Leitlinien & Arzneimittelsicherheit

HOS-098743 · has-adverse-reaction-information · PDF-Seite 7

Summary of safety profile The most frequent adverse reactions reported in the Inbrija clinical studies were cough (15.6%), fall (8.7%), upper respiratory tract infection (5.8%), dyskinesia (5.7%) and sputum discoloured (2.8%). Serious adverse reactions of allergic oedema have been reported with levodopa medicinal products but not in clinical studies with Inbrija. A symptom complex resembling neuroleptic malignant syndrome and rhabdomyolysis may occur with levodopa/dopa-decarboxylase inhibitor medicinal products, although no cases have been identified in clinical studies with Inbrija. Gastrointestinal haemorrhage has been reported with levodopa medicinal products and was observed once in Inbrija clinical studies. Tabulated list of adverse reactions Adverse reactions are presented by system organ class and frequency in Table 1 below. Frequency categories are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), not known (cannot be estimated from the available data). Table 1: Adverse reactions Adverse reactions with Inbrija Adverse reactions reported with oral levodopa System Organ Very common Common Not known Not known Class Neoplasm benign, Malignant melanoma malignant and unspecified (incl. cysts and polyps) Blood and Anaemia, lymphatic system Agranulocytosis, disorders Thrombocytopenia, Leukopenia Immune system Allergic oedema disorder Metabolism and Decreased appetite nutrition disorders Psychiatric Confusional state, disorders Hallucination,

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HOS-098739 · has-contraindication-information · PDF-Seite 3

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - Narrow-angle glaucoma. - Phaeochromocytoma. - Co-administration with non-selective monoamine oxidase (MAO) inhibitors. These inhibitors should already be discontinued for at least two weeks prior to initiating therapy due to the established underlying levodopa therapy (see section 4.5). - A previous history of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis.

HOS-098738 · has-indication-information · PDF-Seite 2

Inbrija is indicated for the intermittent treatment of episodic motor fluctuations (OFF episodes) in adult patients with Parkinson’s disease (PD) treated with a levodopa/dopa-decarboxylase inhibitor.

HOS-098741 · has-interaction-information · PDF-Seite 5

Non-selective Monoamine Oxidase (MAO) inhibitors The use of non-selective MAO inhibitors with levodopa is contraindicated (see section 4.3). Any non- selective MAO inhibitors should be discontinued at least 14 days prior to initiating levodopa. Selective Monoamine Oxidase (MAO) inhibitors The use of selective MAO-B inhibitors (e.g. rasagiline, selegiline, and safinamide) with levodopa may be associated with orthostatic hypotension. Patients who are taking these medicinal products should be monitored closely. Dopamine D2 receptor antagonists and isoniazid Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones, risperidone, metoclopramide) and isoniazid may reduce the effectiveness of levodopa. Patients who are taking these medicinal products should be monitored for worsening Parkinson’s symptoms (see section 4.4). Antihypertensives 5 Symptomatic postural hypotension has occurred when combinations of levodopa and a dopa- decarboxylase inhibitor are added to the treatment of patients already receiving certain antihypertensives. Dose adjustment of the antihypertensive medicinal products may be required during concomitant use of Inbrija. Anticholinergics Anticholinergic medicinal products can work synergistically with levodopa, in order to improve tremor. Concurrent use can, however, cause a worsening of involuntary motor disorders. Anticholinergic medicinal products may impair the effect of oral levodopa medicinal products, due to a delayed absorption. A dose adjustment of levodopa may be required. COMT inhibitors The addition of entacapone to a levodopa/dopa-decarboxylase inhibitor has been demonstrated to increase the levodopa bioavailability by 30%. A dose adjustment of levodopa may be required with concomitant use of COMT inhibitors. Tricyclic antidepressants There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and a levodopa/dopa-decarboxylase inhibitor. Amantadine Concurrent administration of levodopa and amantadine may increase confusion, hallucinations, nightmares, gastro-intestinal disturbances, or other atropine-like side effects. Psychotic reactions have been observed in patients receiving amantadine and levodopa. Local or systemic pulmonary medicinal products Interactions of Inbrija with local or systemic pulmonary medicinal products were not investigated because Inb

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HOS-098742 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are no or limited amount of data from the use of levodopa in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Inbrija is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding Levodopa is excreted in human milk. There is insufficient information on the effects of levodopa in newborns/infants. Breast-feeding should be discontinued during treatment with Inbrija. Fertility There are no data on the effects of levodopa on human fertility. Animal studies indicated no effect on fertility (see section 5.3). 6

HOS-098740 · has-warning-information · PDF-Seite 3

Bronchospasm in patients with lung disease Because of the risk of bronchospasm, use of levodopa inhalation powder in patients with asthma, chronic obstructive pulmonary disease (COPD), or other chronic underlying lung disease is not recommended. There is limited data regarding chronic effect of Inbrija in respiratory compromised patients. Central Nervous System (CNS) effects and mental disturbances Somnolence and episodes of sudden sleep onset Levodopa has been associated with somnolence and episodes of sudden sleep onset (see section 4.7). Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while 3 driving or operating machines during treatment (see section 4.7). Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dose or termination of therapy may be considered. Withdrawal-emergent hyperpyrexia and confusion A symptom complex that resembles neuroleptic malignant syndrome (characterised by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious aetiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in the background dopaminergic therapy. Therefore, any abrupt dose reduction or withdrawal of any levodopa medicinal product should be carefully observed, particularly in patients who are also receiving neuroleptics. Mental disturbances Patients may experience new or worsening mental status and behavioural changes, which may be severe, including psychotic-like and suicidal behaviour during levodopa treatment or after starting or increasing the dose of levodopa. This abnormal thinking and behaviour can consist of one or more of a variety of manifestations including anxiety, depression, paranoid ideation, delusions, hallucinations, confusion, psychotic-like behaviour, disorientation, aggressive behaviour, agitation, and delirium. Patients with a major psychotic disorder or a history of psychotic disorder must be treated cautiously with a levodopa/dopa-decarboxylase inhibitor because of the risk of exacerbating psychosis. In addition, certain medicinal products used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effective

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