Drug reference
Siponimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the central nervous system. The anti-lymphocyte monoclonal antibodies cause lysis of B lymphocytes.
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Multiple sclerosis [secondary progressive, with active disease] (initiated by a specialist) ▶BY MOUTH ▶Adult: Initially 0.25 mg once daily on days 1 and 2, followed by 0.5 mg once daily on day 3, followed by Immune system and malignant disease 0.75 mg once daily on day 4, followed by 1.25 mg once daily on day 5, dose to be taken in the morning for the first 5 days; maintenance 2 mg once daily from day 6 onwards, in patients with a CYP2C9*1*3 or CYP2C9*2*3 genotype a reduced maintenance dose of 1 mg once daily is used from day 6 onwards. For dose adjustments based on lymphocyte count—consult product literature
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Active malignancies. cryptococcal meningitis. decompensated heart failure (requiring inpatient treatment) in the previous 6 months. heart failure in the previous 6 months (New York Heart Association class III or IV). immunodeficiency syndrome. macular oedema. myocardial infarction in the previous 6 months. patients homozygous for CYP2C9*3*3 genotype (poor metabolisers). phototherapy with UV-B radiation or PUVA-photochemotherapy (increased risk of cutaneous neoplasms). progressive multifocal leukoencephalopathy. second-degree Mobitz type II atrioventricular block or third-degree AV block, or sick-sinus syndrome, if the patient does not have a pacemaker. severe active infection . stroke (including transient ischaemic attack) in the previous 6 months. unstable angina pectoris in the previous 6 months
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Administration of vaccinations (may be less effective during siponimod treatment—consult product literature for further information). diabetes mellitus (increased risk of macular oedema). elderly (limited information available). exposure to sunlight (increased risk of cutaneous neoplasms). first- or second-degree Mobitz type I atrioventricular block. heart failure (New York Heart Association class I and II). myocardial infarction. patients receiving QT-prolonging or heart rate- lowering drugs, including beta-blockers and heart rate- lowering calcium-channel blockers (seek advice from cardiologist regarding switching to alternative drugs or appropriate monitoring). recurrent syncope. retinal disease (increased risk of macular oedema). risk of discontinuation effects, including disease rebound. severe sleep apnoea. significant QT prolongation (QTc greater than 500 milliseconds). sinus bradycardia (heart rate below 55 beats per minute). uncontrolled hypertension. uveitis (increased risk of macular oedema) CAUTIONS, FURTHER INFORMATION ▶Bradycardia and cardiac rhythm disturbance Siponimod may cause transient bradycardia, atrioventricular conduction delays and heart block after the first dose. Siponimod is not recommended in patients with a history of symptomatic bradycardia or recurrent syncope, uncontrolled hypertension, severe untreated sleep apnoea, or significant QT prolongation unless the anticipated benefits outweigh the potential risks, and advice from a cardiologist (including monitoring advice) is sought before initiation.
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Manufacturer advises contra-indicated in patients with hypersensitivity to peanut or soya products.
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Manufacturer advises CYP2C9 genotyping before treatment initiation—consult product literature. Manufacturer advises check varicella zoster virus status in patients with unconfirmed or incomplete vaccination history. A full course of vaccination against varicella zoster is required 1 month before initiating treatment in antibody-negative patients. All patients should be screened for hepatitis B before treatment.
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The manufacturer of Mayzent ® has provided a Physician Education Pack.
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→Appendix 1: siponimod
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▶Common or very common Arrhythmias. asthenia. cardiac conduction disorders. diarrhoea. dizziness. headache. hypertension. increased risk of infection. lymphopenia. macular oedema. nausea. neoplasms. pain in extremity. peripheral oedema. seizure. tremor ▶Frequency not known Meningitis cryptococcal. vision disorders ▶Common or very common Alopecia. anaemia. anaphylactic reaction. arthralgia. asthenia. conjunctivitis. constipation. cough. depression. diarrhoea. fever. headache. hypersensitivity (discontinue permanently). increased risk of infection. infusion related reaction. leucopenia. myocardial infarction. neutropenia. night sweats. pain. thrombocytopenia. vomiting ▶Uncommon Haemolytic anaemia. progressive multifocal leukoencephalopathy (PML) ▶Rare or very rare Hepatitis B reactivation SIDE-EFFECTS, FURTHER INFORMATION Infusion-related side-effects In rare cases infusion reactions may be fatal. Infusion-related side-effects occur predominantly during the first infusion. Patients should receive premedication before administration of anti-lymphocyte monoclonal antibodies to reduce these effects—consult product literature for details of individual regimens. The infusion may have to be stopped temporarily and the infusion- related effects treated—consult product literature for appropriate management. Cytokine release syndrome Fatalities following severe cytokine release syndrome (characterised by severe dyspnoea) and associated with features of tumour lysis syndrome have occurred after infusions of anti- lymphocyte monoclonal antibodies. Patients with a high tumour burden as well as those with pulmonary insufficiency or infiltration are at increased risk and should be monitored very closely (and a slower rate of infusion considered).
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Manufacturer advises exclude pregnancy before treatment; females of childbearing potential should use effective contraception during treatment and for 10 days after last dose.
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Manufacturer advises avoid—toxicity in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises caution when initiating treatment in mild to moderate impairment; avoid in severe impairment.
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▶Manufacturer advises regular monitoring of heart rate, particularly during treatment initiation, and of blood pressure. ▶Manufacturer advises patients with certain pre-existing cardiac conditions should be monitored for bradycardia for 6 hours after the first dose. An ECG should be obtained before dosing and after 6 hours—consult product literature for further information. ▶Manufacturer advises monitor full blood count before initiation and periodically during treatment (reduce dosage or interrupt treatment if lymphocyte count reduced)—consult product literature. ▶Manufacturer advises monitor hepatic transaminases and bilirubin before initiation of treatment and then as clinically indicated (interrupt treatment if significant liver injury occurs). ▶Manufacturer advises eye examination recommended 3–4 months after initiation of treatment (and before initiation of treatment in patients with diabetes or history of uveitis or retinal disease). Patients should also be monitored for cytopenias—consult product literature for specific recommendations. eiiii F above
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All anti-lymphocyte monoclonal antibodies should be given under the supervision of an experienced specialist, in an environment where full resuscitation facilities are immediately available.
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There can be variation in the licensing of different medicines containing the same drug. Tablet EXCIPIENTS: May contain Lecithin A ▶Mayzent (Novartis Pharmaceuticals UK Ltd) Siponimod (as Siponimod fumaric acid) 250 microgram Mayzent 0.25mg tablets | 12 tablet P £293.52 (Hospital only) | 120 tablet P £1,761.12 (Hospital only) Siponimod (as Siponimod fumaric acid) 2 mg Mayzent 2mg tablets | 28 tablet P £1,643.72 (Hospital only) IMMUNOSUPPRESSANTS › MONOCLONAL ANTIBODIES › ANTI-LYMPHOCYTE Anti-lymphocyte monoclonal f antibodies
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Manufacturer advises patients to avoid exposure to sunlight without protection. Manufacturer advises patients should promptly report symptoms of infection. Missed doses Manufacturer advises if a dose is missed during treatment initiation (days 1–6), the initial titration regimen should be restarted. If a maintenance dose is missed (after day 6), the missed dose should not be taken, and the next dose should be taken at the normal time. If 4 or more consecutive doses are missed, the initial titration regimen should be used to restart treatment. Driving and skilled tasks Manufacturer advises patients should be counselled on the effects on driving and performance of skilled tasks—increased risk of dizziness during treatment initiation.
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Initially 0.25 mg once daily on days 1 and 2,
First-line fragment. Read the complete Indications and Dose section above.
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