Sirolimus (Page 11 of 12)
14.5 Conversion from a CNI-based Regimen to a Sirolimus-based Regimen in Liver Transplant Patients
Conversion from a CNI-based regimen to a sirolimus-based regimen was assessed in stable liver transplant patients 6 to 144 months post-transplant. The clinical study was a 2:1 randomized, multi-center, controlled trial conducted at 82 centers globally, including the US and Europe, and was intended to show that renal function was improved by conversion from a CNI to sirolimus without adversely impacting efficacy or safety. A total of 607 patients were enrolled.
The study failed to demonstrate superiority of conversion to a sirolimus-based regimen compared to continuation of a CNI-based regimen in baseline-adjusted GFR, as estimated by Cockcroft-Gault, at 12 months (62 mL/min in the sirolimus conversion group and 63 mL/min in the CNI continuation group). The study also failed to demonstrate non-inferiority, with respect to the composite endpoint consisting of graft loss and death (including patients with missing survival data) in the sirolimus conversion group compared to the CNI continuation group (6.6% versus 5.6%). The number of deaths in the sirolimus conversion group (15/393, 3.8%) was higher than in the CNI continuation group (3/214, 1.4%), although the difference was not statistically significant. The rates of premature study discontinuation (primarily due to adverse events or lack of efficacy), adverse events overall (infections, specifically), and biopsy-proven acute liver graft rejection at 12 months were all significantly greater in the sirolimus conversion group compared to the CNI continuation group
14.6 Pediatric Renal Transplant Patients
Sirolimus was evaluated in a 36-month, open-label, randomized, controlled clinical trial at 14 North American centers in pediatric (aged 3 to <18 years) renal transplant patients considered to be at high- immunologic risk for developing chronic allograft nephropathy, defined as a history of one or more acute allograft rejection episodes and/or the presence of chronic allograft nephropathy on a renal biopsy. Seventy-eight (78) subjects were randomized in a 2:1 ratio to sirolimus (sirolimus target concentrations of 5 to 15 ng/mL, by chromatographic assay, n = 53) in combination with a calcineurin inhibitor and corticosteroids or to continue calcineurin-inhibitor-based immunosuppressive therapy (n = 25). The primary endpoint of the study was efficacy failure as defined by the first occurrence of biopsy-confirmed acute rejection, graft loss, or death, and the trial was designed to show superiority of sirolimus added to a calcineurin-inhibitor-based immunosuppressive regimen compared to a calcineurin-inhibitor-based regimen. The cumulative incidence of efficacy failure up to 36 months was 45.3% in the sirolimus group compared to 44.0% in the control group, and did not demonstrate superiority. There was one death in each group. The use of sirolimus in combination with calcineurin inhibitors and corticosteroids was associated with an increased risk of deterioration of renal function, serum lipid abnormalities (including, but not limited to, increased serum triglycerides and cholesterol), and urinary tract infections [ see Warnings and Precautions (5.8) ]. This study does not support the addition of sirolimus oral solution to calcineurin-inhibitor-based immunosuppressive therapy in this subpopulation of pediatric renal transplant patients.
15 REFERENCES
Clinical Therapeutics , Volume 22, Supplement B, April 2000 [ see Dosage and Administration (2.5) ].
16 HOW SUPPLIED/STORAGE AND HANDLING
Since sirolimus oral solution is not absorbed through the skin, there are no special precautions. However, if direct contact of the oral solution occurs with the skin or eyes, wash skin thoroughly with soap and water; rinse eyes with plain water.
Do not use sirolimus oral solution after the expiration date. The expiration date refers to the last day of that month.
16.1 Sirolimus Oral Solution
Each Sirolimus Oral Solution carton, NDC 13668-658-87, contains one 2 oz (60 mL fill) amber glass bottle of sirolimus (concentration of 1 mg/mL), one oral syringe adapter for fitting into the neck of the bottle, sufficient disposable amber oral syringes and caps for daily dosing, and a carrying case.
Sirolimus oral solution bottles should be stored protected from light and refrigerated at 2 o C to 8 o C (36 o F to 46 o F). Once the bottle is opened, the contents should be used within one month. If necessary, the patient may store the bottles at 20 o to 25 o C (68 o to 77 o F) [see USP Controlled Room Temperature] for a short period of time (e.g. not more than 15 days for the bottles).
An amber syringe and cap are provided for dosing, and the product may be kept in the syringe for a maximum of 24 hours at room temperatures at 20 o to 25°C (68 o to 77°F) [see USP Controlled Room Temperature] or refrigerated at 2°C to 8°C (36°F to 46°F). The syringe should be discarded after one use. After dilution, the preparation should be used immediately.
Sirolimus oral solution provided in bottles may develop a slight haze when refrigerated. If such a haze occurs, allow the product to stand at room temperature and shake gently until the haze disappears. The presence of this haze does not affect the quality of the product.
17 PATIENT COUNSELING INFORMATION
Advise patients, their families, and their caregivers to read the Medication Guide and Instructions for Use for the oral solution and assist them in understanding its contents. The complete text of the Medication Guide and Instructions for Use for the oral solution are reprinted at the end of the document.
See FDA-Approved Medication Guide and Instructions for Use for the Oral Solution.
17.1 Dosage
Patients should be given complete dosage instructions [ see FDA-Approved Medication Guide ].
17.2 Skin Cancer Events
Advise patients that exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a broad spectrum sunscreen with a high protection factor because of the increased risk for skin cancer [ see Warnings and Precautions (5.18) ].
17.3 Pregnancy and Lactation
Advise female patients of reproductive potential to avoid becoming pregnant throughout treatment and for 12 weeks after sirolimus therapy has stopped. Sirolimus can cause fetal harm if taken during pregnancy. Advise a pregnant woman of the potential risk to her fetus. Before making a decision to breastfeed, inform the patient that the effects of breastfeeding in infants while taking this drug are unknown, but there is potential for serious adverse effects [ see Warnings and Precautions (5.15), Use in Specific Populations (8.1, 8.2, 8.3) ].
17.4 Infertility
Inform male and female patients that sirolimus may impair fertility [see Warnings and Precautions (5.16), Adverse Reactions (6.7), Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].
This product’s label may have been updated. For current Full Prescribing Information, please visit www.torrentpharma.com
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Manufactured by:
Cambrex Whippany, NJ 07981
Manufactured For: TORRENT PHARMA INC., Levittown, PA 19057.
Issued: January 2022
MEDICATION GUIDE Sirolimus ( sir oh’ li mus ) Oral Solution |
What is the most important information I should know about sirolimus oral solution? Sirolimus oral solution can cause serious side effects, including: Increased risk of getting infections. Serious infections can happen including infections caused by viruses, bacteria, and fungi (yeast). Your doctor may put you on medicine to help prevent some of these infections.Call your doctor right away if you have symptoms of infection including fever or chills while taking sirolimus oral solution. Increased risk of getting certain cancers. People who take sirolimus oral solution have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Talk with your doctor about your risk for cancer.Sirolimus oral solution has not been shown to be safe and effective in people who have had liver or lung transplants. Serious complications and death may happen in people who take sirolimus oral solution after a liver or lung transplant. You should not take sirolimus oral solution if you have had a liver or lung transplant without talking with your doctor. See the section “What are the possible side effects of sirolimus oral solution?” for information about other side effects of sirolimus oral solution. |
What is sirolimus oral solution? Sirolimus oral solution is a prescription medicine used to prevent rejection (anti-rejection medicine) in people 13 years of age and older who have received a kidney transplant. Rejection is when your body’s immune system recognizes the new organ as a “foreign” threat and attacks it. Sirolimus oral solution is used with other medicines called cyclosporine (Gengraf, Neoral, Sandimmune), and corticosteroids. Your doctor will decide:
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Who should not take sirolimus oral solution? Do not take sirolimus oral solution if you are allergic to sirolimus or any of the other ingredients in sirolimus oral solution. See the end of this leaflet for a complete list of ingredients in sirolimus oral solution |
What should I tell my doctor before taking sirolimus oral solution?
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Using sirolimus oral solution with certain medicines may affect each other causing serious side effects. Sirolimus oral solution may affect the way other medicines work, and other medicines may affect how sirolimus oral solution works. Especially tell your doctor if you take:
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How should I take sirolimus oral solution?
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What should I avoid while taking sirolimus oral solution ?
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What are the possible side effects of sirolimus oral solution ? Sirolimus oral solution may cause serious side effects, including:
The most common side effects of sirolimus oral solution in people with renal transplant include:
Other side effects that may occur with sirolimus oral solution:
Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of sirolimus oral solution. For more information ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
How should I store sirolimus oral solution? Sirolimus oral solution:
Do not use sirolimus oral solution after the expiration date. The expiration date refers to the last day of that month. Safely throw away medicine that is out of date or no longer needed. Keep sirolimus oral solution and all medicines out of the reach of children. |
General Information about the safe and effective use of sirolimus oral solution. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use sirolimus oral solution for a condition for which it was not prescribed. Do not give sirolimus oral solution to other people even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about sirolimus oral solution . If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about sirolimus oral solution that is written for health professionals. For more information, go to www.torrentpharma.com or call 1-800-912-9561 |
What are the ingredients in sirolimus oral solution? Active ingredients: sirolimus Inactive ingredients: Sirolimus oral solution: Phosal 50 PG ® ( alcohol (ethanol), ascorbyl palmitate,phosphatidylcholine, propylene glycol, soy acid (fatty acid), sunflower seed oil glyceride, and tocopherol ) and polysorbate 80. Sirolimus oral solution contains 1.5% to 2.5% ethanol.
Manufactured by: Cambrex Whippany, NJ 07981 Manufactured For TORRENT PHARMA INC., Levittown, PA 19057 |
This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued 01/2022
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