CREXONT

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 ) Cardiovascular Events: Monitor patients with a history of cardiovascular disease. ( 5.3 ) Hallucinations/Psychosis may occur. ( 5.4 ) Impulse Control Disorders: Consider dose reduction or stopping CREXONT if occurs. ( 5.5 ) May cause or exacerbate dyskinesia: Consider dose reduction. ( 5.6 ) 5.1 Falling Asleep During Activities of Daily Living and Somnolence Patients treated with levodopa, a component of CREXONT, 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 while on levodopa, some perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event (sleep attack). Some of these events have been reported more than 1 year after initiation of treatment. Falling asleep while engaged in activities of daily living usually occurs in patients experiencing preexisting somnolence, although patients may not give such a history. For this reason, prescribers should reassess for drowsiness or sleepiness in CREXONT-treated patients, especially since some of the events occur well after the start of treatment. 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 CREXONT, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with CREXONT, such as concomitant sedating medications or the presence of a sleep disorder. Consider discontinuing CREXONT in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.). If a decision is made to continue CREXONT, patients should be advised not to drive and to avoid other potentially dangerous 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. Avoid sudden discontinuation or rapid dose reduction in patients taking CREXONT. If the decision is made to discontinue CREXONT, the dose should be tapered to reduce the risk of hyperpyrexia and confusion [see Dosage and Administration (2.6) ] . 5.3 Cardiovascular Ischemic Events Cardiovascular ischemic events have occurred in patients taking CREXONT. In Study 1 [see Clinical Studies (14) ], 4/589 (0.7%) of CREXONT-treated patients experienced cardiovascular ischemic adverse reactions compared to 2/630 (0.3%) of oral immediate-release carbidopa-levodopa-treated patients. These patients all had a previous history of ischemic heart disease or risk factors for ischemic heart disease. In patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias, cardiac function should be monitored in an intensive cardiac care facility during the period of initial dosage adjustment. 5.4 Hallucinations/Psychosis There is an increased risk for hallucinations in patients taking CREXONT. In Study 1, 17/589 (3%) of CREXONT-treated patients reported hallucinations compared to 2/630 (0.3%) of oral immediate-release carbidopa-levodopa-treated patients. Hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. 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 not be treated with CREXONT. 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 CREXONT [see Drug Interactions (7.2) ] . 5.5 Impulse Control/Compulsive Behaviors Case reports suggest that patients 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, including CREXONT, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease. 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 CREXONT. Consider a dose reduction or stopping the medication if a patient develops such urges while taking CREXONT. 5.6 Dyskinesia CREXONT can cause dyskinesias that may require a dosage reduction of CREXONT or other medications used for the treatment of Parkinson’s disease. 5.7 Vitamin B6 Deficiency and Seizures Treatment with carbidopa-levodopa, including CREXONT, may contribute to reduced vitamin B6 levels. Higher doses of carbidopa/levodopa may increase the risk of vitamin B6 deficiency. Seizures associated with vitamin B6 deficiency have been reported in the postmarketing setting in patients taking carbidopa/levodopa. In these reported cases, seizures were refractory to traditional anti-seizure medications and only resolved after vitamin B6 administration. Other symptoms of vitamin B6 deficiency may occur, including depression, confusion, cheilosis, glossitis, dermatitis, anemia, and/or neuropathy. Evaluate vitamin B6 levels prior to initiation of CREXONT and periodically while on treatment or if symptoms associated with vitamin B6 deficiency are identified. Supplement with vitamin B6 as necessary. 5.8 Peptic Ulcer Disease Treatment with CREXONT may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer. 5.9 Glaucoma CREXONT may cause increased intraocular pressure in patients with glaucoma. Monitor intraocular pressure in patients with glaucoma after starting CREXONT.