Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label.
Increased susceptibility to infection, lymphoma, and malignancy [ see Boxed Warning, Warnings and Precautions ( 5.1 ) ] Excess mortality, graft loss, and hepatic artery thrombosis in liver transplant patients [ see Boxed Warning, Warnings and Precautions ( 5.2 ) ] Bronchial anastomotic dehiscence in lung transplant patients [ see Boxed Warning, Warnings and Precautions ( 5.3 ) ] Hypersensitivity reactions [ see Warnings and Precautions ( 5.4 ) ] Exfoliative dermatitis [ see Warnings and Precautions ( 5.4 ) ] Angioedema [ see Warnings and Precautions ( 5.5 ) ] Fluid accumulation and impairment of wound healing [ see Warnings and Precautions ( 5.6 ) ] Hypertriglyceridemia, hypercholesterolemia [ see Warnings and Precautions ( 5.7 ) ] Decline in renal function in long-term combination of cyclosporine with sirolimus [ see Warnings and Precautions ( 5.8 ) ] Proteinuria [ see Warnings and Precautions ( 5.9 ) ] Interstitial lung disease [ see Warnings and Precautions ( 5.11 ) ] Increased risk of calcineurin inhibitor-induced HUS/TTP/TMA [ see Warnings and Precautions ( 5.13 ) ] Embryo-fetal toxicity [see Warnings and Precautions ( 5.15 )] Male infertility [see Warnings and Precautions ( 5.16 )] The most common (≥ 30%) adverse reactions observed with sirolimus in clinical studies for organ rejection prophylaxis in recipients of renal transplantation are: peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, constipation, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia.
The most common (≥20%) adverse reactions observed with sirolimus in the clinical study for the treatment of LAM are: stomatitis, diarrhea, abdominal pain, nausea, nasopharyngitis, acne, chest pain, peripheral edema, upper respiratory tract infection, headache, dizziness, myalgia, and hypercholesterolemia.
The following adverse reactions resulted in a rate of discontinuation of > 5% in clinical trials for renal transplant rejection prophylaxis: creatinine increased, hypertriglyceridemia, and TTP.
In patients with LAM, 11% of subjects discontinued due to adverse reactions, with no single adverse reaction leading to discontinuation in more than one patient being treated with sirolimus.
Prophylaxis of organ rejection in patients receiving renal transplants: Most common adverse reactions (incidence ≥ 30%) are peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia ( 6 ).
Lymphangioleiomyomatosis: Most common adverse reactions (incidence ≥20%) are stomatitis, diarrhea, abdominal pain, nausea, nasopharyngitis, acne, chest pain, peripheral edema, upper respiratory tract infection, headache, dizziness, myalgia, and hypercholesterolemia ( 6.6 ).
To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc.
at 1-877-993-8779, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Studies Experience in Prophylaxis of Organ Rejection Following Renal Transplantation The safety and efficacy of sirolimus oral solution for the prevention of organ rejection following renal transplantation were assessed in two randomized, double blind, multicenter, controlled trials [ see Clinical Studies ( 14.1 ) ].
5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions ( 5.4 ) Angioedema ( 5.5 ) Fluid Accumulation and Impairment of Wound Healing ( 5.6 ) Hyperlipidemia ( 5.7 ) Decline in Renal Function ( 5.8 ) Proteinuria ( 5.9 ) Latent Viral Infections ( 5.10 ) Interstitial Lung Disease/Non-Infectious Pneumonitis ( 5.11 ) De Novo Use Without Cyclosporine ( 5.12 ) Increased Risk of Calcineurin Inhibitor-Induced Hemolytic Uremic Syndrome/ Thrombotic Thrombocytopenic Purpura/ Thrombotic Microangiopathy ( 5.13 ) Embryo-Fetal Toxicity: Can cause fetal harm.
Use of highly effective contraception is recommended for females of reproductive potential during treatment and for 12 weeks after final dose of sirolimus ( 5.15 , 8.1 ) Male Infertility: Azoospermia or oligospermia may occur ( 5.16 , 13.1 ) Immunizations: Avoid live vaccines ( 5.19 ) 5.1 Increased Susceptibility to Infection and the Possible Development of Lymphoma Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly of the skin, may result from immunosuppression.
The rates of lymphoma/lymphoproliferative disease observed in Studies 1 and 2 were 0.7 to 3.2% (for sirolimus-treated patients) versus 0.6 to 0.8% (azathioprine and placebo control) [ see Adverse Reactions ( 6.1 ) and ( 6.2 ) ].
Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections such as tuberculosis, fatal infections, and sepsis.
Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should use sirolimus for prophylaxis of organ rejection in patients receiving renal transplants.
Like all medications, Sirolimus can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: