Levodopa

5 WARNINGS AND PRECAUTIONS May cause falling asleep during activities of daily living ( 5.1 ) Avoid sudden discontinuation or rapid dose reduction to reduce the risk of withdrawal-emergent hyperpyrexia and confusion ( 5.2 ) Hallucinations/exacerbation of psychosis may occur. Patients with a major psychotic disorder should not be treated with INBRIJA ( 5.3 , 7.2 ) Impulse Control Disorders: consider dose reduction or stopping INBRIJA ( 5.4 ) May cause or exacerbate dyskinesia: adjustment of levodopa therapy may be considered, including stopping INBRIJA ( 5.5 ) Not recommended in patients with asthma, COPD, or other chronic underlying lung disease ( 5.6 ) 5.1 Falling Asleep During Activities of Daily Living and Somnolence Patients treated with levodopa, the active ingredient in INBRIJA, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence, some reported no warning signs (sleep attack) and believed that they were alert immediately prior to the event. Some of these events have been reported more than 1 year after the initiation of treatment. Prescribers should reassess patients for drowsiness or sleepiness. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Before initiating treatment with INBRIJA, advise patients about the potential to develop drowsiness and ask about factors that may increase the risk for somnolence with INBRIJA such as the concomitant use of sedating medications and the presence of sleep disorders. Consider discontinuing INBRIJA in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.). If treatment with INBRIJA continues, patients should be advised not to drive and to avoid other activities that might result in harm if the patients become somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. 5.2 Withdrawal-Emergent Hyperpyrexia and Confusion A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. 5.3 Hallucinations/Psychosis In placebo-controlled trials [see Clinical Studies (14) ], hallucinations were reported in less than 2% of patients treated with INBRIJA. Hallucinations may be responsive to reducing levodopa therapy. Hallucinations may be accompanied by confusion, insomnia, and excessive dreaming. Abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium. Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should ordinarily not be treated with INBRIJA. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of INBRIJA [see Drug Interactions (7.2) ]. 5.4 Impulse Control/Compulsive Behaviors Patients treated with INBRIJA can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with INBRIJA. Consider stopping the medication if a patient develops such urges while taking INBRIJA. 5.5 Dyskinesia INBRIJA may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, prescribers may need to consider stopping treatment with INBRIJA and/or adjusting the patient's daily medications for the treatment of Parkinson's disease. In Study 1, 4% of patients treated with INBRIJA 84 mg reported dyskinesia, compared with 1% for patients on placebo [see Adverse Reactions (6.1) ] . 5.6 Bronchospasm in Patients with Lung Disease Because of the risk of bronchospasm, use of INBRIJA in patients with asthma, COPD, or other chronic underlying lung disease is not recommended. In a double-blind, placebo-controlled, crossover clinical study, 25 otherwise healthy subjects with mild or moderate asthma on a stable regimen of asthma medication received placebo or INBRIJA 84 mg every 4 hours for a total of three doses. Cough was the most frequent adverse reaction, reported by 60% of subjects following administration of INBRIJA and 0% following administration of placebo. Following administration of INBRIJA, 10 subjects (40%) had temporary reductions from baseline (between 15% and 59%) for FEV 1 ; 4 of these subjects also had a reduction in FEV 1 following administration of placebo. Subjects with a reduction in FEV 1 remained asymptomatic and did not require rescue treatment. 5.7 Glaucoma INBRIJA may cause increased intraocular pressure in patients with glaucoma. Monitor patients for increased intraocular pressure during therapy with INBRIJA. 5.8 Laboratory Test Abnormalities Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, AST, ALT, lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN), hemolytic anemia and positive direct antibody test have also been reported. Patients taking levodopa or carbidopa-levodopa may have increased levels of catecholamines and their metabolites in plasma and urine giving false positive results suggesting the diagnosis of pheochromocytoma in patients on levodopa and carbidopa-levodopa.