Why does Zeposia (ozanimod) slow down your heart rate?

The reason ozanimod (Zeposia) may slow down your heart rate temporarily when you first start taking it is thought to be due to the action of ozanimod binding to one of the S1P receptors' subunits, S1P1R, which also has an effect of potassium channels in cardiac muscle cells. This reduces how responsive the cardiac cells are and reduces their firing rate, which slows down the heart.

How does ozanimod affect your heart rate?

The reason a decrease in heart rate is seen with the very first dose of ozanimod is thought to be due to the presence of S1P receptors on cardiac muscle cells. So, in addition to binding to lymphocyte S1P receptors, ozanimod also influences cardiac muscle cell S1P receptors which activate inward potassium channels, reducing the excitability of muscle cells and decreasing how frequently they fire. This has the effect of slowing down the heart rate.

The reason this only happens temporarily – usually only with the first dose of ozanimod and then not again – is thought to be explained by the cardiac muscle cell receptors becoming desensitized to ozanimod or internalization or degradation or the S1P receptor, meaning it no longer responds.

Many people experience transient decreases in heart rate when starting ozanimod. The incidence of this can be reduced by using a starting dose of 0.23mg ozanimod and increasing the dosage slowly over a week to the required maintenance dose.