Sirolimus

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Generic Name: Sirolimus Brand Name(s): Generics only. No brands available.

Uses

What is Sirolimus used for?

Sirolimus is used with other medications to prevent rejection of a kidney transplant. This medication belongs to a class of drugs known as immunosuppressants. It works by weakening your body’s defense system (immune system) to help your body accept the new organ as if it were your own.

Sirolimus may also be used to treat a certain lung disease (lymphangioleiomyomatosis-LAM).

How should I take Sirolimus?

Take this medication by mouth as directed by your doctor, usually once daily. Swallow this medication whole. Do not crush, chew, or split the tablets. If you have nausea or an upset stomach, you may take this medication with food. However, it is important to choose one way (with food or without food) and take this medication the same way with every dose. Consult your doctor or pharmacist for more details.

The dosage is based on your weight, medical condition, laboratory tests (such as sirolimus trough levels), and response to treatment.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Also, do not stop taking this medication without consulting your doctor.

If you are also taking cyclosporine, take sirolimus 4 hours after your cyclosporine dose. Consult your pharmacist for more information.

If you are taking this medication to treat LAM, tell your doctor if your condition worsens.

How do I store Sirolimus?

Store sirolimus tablets at room temperature, away from heat, moisture, and light.

Store sirolimus liquid in the refrigerator. Do not freeze. You may notice a slight haze to the liquid. This haze should disappear when the liquid reaches room temperature.

If you are using sirolimus oral liquid with a disposable syringe, you may store a loaded syringe in the carrying case provided. Keep the case at room temperature and use the medicine within 24 hours. Use a disposable syringe only once and then throw it away.

To prevent drug damage, you should not store Sirolimus in the bathroom or the freezer. There may be different brands of Sirolimus that may have different storage needs. It is important to always check the product package for instructions on storage, or ask your pharmacist. For safety, you should keep all medicines away from children and pets.

You should not flush Sirolimus down the toilet or pour them into a drain unless instructed to do so. It is important to properly discard this product when it is expired or no longer needed. Consult your pharmacist for more details about how to safely discard your product.

Precautions & warnings

What should I know before using Sirolimus?

Before taking sirolimus, tell your doctor or pharmacist if you are allergic to it; or to temsirolimus; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, high cholesterol/triglyceride levels, cancer, any recent/current infections.

Sirolimus can make you more likely to get infections or may worsen any current infections. Wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

This medication may increase your risk of developing skin cancer. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication must not be used during pregnancy. It may harm an unborn baby. It is important to prevent pregnancy while taking this medication and for 12 weeks after treatment. Women must use reliable forms of birth control (such as condoms, birth control pills) before starting treatment, during treatment, and for 12 weeks after the end of treatment. If you become pregnant or think you may be pregnant, tell your doctor right away.

This medication may pass into breast milk and may have undesirable effects on a nursing infant. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Is it safe during pregnancy or breast-feeding?

There are no adequate studies in women for determining risk when using this Sirolimus during pregnancy or while breastfeeding. Please always consult with your doctor to weigh the potential benefits and risks before taking Sirolimus. Sirolimus is pregnancy risk category C according to the US Food and Drug Administration (FDA).

FDA pregnancy risk category reference below:

  • A=No risk,
  • B=No risk in some studies,
  • C=There may be some risk,
  • D=Positive evidence of risk,
  • X=Contraindicated,
  • N=Unknown

Side effects

What side effects can occur from Sirolimus?

Diarrhea, joint pain, shaking, acne, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn’t stop, yellowing eyes/skin, dark urine, muscle pain/cramps, bone pain, increased thirst/hunger, frequent urination, hearing problems (such as hearing loss, ringing in the ears), unusual tiredness, fast/slow/irregular heartbeat, easy bruising/bleeding, mental/mood changes, swelling ankles/feet, severe headache, dizziness, stomach/abdominal pain, missed/heavy/painful periods, signs of kidney problems (such as change in the amount of urine, frothy urine), pain/redness/swelling of arms or legs, swelling abdomen.

Get medical help right away if you have any very serious side effects, including: chest pain, shortness of breath.

This medication may increase your risk of getting a rare but very serious (possibly fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if you have any of these side effects: clumsiness, loss of coordination/balance, weakness, sudden change in your thinking (such as confusion, difficulty concentrating, memory loss), difficulty talking/walking, seizure, vision changes.

Sirolimus may slow wound healing after surgery. Tell your doctor right away if you have signs that your surgery wound is not healing well (such as redness, swelling, pain). The risk of poor wound healing is higher if you are obese.

Sirolimus may cause your cholesterol/triglycerides to increase. You may be required to have your cholesterol/triglycerides checked periodically and/or take another medication to control your cholesterol/triglycerides.

Sirolimus can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Get medical help right away if you develop any rash.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Not everyone experiences these side effects. There may be some side effects not listed above. If you have any concerns about a side-effect, please consult your doctor or pharmacist.

Interactions

What drugs may interact with Sirolimus?

Some products that may interact with this drug include: ACE inhibitors (such as benazepril, lisinopril), other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab, tacrolimus).

Other medications can affect the removal of sirolimus from your body, which may affect how sirolimus works. Examples include azole antifungals (such as itraconazole, ketoconazole, voriconazole), enzalutamide, macrolide antibiotics (such as clarithromycin, erythromycin), mifepristone, HIV and HCV protease inhibitors (such as indinavir, ritonavir, telaprevir), rifamycins (such as rifampin, rifabutin), St. John’s wort, among others.

Sirolimus is very similar to temsirolimus. Do not use medications containing temsirolimus while using sirolimus.

Sirolimus may interact with other drugs that you are currently taking, which can change how your drug works or increase your risk for serious side effects. To avoid any potential drug interactions, you should keep a list of all the drugs you are using (including prescription drugs, nonprescription drugs and herbal products) and share it with your doctor and pharmacist. For your safety, do not start, stop, or change the dosage of any drugs without your doctor’s approval.

Does food or alcohol interact with Sirolimus?

Sirolimus may interact with food or alcohol by altering the way the drug works or increase the risk for serious side effects. Please discuss with your doctor or pharmacist any potential food or alcohol interactions before using this drug.

Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.

What health conditions may interact with Sirolimus?

Sirolimus may interact with your health condition. This interaction may worsen your health condition or alter the way the drug works. It is important to always let your doctor and pharmacist know all the health conditions you currently have.

Dosage

The information provided is not a substitute for any medical advice. You should ALWAYS consult with your doctor or pharmacist before using this Sirolimus.

What is the dose of Sirolimus for an adult?

Usual Adult Dose for Organ Transplant – Rejection Prophylaxis

FOR PATIENTS AT LOW TO MODERATE IMMUNOLOGIC RISK:

Dosing by body weight:

-Less than 40 kg:

Loading dose: 3 mg/m2 on day 1

Maintenance: 1 mg/m2 once daily

-Greater than or equal to 40 kg:

Loading dose: 6 mg orally on day 1

Maintenance: 2 mg orally once daily

IN PATIENTS AT HIGH IMMUNOLOGIC RISK (defined as Black transplant 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 greater than 80%]):

-For patients receiving sirolimus with cyclosporine:

Loading Dose: Up to 15 mg on day one post-transplantation

Maintenance Dose: Beginning on day 2, an initial maintenance dose of 5 mg/day should be given. A trough level should be obtained between days 5 and 7, and the daily dose of sirolimus should be adjusted thereafter.

-Antibody induction therapy may be used.

Comments:

-It is recommended that this sirolimus be used in a regimen with cyclosporine and corticosteroids.

-Sirolimus should be taken consistently with or without food.

-Once the sirolimus maintenance dose is adjusted, patients should continue on the new maintenance dose for at least 7 to 14 days before further dosage adjustment with concentration monitoring.

MAINTENANCE THERAPY AFTER WITHDRAWAL OF CYCLOSPORINE:

-Cyclosporine withdrawal is not recommended in high-immunological risk patients. Following 2 to 4 months of combined therapy, withdrawal of cyclosporine may be considered in low-to-moderate risk patients. Cyclosporine should be discontinued over 4 to 8 weeks, and a necessary increase in the dosage of sirolimus (up to 4-fold) should be anticipated due to removal of metabolic inhibition by cyclosporine and to maintain adequate immunosuppressive effects. -Dose-adjusted trough target concentrations are typically 16 to 24 ng/mL for the first year post-transplant and 12 to 20 ng/mL thereafter (measured by chromatographic methodology).

Use:

-As an immunosuppressive agent indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplant.

Usual Adult Dose for Pulmonary Lymphangioleiomyomatosis

-Initial dose: 2 mg/day

-Sirolimus whole blood trough concentrations should be measured in 10 to 20 days, with dosage adjustment to maintain concentrations between 5 and 15 ng/mL.

Comment:

-This drug should be taken consistently with or without food.

General Use:

-For the treatment of patients with lymphangioleiomyomatosis

Renal Dose Adjustments

No dosage adjustment is necessary in loading or maintenance dose. However, adjustment of the regimen (including discontinuation of therapy) should be considered when used concurrently with cyclosporine and elevated or increasing serum creatinine is noted.

Liver Dose Adjustments

Loading dose: No adjustment required

Maintenance dose:

-Mild-to-moderate hepatic impairment: Reduce maintenance dose by approximately 33%

-Severe hepatic impairment: Reduce maintenance dose by approximately 50%

Dose Adjustments

-Sirolimus dosages should be adjusted to maintain trough concentrations within the desired range based on risk and concomitant therapy. Maximum daily dose: 40 mg. The dosage should be adjusted at intervals of 7 to 14 days to account for the long half-life of sirolimus. In general, dose proportionality may be assumed. The new sirolimus dose equals current dose multiplied by (target concentration/current concentration).

-If a large dose increase is required, consider loading dose calculated as:

Loading dose equals (new maintenance dose minus current maintenance dose) multiplied by 3.

-Maximum dose in one day: 40 mg

-If the required dose is greater than 40 mg (due to loading dose), then the dose should be divided over 2 days. Serum concentrations should not be used as the sole basis for dosage adjustment. Clinical signs/symptoms, tissue biopsy, and laboratory parameters should also be monitored.

Precautions

-IMMUNOSUPPRESSION: Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use this drug for prophylaxis of organ rejection in patients receiving renal transplants.

-USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS: The safety and efficacy of this drug as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended:

-Liver Transplantation: Excess mortality, graft loss, and hepatic artery thrombosis

-Lung Transplantation: Bronchial anastomotic dehiscence

NARROW THERAPEUTIC INDEX:

-This drug should be considered a narrow therapeutic index (NTI) drug as small differences in dose or blood concentrations may lead to serious therapeutic failures or adverse drug reactions.

Recommendations:

– Generic substitution should be done cautiously, if at all, as current bioequivalence standards are generally insufficient for NTI drugs.

-Additional and/or more frequent monitoring should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities.

The safety and efficacy of conversion from calcineurin inhibitors to sirolimus in maintenance renal transplant population has not been established.

Other Comments

Administration advice:

-This drug should be administered as soon as possible after transplantation.

-Tablets should be swallowed whole and not crushed, chewed, or split.

-This drug should be taken consistently with or without food. Patients unable to take the oral tablets should be prescribed the oral solution.

-It is recommended that this drug be taken 4 hours after administration of cyclosporine.

-This drug should not be taken with grapefruit juice.

General:

-The oral solution may develop a slight haze when refrigerated; however, this does not affect the quality of the drug and may be remedied by allowing the bottle to stand at room temperature and then shaking gently until the haze disappears.

-The 24 hour trough concentration ranges recommended by the manufacturer are based on chromatographic methods and are not interchangeable with immunoassay methods.

-The oral solution should not be emptied into a plastic, paper or polystyrene cup. The dosing syringe should be used to withdraw the prescribed dose from the bottle, emptied from the syringe into a glass container with at least 60 mL of water or orange juice, stirred vigorously, and then drunk immediately. The glass container should then be refilled with at least 120 mL of water or orange juice, stirred vigorously, and drunk immediately. A new dosing syringe should be used for each dose. The oral solution produces a white to off-white dispersion when it is mixed with water or orange juice.

-The tablets and oral solution are not bioequivalent due to differences in absorption. However, clinical equivalence has been demonstrated at the 2 mg dose level.

-It is recommended that sirolimus be taken 4 hours after administration of cyclosporine oral solution and/or cyclosporine capsules.

-The sirolimus dose should be individualized, to obtain whole blood trough levels of 4 to 12 ng/mL.

-In patients at low to moderate immunological risk, it is recommended that this drug be used initially in a regimen with cyclosporine and corticosteroids. Cyclosporine should be withdrawn 2 to 4 months after transplantation and the sirolimus dose should be increased to reach recommended blood concentrations.

-The safety and efficacy of cyclosporine withdrawal in high risk patients have not been adequately studied and therefore is not recommended. This high risk group includes patients with Banff grade III acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis dependent, or with serum creatinine greater than 4.5 mg/dL, black patients, retransplants, multi-organ transplants, and patients with a high panel of reactive antibodies. The duration of cyclosporine and sirolimus coadministration should not exceed 3 months, after which immunosuppressant treatment should be initiated.

Storage requirements:

-The oral solution should be stored at 2 to 8 degrees C (36 to 46 degrees F). Unused contents should be discarded one month after opening. A dose drawn up in a dosing syringe may be kept at room temperature up to 25 degrees C (77 degrees F) or refrigerated at 2 to 8 degrees C (36 to 46 degrees F) in the dosing syringe for up to 24 hours. However, it should be used immediately after dilution.

-Antimicrobial prophylaxis against cytomegalovirus (CMV) should be administered for 3 months, and Pneumocystis jiroveci infections for 1 year post-transplant.

Monitoring:

-Monitoring of triglycerides and cholesterol should be included as part of routine post-transplant patient management.

-Blood sirolimus levels should be monitored in pediatric patients, patients with hepatic impairment, and/or if cyclosporine dosing is markedly reduced or discontinued.

What is the dose of Sirolimus for a child?

Usual Pediatric Dose for Organ Transplant – Rejection Prophylaxis

FOR PATIENTS AT LOW TO MODERATE IMMUNOLOGIC RISK:

Greater than or equal to 13 years of age:

Dosing by body weight:

-Less than 40 kg:

Loading dose: 3 mg/m2 on day 1

Maintenance: 1 mg/m2 once daily

-Greater than or equal to 40 kg:

Loading dose: 6 mg orally on day 1

Maintenance: 2 mg orally once daily

Use:

-As an immunosuppressive agent indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplant.

Precautions

Safety and efficacy have not been established in patients less than 13 years old, or in pediatric (less than 18 years) renal transplant patients considered at high-immunologic risk.

How is Sirolimus available?

Sirolimus is available in the following dosage forms and strengths:

  • Oral solution,
  • Oral tablet.

What should I do in case of an emergency or overdose?

In case of an emergency or an overdose, call your local emergency services or go to your nearest emergency room.

What should I do if I miss a dose?

If you miss a dose of Sirolimus, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take your regular dose as scheduled. Do not take a double dose.

Hello Health Group does not provide medical advice, diagnosis or treatment.

Review Date: April 26, 2018 | Last Modified: April 26, 2018

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