INBRIJA^® has a well‑established 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^®. Gastrointestinal haemorrhage has been reported with levodopa medicinal products and was observed once in INBRIJA^® clinical studies.

Bronchospasm in patients with lung disease

Because of the risk of bronchospasm use of INBRIJA^® in patients with a chronic underlying lung disease is not recommended.

Central Nervous System (CNS) effects and mental disturbances

• Somnolence and episodes of sudden sleep onset: Patients must be informed and advised to exercise caution while driving or operating machines during treatment. If an episode of either of the above has been experienced, driving or operating machines must be refrained from.
• Withdrawal-emergent hyperpyrexia and confusion: Any abrupt dose reduction or withdrawal of any levodopa medicinal product should be carefully observed, particularly in patients receiving neuroleptics.
• Mental disturbances: Concomitant use of antipsychotics should be monitored carefully for worsening of motor symptoms especially when D-2 receptor antagonists are used.
• Impulse control disorders: Patients should be regularly monitored. Patients and carers must be made aware of the potential development of symptoms. Review of treatment is recommended if symptoms develop.
• Dyskinesia: INBRIJA^® may cause dyskinesia, adjustment of levodopa or other Parkinson’s disease treatment may be necessary.

Cardiovascular ischaemic events: INBRIJA^® should be administered in caution with patients with severe cardiovascular disease. Care should be exercised when INBRIJA^® is administered to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. Cardiac function should be monitored with particular care in such patients during the initiation of treatment with INBRIJA^®.

Peptic ulcer disease: Levodopa should be administered cautiously to patients with a history of peptic ulcer disease.

Glaucoma: Levodopa may cause increased intraocular pressure in patients with glaucoma. Patients with chronic glaucoma may be treated cautiously with levodopa provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.

Melanoma: Periodic skin examinations are recommended to monitor for melanoma in patients receiving INBRIJA^®.

Orthostatic hypotension: Levodopa can cause orthostatic hypotension. INBRIJA^® should be used with caution in case of concomitant use of medicinal products that may cause orthostatic hypotension.

Intercurrent respiratory infection: There is limited data available on the use of INBRIJA^® during a respiratory infection. Based on individual assessments of the severity of the intercurrent respiratory infection INBRIJA^® may be continued or discontinued until the respiratory symptoms resolve.

Please refer to the Summary of Product Characteristics for full information regarding the above warnings and precautions.

• Hypersensitivity to the active substance or to any of the excipients.
• 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.
• A previous history of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis.

Interaction with other medicinal products:

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.

Antihypertensives: 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 Inbrija is not recommended in patients with asthma, chronic obstructive pulmonary disease (COPD), or other chronic underlying lung disease.

• INBRIJA^® is not recommended during pregnancy and in women of childbearing potential not using contraception.
• 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^®.
• There are no data on the effects of levodopa on human fertility. Animal studies indicated no effect on fertility.

Levodopa may have a major influence on the ability to drive and use machines. Certain side effects such as sleepiness and dizziness, that have been reported with other forms of levodopa medicinal products, may affect some patients’ ability to drive or use machines.

Patients being treated with levodopa medicinal products and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. use machines), until such recurrent episodes and somnolence have resolved.