MS- Siponimod DI

Question 1

Siponimod brand name

Answer 1

Mayzent

Question 2

Siponimod indications

Answer 2

CIS, active SPMS, RRMS

Question 3

Siponimod MoA

Answer 3

Binds to S1P1 and S1P5 to block the lymphocytes’ ability to emerge from the lymph nodes –> amount of lymphocytes available to the CNS is decreased and reduces central inflammation

Question 4

What does siponimod dosing depend on?

Answer 4

CYP2C9 genotype!

Question 5

Siponimod starting dose for 1/1, 1/2, 2/2

Answer 5

0.25mg on days 1-2, 0.5mg on day 3, 0.75mg on day 4, 1.25mg on day 5

Question 6

Siponimod maintenance dose for 1/1, 1/2, 2/2

Answer 6

2mg QD starting on day 6

Question 7

Siponimod starting dose for 1/3, 2/3

Answer 7

Basically the same as the dose for 1/1, 1/2, 2/2 minus the day 5 dose of 1.25mg

Question 8

Siponimod maintenance dose for 1/3, 2/3

Answer 8

1mg QD starting on day 5

Question 9

Siponimod dose for 3/3

Answer 9

Trick question- IT’S CONTRAINDICATED!

Question 10

What to do with a missed siponimod dose

Answer 10

If it’s missed during the titration phase, start over with day 1 dose (0.25mg)

If it’s interrupted for 4 or more consecutive daily doses during maintenance, start over with 0.25mg of the titration regimen

Question 11

Warnings/precautions of siponimod

Answer 11

Infections, immunizations, PML, macular edema, bradycardia, atrioventricular conduction delays, QTc prolongation, CVD, respiratory effects, hepatic effects, HTN, neurotoxicity, malignancy, D/C of treatment

Question 12

Siponimod ADEs

Answer 12

HTN, HA, increased serum transaminases, peripheral edema, bradycardia, 1st and 2nd degree AV block, dizziness, seizure, nausea, diarrhea, lymphocytopenia, increased serum bilirubin, AST, ALT, herpes virus and herpes zoster infections, limb pain, asthenia, tremor, macular edema, reduced FEV, facial swelling, infection, malignant melanoma, cryptococcal meningitis, seminoma, varicella zoster infection

Question 13

Siponimod is metabolized by what enzymes?

Answer 13

2C9 and 3A4

Question 14

Siponimod DDIs

Answer 14

Immunosuppresants can enhance the adverse/toxic effects of live vaccines
Bradycardia, AV-blocking, and QTc-prolongation agents 2C9/3A4 inducers can decrease concentrations
2C9/3A4 inhibitors can increase concentrations
Echinacea may decrease the therapeutic effect
Siponimod may diminish therapeutic effect of inactivated vaccines
Siponimod may enhance the adverse effects of live vaccines and thrombocytopenic effect of live vaccines

Question 15

Siponimod CIs

Answer 15

3/3 genotype, recent MI (within the last 6 months), unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III or IV HF, Mobitz type II second-degree, third-degree AV block, sick sinus syndrome (exception is if patient has a functioning pacemaker)

Question 16

Siponimod monitoring

Answer 16

FIRST DOSE MONITORING, CBC with lymphocyte counts, bilirubin and transaminase, ECG, eye exam, FEV, VZV antibodies, BP, signs and symptoms of infection, PML/PRES, skin lesions, severe increase in disability following D/C

Question 17

Siponimod first-dose monitoring

Answer 17

Monitor the patient for 6 hours following the first dose for signs/symptoms of bradycardia and assess HR and BP hourly, ECG at 6 hours

Question 18

Siponimod and pregnancy

Answer 18

May cause fetal harm, patients should use effective contraception during therapy and for 10 days after the last dose

Question 19

Siponimod and breastfeeding

Answer 19

Not known if it’s present in breastmilk