Drugs List

Therapeutic Indications

Uses

Treatment of secondary progressive multiple sclerosis

Treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.

Contraindications

Children under 18 years
History of cryptococcal meningitis
Bradycardia
Breastfeeding
CYP2C9 poor metaboliser genotype
Decompensated cardiac failure
Galactosaemia
History of progressive multifocal leukoencephalopathy (PML)
Immunodeficiency syndromes
Malignant neoplasm
New York Heart Association class III failure
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
Pregnancy
Progressive multifocal leukoencephalopathy (PML)
Recent myocardial infarction
Recurrent syncope
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Severe sleep apnoea
Transient ischaemic attack
Uncontrolled hypertension
Unstable angina

Precautions and Warnings

Females of childbearing potential
Patients over 65 years
Diabetes mellitus
Glucose-galactose malabsorption syndrome
History of atrioventricular block
History of cardiac failure
History of hepatic impairment
History of myocardial infarction
History of retinal disorder
Lactose intolerance
QTc interval greater than or equal to 500 msec
Severe obstructive aortic valve disease
Sinus bradycardia
Uveitis

Monitor ECG for 6 hrs after first dose in patients with cardiac conditions
Advise patient dizziness may affect ability to drive or operate machinery
Determine CYP2C9 metaboliser status before initiation of treatment
Perform skin examination prior to and every 6 to 12 months during treatment
Refer to cardiologist if QT prolonging drugs used concomitantly
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Contains lactose
Contains soya or soya derivative
Planned vaccination: Stop treatment 1 week before until 4 weeks after
Blood counts should be performed before and periodically during treatment
Exclude pregnancy prior to initiation of treatment
Monitor serum transaminases before treatment
Extend monitoring if significant cardiac effects following first dose
Monitor bilirubin levels before treatment
Monitor blood pressure
Monitor levels of hepatic enzymes and bilirubin
Perform ophthalmic examination 3-4 months after treatment initiation
Advise patient to immediately report new skin lesions
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report new visual problems and symptoms
Advise patient to report signs of basal-cell carcinoma
Advise patient to report symptoms of infection immediately
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
May interfere with certain laboratory measurements
Follow washout procedure when switching between disease modifying therapies
Discontinue if macular oedema occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if severe hepatic changes occur
Interrupt treatment if severe infection develops
Suspend if drug induced liver injury is suspected
Female: Contraception required during and for 10 days after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment

Residual pharmacodynamic effects, such as lowering of peripheral lymphocyte count, can persist up to three to four weeks after discontinuation. Use of immunosuppressants between these periods may lead to an additive effect on the immune system.

A case of cryptococcal meningitis (CM) has been reported for siponimod. Patients with signs and symptoms consistent with CM should undergo prompt evaluation. If CM is suspected, siponimod should be suspended until CM has been excluded.

Monitor symptoms or MRI imaging findings that may be suggestive of progressive multifocal leukoencephalopathy (PML). If PML is suspected, siponimod should be suspended until PML has been excluded.

Cases of posterior reversible encephalopathy syndrome (PRES) have been reported for another sphingosine 1-phosphate (S1P) receptor module. Should patients develop signs and symptoms associated with PRES, a physical/neurological examination and MRI should be considered.

When siponimod is added to beta-blocker therapy, the resting heart rate should be above 50bpm. If below 50bpm, beta-blocker should be suspended until heart rate is above 50bpm and treatment with siponimod can be initiated. The beta-blocker can be reinitiated once siponimod has been titrated up to maintenance dose.

Pregnancy and Lactation

Pregnancy

Siponimod is contraindicated during pregnancy.

The manufacturer recommends that siponimod should be discontinued at least 10 days before a pregnancy is planned. Animal studies have shown foetotoxic and teratogenic effects. Patient should be informed of the risks to the foetus associated with siponimod treatment and perform ultrasonography examinations if a pregnancy occurs.

Lactation

Siponimod is contraindicated during breastfeeding.

The manufacturer states that siponimod should not be used during breastfeeding as it is unknown whether siponimod or its metabolites are excreted in human milk. Animal studies have shown siponimod and its metabolites are excreted in milk.

Side Effects

Abnormal liver function tests
Asthenia
Atrioventricular block
Basal cell carcinoma
Blurred vision
Bradycardia
Diarrhoea
Dizziness
Extremity pain
Headache
Herpes zoster
Hypertension
Lymphocytopenia
Macular oedema
Melanocytic naevus
Nausea
Oedema
Pulmonary function test abnormal
Seizures
Tremor

Presentation

Oral formulations of siponimod.

Drugs List

Therapeutic Indications

Uses

Treatment of secondary progressive multiple sclerosis

Treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.

Dosage

Adults

Additional Dosage Information

Contraindications

Children under 18 years
History of cryptococcal meningitis
Bradycardia
Breastfeeding
CYP2C9 poor metaboliser genotype
Decompensated cardiac failure
Galactosaemia
History of progressive multifocal leukoencephalopathy (PML)
Immunodeficiency syndromes
Malignant neoplasm
New York Heart Association class III failure
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
Pregnancy
Progressive multifocal leukoencephalopathy (PML)
Recent myocardial infarction
Recurrent syncope
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Severe sleep apnoea
Transient ischaemic attack
Uncontrolled hypertension
Unstable angina

Precautions and Warnings

Females of childbearing potential
Patients over 65 years
Diabetes mellitus
Glucose-galactose malabsorption syndrome
History of atrioventricular block
History of cardiac failure
History of hepatic impairment
History of myocardial infarction
History of retinal disorder
Lactose intolerance
QTc interval greater than or equal to 500 msec
Severe obstructive aortic valve disease
Sinus bradycardia
Uveitis

Monitor ECG for 6 hrs after first dose in patients with cardiac conditions
Advise patient dizziness may affect ability to drive or operate machinery
Determine CYP2C9 metaboliser status before initiation of treatment
Perform skin examination prior to and every 6 to 12 months during treatment
Refer to cardiologist if QT prolonging drugs used concomitantly
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Contains lactose
Contains soya or soya derivative
Planned vaccination: Stop treatment 1 week before until 4 weeks after
Blood counts should be performed before and periodically during treatment
Exclude pregnancy prior to initiation of treatment
Monitor serum transaminases before treatment
Extend monitoring if significant cardiac effects following first dose
Monitor bilirubin levels before treatment
Monitor blood pressure
Monitor levels of hepatic enzymes and bilirubin
Perform ophthalmic examination 3-4 months after treatment initiation
Advise patient to immediately report new skin lesions
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report new visual problems and symptoms
Advise patient to report signs of basal-cell carcinoma
Advise patient to report symptoms of infection immediately
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
May interfere with certain laboratory measurements
Follow washout procedure when switching between disease modifying therapies
Discontinue if macular oedema occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if severe hepatic changes occur
Interrupt treatment if severe infection develops
Suspend if drug induced liver injury is suspected
Female: Contraception required during and for 10 days after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment

Residual pharmacodynamic effects, such as lowering of peripheral lymphocyte count, can persist up to three to four weeks after discontinuation. Use of immunosuppressants between these periods may lead to an additive effect on the immune system.

A case of cryptococcal meningitis (CM) has been reported for siponimod. Patients with signs and symptoms consistent with CM should undergo prompt evaluation. If CM is suspected, siponimod should be suspended until CM has been excluded.

Monitor symptoms or MRI imaging findings that may be suggestive of progressive multifocal leukoencephalopathy (PML). If PML is suspected, siponimod should be suspended until PML has been excluded.

Cases of posterior reversible encephalopathy syndrome (PRES) have been reported for another sphingosine 1-phosphate (S1P) receptor module. Should patients develop signs and symptoms associated with PRES, a physical/neurological examination and MRI should be considered.

When siponimod is added to beta-blocker therapy, the resting heart rate should be above 50bpm. If below 50bpm, beta-blocker should be suspended until heart rate is above 50bpm and treatment with siponimod can be initiated. The beta-blocker can be reinitiated once siponimod has been titrated up to maintenance dose.

Pregnancy and Lactation

Pregnancy

Siponimod is contraindicated during pregnancy.

The manufacturer recommends that siponimod should be discontinued at least 10 days before a pregnancy is planned. Animal studies have shown foetotoxic and teratogenic effects. Patient should be informed of the risks to the foetus associated with siponimod treatment and perform ultrasonography examinations if a pregnancy occurs.

Lactation

Siponimod is contraindicated during breastfeeding.

The manufacturer states that siponimod should not be used during breastfeeding as it is unknown whether siponimod or its metabolites are excreted in human milk. Animal studies have shown siponimod and its metabolites are excreted in milk.

Counselling

Advise patient to report any signs of blurred vision or decreased visual acuity at any time.
Advise patient to report symptoms of infection during therapy.
Advise patient to report signs of hepatic dysfunction e.g. malaise, jaundice, dark urine or abdominal pain.
Advise patient to report signs of basal-cell carcinoma.
Women of childbearing potential must use effective contraception during and up to 10 days after treatment. Provide pregnancy specific Patient Guide.
Advise patients not to drive or operate machinery if affected by side effects such as dizziness or drowsiness.
Advise patients to immediately report new skin lesions.

Side Effects

Abnormal liver function tests
Asthenia
Atrioventricular block
Basal cell carcinoma
Blurred vision
Bradycardia
Diarrhoea
Dizziness
Extremity pain
Headache
Herpes zoster
Hypertension
Lymphocytopenia
Macular oedema
Melanocytic naevus
Nausea
Oedema
Pulmonary function test abnormal
Seizures
Tremor

Effects on Laboratory Tests

Siponimod reduces blood lymphocyte counts via re-distribution in secondary lymphoid organs therefore peripheral blood lymphocyte counts cannot be utilised to evaluate the lymphocyte subset status of a patient treated with siponimod. Laboratory tests involving the use of circular mononuclear cells require larger blood volumes due to reduction in the number of circulating lymphocytes.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2020

Reference Sources

Summary of product characteristics: Mayzent 0.25mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised January 2021.
Summary of product characteristics: Mayzent 2mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised January 2021.