"Nov. 6, 2012 -- Exercise helps put people with Parkinson's disease on a path to better health, a new study shows.
All Parkinson's patients reach a point in their disease where they begin to have trouble walking. Typically, a person st"...
A total of 578 patients received ZELAPAR® (selegiline hydrochloride) in clinical trials. Because the controlled trials performed during premarketing development both used a titration design (1.25 mg per day for 6 weeks, followed by 2.5 mg per day for 6 weeks), with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse events.
The most commonly observed adverse events, which were greater than placebo, reported in the double-blind, placebo-controlled trials during ZELAPAR® (selegiline hydrochloride) treatment were dizziness, nausea, pain, headache, insomnia, rhinitis, dyskinesia, back pain, stomatitis, and dyspepsia.
Of the 194 patients treated with ZELAPAR® (selegiline hydrochloride) in the double-blind, placebo-controlled trials, 5.2% discontinued due to adverse events compared to 1.0% of the 98 patients who received placebo. Events causing discontinuation of treatment included dizziness, chest pain, accidental injury, and myasthenia.
Incidence In Controlled Clinical Trials Under Adverse Reactions
Table 1 lists the adverse events reported in the placebo-controlled trials after at least one dose of ZELAPAR® (selegiline hydrochloride) (incidence ≥ 2%). The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients may differ.
Table 1: Treatment-Emergent Adverse Events* Incidence in
Double-Blind, Placebo-Controlled Trials (Events ≥ 2% of Patients Treated
with ZELAPAR® (selegiline hydrochloride) and Numerically More Frequent than the Placebo Group)
| Body System/
| ZELAPAR® (selegiline hydrochloride) †
|Body as a Whole|
|Hemic and Lymphatic System|
|Metabolic and Nutritional Disorders|
|Skin and Appendages|
|*Patients may have reported multiple adverse experiences during
the study or at discontinuation; thus patients may be included in more than
** Skin disorders represent any new skin abnormality that would not be characterized as rash or neoplastic lesion.
†Patients received concomitant levodopa.
Treatment emergent adverse events were reported at a higher frequency by patients ≥ 65 years of age compared to patients < 65 years old. Analysis of adverse event incidence in each group was conducted to calculate and compare relative risk (ZELAPAR® (selegiline hydrochloride) % / Placebo%) for each treatment. The relative risk was ≥ 2 fold higher for ZELAPAR® (selegiline hydrochloride) treatment in the geriatric patients compared to the non-geriatric patients for hypertension, orthostatic/postural hypotension (See WARNINGS - orthostatic hypotension), dizziness, somnolence, ECG abnormality, nausea, dyspepsia, abnormal dreams, anxiety, cheilitis, diarrhea, hyperkalemia, pharyngitis, flu syndrome, and infection.
No consistent differences in the incidences of adverse events were observed between male and female patients.
There were insufficient data to assess the impact of race on the incidence of adverse events.
Other Adverse Events Observed During all Clinical Trials
ZELAPAR® (selegiline hydrochloride) has been administered to 578 patients for whom complete adverse event data was captured during all clinical trials, only some of which were placebo controlled. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. Similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. All reported events are included below except those already listed elsewhere in labeling, those too general to be informative, and those not reasonably associated with the use of the drug.
Nervous System: abnormal gait, agitation, akinesia, aphasia, CNS neoplasia, dementia, dystonia, emotional lability, encephalopathy, hyperkinesias, hypertonia, hypokinesia, hypotonia, incoordination, increased salivation, myclonus, nervousness, neuralgia, neuropathy, paranoid reaction, paresthesia, peripheral neuritis, personality disorder, psychosis, reflexes decreased, sleep disorder, subdural hematoma, thinking abnormal, vertigo, migraine.
Digestive System: anorexia, cholecystitis, cholelithiasis, colitis, esophageal ulcer, esophagitis, gamma glutamyl transpeptidase increased, gastritis, gastroenteritis, gingivitis, hepatitis, intestinal obstruction, liver function tests abnormal, peptic ulcer, tongue edema.
Cardiovascular System: angina pectoris, atrial fibrillation, atrial flutter, AV block first degree, bigeminy, cardiomegaly, cardiomyopathy, cerebral ischemia, congestive heart failure, heart arrest, hypotension, migraine, myocardial infarct, myocardial ischemia, pallor, sinus bradycardia, supraventricular tachycardia, syncope, vascular disorder, vasodilation.
Skin and Appendages: contact dermatitis, dry skin, eczema, fungal dermatitis, herpes simplex, herpes zoster, pruritis, seborrhea, skin benign neoplasm, skin carcinoma, skin hypertrophy, skin melanoma, skin discoloration, skin ulcer, sweating.
Metabolic and Nutritional Disorders: avitaminosis, dehydration, diabetes mellitus, edema, gout, hyperchloestermia, hyperglycemia, hyperkalemia, hyperlipidemia, hyperphosphatemia, hypoglycemia, albuminuria, hyponatremia, hypoproteinemia, SPGT increased.
Urogenital Disorders: breast carcinoma, cystitis, epididymitis, kidney calculus, ovarian disorder, prostatic carcinoma, prostatic specific antigen increase, urinary frequency, urination impaired, urinary incontinence, urinary urgency.
Special Senses: abnormal vision, amblyopia, blindness, cataract specified, conjunctivitis, deafness, diplopia, dry eyes, eye hemorrhage, glaucoma, otitis externa, retinal artery occlusion, retinal detachment, taste loss, taste perversion, tinnitus.
There have been reports of the following adverse reactions: pathological gambling, increased libido including hypersexuality, and impulse control symptoms while taking one or more of the medications that are generally used for the treatment of Parkinson's disease.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a casual relationship to drug exposure.
Read the Zelapar (selegiline hydrochloride) Side Effects Center for a complete guide to possible side effects »
Meperidine: Serious, sometimes fatal reactions have been precipitated with concomitant use of meperidine (e.g., Demerol and other tradenames) and MAO inhibitors including selective MAO-B inhibitors. (See CONTRAINDICATIONS.)
Dextromethorphan: The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Therefore, in view of ZELAPAR® (selegiline hydrochloride) 's MAO inhibitory activity, dextromethorphan should not be used concomitantly with ZELAPAR®. (See CONTRAINDICATIONS.)
Selegiline Products: ZELAPAR® (selegiline hydrochloride) should not be administered along with other selegiline products (e.g., ELDEPRYL®) because of the increased risk of non-selective MAO inhibition that may lead to a hypertensive crisis. (See CONTRAINDICATIONS.)
Sympathomimetic medications: One case of hypertensive crisis has been reported in a patient taking the recommended dose of swallowed selegiline and a sympathomimetic medication (ephedrine).
Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors: Severe toxicity has also been reported in patients receiving the combination of tricyclic antidepressants and swallowed selegiline and selective serotonin reuptake inhibitors and swallowed selegiline. (See WARNINGS.)
Cytochrome P450 Enzymes: CYP2B6 and CYP3A4 are involved in the metabolism of selegiline. CYP2A6 may have a minor role in the metabolism of selegiline.
Effect of the CYP3A inhibitor itraconazole: Itraconazole (200 mg QD) did not affect the pharmacokinetics of selegiline (single 10 mg oral, swallowed dose).
Drugs that induce CYP450: Although adequate studies have not been done investigating the effect of CYP3A4-inducers on selegiline, drugs that induce CYP3A4 (e.g. phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution.
Drug Interaction Studies: No drug interaction studies have been conducted to evaluate the effects of other drugs on the pharmacokinetics of ZELAPAR® (selegiline hydrochloride) or the effect of selegiline on other drugs. In vitro studies have demonstrated that selegiline is not an inhibitor of CYP450 enzymes. The induction potential of selegiline has not been adequately characterized. Drugs that induce CYP3A4 (phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution.
Last reviewed on RxList: 2/19/2009
This monograph has been modified to include the generic and brand name in many instances.
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