Ponvory

HOS-099267 · has-adverse-reaction-information · PDF-Seite 13

Summary of the safety profile The most commonly reported adverse reactions are nasopharyngitis (19.7%), alanine aminotransferase increased (17.9%) and upper respiratory tract infection (11%). Tabulated list of adverse reactions Adverse reactions reported with ponesimod in controlled clinical trials and uncontrolled extension trials are ranked by frequency, with the most frequent reactions first. Frequencies were defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). 13  Table 2: Tabulated list of adverse reactions System Organ Very common Common Uncommon Class (SOC) urinary tract infection, bronchitis, influenza, rhinitis, respiratory tract nasopharyngitis, upper Infections and infection, respiratory tract respiratory tract infestations infection viral, infection pharyngitis, sinusitis, viral infection, herpes zoster, laryngitis, pneumonia Blood and lymphopenia, lymphocyte lymphatic system count decreased disorders Psychiatric depression, insomnia, disorders anxiety dizziness, hypoaesthesia, Nervous system somnolence, migraine, disorders seizure Eye disorders macular oedema Ear and labyrinth vertigo disorders Cardiac disorders bradycardia Vascular disorders hypertension Respiratory, thoracic and dyspnoea, cough medi

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099263 · has-contraindication-information · PDF-Seite 5

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - Immunodeficient state (see section 4.4). - Patients who in the last 6 months experienced 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. 5 - Patients who have presence of Mobitz type II second-degree, third-degree atrioventricular (AV) block, or sick sinus syndrome, unless patient has a functioning pacemaker (see section 4.4). - 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 (see section 4.6).

HOS-099262 · has-indication-information · PDF-Seite 4

Ponvory is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features.

HOS-099265 · has-interaction-information · PDF-Seite 11

Anti-neoplastic, immune-modulating, or immunosuppressive therapies Ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during such therapy and in the weeks following administration (see section 4.4). Anti-arrhythmic medicinal products, QT prolonging medicinal products, medicinal products that may decrease heart rate Ponesimod has not been studied in patients taking QT prolonging medicinal products (see section 4.4). Beta-blockers The negative chronotropic effect of co-administration of ponesimod and propranolol was evaluated in a dedicated pharmacodynamics safety study. The addition of ponesimod to propranolol at steady-state has an additive effect on HR effect. In a drug-drug interaction study, the up-titration regimen of ponesimod (see section 4.2) was administered to subjects receiving propranolol (80 mg) once daily at steady-state. Compared to ponesimod alone, the combination with propranolol after the first dose of ponesimod (2 mg) had a 12.4 bpm (90% CI: -15.6 to -9.1) decrease in mean hourly heart rate and at the first dose of ponesimod (20 mg) after up-titration a 7.4 bpm (90% CI: -10.9 to -3.9) decrease in mean hourly heart rate. No significant changes in pharmacokinetics of ponesimod or propranolol were observed. Vaccines Vaccinations may be less effective if administered while being treated with ponesimod and up to 1 week after its discontinuation (see section 4.4). The use of live attenuated vaccines may carry the risk of infection and should therefore be avoided during ponesimod treatment and up to 1 week after its discontinuation of treatment with ponesimod (see section 4.4). Effect of other medicinal products on ponesimod Medicinal products that are inhibitors of major CYP or UGT enzymes are unlikely to impact the pharmacokinetics of ponesimod (see section 5.2). 11 No dose adjustment is needed when ponesimod is co-administered with strong CYP3A4 and UGT1A1 inducers. Co-administration of carbamazepine 300 mg twice daily (a strong CYP3A4 and UGT1A1 inducer) at steady-state decreased ponesimod Cmax by 19.6% and AUC by 25.7%. This decrease is not clinically relevant. Ponesimod is not a substrate of P-gp, BCRP, OATP1B1 or OATP1B3 transporters. Medicinal products that are inhibitors of these transporters are unlikely

Auszug; vollständigen Abschnitt im Original lesen.

HOS-099266 · has-pregnancy-information · PDF-Seite 12

Women of childbearing potential/Contraception in females Ponvory is contraindicated in women of childbearing potential not using effective contraception (see section 4.3). Before initiation of Ponvory treatment in women of childbearing potential a negative pregnancy test result must be available, and women should be counselled on the potential for a serious risk to the foetus and the need for effective contraception during treatment with ponesimod. Since it takes approximately 1 week to eliminate ponesimod from the body after stopping treatment, the potential risk to the foetus may persist and women must use effective contraception during this period (see section 4.4). Specific measures are also included in the Healthcare Professional checklist. These measures must be implemented before ponesimod is prescribed to female patients and during treatment. When stopping ponesimod therapy for planning a pregnancy, the possible return of disease activity should be considered (see section 4.4). Pregnancy Ponvory is contraindicated during pregnancy (see section 4.3). Although there are no data from the use of ponesimod in pregnant women, studies in animals have shown reproductive toxicity (see section 5.3). If a woman becomes pregnant during treatment, ponesimod must be immediately discontinued. Medical advice should be given regarding the risk of harmful effects to the foetus associated with treatment (see section 5.3) and follow-up examinations should be performed. Based on clinical experience in patients receiving another S1P receptor modulator, the use is associated with an increased risk of major congenital malformations. 12 Breast-feeding It is unknown whether ponesimod or its metabolites are excreted in human milk. A study in lactating rats has indicated excretion of ponesimod in milk (see section 5.3). A risk to newborns/infants cannot be excluded. Ponvory should not be used during breast-feeding. Fertility The effect of ponesimod on human fertility has not been evaluated. Data from preclinical studies do not suggest that ponesimod would be associated with an increased risk of reduced fertility (see section 5.3).

HOS-099264 · has-warning-information · PDF-Seite 6

Bradyarrhythmia Initiation of treatment with ponesimod Prior to treatment initiation with ponesimod, an electrocardiogram (ECG) in all patients should be obtained to determine whether pre-existing conduction abnormalities are present. In patients with certain pre-existing conditions, first-dose monitoring is recommended (see below). Initiation of ponesimod treatment may result in a transient decrease in heart rate (HR) and AV conduction delays (see sections 4.8 and 5.1), therefore an up-titration scheme must be used to reach the maintenance dose of ponesimod (20 mg) (see section 4.2). After the first dose of ponesimod, the decrease in HR typically begins within an hour and reaches its nadir within 2-4 hours. The HR typically recovers to baseline levels 4-5 hours after administration. The mean decrease in HR on day 1 of dosing (2 mg) was 6 bpm. With up-titration after day 1, the decrease in HR is less pronounced with no further post-dose decrease in HR observed after day 3. 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 (see section below and section 4.5). 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. Treatment with ponesimod can then be initiated and treatment with a beta-blocker can be reinitiated after ponesimod has been up-titrated to the target maintenance dose (see section 4.5). Beta-blocker treatment can be initiated in patients receiving stable doses of ponesimod. First dose monitoring in patients with certain pre-existing cardiac conditions Because initiation of ponesimod treatment may result in a decrease in HR, 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 (see section 5.1). Administer the first dose of ponesimod in a setting where resources to

Auszug; vollständigen Abschnitt im Original lesen.