Siponimod is available by the brand name of Mayzent (Novartis Pharmaceuticals) is a once-daily oral medicine that is used to treat patients with multiple sclerosis. It exerts its action by acting as a selective sphingosine-1-phosphate receptor modulator.

Siponimod (Mayzent) Uses:

• Multiple sclerosis:

  • It is indicated for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing/remitting disease, and active secondary progressive disease in adults.

Siponimod (Mayzent) Dose in adults:

Note:

CYP2C9 genotype and dose should be determined before giving the drug. Six-hour monitoring is necessary with the first dose and certain preexisting cardiac conditions such as myocardial infarction or cardiac failure, sinus bradycardia, first/second degree AV block.

Siponimod (Mayzent) dose in the treatment of multiple sclerosis:

• CYP2C9 Genotype *1/*1, *1/*2, or *2/*2:

  • Initial:

    • 0.25 mg per ora once daily on Days 1 and 2, then 0.5 mg once daily on Day 3, then 0.75 mg once daily on Day 4, then 1.25 mg once daily on Day 5.

  • Maintenance:

    • 2 mg once daily, beginning on Day 6.

• CYP2C9 Genotype *1/*3 or *2/*3:

  • Initial:

    • 0.25 mg per oral once daily on Days 1 and 2, then 0.5 mg once daily on Day 3, then 0.75 mg once daily on Day 4.

  • Maintenance:

    • 1 mg once daily, beginning on Day 5.

• Missed dose:

  • Restarting with Day 1 of the titration regimen is necessary in case of a dose missed for more than 24 hours during the initial phase.
  • Interruption for 4 or more consecutive daily doses after completion of initial titration requires rechallenging treatment with Day 1 of the titration regimen including first dose monitoring when appropriate.

Siponimod (Mayzent) use in Children:

The safety and efficacy of its use in children is not known.

Siponimod (Mayzent) Pregnancy Risk Factor: D

• Research on animal reproduction has shown that fetal harm can be demonstrated, so it is not recommended for pregnant women.
• It is essential to use effective contraception during treatment and for at least 10 days following the last siponimod dosage.

Use Siponimod while breastfeeding

• It is unknown if siponimod is excreted in breast milk.
• According to the manufacturer the decision to breastfeed during therapy depends on the risks and benefits to infants as well as the mother's health.

Siponimod (Mayzent) Dose adjustment in renal disease:

No dosage adjustments necessary.

Siponimod (Mayzent) Dose adjustment in liver disease:

No dosage adjustments necessary.

Common Side Effects of Siponimod (Mayzent):

• Cardiovascular:

  • Hypertension

• Central Nervous System:

  • Headache
  • Falling

• Hepatic:

  • Increased Serum Transaminases

Uncommon Side Effects of Siponimod (Mayzent):

• Cardiovascular:

  • Peripheral Edema
  • Bradycardia
  • First Degree Atrioventricular Block
  • Second Degree Atrioventricular Block

• Central Nervous System:

  • Dizziness
  • Seizure

• Gastrointestinal:

  • Nausea
  • Diarrhea

• Hematologic & Oncologic:

  • Lymphocytopenia

• Hepatic:

  • Increased Serum Bilirubin
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

• Infection:

  • Herpes Virus Infection
  • Herpes Zoster Infection

• Neuromuscular & Skeletal:

  • Limb Pain
  • Asthenia
  • Tremor

• Ophthalmic:

  • Macular Edema

• Respiratory:

  • Reduced Forced Expiratory Volume

Side effects of Siponimod with frequency not defined:

• Dermatologic:

  • Facial Swelling

• Infection:

  • Infection

Contraindication to Siponimod (Mayzent):

These include:

• CYP2C9*3/*3 genotype
• Infarction of the myocardium in the last 6 months
• Instabile angina
• stroke/Transient ischemic attack
• Heart failure of class III or IV
• Second/third degree AV Block
• Sinusitis is a serious condition.

Warnings and precautions

• Cardiovascular disease

  • First or second degree AV block can develop with additional bradycardia. Treatment with siponimod is possible.
  • The heart rate drops in the first hour after the dose, with the maximum drop occurring in the third to fourth hours. It then starts to increase after day 6, and returns to baseline after 10 consecutive days.
  • QT prolongation may occur. Therefore, ECG monitoring is necessary.

• Hepatic effects

  • Before therapy is initiated, baseline liver enzymes and Bilirubin should all be checked.
  • Monitoring should also be done for hepatic dysfunction symptoms such as nausea/vomiting and abdominal pain, fatigue and anorexia.
  • With liver injury, treatment should be stopped immediately. Within one month, transaminases will return to normal.

• Hypertension

  • One month after therapy begins, you may notice an increase in blood pressure.

• Infections

  • A decreased number of peripheral lymphocytes increases the likelihood of developing life-threatening infections.
  • Very rare cases of cryptococcal meningitis and herpes viral infections can also occur, including reactivation or reactivation varicella-zoster infection.

• Macular edema

  • Patients may have blurred vision or decreased visual acuity.
  • If vision has changed, ophthalmologic examinations should be performed at baseline.

• Neurotoxicity:

  • The symptoms of posterior reversible syndrome include behavioral changes, cognitive impairments, and increased intracranial pressure. This can lead to ischemic strokes or cerebral hemorhage.

• Progressive multifocal Leukoencephalopathy

  • Immune compromise and immunosuppressant monopharmacy are risk factors for progressive multifocal encephalopathy.
  • Progressive weakness or clumsiness on one side of your body, vision problems, mental changes, and clumsiness on the limbs are some of the symptoms.
  • It is important to immediately stop using the drug and have an MRI done.

• Respiratory effects

  • FEV (forced expiratory volume) is decreased based on doses within the first three months of therapy.
  • Therefore, a spirometric assessment of respiratory function should always be done during therapy.

Siponimod: Drug Interaction

Monitoring parameters:

These include:

• Complete blood count, including lymphocyte counts
• Tests of liver function such as transaminase and baseline bilirubin levels prior to therapy or in patients with symptoms of hepatic impairment.
• ECG
• BP
• Ophthalmologic examination of the fundus, including examination of the macula
• If clinically indicated, respiratory function (Forced exhalatory volume)
• Before starting treatment for patients who have never had chickenpox, it is important to test for antibodies against varicella-zoster virus.
• Signs and symptoms of infection
• Signs and symptoms of progressive multifocal encephalopathy/ posterior-reversible syndrome

How to administer Siponimod (Mayzent)?

It should be given orally with or without food.

Mechanism of action of Siponimod (Mayzent):

• Siponimod is a modulator of the sphingosine-1phosphate (S1P), receptor. It binds to the sphingosine-1phosphate receptors 1 & 5.
• Siponimod blocks lymphocytes' ability to arise from lymph nodes.
• It reduces the availability of lymphocytes to the central nervous systems, which in turn decreases central inflammation.

Absorption: Extensive.

Protein binding: >99.9%.

Metabolism: Extensively metabolized, via CYP2C9 (79.3%) and CYP3A4 (18.5%) to inactive metabolites, M3 and M17.

Bioavailability: 84%.

Half-life elimination: 30 hours.

Time to peak: 4 hours (range 3 to 8 hours).

Excretion: Biliary/fecal (as inactive metabolites).

Siponimod Brand Names (International):

• Mayzent
• Mayzent Starter Pack

Siponimod Brand Names in Pakistan:

No Brands Available in Pakistan.