Gilenya Disease Interactions

Fingolimod is contraindicated in patients who have had a recent myocardial infarction, those with unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure, a history of Mobitz Type II 2nd degree or 3rd degree AV block or sick sinus syndrome, unless the patient has a pacemaker, baseline QTc interval of >= to 500 msec., or those patients being treated with Class Ia or Class III anti-arrhythmic drugs.

Cases of liver injury with hepatocellular and/or cholestatic hepatitis have been reported with fingolimod in the postmarketing setting. Patients with preexisting liver disease may be at increased risk of developing elevated liver enzymes when taking fingolimod. It is recommended to obtain liver enzyme results before initiation of therapy. No dose adjustment is needed in patients with mild or moderate hepatic impairment. Closely monitor patients with severe hepatic impairment as this agent exposure is doubled in these patients and the risk of adverse reactions is greater. Discontinue if significant liver injury occurs.

Hypertension was reported as an adverse reaction in patients on fingolimod. Blood pressure should be monitored during treatment with this agent as it can increase the blood pressure of patients with hypertension.

Fingolimod may increase the risk of infections, and some serious infections with opportunistic pathogens including viruses have been reported. Prior to treatment, a recent CBC (i.e., within 6 months or after discontinuation of prior therapy) should be available. Consider withholding treatment if a patient develops a serious infection, and reassess the benefits and risks prior to reinitiation of therapy.

Fingolimod increases the risk of macular edema. Patients with a history of uveitis, and those with diabetes mellitus are at increased risk of macular edema. It is recommended to perform an examination of the fundus including the macula in all patients before starting treatment, again 3-4 months after starting treatment, and again at any time after a patient reports visual disturbances. A decision on whether or not to discontinue therapy should include an assessment of the potential benefits and risks.

Cases of dyspnea in patients using fingolimod have been reported during clinical trials. Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) were observed in patients treated with fingolimod as early as 1 month after treatment initiation. Caution with patients at risk of dyspnea and spirometric evaluation of respiratory function and evaluation of DLCO should be performed during therapy if clinically indicated.

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.

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.

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.