Interactions between Rapamune and Ripretinib

The sirolimus in Rapamune has a moderate potential interaction with Angioedema.

Sirolimus has been associated with the development of angioedema. Patients at risk of developing angioedema and those using concomitant drugs known to cause angioedema, such as ACE inhibitors, may be at increased risk of developing angioedema. Care should be taken when prescribing this agent in patients at risk and close monitoring is recommended.

Ripretinib has a moderate potential interaction with Bleeding Disorder.

Ripretinib has the potential to affect wound healing adversely. Do not administer ripretinib for at least two weeks following major surgery and until adequate wound healing. It is recommended to withhold ripretinib for at least one week before elective surgery. Care should be exercised when using this agent in patients with impaired wound complications. The safety of this agent after the resolution of wound healing complications has not been established.

Ripretinib has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Ripretinib may cause cardiac dysfunction. The safety of ripretinib has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or multiple gated acquisition (MUGA) scan prior to initiating treatment with ripretinib and during treatment, as clinically indicated. Permanently discontinue therapy for Grade 3 or 4 left ventricular systolic dysfunction.

Ripretinib has a moderate potential interaction with Coagulation Defects and Disorders.

Ripretinib has the potential to affect wound healing adversely. Do not administer ripretinib for at least two weeks following major surgery and until adequate wound healing. It is recommended to withhold ripretinib for at least one week before elective surgery. Care should be exercised when using this agent in patients with impaired wound complications. The safety of this agent after the resolution of wound healing complications has not been established.

Ripretinib has a moderate potential interaction with Heart Disease.

Ripretinib may cause cardiac dysfunction. The safety of ripretinib has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or multiple gated acquisition (MUGA) scan prior to initiating treatment with ripretinib and during treatment, as clinically indicated. Permanently discontinue therapy for Grade 3 or 4 left ventricular systolic dysfunction.

Ripretinib has a moderate potential interaction with High Blood Pressure.

Ripretinib may cause hypertension. It is recommended to control blood pressure prior to initiating therapy and monitor blood pressure as clinically indicated during treatment. Based on severity, withhold treatment with ripretinib and resume at the same or reduced dose or permanently discontinue. Do not initiate ripretinib in patients with uncontrolled hypertension.

The sirolimus in Rapamune has a moderate potential interaction with High Cholesterol.

The use of sirolimus may increase serum cholesterol and triglycerides. Care should be taken when prescribing this agent to hyperlipidemic patients. It is recommended to assess the risk/benefit carefully when considering this agent in patients with established hyperlipidemia before initiating therapy. It is recommended to monitor patients regularly for elevated lipids.

The sirolimus in Rapamune has a major potential interaction with Immunodeficiency.

Immunosuppressive agents may increase the risk of progressive multifocal leukoencephalopathy (PML). Certain agents are contraindicated in patients who have or have had PML. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with these agents. Health care professionals should monitor patients for any new sign or symptom suggestive of PML. Therapy dosing should be withheld immediately and an appropriate diagnostic evaluation should be performed at the first sign or symptom suggestive of PML.

The sirolimus in Rapamune has a major potential interaction with Infection.

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents. Patients receiving immunosuppressants are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections including opportunistic infections. Caution should be exercised when considering their use in patients with severe or chronic infections. It is recommended to interrupt therapy in patients who develop a new infection while undergoing treatment and to monitor these patients closely for any sign or symptom indicative of infection.

The sirolimus in Rapamune has a moderate potential interaction with Liver Disease.

Sirolimus is extensively metabolized in the intestinal wall and liver and undergoes counter-transport from enterocytes of the small intestine into the gut lumen. The maintenance dose of sirolimus should be reduced by approximately one third in patients with mild or moderate hepatic impairment and by approximately one half in patients with severe hepatic impairment. It is not necessary to modify the sirolimus loading dose. Care should be taken when prescribing this agent to patients with liver impairment and close monitoring is recommended.

The sirolimus in Rapamune has a moderate potential interaction with Organ Transplant.

The use of sirolimus in lung transplant patients is not recommended as the safety and efficacy of this agent as immunosuppressive therapy has not been established in these patients. Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus has been used as part of an immunosuppressive regimen.

The sirolimus in Rapamune has a moderate potential interaction with Organ Transplant.

The use of sirolimus is not recommended in liver transplant patients as its safety and efficacy has not been established in these patients. The use of sirolimus has been associated with adverse outcomes in patients following liver transplantation, including excess mortality, graft loss and hepatic artery thrombosis.

The sirolimus in Rapamune has a moderate potential interaction with Pulmonary Impairment.

Interstitial Lung Disease (ILD)/Pneumonitis, including pneumonitis, bronchiolitis obliterans organizing pneumonia, and pulmonary fibrosis, some fatal, with no identified infectious etiology have occurred with the use of sirolimus. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis and discontinue sirolimus and assess patients developing ILD or pneumonitis.

The sirolimus in Rapamune has a moderate potential interaction with Renal Dysfunction.

Renal function should be closely monitored during the co-administration of sirolimus with cyclosporine, because long-term administration of the combination has been associated with deterioration of renal function. It is recommended to adjust therapy regimen, including discontinuation of sirolimus and/or cyclosporine in patients with elevated or increasing serum creatinine levels. Caution should be exercised when using agents (e.g., aminoglycosides and amphotericin B) that are known to have a deleterious effect on renal function. Periodic monitoring of renal function is recommended, including quantitative monitoring of urinary protein excretion.