2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 20 mg film-coated tabletsPRESCRIBING INFORMATION
ACTIVE INGREDIENT: Ponesimod
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
INDICATION: Indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features.
DOSAGE & ADMINISTRATION: Treatment should be initiated under the supervision of a physician experienced in the management of multiple sclerosis. Before treatment: Obtain an electrocardiogram (ECG) prior to treatment initiation to determine whether first-dose monitoring is needed. In patients with certain pre-existing conditions, first dose monitoring is recommended (refer to SmPC for full details). Review results from a recent complete blood count (CBC) with differential (including lymphocyte count) obtained within 6 months prior to treatment initiation or after discontinuation of prior therapy. Patients without a healthcare professional confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating treatment. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment. Recent (i.e., within last 6 months) transaminase and bilirubin levels should be reviewed before initiation of ponesimod therapy. Before starting treatment in women of childbearing potential a negative pregnancy test result must be available. Adults: Treatment must be started with the 14‑day treatment initiation pack. Treatment starts with one 2 mg tablet orally once daily on day 1 and dose‑escalation progresses following titration regime:
|Titration day||Daily dose|
Day 1 and 2
|Day 3 and 4||
|Day 5 and 6||4 mg|
|Day 7||5 mg|
|Day 8||6 mg|
|Day 9||7 mg|
|Day 10||8 mg|
|Day 11||9 mg|
|Day 12, 13 and 14||10 mg|
After dose titration is complete, the recommended maintenance dose of Ponvory is one 20 mg tablet taken orally once daily.
Children and adolescents aged less than 18 years: No safety or efficacy data available. Elderly: No safety or efficacy data available. Ponesimod should be prescribed with caution in patients aged 65 years and over. Renal impairment: No dose adjustment is needed in patients with mild to severe renal impairment. Hepatic impairment: No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A).
CONTRAINDICATIONS: Hypersensitivity to the active substance or excipients. Immunodeficient state. Patients with a history in the last 6 months of a myocardial infarction, unstable angina, stroke, transient ischaemic attack (TIA), decompensated heart failure requiring hospitalisation, or New York Heart Association (NYHA) Class III or IV heart failure. Presence of Mobitz type II second-degree, third-degree atrioventricular (AV) block, or sick sinus syndrome, unless patient has a functioning pacemaker. Severe active infections, active chronic infections. Active malignancies. Moderate or severe hepatic impairment (Child-Pugh class B and C, respectively). During pregnancy and in women of childbearing potential not using effective contraception.
SPECIAL WARNINGS & PRECAUTIONS: Bradyarrhythmia Initiation of ponesimod treatment may result in a transient decrease in heart rate (HR) and AV conduction delays, therefore an up‑titration scheme must be used to reach the maintenance dose of ponesimod (20 mg). Caution should be applied when ponesimod is initiated in patients receiving treatment with a beta‑blocker because of the additive effects on lowering heart rate; temporary interruption of the beta‑blocker treatment may be needed prior to initiation of ponesimod. For patients receiving a stable dose of a beta‑blocker, the resting HR should be considered before introducing ponesimod treatment. If the resting HR is greater than 55 bpm under chronic beta‑blocker treatment, ponesimod can be introduced. If resting HR is less than or equal to 55 bpm, beta-blocker treatment should be interrupted until the baseline HR is greater than 55 bpm. Initiation of ponesimod treatment may result in a decrease in HR, therfore first-dose 4‑hour monitoring is recommended for patients with sinus bradycardia [HR less than 55 beats per minute (bpm)], first- or second‑degree [Mobitz type I] AV block, or a history of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in stable condition. Administer the first dose of ponesimod in a setting where resources to appropriately manage symptomatic bradycardia are available. Monitor patients for 4 hours after the first dose for signs and symptoms of bradycardia with a minimum of hourly pulse and blood pressure measurements. Obtain an ECG in these patients at the end of the 4-hour observation period. Cardiologist advice should be obtained before initiation of ponesimod to determine overall benefit risk and the most appropriate monitoring strategy in the following patients: with significant QT prolongation (QTc greater than 500 msec) or who are already being treated with QT‑prolonging medicinal products with known arrhythmogenic properties (risk of torsades de pointes), with atrial flutter/fibrillation or arrhythmias treated with Class Ia (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) anti-arrhythmic medicinal products (In patients with unstable ischaemic heart disease, cardiac decompensated failure occurring more than 6 months prior to treatment initiation, history of cardiac arrest, cerebrovascular disease (TIA, stroke occurring more than 6 months prior to treatment initiation), and uncontrolled hypertension, since significant bradycardia may be poorly tolerated in these patients, treatment is not recommended, with a history of Mobitz Type II second degree AV block or higher‑grade AV block, sick-sinus syndrome, or sino-atrial heart block, with a history of recurrent syncope or symptomatic bradycardia, receiving concurrent therapy with drugs that decrease heart rate (e.g., beta-blockers, non‑dihydropyridine calcium channel blockers - diltiazem and verapamil, and other drugs that may decrease HR such as digoxin).
Infections: Ponesimod may increase the risk of infections. Life‑threatening and rare fatal infections have been reported in association with sphingosine 1‑phosphate (S1P) receptor modulators. Before initiating treatment with ponesimod, results from a recent complete blood count (CBC) with differential (including lymphocyte count) (i.e., within 6 months or after discontinuation of prior therapy) should be reviewed. Initiation of treatment with ponesimod should be delayed in patients with severe active infection until resolution. Cases of herpes viral infection have been reported in the development program of ponesimod. Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections have been reported with other S1P receptor modulators. No cases of CM have been reported in ponesimod‑treated patients in the development program. No cases of PML have been reported in ponesimod‑treated patients in the development program; however, PML has been reported in patients treated with a S1P receptor modulator and other multiple sclerosis (MS) therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). In patients that are taking anti‑neoplastic, immune‑modulating, or immunosuppressive therapies (including corticosteroids), or if there is a history of prior use of these medicinal products, possible unintended additive immune system effects should be considered before initiating treatment with ponesimod. No clinical data are available on the efficacy and safety of vaccinations in patients taking ponesimod. Avoid the use of live attenuated vaccines. If the use of live attenuated vaccine immunisation is required, ponesimod treatment should be paused from 1 week prior to 4 weeks after a planned vaccination. Macular oedema: Ponesimod increases the risk of macular oedema. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and again at any time if a patient reports any change in vision while on ponesimod therapy. Ponesimod therapy should not be initiated in patients with macular oedema until resolution. Patients with a history of uveitis and patients with diabetes mellitus should have regular examinations of the fundus, including the macula, prior to treatment initiation with ponesimod and have follow-up evaluations while receiving therapy. Respiratory effects Use with caution in patients with severe respiratory disease, pulmonary fibrosis and chronic obstructive pulmonary disease. Spirometry evaluation of respiratory function should be performed during therapy with ponesimod if clinically indicated.
Liver injury Elevations of transaminases may occur. Recent (i.e., within last 6 months) transaminase and bilirubin levels should be reviewed before initiation of ponesimod therapy. Patients who develop symptoms suggestive of hepatic dysfunction should be monitored for hepatotoxicity. Increased blood pressure Blood pressure should be regularly monitored during treatment with ponesimod and managed appropriately. Cutaneous neoplasm patients treated with ponesimod should be cautioned against exposure to sunlight without protection. These patients should not receive concomitant phototherapy with UV‑B‑radiation or PUVA‑photochemotherapy.
Women of childbearing potential Due to the risk to the foetus, ponesimod is contraindicated during pregnancy and in women of childbearing potential not using effective contraception. Before initiation of treatment in women of childbearing potential, a negative pregnancy test result must be available. Women of childbearing potential should use effective contraception to avoid pregnancy during and for 1 week after stopping ponesimod treatment. If a woman becomes pregnant during treatment, ponesimod must be immediately discontinued. Posterior reversible encephalopathy syndrome Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving a S1P receptor modulator. If PRES is suspected, ponesimod should be discontinued. Return of disease activity after ponesimod discontinuation The possibility of severe exacerbation of disease should be considered after stopping ponesimod treatment. Patients should be observed for a severe exacerbation or return of high disease activity upon ponesimod discontinuation and appropriate treatment should be instituted, as required. Excipients Ponvory contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
SIDE EFFECTS: Very common: nasopharyngitis, upper respiratory tract infection, alanine aminotransferase increased. Common: urinary tract infection, bronchitis, influenza, rhinitis, respiratory tract infection, respiratory tract infection viral, pharyngitis, sinusitis, viral infection, herpes zoster, laryngitis, pneumonia, lymphopenia, lymphocyte count decreased, depression, insomnia, anxiety, dizziness, hypoaesthesia, somnolence, migraine macular oedema, vertigo, hypertension, dyspnoea, cough, dyspepsia, back pain, arthralgia, pain in extremity, ligament sprain, fatigue, pyrexia, oedema peripheral, chest discomfort, aspartate aminotransferase increased, hypercholesterolaemia, hepatic enzyme increased, C-reactive protein increased, transaminases increased, blood cholesterol increased. Other side effects: bradycardia.
Refer to SmPC for other side effects.
PREGNANCY: Contraindicated in women of childbearing potential not using effective contraception. Negative pregnancy test result must be available before initiation of treatment in women of childbearing potential, women should be counselled on the potential for a serious risk to the foetus and the need for effective contraception during treatment. Specific measures are also included in the Healthcare Professional checklist and must be implemented before ponesimod is prescribed to female patients and during treatment.
LACTATION: Should not be used during breastfeeding.
INTERACTIONS: Anti‑neoplastic, immune‑modulating, or immunosuppressive therapies. No data. Caution should be used during concomitant administration because of the risk of additive immune effects during such therapy and in the weeks following administration Beta-blockers The addition of ponesimod to propranolol at steady state has an additive effect on HR effect. Vaccines Vaccinations may be less effective if administered while being treated with ponesimod and up to 1 week after its discontinuation. Use of live attenuated vaccines should be avoided during ponesimod treatment and up to 1 week after its discontinuation of treatment with ponesimod.
Refer to SmPC for full details of interactions.
LEGAL CATEGORY: Prescription Only Medicine (POM)
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
|PRESENTATIONS||PACK SIZES||MARKETING AUTHORISATION NUMBER(S)||BASIC NHS COSTS|
|Treatment initiation pack (Northern Ireland) 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg blister pack||14 tablets which contains: 2 x 2mg tablets, 2 x 3mg tablets, 2 x 4mg tablets, 1 x 5mg tablet, 1 x 6 mg tablet, 1 x 7mg tablet, 1 x 8mg tablet, 1 x 9mg tablet, 3 x 10mg tablets||EU/1/21/1550/001||£536.99|
|Maintenance pack (Northern Ireland) 20 mg blister pack||28 tablets||EU/1/21/1550/002||£1073.97|
|Treatment initiation pack (Great Britain) 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg blister pack||14 tablets which contains: 2 x 2mg tablets, 2 x 3mg tablets, 2 x 4mg tablets, 1 x 5mg tablet, 1 x 6 mg tablet, 1 x 7mg tablet, 1 x 8mg tablet, 1 x 9mg tablet, 3 x 10mg tablets||PLGB 00242/0743||£536.99|
|Maintenance pack (Great Britain) 20 mg blister pack||28 tablets||PLGB 00242/0739||£1073.97|
MARKETING AUTHORISATION HOLDER:
Great Britain: Janssen-Cilag Ltd, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK
Northern Ireland (EU): Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
© Janssen-Cilag Limited 2021
Prescribing information last revised: July 2021