Ongentys · 4.4 Special warnings and precautions for use · 1

HOS-096794 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most common adverse reactions reported were nervous system disorders. Dyskinesia was the most frequently reported treatment-emergent adverse reaction (17.7%). Tabulated list of adverse reactions In the table below (Table 1) all adverse reactions are presented by System Organ Class and frequency. Frequency categories are defined as follows: 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). Table 1 – Frequency of adverse reactions (MedDRA) in placebo-controlled Phase 3 studies System Organ Class Very common Common Uncommon Metabolism and Decreased appetite, nutrition disorders Hypertriglyceridaemia Psychiatric disorders Abnormal dreams, Anxiety, Hallucination, Depression, Hallucination visual, Hallucination auditory, Insomnia Confusional state, Nightmare, Sleep disorder Nervous system Dyskinesia Dizziness, Dysgeusia, disorders Headache, Hyperkinesia, Somnolence Syncope Eye disorders Dry eye Ear and labyrinth Ear congestion disorders Cardiac disorders Palpitations Vascular disorders Orthostatic Hypertension, Hypotension Hypotension Respiratory, thoracic Dyspnoea and mediastinal disorders Gastrointestinal Constipation, Abdominal distention, disorders Dry mouth, Abdominal pain, Nausea, Abdominal pain upper,

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096790 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms. History of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis. 3 Concomitant use with monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson’s disease (see section 4.5).

HOS-096789 · has-indication-information · PDF-Seite 2

Ongentys is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors (DDCI) in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. 2

HOS-096792 · has-interaction-information · PDF-Seite 4

Monoamino oxidase (MAO) inhibitors Combination of opicapone and MAO inhibitors could result in inhibition of the majority of the pathways responsible for the metabolism of catecholamines. Because of this, concomitant use of opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson’s disease is contraindicated (see section 4.3). Concomitant use of opicapone and MAO inhibitors for the treatment of Parkinson’s disease, e.g. rasagiline (up to 1 mg/day) and selegiline (up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation), is permissible. There is no experience with opicapone when used concomitantly with the MAO-B inhibitor safinamide. Therefore, their concomitant use should be considered with appropriate caution. 4 Medicinal products metabolised by COMT Opicapone may interfere with the metabolism of medicinal products containing a catechol group that are metabolised by COMT, e.g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dopexamine or dobutamine, leading to potentiated effects of these medicinal products. Careful monitoring of patients being treated with these medicinal products is advised when opicapone is used. Tricyclic antidepressants and noradrenaline re-uptake inhibitors There is limited experience with opicapone when used concomitantly with tricyclic antidepressants and noradrenaline re-uptake inhibitors (e.g. venlafaxine, maprotiline and desipramine). Thus, their concomitant use should be considered with appropriate caution. Quinidine A study conducted in healthy volunteers showed that when a single dose of 50 mg opicapone was co- administered (within 1 hour) with a single dose of quinidine (600 mg), systemic exposure of opicapone decreased by 37% (AUC0-tlast). Thus, particular consideration should be given to cases where quinidine needs to be administered together with opicapone as their co-administration should be avoided. CYP2C8 and OATP1B1 substrates Opicapone is a weak in vitro inhibitor of CYP2C8 and OATP1B1, whereas repaglinide is a sensitive CYP2C8 and OATP1B1 substrate. A study conducted in healthy subjects showed that there were no changes in repaglinide’s exposure when repaglinide was administered following multiple once-daily administration of opicapone 50 mg.

HOS-096793 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited amount of data from the use of opicapone in pregnant women. Opicapone crossed the placenta in rats. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Ongentys is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding Opicapone levels in the milk of lactating rats were equivalent to those in plasma. It is unknown whether opicapone or its metabolites are excreted into human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Ongentys. Fertility The effects of opicapone on fertility in humans have not been studied. Animal studies with opicapone do not indicate harmful effects with respect to fertility (see section 5.3).

HOS-096791 · has-warning-information · PDF-Seite 4

Dose adjustments of antiparkinsonian therapy Ongentys is to be administered as an adjunct to levodopa treatment. Hence, the precautions valid for levodopa treatment should also be taken into account for Ongentys. Opicapone enhances the effects of levodopa. To reduce levodopa-related dopaminergic adverse reactions (e.g. dyskinesia, hallucinations, nausea, vomiting and orthostatic hypotension), it is often necessary to adjust the daily dose of levodopa by extending the dosing intervals and/or reducing the amount of levodopa per dose within the first days to first weeks after initiating treatment with Ongentys, according to the clinical condition of the patient (see section 4.2). If Ongentys is discontinued it is necessary to adjust the dosing of the other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of control of the symptoms. Psychiatric disorders Patients and care-givers should be made aware that impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments. Patients should be monitored regularly for the development of impulse control disorders and review of treatment is recommended if such symptoms develop. Others Increases in liver enzymes were reported in studies with nitrocatechol inhibitors of catechol-O- methyltransferase (COMT). For patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time, a general medical evaluation including liver function should be considered. Excipients Ongentys contains lactose. Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Ongentys contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium- free’.