warnings and cautions
5 WARNINGS AND PRECAUTIONS Infections : PONVORY may increase the risk of infections. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment and for 1–2 weeks after discontinuation. Do not start PONVORY in patients with active infection. ( 5.1 ) Bradyarrhythmia and Atrioventricular Conduction Delays : PONVORY may result in a transient decrease in heart rate; titration is required for treatment initiation. Check an electrocardiogram (ECG) to assess for preexisting cardiac conduction abnormalities before starting PONVORY. Consider cardiology consultation for conduction abnormalities or concomitant use with other drugs that decrease heart rate. ( 5.2 , 7.2 , 7.3 ) Respiratory Effects : May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated. ( 5.3 ) Liver Injury : Discontinue if significant liver injury is confirmed. Obtain liver function tests before initiating PONVORY. ( 5.4 ) Increased Blood Pressure (BP) : Monitor BP during treatment. ( 5.5 ) Cutaneous Malignancies: Periodic skin examination is recommended. ( 5.6 ) Fetal Risk : Women of childbearing potential should use effective contraception during and for 1 week after stopping PONVORY. ( 5.7 ) Macular Edema : An ophthalmic evaluation is recommended before starting treatment and if there is any change in vision while taking PONVORY. Diabetes mellitus and uveitis increase the risk. ( 5.8 ) 5.1 Infections Risk of Infections PONVORY causes a dose-dependent reduction in peripheral lymphocyte count to 30–40% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues [see Clinical Pharmacology (12.2) ] . PONVORY may therefore increase the susceptibility to infections. Life-threatening and rare fatal infections have been reported in association with other sphingosine 1-phosphate (S1P) receptor modulators. In Study 1 [see Clinical Studies (14) ] , the overall rate of infections was comparable between the PONVORY-treated patients and those receiving teriflunomide 14 mg (54.2% vs 52.1%, respectively). PONVORY increased the risk of upper respiratory tract infections. Serious or severe infections occurred in 1.6% of PONVORY-treated patients compared to 0.9% of patients receiving teriflunomide 14 mg. Before initiating treatment with PONVORY, results from a recent (i.e., within 6 mon...