SIDE EFFECTS
Introduction: The number of patients who received selegiline
in prospectively monitored pre-marketing studies is limited.
While other sources of information about the use of selegiline
are available (e.g., literature reports, foreign post-marketing
reports, etc.) they do not provide the kind of information
necessary to estimate the incidence of adverse events.
Thus, overall incidence figures for adverse reactions
associated with the use of selegiline cannot be provided.
Many of the adverse reactions seen have also been reported
as symptoms of dopamine excess.
Moreover, the importance and severity of various reactions
reported often cannot be ascertained. One index of relative
importance, however, is whether or not a reaction caused
treatment discontinuation. In prospective pre-marketing
studies, the following events led, in decreasing order
of frequency, to discontinuation of treatment with selegiline:
nausea, hallucinations, confusion, depression, loss of
balance, insomnia, orthostatic hypotension, increased
akinetic involuntary movements, agitation, arrhythmia,
bradykinesia, chorea, delusions, hypertension, new or
increased angina pectoris, and syncope. Events reported
only once as a cause of discontinuation are ankle edema,
anxiety, burning lips/mouth, constipation, drowsiness/lethargy,
dystonia, excess perspiration, increased freezing, gastrointestinal
bleeding, hair loss, increased tremor, nervousness, weakness,
and weight loss.
Experience with selegiline hydrochloride obtained in
parallel, placebo controlled, randomized studies provides
only a limited basis for estimates of adverse reaction
rates. The following reactions that occurred with greater
frequency among the 49 patients assigned to selegiline
as compared to the 50 patients assigned to placebo in
the only parallel, placebo controlled trial performed
in patients with Parkinson's disease are shown in TABLE
1. None of these adverse reactions led to a discontinuation
of treatment.
TABLE 1 - Incidence Of Treatment-Emergent
Adverse Experiences In The Placebo-Controlled Clinical
Trial
|
Adverse Event
|
Number of
Patients Reporting Events |
| selegiline
HCl |
placebo |
| N=49 |
N=50 |
|
Nausea
|
10 |
3 |
|
Dizziness/ Lightheaded/ Fainting
|
7 |
1 |
|
Abdominal Pain
|
4 |
2 |
|
Confusion
|
3 |
0 |
|
Hallucinations
|
3 |
1 |
|
Dry mouth
|
3 |
1 |
|
Vivid Dreams
|
2 |
0 |
|
Dyskinesias
|
2 |
5 |
|
Headache
|
2 |
1 |
|
The following events were reported once
in either or both groups:
|
|
Ache, generalized
|
1 |
0 |
|
Anxiety/Tension
|
1 |
1 |
|
Anemia
|
0 |
1 |
|
Diarrhea
|
1 |
0 |
|
Hair Loss
|
0 |
1 |
|
Insomnia
|
1 |
1 |
|
Lethargy
|
1 |
0 |
|
Leg pain
|
1 |
0 |
|
Low back pain
|
1 |
0 |
|
Malaise
|
0 |
1 |
|
Palpitations
|
1 |
0 |
|
Urinary Retention
|
1 |
0 |
|
Weight Loss
|
1 |
0 |
In all prospectively monitored investigations, enrolling
approximately 920 patients, the following adverse events,
classified by body system, were reported.
Central Nervous System: Motor/Coordination/Extrapyramidal:
increased tremor, chorea, loss of balance, restlessness,
blepharospasm, increased bradykinesia, facial grimace,
falling down, heavy leg, muscle twitch*, myoclonic jerks*,
stiff neck, tardive dyskinesia, dystonic symptoms, dyskinesia,
involuntary movements, freezing, festination, increased
apraxia, muscle cramps. Mental Status/Behavioral/Psychiatric:
hallucinations, dizziness, confusion, anxiety, depression,
drowsiness, behavior/mood change, dreams/nightmares, tiredness,
delusions, disorientation, lightheadedness, impaired memory*,
increased energy*, transient high*, hollow feeling, lethargy/malaise,
apathy, overstimulation, vertigo, personality change,
sleep disturbance, restlessness, weakness, transient irritability.
Pain/Altered Sensation: headache, back pain, leg pain,
tinnitus, migraine, supraorbital pain, throat burning,
generalized ache, chills, numbness of toes/fingers, taste
disturbance.
Autonomic Nervous System: dry mouth,
blurred vision, sexual dysfunction.
Cardiovascular: orthostatic hypotension,
hypertension, arrhythmia, palpitations, new or increased
angina pectoris, hypotension, tachycardia, peripheral
edema, sinus bradycardia, syncope.
Gastrointestinal: nausea/vomiting, constipation,
weight loss, anorexia, p.o. appetite, dysphagia, diarrhea,
heartburn, rectal bleeding, bruxism*, gastrointestinal
bleeding (exacerbation of preexisting ulcer disease).
Genitourinary/Gynecologic/Endocrine:
slow urination, transient anorgasmia*, nocturia, prostatic
hypertrophy, urinary hesitancy, urinary retention, decreased
penile sensation*, urinary frequency.
Skin and Appendages: increased sweating,
diaphoresis, facial hair, hair loss, hematoma, rash, photosensitivity.
Miscellaneous: asthma, diplopia, shortness
of breath, speech affected.
Postmarketing Reports: The following
experiences were described in spontaneous post-marketing
reports. These reports do not provide sufficient information
to establish a clear causal relationship with the use
of selegiline hydrochloride.
CNS: Seizure in dialyzed chronic renal
failure patient on concomitant medications.
* indicates events reported only at doses greater than
10 mg/day.
DRUG INTERACTIONS
The occurrence of stupor, muscular rigidity, severe agitation,
and elevated temperature has been reported in some patients
receiving the combination of selegiline and meperidine.
Symptoms usually resolve over days when the combination
is discontinued. This is typical of the interaction of
meperidine and MAOIs. Other serious reactions (including
severe agitation, hallucinations, and death) have been
reported in patients receiving this combination (see CONTRAINDICATIONS).
Severe toxicity has also been reported in patients receiving
the combination of tricyclic antidepressants and selegiline
hydrochloride and selective serotonin reuptake inhibitors
and selegiline hydrochloride. (See WARNINGS for details.)
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