SIROLIMUS solution

Maa: Yhdysvallat

Kieli: englanti

Lähde: NLM (National Library of Medicine)

Aktiivinen ainesosa:

SIROLIMUS (UNII: W36ZG6FT64) (SIROLIMUS - UNII:W36ZG6FT64)

Saatavilla:

VistaPharm, LLC

Antoreitti:

ORAL

Prescription tyyppi:

PRESCRIPTION DRUG

Käyttöaiheet:

Sirolimus Oral Solution is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. In patients at low-to moderate-immunologic risk , it is recommended that Sirolimus Oral Solution be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see Dosage and Administration (2.2) ]. In patients at high-immunologic risk (defined as Black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [PRA; peak PRA level > 80%]), it is recommended that Sirolimus Oral Solution be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see Dosage and Administration (2.3), Clinical Studies (14.3) ]. Cyclosporine withdrawal has not been studied in patients with Banff Grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, those with serum creatinine > 4.5 mg/dL, Black patients, patients of multi-organ transplants, secondary transplants, or those with high levels of panel-reactive antibodies [see Clinical Studies (14.2) ]. In patients at high-immunologic risk , the safety and efficacy of Sirolimus Oral Solution used in combination with cyclosporine and corticosteroids has not been studied beyond one year; therefore after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient [see Clinical Studies (14.3) ]. In pediatric patients , the safety and efficacy of Sirolimus Oral Solution have not been established in patients < 13 years old, or in pediatric (< 18 years) renal transplant patients considered at high-immunologic risk [see Adverse Reactions (6.5), Clinical Studies (14.6) ]. The safety and efficacy of de novo use of Sirolimus Oral Solution without cyclosporine have not been established in renal transplant patients [see Warnings and Precautions (5.12) ]. The safety and efficacy of conversion from calcineurin inhibitors to Sirolimus Oral Solution  in maintenance renal transplantpatients have not been established [see Clinical Studies (14.4) ]. Sirolimus Oral Solution is contraindicated in patients with a hypersensitivity to sirolimus [see Warnings and Precautions (5.4) ]. Risk Summary Based on animal studies and the mechanism of action, Sirolimus can cause fetal harm when administered to a pregnant woman [see Data, Clinical Pharmacology (12.1) ]. There are limited data on the use of sirolimus during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal studies, sirolimus was embryo/fetotoxic in rats at sub-therapeutic doses [see Data ]. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Sirolimus crossed the placenta and was toxic to the conceptus. In rat embryo-fetal development studies, pregnant rats were administered sirolimus orally during the period of organogenesis (Gestational Day 6-15). Sirolimus produced embryo-fetal lethality at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg, on a body surface area basis) and reduced fetal weight at 1 mg/kg (5-fold the clinical dose of 2 mg). The no observed adverse effect level (NOAEL) for fetal toxicity in rats was 0.1 mg/kg (0.5-fold the clinical dose of 2 mg). Maternal toxicity (weight loss) was observed at 2 mg/kg (10-fold the clinical dose of 2 mg). The NOAEL for maternal toxicity was 1 mg/kg. In combination with cyclosporine, rats had increased embryo-fetal mortality compared with sirolimus alone. In rabbit embryo-fetal development studies, pregnant rabbits were administered sirolimus orally during the period of organogenesis (Gestational Day 6-18). There were no effects on embryo-fetal development at doses up to 0.05 mg/kg (0.5-fold the clinical dose of 2 mg, on a body surface area basis); however, at doses of 0.05 mg/kg and above, the ability to sustain a successful pregnancy was impaired (i.e., embryo-fetal abortion or early resorption). Maternal toxicity (decreased body weight) was observed at 0.05 mg/kg. The NOAEL for maternal toxicity was 0.025 mg/kg (0.25-fold the clinical dose of 2 mg). In a pre-and post-natal development study in rats, pregnant females were dosed during gestation and lactation (Gestational Day 6 through Lactation Day 20). An increased incidence of dead pups, resulting in reduced live litter size, occurred at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg/kg on a body surface area basis). At 0.1 mg/kg (0.5-fold the clinical dose of 2 mg), there were no adverse effects on offspring. Sirolimus did not cause maternal toxicity or affect developmental parameters in the surviving offspring (morphological development, motor activity, learning, or fertility assessment) at 0.5 mg/kg, the highest dose tested. Risk Summary It is not known whether sirolimus is present in human milk. There are no data on its effects on the breastfed infant or milk production. The pharmacokinetic and safety profiles of sirolimus in infants are not known. Sirolimus is present in the milk of lactating rats. There is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action [see Clinical Pharmacology (12.1) ]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sirolimus and any potential adverse effects on the breastfed child from Sirolimus. Contraception Females should not be pregnant or become pregnant while receiving Sirolimus. Advise females of reproductive potential that animal studies have been shown Sirolimus to be harmful to the developing fetus. Females of reproductive potential are recommended to use highly effective contraceptive method. Effective contraception must be initiated before Sirolimus therapy, during Sirolimus therapy, and for 12 weeks after Sirolimus therapy has been stopped [see Warnings and Precautions (5.15), Use in Specific Populations (8.1) ]. Infertility Based on clinical findings and findings in animals, male and female fertility may be compromised by the treatment with Sirolimus [see Adverse Reactions (6.7), Nonclinical Toxicology (13.1) ]. Ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) have been reported in females with the use of Sirolimus. Azoospermia has been reported in males with the use of Sirolimus and has been reversible upon discontinuation of Sirolimus in most cases. Renal Transplant The safety and efficacy of sirolimus in pediatric patients < 13 years have not been established. The safety and efficacy of Sirolimus Oral Solution have been established for prophylaxis of organ rejection in renal transplantation in children ≥ 13 years judged to be at low- to moderate-immunologic risk. Use of Sirolimus Oral Solution in this subpopulation of children ≥ 13 years is supported by evidence from adequate and well-controlled trials of Sirolimus Oral Solution in adults with additional pharmacokinetic data in pediatric renal transplantation patients [see Clinical Pharmacology (12.3) ]. Safety and efficacy information from a controlled clinical trial in pediatric and adolescent (< 18 years of age) renal transplant patients judged to be at high-immunologic risk, defined as a history of one or more acute rejection episodes and/or the presence of chronic allograft nephropathy, do not support the chronic use of Sirolimus Oral Solution in combination with calcineurin inhibitors and corticosteroids, due to the higher incidence of lipid abnormalities and deterioration of renal function associated with these immunosuppressive regimens compared to calcineurin inhibitors, without increased benefit with respect to acute rejection, graft survival, or patient survival [see Clinical Studies (14.6) ]. Clinical studies of Sirolimus Oral Solution did not include sufficient numbers of patients ≥ 65 years to determine whether they respond differently from younger patients. Data pertaining to sirolimus trough concentrations suggest that dose adjustments based upon age in geriatric renal patients are not necessary. Differences in responses between the elderly and younger patients have not been identified. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, or cardiac function, and of concomitant disease or other drug therapy. The maintenance dose of sirolimus should be reduced in patients with hepatic impairment [see Dosage and Administration (2.7), Clinical Pharmacology (12.3) ]. Dosage adjustment is not required in patients with renal impairment [see Dosage and Administration (2.8), Clinical Pharmacology (12.3) ]. Sirolimus (sir-OH-li-mus) Oral Solution Be sure that you read and understand the following instructions for the correct way to dilute and take Sirolimus Oral Solution. Ask your pharmacist or doctor if you are not sure. Important: - Always keep the bottle in an upright position. - You may store Sirolimus Oral Solution that is in a syringe at room temperature up to 77°F (25°C) or in the refrigerator at 36°F to 46°F (2°C to 8°C) for up to 24 hours. See “How should I store Sirolimus Oral Solution?” at the end of these Instructions for Use. - Sirolimus Oral Solution can develop a slight haze when it is refrigerated. If this happens, bring the Sirolimus Oral Solution to room temperature and then gently shake the bottle until the haze goes away. - Only use a glass or plastic cup to dilute Sirolimus Oral Solution. - If you are a caregiver, do not let Sirolimus Oral Solution come in contact with your skin or eyes. If you get the oral solution on your skin, wash the area well with soap and water. If you get the oral solution in your eyes, rinse with plain water. - If you spill Sirolimus Oral Solution, dry the area with a dry paper towel and then wipe the area with a wet paper towel. Throw away the paper towels in the trash and wash your hands well with soap and water. Each Sirolimus Oral Solution carton contains: a) a 2 oz. (60 mL fill) amber glass bottle of sirolimus (concentration of 1 mg/mL) b) 1 oral syringe adapter for fitting into the neck of the bottle c) enough disposable amber oral syringes and caps for daily dosing d) 1 carrying case You will also need: - glass or plastic cup - 6 oz. of water or orange juice only. 1. Opening the Solution bottle. - Remove the safety cap by pushing down and turning counterclockwise (Figure 1). 2. The first time you use a bottle of Sirolimus Oral Solution: - Insert the oral syringe adapter (plastic tube with stopper) tightly into the bottle until it is even with the top of the bottle (Figure 2). - Do not remove the oral syringe adapter from the bottle once inserted.  3. Use a new disposable amber oral syringe for each dose of Sirolimus Oral Solution. - Fully push down (depress) on the plunger of the disposable amber oral syringe. - Then, tightly insert the oral syringe into the opening in the adapter (Figure 3). 4. Withdraw the prescribed amount of Sirolimus Oral Solution: - Gently pull back the plunger of the syringe until the level of the oral solution is even with the marking on the syringe for your prescribed dose. - Always keep the bottle in an upright position. - If bubbles form within the oral solution in the syringe, empty the syringe into the bottle and repeat step 4 (Figure 4). - You may need to repeat step 4 more than once to draw up your prescribed dose. 5. If your doctor tells you to carry your medicine with you: - Each dose of Sirolimus Oral Solution should be placed in an oral syringe. Place a cap securely on each syringe. The cap should snap into place (Figure 5). Figure 6: Placing syringe in carrying case - Place the capped syringe in the enclosed carrying case (Figure 6). If you need more than 1 carrying case, talk with your doctor or pharmacist. - See `How should I store Sirolimus Oral Solution? ' for storage instructions. Figure 7: Emptying syringe into glass 6. Taking a dose of Sirolimus Oral Solution: - Choose a clean flat work surface. Place a clean paper towel on the work surface. Wash and dry your hands. - Empty the syringe into a glass or plastic cup containing at least 2 ounces (1/4 cup, 60 mL) of water or orange juice, stir vigorously for 1 minute and drink right away (Figure 7). - If more than 1 syringe is needed for your prescribed dose, empty the oral solution from each syringe into the same glass or plastic cup of water or orange juice. - Refill the container with at least 4 ounces (1/2 cup, 120 mL) of water or orange juice, stir vigorously again and drink the rinse solution.Do not mix Sirolimus Oral Solution with apple juice, grapefruit juice, or other liquids. Only glass or plastic cups should be used to mix Sirolimus Oral Solution. - The syringe and cap should be used only one time and then thrown away. - Throw away the paper towel and clean the work surface. Wash your hands. 7. Always store the bottles of medication in the refrigerator. How should I store Sirolimus Oral Solution? - Store bottles of Sirolimus Oral Solution in the refrigerator at 36°F to 46°F (2°C to 8°C) - Protect from light - Store Sirolimus Oral Solution that is in a syringe at room temperature up to 77°F (25°C) or in the refrigerator at 36°F to 46°F (2°C to 8°C) for up to 24 hours - If necessary, bottles of Sirolimus Oral Solution can be stored at room temperature up to 77°F (25°C) for up to 15 days - When a bottle of Sirolimus Oral Solution is opened, it should be used within 1 month - Use any diluted Sirolimus Oral Solution right away Keep Sirolimus Oral Solution and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured by: Novitium Pharma LLC 70 Lake Drive, East Windsor New Jersey 08520 Distributed by: VistaPharm, Inc. Largo, FL 33771 USA Trademarks are the property of their respective owners. Revised: April, 2022 LB4062-05

Tuoteyhteenveto:

Since sirolimus 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. Sirolimus Oral Solution is a yellow colored solution. Each Sirolimus Oral Solution carton, NDC 66689-347-02, 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°C to 8°C (36°F to 46°F). Once the bottle is opened, the contents should be used within one month. If necessary, the patient may store the bottles at room temperatures up to 25°C (77°F) 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 up to 25°C (77°F) 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.

Valtuutuksen tilan:

Abbreviated New Drug Application

Pakkausseloste

VistaPharm, Inc.
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MEDICATION GUIDE
Sirolimus (sir-OH-li-mus) Oral Solution
What is the most important information I should know about sirolimus?
Sirolimus can cause serious side effects, including:
1. 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.
2. Increased risk of getting certain cancers. People who take
sirolimus have a higher risk of getting
lymphoma, and other cancers, especially skin cancer. Talk with your
doctor about your risk for cancer.
Sirolimus 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 after a liver or lung transplant.
You should not take sirolimus 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?”
for information about other side effects of
sirolimus.
What is sirolimus?
Sirolimus 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 is used with other medicines called cyclosporine (Gengraf,
Neoral, Sandimmune), and
corticosteroids. Your doctor will decide:
•
if sirolimus is right for you, and
•
how to best use it with cyclosporine and corticosteroids after your
transplant.
It is not known if sirolimus is safe and effective in children under
13 years of age.
Who should not take sirolimus?
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 ingredient

Valmisteyhteenveto

SIROLIMUS- SIROLIMUS SOLUTION
VISTAPHARM, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SIROLIMUS ORAL
SOLUTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
SIROLIMUS ORAL
SOLUTION.
SIROLIMUS ORAL SOLUTION
INITIAL U.S. APPROVAL: 1999
WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG
TRANSPLANT PATIENTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INCREASED SUSCEPTIBILITY TO INFECTION AND THE POSSIBLE DEVELOPMENT OF
LYMPHOMA AND
OTHER MALIGNANCIES MAY RESULT FROM IMMUNOSUPPRESSION (5.1). ONLY
PHYSICIANS
EXPERIENCED IN IMMUNOSUPPRESSIVE THERAPY AND MANAGEMENT OF RENAL
TRANSPLANT
PATIENTS SHOULD USE SIROLIMUS FOR PROPHYLAXIS OF ORGAN REJECTION IN
PATIENTS RECEIVING
RENAL TRANSPLANTS.
THE SAFETY AND EFFICACY OF SIROLIMUS AS IMMUNOSUPPRESSIVE THERAPY HAVE
NOT BEEN
ESTABLISHED IN LIVER OR LUNG TRANSPLANT PATIENTS, AND THEREFORE, SUCH
USE IS NOT
RECOMMENDED (5.2, 5.3). − LIVER TRANSPLANTATION – EXCESS MORTALITY, GRAFT LOSS, AND
HEPATIC ARTERY THROMBOSIS
(5.2). − LUNG TRANSPLANTATION – BRONCHIAL ANASTOMOTIC DEHISCENCE (5.3).
RECENT MAJOR CHANGES
Warnings and Precautions, Male Infertility (5.16)
07/2019
Warnings and Precautions, Immunizations (5.19)
07/2019
INDICATIONS AND USAGE
Sirolimus is an mTOR inhibitor immunosuppressant indicated for the
prophylaxis of organ rejection in
patients aged ≥13 years receiving renal transplants.
− Patients at low- to moderate-immunologic risk: Use initially with
cyclosporine (CsA) and corticosteroids.
CsA withdrawal is recommended 2 to 4 months after transplantation
(1.1).
− Patients at high-immunologic risk: Use in combination with CsA and
corticosteroids for the first 12
months following transplantation (1.1). Safety and efficacy of CsA
withdrawal has not been established in
high risk patients (1.1, 1.2, 14.3).
DOSAGE AND ADMINISTRATION
Renal Transplant Patients:
Administer once daily by mouth, consistently with or without food (2).
Administer the