukocytosis, lymphadenopathy, erythrocytosis, hyperkalemia, weight gain, acidosis, increased BUN, increased creatine phosphokinase, dehydration, hypercalcemia, hypocalcemia, hyperphosphatemia, hypoglycemia, hypomagnesemia, hyponatremia, weight loss, arthrosis, leg cramps, myalgia, osteoporosis, stiffness, tremor, anxiety, confusion, depression, dizziness, emotional instability, hypertonia, sensory loss, hypotonia, insomnia, neuropathy, paresthesia, drowsiness, dyspnea, asthma, atelectasis, increased cough, hypoxia, pulmonary edema, fungal dermatitis, hirsutism, pruritus, skin hypertrophy, skin ulcer, sweating, visual abnormality, cataract, hearing loss, tinnitus, dysuria, hematuria, hydronephrosis, erectile dysfunction, renal colic, tubular necrosis, nocturia, oliguria, pyuria, testicular disorders, toxic nephropathy, frequent urination, urinary incontinence, urinary retention, polyuria, localized reaction to surgery, stomatitis, nasopharyngitis, chest pain, upper respiratory infection, dizziness, muscle pain, hypercholesterolemia, constipation, elevated serum cholesterol, pain at the surgical site, hypercholesterolemia, anemia, elevated serum creatinine, herpes zoster, urinary tract infection, gastritis, azotemia, transplant rejection, pneumonia, intestinal obstruction, increased susceptibility to infection, hypertension, fracture, agranulocytosis, abscess, cholangitis, cystitis, vesicoureteral reflux, ascites, hyperplasia of the adrenal gland, contact dermatitis, polyomavirus infection, dyspnea, increased plasma osmolality, exacerbation of angina, cholangitis, renal artery occlusion, dental caries

This medication should be stored in a sealed container to protect it from air and light, ideally at room temperature between 20 and 25 degrees Celsius away from direct sunlight.

Appearance

Light brown triangular coated tablet

Package unit

100 tablets (10 tablets/PTP x 10)