FDA APPROVES CARBIDOPA/LEVODOPA ER (RYTARY) IN PARKINSON’S

Many people in the Parkinson’s world are very excited by the approval of Extended Release (ER) Rytary by the FDA. The drug should be available around the middle of February 2015. The press release starts out: Impax Pharmaceuticals, a division of Impax Laboratories, Inc. IPXL, +3.72% today announced that the U.S. Food and Drug Administration (FDA) approved RYTARY, an extended-release oral capsule formulation of carbidopa-levodopa, for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication and/or manganese intoxication. RYTARY is not for use in patients using nonselective monoamine oxidase inhibitors (MAO) inhibitors. The price of Impax stock runs around $38 per share. Had you been an investor when the price per share was around $5, today your 1,000 share value would have increased from $5,000 to $38,000.

What you should know about RYTARY - IMPORTANT SAFETY INFORMATION

Rytary is contraindicated (a contraindication  is a specific situation in which a drug, procedure, or surgery should not be used because it may be harmful to the patient) in patients who are currently taking or have recently (within 2 weeks) taken a nonselective monoamine oxidase (MAO) inhibitor. Hypertension can occur if these drugs are used concurrently. Patients treated with levodopa (a component of Rytary) 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 (a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods) while on levodopa, some perceived that they had no warning signs (sleep attack), such as excessive drowsiness, and believed that they were alert immediately prior to the event.

Some of these events have been reported more than 1 year after initiation of treatment. Before initiating treatment with Rytary, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with Rytary such as concomitant sedating medications or the presence of a sleep disorder. Prescribers should consider discontinuing Rytary 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 Rytary, patients should be advised not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent. 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 Rytary. If the decision is made to discontinue Rytary, the dose should be tapered to reduce the risk of hyperpyrexia and confusion.

Cardiovascular ischemic events have occurred in patients taking Rytary. In patients with a history of myocardial infarction (commonly known as a heart attack) 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. There is an increased risk for hallucinations and psychosis in patients taking Rytary. Hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion and sleep disorder (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 Rytary. 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 Rytary.

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 Rytary, 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 Rytary. Consider a dose reduction or stopping the medication if a patient develops such urges while taking Rytary. Rytary can cause dyskinesia that may require a dosage reduction of Rytary or other medications used for the treatment of Parkinson’s disease.

Treatment with RYTARY may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer and may cause increased intraocular pressure in patients with glaucoma. Rytary should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.  Caution should be exercised when Rytary is administered to a nursing woman.

Overdosage

The acute symptoms of levodopa/dopa decarboxylase inhibitor overdosage can be expected to arise from dopaminergic overstimulation (cardiovascular and CNS disturbances).

Drug Interactions

Monitor patients taking selective MAO-B inhibitors and carbidopa-levodopa. The combination may be associated with orthostatic hypotension (is a form of low blood pressure that happens when you stand up from sitting or lying down. Orthostatic hypotension can make you feel dizzy or lightheaded, and maybe even faint). Rytary should be co-administered cautiously with: dopamine D2 antagonists (metoclopramide), isoniazid, and iron salts. Rytary should not be chewed, divided, or crushed.