Mayzent 0.25mg Tablets
It is used to treat MS (multiple sclerosis).
Drug Class
Immunomodulator; Disease-modifying therapy (DMT) for Multiple Sclerosis
Pharmacologic Class
Sphingosine 1-phosphate (S1P) receptor modulator
Pregnancy Category
Category D
FDA Approved
Mar 2019
DEA Schedule
Not Controlled
Overview
What is this medicine?
Mayzent (siponimod) is a medication used to treat multiple sclerosis (MS). It works by trapping certain immune cells (lymphocytes) in your lymph nodes, preventing them from entering your brain and spinal cord where they can cause damage. This helps to reduce MS relapses and slow down the progression of the disease.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole - do not chew, break, or crush it. Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
To maintain the quality of your medication, store unopened containers in a refrigerator or at room temperature. Avoid freezing. Once opened, store the medication at room temperature in a dry place, away from the bathroom. If stored at room temperature, discard any unused medication after 3 months. Note that once the medication has been stored at room temperature, it should not be returned to the refrigerator.
What to Do If You Miss a Dose
When you first start taking this medication, your dose will be gradually increased. If you miss a dose during this time, contact your doctor for guidance. If you miss a dose after you've reached your regular dose, take it as soon as you remember. Then, return to your usual schedule. Do not take two doses at the same time or take extra doses. If you miss four doses, contact your doctor for further instructions.
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole - do not chew, break, or crush it. Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
To maintain the quality of your medication, store unopened containers in a refrigerator or at room temperature. Avoid freezing. Once opened, store the medication at room temperature in a dry place, away from the bathroom. If stored at room temperature, discard any unused medication after 3 months. Note that once the medication has been stored at room temperature, it should not be returned to the refrigerator.
What to Do If You Miss a Dose
When you first start taking this medication, your dose will be gradually increased. If you miss a dose during this time, contact your doctor for guidance. If you miss a dose after you've reached your regular dose, take it as soon as you remember. Then, return to your usual schedule. Do not take two doses at the same time or take extra doses. If you miss four doses, contact your doctor for further instructions.
Lifestyle & Tips
- Take Mayzent exactly as prescribed, especially during the initial 5-day titration period.
- Do not stop taking Mayzent without consulting your doctor, as stopping can lead to a severe worsening of MS.
- Avoid live attenuated vaccines during treatment and for 4 weeks after stopping Mayzent.
- Report any signs of infection (fever, chills, flu-like symptoms) immediately.
- Be aware of potential cardiac side effects, especially during the first few days of treatment. Report any dizziness, lightheadedness, or slow heart rate.
- Monitor for changes in vision and report them to your doctor promptly.
- Women of childbearing potential must use effective contraception during treatment and for at least 10 days after the last dose due to risk of fetal harm.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial titration required for 5 days, followed by maintenance dose. Maintenance dose is 2 mg orally once daily for most patients, or 1 mg orally once daily for patients with CYP2C9 *2/*2, *1/*3, or *2/*3 genotypes. The 0.25mg tablet is used during the initial 5-day titration phase (Day 1: 0.25 mg, Day 2: 0.5 mg, Day 3: 0.75 mg, Day 4: 1 mg, Day 5: 1.25 mg) and can be used to achieve the 1 mg maintenance dose (four 0.25mg tablets).
Dose Range:
0.25 - 2 mg
Condition-Specific Dosing:
Relapsing forms of Multiple Sclerosis (RMS):
Initial titration followed by 2 mg (or 1 mg based on CYP2C9 genotype) orally once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed.
Moderate:
No dose adjustment needed.
Severe:
No dose adjustment needed.
Dialysis:
No dose adjustment needed; siponimod is not significantly removed by dialysis.
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A).
Moderate:
Contraindicated (Child-Pugh B).
Severe:
Contraindicated (Child-Pugh C).
Pharmacology
Mechanism of Action
Siponimod is a sphingosine 1-phosphate (S1P) receptor modulator. It binds with high affinity to S1P receptors 1 and 5 (S1P1 and S1P5). By binding to S1P1 receptors on lymphocytes, siponimod prevents the egress of lymphocytes from lymphoid organs into the peripheral blood, thereby reducing the number of circulating lymphocytes that can cross the blood-brain barrier and contribute to central nervous system inflammation in multiple sclerosis.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80%
Tmax:
Approximately 4 hours
FoodEffect:
High-fat meal decreases Cmax by 34% and AUC by 21%, but this is not considered clinically significant. Can be taken with or without food.
Distribution:
Vd:
Approximately 163 L
ProteinBinding:
>99.9%
CnssPenetration:
Yes (active metabolites cross the blood-brain barrier)
Elimination:
HalfLife:
Approximately 30 hours
Clearance:
Not readily available as a single rate, but primarily hepatic metabolism and fecal excretion.
ExcretionRoute:
Primarily feces (89%), minor urine (1%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Lymphocyte count reduction typically begins within hours of the first dose.
PeakEffect:
Maximum lymphocyte count reduction typically occurs within 2-4 weeks.
DurationOfAction:
Lymphocyte counts return to normal range within 10 days after discontinuation.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Meningitis: Headache with fever, stiff neck, stomach upset, confusion, or sensitivity to light.
Shingles: Pain, itching, or tingling, fever, muscle aches, or a rash with or without blisters.
Liver Problems: Dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes.
Skin Cancer: New wart, lump, or skin growth; a sore that bleeds or doesn't heal; a shiny, white, pink, red, or skin-colored bump that bleeds or doesn't heal; or a change in the color or size of a mole.
High Blood Pressure: Severe headache or dizziness, fainting, or changes in vision.
Respiratory Issues: Shortness of breath or worsening breathing difficulties.
Swelling: Swelling in the arms or legs.
Heart Problems: Slow or abnormal heartbeat, especially after the first dose. People with pre-existing heart conditions will require close monitoring.
Confusion or Dizziness: If you experience confusion, dizziness, slow or abnormal heartbeat, fatigue, or chest pain, contact your doctor immediately.
Additional Warnings:
Macular Edema: An eye problem that can lead to permanent vision loss, especially in people with diabetes or a history of uveitis. If you notice light sensitivity, abnormal colors, blurriness, shadows, or a blind spot in your vision, contact your doctor right away.
Blood Vessel Problems: Rarely, blood vessel problems, including strokes, blood clots in the lungs, and heart attacks, can occur. Seek medical help if you experience chest, arm, back, neck, or jaw pain; coughing up blood; numbness or weakness on one side of your body; trouble speaking or thinking; changes in balance or vision; shortness of breath; or swelling, warmth, or pain in the leg or arm.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially life-threatening brain problem. Contact your doctor if you experience confusion, decreased alertness, changes in vision, loss of vision, seizures, or a severe headache.
Progressive Multifocal Leukoencephalopathy (PML): A severe brain problem that can cause disability or be life-threatening. If you notice confusion, memory problems, depression, changes in behavior, uneven strength, trouble speaking or thinking, changes in balance or vision, contact your doctor immediately.
Common Side Effects:
While many people may not experience side effects or only have mild ones, it's essential to discuss any concerns with your doctor. Common side effects include:
Dizziness or headache
Upset stomach
Diarrhea
* Pain in the arms or legs
Reporting Side Effects:
If you experience any side effects, contact your doctor or report them to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Meningitis: Headache with fever, stiff neck, stomach upset, confusion, or sensitivity to light.
Shingles: Pain, itching, or tingling, fever, muscle aches, or a rash with or without blisters.
Liver Problems: Dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes.
Skin Cancer: New wart, lump, or skin growth; a sore that bleeds or doesn't heal; a shiny, white, pink, red, or skin-colored bump that bleeds or doesn't heal; or a change in the color or size of a mole.
High Blood Pressure: Severe headache or dizziness, fainting, or changes in vision.
Respiratory Issues: Shortness of breath or worsening breathing difficulties.
Swelling: Swelling in the arms or legs.
Heart Problems: Slow or abnormal heartbeat, especially after the first dose. People with pre-existing heart conditions will require close monitoring.
Confusion or Dizziness: If you experience confusion, dizziness, slow or abnormal heartbeat, fatigue, or chest pain, contact your doctor immediately.
Additional Warnings:
Macular Edema: An eye problem that can lead to permanent vision loss, especially in people with diabetes or a history of uveitis. If you notice light sensitivity, abnormal colors, blurriness, shadows, or a blind spot in your vision, contact your doctor right away.
Blood Vessel Problems: Rarely, blood vessel problems, including strokes, blood clots in the lungs, and heart attacks, can occur. Seek medical help if you experience chest, arm, back, neck, or jaw pain; coughing up blood; numbness or weakness on one side of your body; trouble speaking or thinking; changes in balance or vision; shortness of breath; or swelling, warmth, or pain in the leg or arm.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare and potentially life-threatening brain problem. Contact your doctor if you experience confusion, decreased alertness, changes in vision, loss of vision, seizures, or a severe headache.
Progressive Multifocal Leukoencephalopathy (PML): A severe brain problem that can cause disability or be life-threatening. If you notice confusion, memory problems, depression, changes in behavior, uneven strength, trouble speaking or thinking, changes in balance or vision, contact your doctor immediately.
Common Side Effects:
While many people may not experience side effects or only have mild ones, it's essential to discuss any concerns with your doctor. Common side effects include:
Dizziness or headache
Upset stomach
Diarrhea
* Pain in the arms or legs
Reporting Side Effects:
If you experience any side effects, contact your doctor or report them to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of infection: fever, chills, body aches, sore throat, unusual fatigue.
- Cardiac symptoms: dizziness, lightheadedness, slow heart rate, chest pain, shortness of breath.
- Liver problems: unexplained nausea, vomiting, stomach pain, dark urine, yellowing of skin or eyes (jaundice).
- Vision changes: blurred vision, blind spots, central vision loss.
- New or worsening headache.
- Symptoms of PRES: sudden severe headache, confusion, seizures, visual changes.
- Symptoms of PML: new or worsening weakness on one side of the body, clumsiness, vision changes, changes in thinking or memory, personality changes.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances. Describe the allergic reaction and its symptoms.
Your CYP2C9 gene type, specifically if you have the CYP2C93/3 gene variant. If you are unsure about your gene type, discuss this with your doctor, as testing may be required before starting treatment.
A history of certain heart conditions, including:
+ Abnormal heart rhythms (heart block, sick sinus syndrome, slow heartbeat, or long QT interval on an electrocardiogram)
+ Chest pain (angina)
+ Heart attack
+ Heart failure
+ Brain blood vessel disease (such as transient ischemic attack or stroke)
+ High blood pressure
+ Sleep apnea
The presence of an active infection
Recent vaccination with the varicella (chickenpox) vaccine within the past month
Recent administration of a live vaccine
Current or planned light therapy; consult your doctor to discuss potential interactions
Previous treatment with alemtuzumab, beta interferon, or glatiramer
Concurrent use of certain medications, including:
+ Carbamazepine
+ Efavirenz
+ Fluconazole
+ Modafinil
+ Rifampin
Use of any medications that can cause a slow heartbeat, prolonged QT interval, or immune system suppression. There are many drugs with these effects; consult your doctor or pharmacist if you are unsure.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications
Natural products
Vitamins
Health problems
Do not start, stop, or change the dosage of any medication without first consulting your doctor to verify the safety of combining it with this medication. This list is not exhaustive, and your doctor and pharmacist will help determine the safety of this medication in conjunction with your other treatments and health conditions.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances. Describe the allergic reaction and its symptoms.
Your CYP2C9 gene type, specifically if you have the CYP2C93/3 gene variant. If you are unsure about your gene type, discuss this with your doctor, as testing may be required before starting treatment.
A history of certain heart conditions, including:
+ Abnormal heart rhythms (heart block, sick sinus syndrome, slow heartbeat, or long QT interval on an electrocardiogram)
+ Chest pain (angina)
+ Heart attack
+ Heart failure
+ Brain blood vessel disease (such as transient ischemic attack or stroke)
+ High blood pressure
+ Sleep apnea
The presence of an active infection
Recent vaccination with the varicella (chickenpox) vaccine within the past month
Recent administration of a live vaccine
Current or planned light therapy; consult your doctor to discuss potential interactions
Previous treatment with alemtuzumab, beta interferon, or glatiramer
Concurrent use of certain medications, including:
+ Carbamazepine
+ Efavirenz
+ Fluconazole
+ Modafinil
+ Rifampin
Use of any medications that can cause a slow heartbeat, prolonged QT interval, or immune system suppression. There are many drugs with these effects; consult your doctor or pharmacist if you are unsure.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications
Natural products
Vitamins
Health problems
Do not start, stop, or change the dosage of any medication without first consulting your doctor to verify the safety of combining it with this medication. This list is not exhaustive, and your doctor and pharmacist will help determine the safety of this medication in conjunction with your other treatments and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor will require you to undergo regular blood tests and heart function checks. Additionally, you will need to have periodic eye and skin exams to monitor your health.
Monitoring for high blood pressure is crucial while taking this drug, so your doctor will instruct you on how often to have your blood pressure checked. In some cases, your doctor may order an MRI scan before starting this medication.
If you have not had chickenpox or received the chickenpox vaccine, it is crucial to discuss this with your doctor. While taking this medication and for 3 to 4 weeks after your last dose, you may be more susceptible to infections, some of which can be severe or life-threatening. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu.
Before receiving any vaccinations while taking this medication and for at least 4 weeks after stopping it, consult with your doctor. The use of this drug may increase the risk of infection or reduce the effectiveness of the vaccine.
When this medication is discontinued, multiple sclerosis (MS) symptoms can recur and may be more severe than before or during treatment. If you stop taking this medication and experience worsening MS symptoms, contact your doctor immediately. Do not discontinue this medication without first consulting the doctor who prescribed it for you.
There is an increased risk of skin cancer associated with this type of medication. To minimize this risk, limit your exposure to sunlight, sunlamps, and tanning beds. Use a broad-spectrum sunscreen with a high Sun Protection Factor (SPF) and wear protective clothing when spending time outdoors.
A specific type of testicular cancer has been reported in patients taking this medication. If you have concerns or questions, discuss them with your doctor.
This medication may harm an unborn baby if taken during pregnancy. If you may become pregnant, use effective birth control while taking this medication and for 10 days after your last dose. If you become pregnant, notify your doctor immediately.
If you are breastfeeding, inform your doctor, as you will need to discuss the potential risks to your baby.
Monitoring for high blood pressure is crucial while taking this drug, so your doctor will instruct you on how often to have your blood pressure checked. In some cases, your doctor may order an MRI scan before starting this medication.
If you have not had chickenpox or received the chickenpox vaccine, it is crucial to discuss this with your doctor. While taking this medication and for 3 to 4 weeks after your last dose, you may be more susceptible to infections, some of which can be severe or life-threatening. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with people who have infections, colds, or flu.
Before receiving any vaccinations while taking this medication and for at least 4 weeks after stopping it, consult with your doctor. The use of this drug may increase the risk of infection or reduce the effectiveness of the vaccine.
When this medication is discontinued, multiple sclerosis (MS) symptoms can recur and may be more severe than before or during treatment. If you stop taking this medication and experience worsening MS symptoms, contact your doctor immediately. Do not discontinue this medication without first consulting the doctor who prescribed it for you.
There is an increased risk of skin cancer associated with this type of medication. To minimize this risk, limit your exposure to sunlight, sunlamps, and tanning beds. Use a broad-spectrum sunscreen with a high Sun Protection Factor (SPF) and wear protective clothing when spending time outdoors.
A specific type of testicular cancer has been reported in patients taking this medication. If you have concerns or questions, discuss them with your doctor.
This medication may harm an unborn baby if taken during pregnancy. If you may become pregnant, use effective birth control while taking this medication and for 10 days after your last dose. If you become pregnant, notify your doctor immediately.
If you are breastfeeding, inform your doctor, as you will need to discuss the potential risks to your baby.
Overdose Information
Overdose Symptoms:
- Bradycardia (slow heart rate)
- AV block
- Hypotension
- Respiratory depression
- Neurological symptoms
What to Do:
There is no specific antidote. Management is supportive. Contact a poison control center or emergency medical services immediately. Call 1-800-222-1222.
Drug Interactions
Contraindicated Interactions
- Strong CYP2C9 and moderate/strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's Wort) due to potential for significant reduction in siponimod exposure and efficacy.
- Patients with CYP2C9 *3/*3 genotype (poor metabolizers) due to significantly increased siponimod exposure and risk of adverse reactions.
- Patients with a history of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III/IV heart failure in the last 6 months.
- Patients with Mobitz Type II second-degree AV block, third-degree AV block, or sick sinus syndrome (unless a functioning pacemaker is present).
- Patients with severe untreated sleep apnea.
Major Interactions
- Antiarrhythmics (Class IA e.g., quinidine, procainamide; Class III e.g., amiodarone, sotalol): Increased risk of bradycardia and AV block. Avoid concomitant use.
- QT-prolonging drugs (e.g., antipsychotics, macrolide antibiotics, fluoroquinolones, tricyclic antidepressants): Increased risk of QT prolongation. Use with caution.
- Beta-blockers, calcium channel blockers (non-dihydropyridine like diltiazem, verapamil), ivabradine, digoxin: Additive bradycardic effects. Use with caution, monitor heart rate.
- Immunosuppressants (e.g., methotrexate, azathioprine, corticosteroids, natalizumab, ocrelizumab, alemtuzumab, cladribine, teriflunomide, dimethyl fumarate, fingolimod, ozanimod, ponesimod): Increased risk of additive immunosuppression and infections. Avoid concomitant use or use with extreme caution.
- Live attenuated vaccines (e.g., MMR, varicella, yellow fever): Risk of vaccine-induced infection. Avoid during and for 4 weeks after treatment.
Moderate Interactions
- Moderate CYP2C9 inhibitors (e.g., fluconazole): May increase siponimod exposure. Dose adjustment of siponimod may be needed for patients with certain CYP2C9 genotypes.
- Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil): May increase siponimod exposure. Monitor for adverse effects.
Minor Interactions
- Not specifically categorized as minor, but general caution with drugs affecting liver enzymes or cardiac function.
Monitoring
Baseline Monitoring
CYP2C9 Genotype
Rationale: To determine appropriate starting and maintenance dose, and to identify patients for whom siponimod is contraindicated (*3/*3 genotype).
Timing: Prior to initiation of treatment.
Complete Blood Count (CBC) with differential
Rationale: To establish baseline lymphocyte count and identify pre-existing cytopenias. Siponimod causes dose-dependent peripheral lymphocyte count reduction.
Timing: Within 6 months prior to initiation.
Liver Function Tests (LFTs) - AST, ALT, bilirubin
Rationale: To establish baseline liver function and identify pre-existing liver disease. Siponimod can cause liver injury.
Timing: Within 6 months prior to initiation.
Electrocardiogram (ECG)
Rationale: To assess for pre-existing cardiac abnormalities (e.g., bradycardia, AV block, QT prolongation) that may contraindicate or require caution with siponimod.
Timing: Prior to initiation.
Ophthalmologic evaluation (macular edema)
Rationale: To establish baseline and identify pre-existing macular edema. Siponimod can cause macular edema.
Timing: Prior to initiation.
Varicella Zoster Virus (VZV) antibody status
Rationale: To assess for immunity to VZV. Patients seronegative for VZV should be vaccinated prior to treatment initiation.
Timing: Prior to initiation.
Blood Pressure
Rationale: Siponimod can cause an increase in blood pressure.
Timing: Prior to initiation.
Routine Monitoring
Complete Blood Count (CBC) with differential (lymphocyte count)
Frequency: At 3 months, 6 months, and then annually, or as clinically indicated.
Target: Not applicable for target range, but monitor for severe lymphopenia (<0.2 x 10^9/L).
Action Threshold: Consider dose interruption or discontinuation if lymphocyte count falls below 0.2 x 10^9/L, or if severe opportunistic infection occurs.
Liver Function Tests (LFTs) - AST, ALT, bilirubin
Frequency: At 3 months, 6 months, and then periodically, or as clinically indicated.
Target: Not applicable for target range, but monitor for elevations.
Action Threshold: Consider dose interruption or discontinuation if transaminase levels are >3-5 times ULN, especially if accompanied by symptoms of liver injury.
Blood Pressure
Frequency: Regularly during treatment.
Target: Maintain within normal limits.
Action Threshold: Manage hypertension as appropriate; consider dose adjustment or discontinuation if uncontrolled.
Ophthalmologic evaluation (macular edema)
Frequency: Periodically, especially if visual symptoms occur. Recommended at 3-4 months after initiation for patients with diabetes mellitus or a history of uveitis.
Target: Not applicable.
Action Threshold: Discontinue siponimod if macular edema is confirmed.
Symptom Monitoring
- Signs of infection (fever, chills, sore throat, unusual fatigue)
- Symptoms of bradycardia (dizziness, lightheadedness, syncope, chest pain)
- Symptoms of liver injury (unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, jaundice)
- New or worsening visual disturbances (blurred vision, central vision loss, blind spots)
- New or worsening headache
- Symptoms of posterior reversible encephalopathy syndrome (PRES) (sudden severe headache, altered mental status, visual disturbances, seizures)
- Symptoms of progressive multifocal leukoencephalopathy (PML) (new or worsening neurological symptoms, cognitive or behavioral changes)
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. Based on animal studies and its mechanism of action, siponimod can cause fetal harm. Women of childbearing potential must use effective contraception during treatment and for at least 10 days after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity and embryofetal toxicity.
Second Trimester:
Potential for fetal harm, including effects on organ development.
Third Trimester:
Potential for fetal harm, including effects on organ development and immune system.
Lactation
Siponimod is excreted in animal milk. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment with siponimod and for 10 days after the last dose.
Infant Risk:
Risk of serious adverse effects (e.g., immunosuppression, cardiac effects) in the infant.
Pediatric Use
Safety and effectiveness in pediatric patients (under 18 years of age) have not been established.
Geriatric Use
Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Use with caution in elderly patients due to potential for increased susceptibility to adverse effects, particularly cardiac effects.
Clinical Information
Clinical Pearls
- CYP2C9 genotyping is mandatory before initiating siponimod to determine the appropriate starting and maintenance dose and to identify patients for whom siponimod is contraindicated (CYP2C9 *3/*3 genotype).
- First-dose observation for bradycardia is recommended for patients with certain pre-existing cardiac conditions or those at higher risk for bradycardia.
- Siponimod requires a 5-day dose titration to mitigate the risk of bradycardia and other cardiac effects.
- Patients should be vaccinated against VZV if seronegative prior to initiation of treatment.
- Risk of progressive multifocal leukoencephalopathy (PML) is low but should be considered in patients presenting with new neurological symptoms.
- Rebound disease activity, potentially severe, can occur upon discontinuation of siponimod. Patients should be monitored for worsening MS symptoms after stopping treatment.
Alternative Therapies
- Fingolimod (Gilenya)
- Ozanimod (Zeposia)
- Ponesimod (Ponvory)
- Natalizumab (Tysabri)
- Ocrelizumab (Ocrevus)
- Alemtuzumab (Lemtrada)
- Cladribine (Mavenclad)
- Dimethyl fumarate (Tecfidera)
- Teriflunomide (Aubagio)
- Interferon beta preparations (e.g., Avonex, Betaseron, Rebif, Plegridy)
- Glatiramer acetate (Copaxone, Glatopa)
Cost & Coverage
Average Cost:
Highly variable, typically >$8,000 - $10,000 per 30 tablets (2mg strength)
Insurance Coverage:
Specialty Tier (requires prior authorization, step therapy, and/or quantity limits)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.