Rayvow · 4.6 Fertility, pregnancy and lactation · 1

HOS-099517 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most commonly occurring adverse reactions are dizziness (19.9 %), somnolence (7.8 %), fatigue (7.7 %), paraesthesia (6.8 %), nausea (4.9 %), vertigo (2.6 %), hypoaesthesia (2.5 %), and muscular weakness (2.3 %). Most of the adverse events showed a dose response. Tabulated list of adverse reactions In the following table, adverse reactions are listed in order of MedDRA body system organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequency gradings are: 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). Table 1. Adverse reactions System organ Very common Common Uncommon Rare class Immune system Hypersensitivity disorders Psychiatric Sleep Confusion disorders abnormalities Hallucinations Euphoric mood Anxiety Restlessness Nervous system Dizziness Incoordination Lethargy Serotonin disorders Paraesthesia Disturbance in syndrome Hypoaesthesia attention Somnolence Cognitive disorder Mental impairment Tremor Speech abnormalities Eye disorders Visual impairment Ear and labyrinth Vertigo disorders Cardiac disorders Palpitations Respiratory, Dyspnoea thoracic and mediastinal disorders Gastrointestinal Vomiting disorders

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HOS-099513 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-099512 · has-indication-information · PDF-Seite 2

RAYVOW is indicated for the acute treatment of the headache phase of migraine attacks, with or without aura in adults. 2

HOS-099515 · has-interaction-information · PDF-Seite 4

Heart rate lowering medicinal products Lasmiditan has been associated with a lowering of heart rate (HR). Propranolol and lasmiditan together decreased HR by a mean maximum of 19.3 beats per minute (bpm), i.e., an additional lowering of 5.1 bpm compared to propranolol alone. This should be taken into consideration for patients in whom these magnitudes of HR decrease may pose a concern, including patients taking medicinal products that lower heart rate. Serotonergic medicinal products Concomitant administration of lasmiditan and medicinal products (e.g., SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome. Clinical experience for the use of 4 lasmiditan and triptans in temporal proximity is limited. The risks of developing serotonin syndrome may be additive. Caution is advised (see section 4.4). Potential for lasmiditan to affect other medicinal products Daily dosing of lasmiditan did not alter the PK of midazolam, caffeine, or tolbutamide, which are substrates of CYP3A, CYP1A2, and CYP2C9, respectively. Coadministration of lasmiditan with sumatriptan (MAO-A and OCT1 substrate) or propranolol (CYP2D6 substrate) resulted in no clinically meaningful changes in exposure of these medicinal products. Following a single dose of lasmiditan, creatinine renal clearance over 24 hours decreased slightly (11 %) compared with placebo, without changes in glomerular filtration rate (GFR). Lasmiditan is an in vitro inhibitor of P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP). In a drug interaction study, lasmiditan increased the systemic exposure of coadministered dabigatran (P-gp substrate) by approximately 25%. Therefore, when RAYVOW is administered with P-gp substrates that have a narrow therapeutic index (such as digoxin), increases in the systemic exposure of the coadministered medication may be clinically meaningful (see section 5.2). In the same study, no significant change in rosuvastatin (BCRP substrate) PK was observed when it was coadministered with lasmiditan. Potential for other medicinal products to affect lasmiditan No change in lasmiditan PK was observed when coadministered with dabigatran etexilate, rosuvastatin, sumatriptan, or propranolol. Based on its metabolism clearance pathways, CYP inhibitors or inducers are unlikely to affect lasmiditan exposure and no change in lasmiditan PK was observed when coadministered with topiramate (CYP3A4 indu

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HOS-099516 · has-pregnancy-information · PDF-Seite 5

Pregnancy There is a limited amount of data from the use of lasmiditan in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The effects of lasmiditan on human foetal development are not known. RAYVOW is not recommended during pregnancy. Breast-feeding Lasmiditan and/or its metabolites were excreted into the milk of lactating rats (see section 5.3). There are no data on the presence of lasmiditan in human milk, the effects of lasmiditan on the breastfed infant, or the effects of lasmiditan on milk production. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from RAYVOW therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Exposure of the newborn can be minimised by avoiding breast-feeding for 24 hours after treatment. Fertility It is unknown whether lasmiditan affects human reproductive potential. Animal studies do not indicate any effect on fertility (see section 5.3).

HOS-099514 · has-warning-information · PDF-Seite 3

Central nervous system (CNS) effects and driving impairment Lasmiditan is associated with CNS adverse reactions. In a simulated driving study in healthy subjects, lasmiditan significantly impaired the ability to drive (see section 4.7). Patients should be advised not to drive or engage in other activities requiring heightened attention until at least 8 hours after taking each dose of lasmiditan, even if they feel well enough to do so. Patients who cannot follow this advice should not take lasmiditan. 3 Serotonin syndrome Serotonin syndrome has been reported and may occur with lasmiditan or when administered with other serotonergic medicinal products [e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors]. Clinical experience for the use of lasmiditan and triptans in temporal proximity is limited. The risks of developing serotonin syndrome may be additive. Serotonin syndrome symptoms may include mental status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (e.g. hyperreflexia, incoordination), and/or gastrointestinal signs and symptoms (e.g. nausea, vomiting, diarrhoea). These reactions can be severe. The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medicinal product. If concomitant treatment with other serotonergic medicinal products is clinically warranted, appropriate observation of the patient is advised, particularly during treatment initiation, and with dose increases. Lasmiditan should be discontinued if serotonin syndrome is suspected. CNS depressants Because of the potential of lasmiditan to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, lasmiditan should be used with caution if used in combination with alcohol or other CNS depressants. Medicinal products misuse or abuse potential In a human abuse potential study with recreational drug users, single lasmiditan doses of 100 or 200 mg were associated with greater drug-liking than placebo. In a separate study, there was no evidence of physical withdrawal in healthy subjects following abrupt cessation after 7 days of dosing. Patients should be evaluated for risk of drug abuse and observed for signs of lasmiditan m

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