Can you take Siponimod with Treosulfan?

Siponimod has a major potential interaction with Cardiovascular Conditions and Disorders.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

Siponimod has a moderate potential interaction with Central Nervous System Disorders.

Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving a sphingosine 1-phosphate receptor modulator. It is recommended to promptly schedule a complete physical and neurological examination and should consider an MRI, if a patient develops any unexpected neurological or psychiatric symptoms/signs, any symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological deterioration. Delay in diagnosis and treatment may lead to permanent neurological sequelae. Exercise care when using this agent in patients with a history of ischemic stroke or cerebral hemorrhage. Treatment should be discontinued if PRES is suspected.

Siponimod has a moderate potential interaction with Diabetes Mellitus.

Macular edema was reported in 1.8% of patients receiving siponimod treatment, the majority of cases occurring within the first four months of therapy. Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during therapy. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and at any time if there is any change in vision while taking siponimod. Patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

Siponimod has a major potential interaction with Heart Disease.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

Siponimod has a major potential interaction with History - Cerebrovascular Disease.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

Siponimod has a major potential interaction with History - Myocardial Infarction.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

Siponimod has a moderate potential interaction with Infection.

Siponimod causes a dose-dependent reduction in peripheral lymphocyte count to 20%-30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues. Initiation of treatment should be delayed in patients with severe active infection until resolution. Before initiating treatment with siponimod, results from a recent complete blood count (i.e., within 6 months or after discontinuation of prior therapy) should be reviewed. Effective diagnostic and therapeutic strategies should be employed in patients with symptoms of infection while on therapy. Suspension of treatment should be considered if a patient develops a serious infection.

Siponimod has a moderate potential interaction with Liver Disease.

Elevations of transaminases may occur in siponimod- treated patients, therefore, transaminase and bilirubin levels should be reviewed before initiation of therapy. Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, or jaundice and/or dark urine during treatment, should have liver enzymes checked. Siponimod should be discontinued if significant liver injury is confirmed. Although there are no data to establish that patients with preexisting liver disease are at increased risk to develop elevated liver function test values when taking siponimod, caution should be exercised when using the medication in patients with a history of significant liver disease.

Treosulfan has a moderate potential interaction with Liver Disease.

Treosulfan has not been studied in patients with moderate or severe liver and renal dysfunction.

Siponimod has a moderate potential interaction with Multiple Sclerosis.

Rare cases of severe exacerbation of multiple sclerosis (MS), including disease rebound, have been reported after discontinuation of sphingosine 1-phosphate receptor modulator in MS treated patients. The possibility of severe exacerbation of disease should be considered after stopping treatment with these agents. Patients should be observed for a severe increase in disability upon discontinuation and appropriate treatment should be instituted, as required.

Treosulfan has a moderate potential interaction with Renal Dysfunction.

Treosulfan has not been studied in patients with moderate or severe liver and renal dysfunction.

Treosulfan has a moderate potential interaction with Seizures.

There have been reports of seizures in patients following treatment with treosulfan. Patients should be monitored for signs of neurological adverse reactions, and clonazepam prophylaxis may be considered for patients at higher risk for seizures, including infants.

Siponimod has a moderate potential interaction with Skin Cancer.

Cases of malignancies, including skin malignancies have been reported in patients treated with some sphingosine -1-receptor (S1P) receptor modulators. Skin examinations are recommended prior and during treatment in all patients, particularly in those with risk factors for skin cancer. Suspicious skin lesions should be promptly evaluated, and patients at increased risk should wear protective clothing and use sunscreen with high protection factor.

Siponimod has a moderate potential interaction with Uveitis.

Macular edema was reported in 1.8% of patients receiving siponimod treatment, the majority of cases occurring within the first four months of therapy. Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during therapy. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and at any time if there is any change in vision while taking siponimod. Patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

Siponimod has a moderate potential interaction with Vaccination.

The use of live attenuated vaccines should be avoided while patients are taking siponimod and for 4 weeks after stopping treatment. Vaccinations may be less effective if administered during treatment. Siponimod treatment discontinuation 1 week prior to and until 4 weeks after a planned vaccination is recommended. Additionally, patients without a healthcare professional confirmed history of chickenpox or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating siponimod treatment. A full course of vaccination for antibody- negative patients with varicella vaccine is recommended prior to commencing treatment, following which initiation of treatment with siponimod should be postponed for 4 weeks to allow the full effect of vaccination to occur.