Mayzent (Siponimod)

What Is Mayzent and What Is It Used For?

Mayzent (siponimod) is a selective sphingosine 1-phosphate (S1P) receptor modulator approved for the treatment of adults with secondary progressive multiple sclerosis (SPMS) who have active disease, as evidenced by relapses or inflammatory activity on MRI imaging.

Mayzent contains the active substance siponimod, which belongs to a class of medicines known as S1P receptor modulators. These drugs work by selectively binding to sphingosine 1-phosphate receptor subtypes 1 and 5 (S1P1 and S1P5) on the surface of lymphocytes, a type of white blood cell that plays a central role in the immune response. By engaging these receptors, siponimod prevents lymphocytes from leaving the lymph nodes where they are produced, effectively reducing the number of these cells circulating in the bloodstream and, crucially, preventing them from reaching the central nervous system (CNS).

Multiple sclerosis (MS) is a chronic autoimmune disease in which the immune system mistakenly attacks the protective myelin sheath that covers nerve fibres in the brain and spinal cord. In secondary progressive MS (SPMS), the disease shifts from a predominantly relapsing pattern to a phase of gradual, continuous worsening of neurological function. SPMS with active disease is characterised by ongoing inflammatory activity, meaning that relapses (acute worsening episodes) still occur or MRI scans show new areas of inflammation in the brain or spinal cord, even as overall disability accumulates progressively.

The selective modulation of S1P1 and S1P5 receptors gives siponimod a dual mechanism of action. Through S1P1, it reduces the migration of pro-inflammatory lymphocytes into the CNS, decreasing the immune-mediated damage to myelin and nerve fibres. Through S1P5, which is expressed on oligodendrocytes (the cells that produce myelin) and certain brain cells, siponimod may exert direct neuroprotective effects within the CNS, potentially supporting remyelination and neuronal survival. This dual action makes Mayzent particularly relevant for SPMS, where both inflammation and neurodegeneration contribute to disease progression.

The efficacy of Mayzent was demonstrated in the pivotal EXPAND clinical trial, a large, randomised, double-blind, placebo-controlled phase 3 study involving 1,651 patients with SPMS. The trial showed that siponimod significantly reduced the risk of 3-month confirmed disability progression by 21% compared to placebo. In patients with active disease (those with relapses in the two years before the study or MRI-evident inflammatory lesions at baseline), the benefit was even more pronounced, with a 33% reduction in the risk of disability progression. The trial also demonstrated significant reductions in brain volume loss and the number of new or enlarging T2 lesions on MRI.

What Should You Know Before Taking Mayzent?

Before starting Mayzent, you must undergo CYP2C9 genotyping (a blood or saliva test), cardiac assessment, blood count and liver function tests, varicella (chickenpox) antibody testing, and an eye examination. Several serious conditions and medications are contraindicated with Mayzent.

Contraindications

You must not take Mayzent if any of the following apply to you:

• Allergy to siponimod, peanuts, or soya – Mayzent tablets contain soya lecithin as an excipient. If you are allergic to peanuts or soya, you must not use this medication
• Immunodeficiency syndrome – conditions that severely weaken the immune system make it unsafe to further suppress immune function
• History of progressive multifocal leukoencephalopathy (PML) or cryptococcal meningitis – these rare but serious brain infections can reactivate with immune suppression
• Active cancer – immunosuppression may interfere with the body’s ability to fight malignant disease
• Severe liver problems – siponimod is extensively metabolised by the liver, and severe hepatic impairment can lead to dangerously elevated drug levels
• Recent cardiovascular events – heart attack, unstable angina, stroke, or certain types of heart failure within the past 6 months
• Certain cardiac arrhythmias without a pacemaker – including second-degree Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, or sino-atrial block
• CYP2C9*3/*3 genotype – blood tests showing that your body cannot metabolise siponimod adequately (homozygous poor metabolisers) mean you must not take this medicine
• Pregnancy or women of childbearing potential not using effective contraception – siponimod can cause serious harm to the developing foetus

Warnings and Precautions

Talk to your doctor before taking Mayzent if you have or have had any of the following conditions. Your doctor will need to assess whether the benefits of treatment outweigh the potential risks for your individual situation:

• Active infection or weakened immune system – Mayzent lowers the number of circulating lymphocytes, which may increase your susceptibility to infections. Some infections can become serious or life-threatening
• No history of chickenpox (varicella) and not vaccinated – you may be at greater risk of complications if you contract varicella during treatment. Your doctor may recommend vaccination before starting Mayzent, with a waiting period of at least 4 weeks after vaccination before beginning treatment
• Eye problems, especially macular oedema or uveitis – Mayzent can cause swelling in the macula (the central area of the retina), which is more likely in patients with a history of these conditions or diabetes. An eye examination is recommended before starting treatment and at 3 to 4 months after initiation
• Diabetes – patients with diabetes have an increased risk of macular oedema and should have regular eye examinations during treatment
• Heart conditions – including any history of serious heart disease, arrhythmias (irregular heartbeat), heart block, slow heart rate, fainting episodes, or sleep apnoea. Mayzent can cause temporary slowing of the heart rate and conduction delays, particularly during the first days of treatment
• Uncontrolled high blood pressure – blood pressure must be monitored regularly during treatment, as Mayzent can increase blood pressure
• Liver problems – liver function tests should be performed before and periodically during treatment, as Mayzent can cause liver enzyme elevations

Pregnancy and Breastfeeding

Mayzent must not be used during pregnancy. Animal studies have shown that siponimod can cause harm to the developing foetus. If you are a woman of childbearing potential, your doctor will explain the risks before starting treatment and require a pregnancy test to confirm you are not pregnant. You must use effective contraception during the entire course of treatment and for at least 10 days after stopping Mayzent, as the drug remains active in the body for approximately this period.

If you become pregnant while taking Mayzent, you must stop the medication immediately and inform your doctor. Specialised monitoring of your pregnancy will be arranged. You should not breastfeed while taking Mayzent, as siponimod can pass into breast milk, and there is a risk of serious side effects in the nursing infant.

Elderly Patients

There is limited clinical experience with Mayzent in patients aged 65 years and older. The EXPAND trial included patients up to age 61, and therefore the safety and efficacy in elderly patients have not been well established. If you are 65 or older, discuss the potential benefits and risks with your doctor before starting treatment.

Children and Adolescents

Mayzent should not be given to children or adolescents under 18 years of age. It has not been studied in this age group, and its safety and efficacy in paediatric patients have not been established.

Driving and Operating Machinery

Your doctor will advise you whether your condition allows you to drive or operate machinery safely. Mayzent itself is not expected to affect your ability to drive or use machinery once you are on a stable maintenance dose. However, during the first day of treatment, you may occasionally feel dizzy or tired due to the cardiac effects of the initial dose. You should not drive or operate machinery on the first treatment day.

Important Information About Excipients

Mayzent tablets contain lactose monohydrate and soya lecithin. If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine. If you are allergic to peanuts or soya, do not use Mayzent.

How Does Mayzent Interact with Other Drugs?

Mayzent can interact with medications that affect heart rate, drugs that suppress the immune system, certain enzyme inhibitors and inducers, live vaccines, and UV phototherapy. Always inform your doctor about all medications, supplements, and treatments you are currently using.

Siponimod is primarily metabolised by the liver enzyme CYP2C9, with a minor contribution from CYP3A4. Drugs that inhibit CYP2C9 can significantly increase siponimod blood levels, while CYP2C9 and CYP3A4 inducers can reduce its effectiveness. Additionally, because Mayzent can slow the heart rate and suppress the immune system, combining it with other drugs that have similar effects requires careful medical evaluation.

Major Interactions

Moderate Interactions

What Is the Correct Dosage of Mayzent?

Mayzent treatment begins with a 5-day dose titration (gradual increase) using 0.25 mg tablets, followed by a maintenance dose of 2 mg once daily for most patients. Some patients with specific CYP2C9 genotypes may require a reduced maintenance dose of 1 mg daily. Treatment must be supervised by a physician experienced in MS management.

Starting Treatment – Dose Titration

To reduce the risk of cardiac side effects (particularly slowing of the heart rate), Mayzent treatment begins with a gradual dose increase over 5 days using the titration pack. This pack contains 0.25 mg tablets in specific quantities for each day. During these first 6 days, it is best to take the tablets in the morning, with or without food.

On day 6, you switch to your regular maintenance dose. If your doctor determines there is a risk of cardiac effects during the titration, you may be monitored more closely in a clinical setting during the first days of treatment.

Adults – Maintenance Dose

Children and Adolescents

Mayzent is not approved for use in patients under 18 years of age. No dosage recommendations are available for this population.

Elderly Patients

No dose adjustment is required based on age alone. However, limited clinical experience exists in patients aged 65 and older, so treatment should be initiated with caution and under close medical supervision.

Missed Dose

The approach to a missed dose depends on when it occurs:

• During the first 6 days (titration): If you miss a dose on any day during the titration, contact your doctor before taking the next dose. You will need a new titration pack and must restart from day 1
• During maintenance (day 7 onwards): Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and continue as normal. Do not take a double dose
• If you have missed 4 or more consecutive days: Contact your doctor. You will need a new titration pack and must restart the titration from day 1

Overdose

If you have taken too many Mayzent tablets, or if you accidentally take your first tablet from the maintenance pack instead of the titration pack, contact your doctor immediately. Your doctor may wish to keep you under observation for monitoring of heart rate and rhythm. There is no specific antidote for siponimod overdose; treatment is supportive and based on symptoms.

What Are the Side Effects of Mayzent?

Like all medicines, Mayzent can cause side effects, though not everyone experiences them. The most common side effects include headache, high blood pressure, and elevated liver enzymes. Serious but less common side effects include herpes zoster (shingles), skin cancer, macular oedema, cardiac conduction disorders, and increased risk of infections.

The side effects of Mayzent reflect its mechanism of action on the immune system, cardiovascular system, and liver. Understanding the frequency and nature of these effects helps you and your doctor monitor for potential problems. Report any new or worsening symptoms to your healthcare provider promptly.

Additionally, cases of cryptococcal infection (a type of fungal infection) and viral meningitis or encephalitis (caused by herpes or varicella zoster virus) have been reported at unknown frequency. Symptoms include headache with neck stiffness, light sensitivity, nausea, or confusion. Seek immediate medical attention if you experience any of these symptoms.

Cardiac Effects During Treatment Initiation

During the first days of treatment, Mayzent can cause temporary slowing of the heart rate (bradycardia) and irregular heart rhythm. You may not notice anything, or you may feel dizzy or tired. These effects are generally mild and resolve as treatment continues. The dose titration schedule is specifically designed to minimise these cardiac effects. If you are at higher risk of cardiac problems, your doctor may decide to monitor you in a clinical setting, refer you to a cardiologist, or determine that Mayzent is not suitable for you.

Skin Cancer and Sun Protection

Skin cancer, including basal cell carcinoma, squamous cell carcinoma, and melanoma, has been reported in patients taking Mayzent. Because Mayzent weakens the immune system, your risk of developing skin cancer may be increased. You should:

• Have a skin examination before starting Mayzent and regularly during treatment
• Limit sun exposure and avoid UV tanning beds
• Wear protective clothing and use broad-spectrum sunscreen with a high SPF regularly
• Report any new or changing skin lesions, moles, or non-healing sores to your doctor promptly

Increased Risk of Infections

Mayzent reduces the number of white blood cells (lymphocytes) in your blood. White blood cells fight infections, so you may be more susceptible to infections during treatment and for 3 to 4 weeks after stopping Mayzent. Some infections can become serious or even life-threatening. Tell your doctor immediately if you develop signs of infection such as fever, chills, persistent sore throat, or unusual fatigue.

How Should You Store Mayzent?

Store Mayzent at or below 25°C (77°F) in the original packaging. Keep out of sight and reach of children. Do not use after the expiry date or if the packaging appears damaged or tampered with.

Keep Mayzent in a safe place where children cannot see or reach it. Store the tablets at room temperature, not exceeding 25°C (77°F). Do not use this medicine after the expiry date which is printed on the carton and blister after “EXP”. The expiry date refers to the last day of the stated month.

Do not use the medicine if you notice that the packaging is damaged or shows signs of tampering. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines that you no longer use. These measures help to protect the environment.

What Does Mayzent Contain?

Mayzent tablets contain siponimod (as siponimod fumarate) as the active substance. They are available in three strengths: 0.25 mg (light red), 1 mg (violet-white), and 2 mg (light yellow). The tablets contain lactose and soya lecithin as excipients.

Active Ingredient

Each tablet contains siponimod in the form of siponimod fumarate. The available strengths are:

• 0.25 mg tablet – light red, round, film-coated, imprinted with the company logo on one side and “T” on the other
• 1 mg tablet – violet-white, round, film-coated, imprinted with the company logo on one side and “L” on the other
• 2 mg tablet – light yellow, round, film-coated, imprinted with the company logo on one side and “II” on the other

Inactive Ingredients

The following excipients are found in Mayzent tablets:

• Tablet core: Lactose monohydrate, microcrystalline cellulose, crospovidone, glycerol dibehenate, colloidal anhydrous silica
• Film coating: Polyvinyl alcohol, titanium dioxide (E171), iron oxide red (E172), iron oxide black (E172) (in 0.25 mg and 1 mg tablets), iron oxide yellow (E172) (in 2 mg tablets), talc, soya lecithin, xanthan gum

How Does Mayzent Work in the Body?

Mayzent works by selectively modulating S1P1 and S1P5 receptors, which prevents lymphocytes from exiting lymph nodes and reaching the central nervous system. This reduces the immune-mediated inflammatory damage to nerve tissue that drives disability progression in SPMS.

Sphingosine 1-phosphate (S1P) is a naturally occurring signalling lipid in the body that plays a crucial role in regulating lymphocyte trafficking. When lymphocytes (a type of immune cell) are in the lymph nodes, they need a signal through the S1P1 receptor to exit into the bloodstream. Siponimod acts as a functional antagonist at this receptor: after initially activating S1P1, it causes the receptor to be internalised and degraded, making the lymphocyte “blind” to the S1P gradient that normally guides it out of the lymph node.

This selective S1P receptor modulation results in a redistribution of lymphocytes rather than their destruction. The cells remain viable within the lymph nodes but are unable to enter the circulation and migrate to the CNS. This is particularly important because it is these CNS-infiltrating lymphocytes that drive much of the inflammatory damage in multiple sclerosis, attacking the myelin sheaths that insulate nerve fibres and causing the neurological symptoms characteristic of the disease.

Siponimod is selective for S1P1 and S1P5, in contrast to first-generation S1P modulators such as fingolimod, which also bind to S1P3 and S1P4. This selectivity is believed to contribute to a more favourable safety profile. The S1P5 receptor is expressed on oligodendrocytes (the cells responsible for producing myelin in the CNS) and on certain neurons. Preclinical studies suggest that modulation of S1P5 may support oligodendrocyte survival, promote remyelination, and have direct neuroprotective effects – properties that are particularly relevant in progressive MS, where ongoing neurodegeneration is a major contributor to disability.

Siponimod is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 4 hours after dosing. Its oral bioavailability is approximately 84%, and it can be taken with or without food. The drug is extensively metabolised in the liver, primarily by the CYP2C9 enzyme and to a lesser extent by CYP3A4. The elimination half-life is approximately 30 hours, supporting once-daily dosing. Because CYP2C9 is the major metabolic pathway, genetic variations in the CYP2C9 gene (polymorphisms) significantly affect how quickly siponimod is cleared from the body, necessitating genotyping before treatment to determine the appropriate dose.

Frequently Asked Questions