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RAPAMUNE is a brand name for Sirolimus, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Rapamune (sirolimus oral solution and tablets) is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants: • In patients at low to moderate immunological risk, it is recommended that Rapamune be used initially in a regimen with cyclosporine and corticosteroids. Cyclosporine…
Verbatim from this product's HC label. Tap a section to expand.
07/2025 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ...........................................................................................
2 TABLE OF CONTENTS ............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................
4 1 INDICATIONS .............................................................................................................. 1 Pediatrics...................................................................................................................
2 Geriatrics ................................................................................................................... 4 2 CONTRAINDICATIONS .................................................................................................
4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 4 4 DOSAGE AND ADMINISTRATION................................................................................. 1 Dosing Considerations ..............................................................................................
2 Recommended Dose and Dosage Adjustment ......................................................... 4 Administration .......................................................................................................... 5 Missed Dose ..............................................................................................................
9 5 OVERDOSAGE............................................................................................................. 9
section. During clinical trials, there were two accidental Rapamune (sirolimus oral solution) ingestions, of 120 mg and 150 mg. One patient, receiving 150 mg, experienced an episode of transient atrial fibrillation. The other patient experienced no adverse effects.
General supportive measures should be followed in all cases of overdose. Based on the poor aqueous solubility and high erythrocyte and plasma protein binding of Rapamune, it is anticipated that Rapamune is not dialyzable to any significant extent.
In mice and rats, the acute oral LD50 was greater than 800 mg/kg. For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada's toll-free number, 1-844 POISON-X (1-844-764- 7669).
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 – Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Oral Solution: 1 mg/mL Tablet: 1 mg Phosal 50 PG® (ascorbyl palmitate, Eethanol, phosphatidyl-choline, propylene glycol, soybean oil fatty acids and sunflower mono and diglycerides) and Polysorbate 80 NF.
Calcium Sulfate Anhydrous NF, Carnauba Wax NF, Glyceryl Monooleate, Lactose Monohydrate NF, Magnesium Stearate NF, Microcrystalline Cellulose NF, Pharmaceutical Glaze NF, Rapamune® (sirolimus) Product Monograph Page 10 of 66 Protected B / Protégé B Availability of Dosage Forms Oral Solution: Rapamune (sirolimus oral solution) is supplied at a concentration of 1 mg/mL in: • Amber glass bottles of 60 mL The bottles are supplied with an oral syringe adapter for fitting into the neck of the bottle and 30 disposable amber oral syringes and 30 caps for daily dosing.
Tablet:
Rapamune (sirolimus tablet) is available as: • a white, triangular-shaped tablet containing 1 mg sirolimus marked “RAPAMUNE 1 mg” on one side The tablets are supplied in: • Bottles of 100 tablets • Unit dose cartons of 100 tablets (10 blister cards of 10 tablets each) 7 WARNINGS AND PRECAUTIONS Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.
– Monitoring and Laboratory Tests – Blood Concentration Monitoring). • Blood sirolimus trough levels should be monitored: • In patients receiving concentration-controlled Rapamune. • In pediatric patients • In patients with hepatic impairment.
• During concurrent administration of inhibitors and inducers of CYP3A4 and P-glycoprotein. • If the cyclosporine dose is markedly reduced, or if cyclosporine is discontinued. 3 Pharmacokinetics - Special Populations and Conditions - Renal Insufficiency).
• It is recommended that the maintenance dose of Rapamune be reduced by approximately one third to one-half in patients with hepatic impairment. It is not necessary to modify the Rapamune loading dose. 3 Pharmacokinetics - Special Populations and Conditions - Hepatic Insufficiency).
In patients with hepatic impairment, it is recommended that sirolimus whole blood trough levels be monitored. • Based on the finding that blood clearance decreases linearly with age, consideration should be given to reducing the Rapamune dose in patients 65 years of age and over.
3 Pharmacokinetics, Special populations and Conditions, Geriatrics). • The safety and efficacy of Rapamune in pediatric patients below the age of 13 years have not been established. The initial loading dose should be 3 mg/m2 in patients 13 years who weigh less than 40 kg.
The maintenance dose should be adjusted, based on body surface area, to 1 mg/m2/day. It is recommended that sirolimus whole blood trough levels be monitored. • The bioavailability of sirolimus (oral solution or tablet) is altered by concomitant food intake after administration.
Rapamune should be taken consistently, either with or without food to minimize blood level variability. • Bioavailability has not been determined for tablets after they have been crushed, chewed, or split and therefore this cannot be recommended.
Rapamune is contraindicated in patients with a hypersensitivity to sirolimus or its derivatives or any ingredient in the formulation, including any non-medicinal ingredient or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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General Rapamune is intended for oral administration only. Rapamune has been approved to be administered concurrently with cyclosporine (liquid and microemulsion) and corticosteroids. The efficacy and safety of the use of Rapamune in combination with other immunosuppressive agents has not been established.
Use in High-Risk Patients The safety and efficacy of cyclosporine withdrawal in high-risk patients have not been adequately studied and it is therefore not recommended. 5 mg/dL), black patients, re-transplants, multi-organ transplants, and patients with high panel of reactive antibodies.
It is recommended that Rapamune be used in combination with cyclosporine and corticosteroids for the first year following transplantation. The safety and efficacy of this combination in high-risk renal transplant patients have not been studied beyond one year.
Therefore, after the first year following transplantation any adjustments to the Polaxamer 188, Polyethylene Glycol 8000 Powdered NF, Polyethylene Glycol Type 20,000, Povidone USP, Vitamin E (dl-alpha tocopherol), Sucrose NF, Talc USP, Titanium Dioxide USP and Ink.
Rapamune® (sirolimus) Product Monograph Page 11 of 66 Protected B / Protégé B immunosuppressive regimen should be considered on the basis of the clinical status of the patient (See 1 INDICATIONS, 4 DOSAGE AND ADMINISTRATION, and 14 CLINICAL TRIALS).
Angioedema The concomitant administration of Rapamune and angiotensin-converting enzyme (ACE) inhibitors has resulted in angioneurotic edema-type reactions. Elevated sirolimus levels (with/without concomitant ACE inhibitors) may also potentiate angioedema.
In some cases, the angioedema has resolved upon discontinuation or dose reduction of Rapamune. Antimicrobial Prophylaxis Cytomegalovirus (CMV) prophylaxis is recommended for 3 months after transplantation, particularly for patients at increased risk for CMV infection.
Cases of Pneumocystis carinii pneumonia have been reported in patients not receiving antimicrobial prophylaxis. Therefore, antimicrobial prophylaxis for Pneumocystis carinii pneumonia should be administered for 1 year following transplantation.
Carcinogenesis and Mutagenesis Patients receiving immunosuppression regimens involving combinations of drugs, including Rapamune, as part of an immunosuppression regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin.
The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. As with all patients at an increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.
Also, see 16 NON-CLINICAL TOXICOLOGY - Chronic Toxicology - Carcinogenicity, Mutagenicity, Reproductive and Developmental Toxicology.
Cardiovascular Hyperlipidemia:
Increased serum cholesterol and triglycerides requiring treatment may occur in patients treated with Rapamune. The risk/benefit should be considered in patients with established hyperlipidemia before initiating an immunosuppressive regimen including Rapamune.
Drug-Drug Interactions Co-administration of Rapamune with strong inhibitors of CYP3A4 and/or P-glycoprotein (P-gp) (such as ketoconazole, voriconazole, itraconazole, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampicin or rifabutin) is not recommended.
Co-administration of agents that inhibit or induce CYP3A4 and/or P-gp will increase or decrease respectively whole blood concentrations of sirolimus. If administered concomitantly with sirolimus, frequent monitoring of sirolimus whole blood […]
Patients unable to take the tablets should be prescribed the oral solution and instructed in its use. 17 vol % ethanol (alcohol). 58 mL wine. This dose could potentially be harmful for those suffering from alcoholism and should be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.
Maintenance doses of 4 mg or less contain small amounts of ethanol (100 mg or less) that are likely to be too low to be harmful. 2 Recommended Dose and Dosage Adjustment Patients at Low to Moderate Immunological Risk Rapamune and Cyclosporine Combination Therapy: The initial dose of Rapamune should be administered as soon as possible after transplantation.
For de novo transplant recipients, a loading dose of Rapamune corresponding to 3 times the maintenance dose should be given. For most patients, the maintenance dose is 2 mg/day, with a loading dose of 6 mg. Although a maintenance dose of 5 mg/day, with a loading dose of 15 mg, was used in clinical trials of the oral solution and was shown to be safe and effective, no efficacy advantage over the 2 mg dose could be established for renal transplant patients.
Patients receiving 2 mg of Rapamune oral solution per day demonstrated an overall better safety profile than did patients receiving 5 mg of Rapamune oral solution per day. Rapamune® (sirolimus) Product Monograph Page 7 of 66 Protected B / Protégé B It is recommended that Rapamune oral solution and tablets be used initially in a regimen with cyclosporine and corticosteroids.
Cyclosporine should be withdrawn 2 to 4 months after renal transplantation in patients at low to moderate immunologic risk, and the Rapamune dose should be increased to reach recommended blood concentrations (See Rapamune Maintenance Regimen).
5 mg/dL, Black patients, re-transplants, multiorgan transplants, or patients with high- panel reactive antibodies (See 14 CLINICAL TRIALS). It is recommended that Rapamune be taken 4 hours after cyclosporine microemulsion [(cyclosporine, USP) MODIFIED] administration.
Rapamune Maintenance Regimen (RMR, Rapamune following cyclosporine withdrawal):
Initially, patients considered for cyclosporine withdrawal should be receiving Rapamune and cyclosporine combination therapy. At 2 to 4 months following transplantation, cyclosporine should be progressively discontinued over 4 to 8 weeks and the Rapamune dose should be adjusted to obtain whole blood trough concentrations within the range of 16 to 24 ng/mL (chromatographic method) for the first year following transplantation.
Thereafter, the target sirolimus concentrations should be 12 to 20 ng/mL (chromatographic method). The actual observations at year 1 and 5 were close to these ranges (See 7 WARNINGS AND PRECAUTIONS – Monitoring and Laboratory Tests – Blood Concentration Monitoring).
Patients at High Immunological Risk Rapamune Combination Therapy:
It is recommended that Rapamune be used in combination with cyclosporine and corticosteroids for the first year following transplantation 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 > 80%]) (See 14 CLINICAL TRIALS).
The safety and efficacy of these combinations in high-risk patients have not been studied beyond one year. Therefore, after the first year following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical […]