A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Buspar Side Effects, and Drug Interactions - Buspirone
Buspar Side Effects, and Drug Interactions - Buspirone
SIDE EFFECTS
(See also PRECAUTIONS)
Commonly Observed
The more commonly observed untoward events associated with the use of
buspirone HCl not seen at an equivalent
incidence among placebo-treated
patients include dizziness, nausea, headache, nervousness, lightheadedness,
and excitement.
Associated with Discontinuation of Treatment
One guide to the relative clinical
importance of adverse events associated with buspirone HCl is provided
by the frequency with which they caused drug discontinuation during clinical
testing. Approximately 10% of the 2200 anxious patients who participated
in the buspirone HCl premarketing clinical efficacy trials in anxiety
disorders lasting 3 to 4 weeks discontinued treatment due to an adverse
event. The more common events causing discontinuation included: central
nervous system
disturbances (3.4%), primarily dizziness, insomnia, nervousness, drowsiness,
and lightheaded feeling; gastrointestinal disturbances (1.2%), primarily
nausea; and miscellaneous disturbances (1.1%), primarily headache
and fatigue. In addition, 3.4%
of patients had multiple complaints, none of which could be characterized
as primary.
Incidence in Controlled Clinical Trials
The table that follows (TABLE
1) enumerates adverse events that occurred at a frequency of 1% or more
among buspirone HCl patients who participated in 4-week, controlled trials
comparing buspirone HCl with placebo. The frequencies were obtained from
pooled data for 17 trials. The prescriber should be aware that these figures
cannot be used to predict the incidence of side
effects in the course of usual medical
practice where patient
characteristics and other factors differ from those which prevailed in
the clinical trials. Similarly,
the cited frequencies cannot be compared with figures obtained from other
clinical investigations involving
different treatments, uses, and investigators. Comparison of the cited
figures, however, does provide the prescribing physician
with some basis for estimating
the relative contribution of drug
and nondrug factors to the side
effect incidence
rate in the population studied.
| TABLE 1 Treatment-Emergent Adverse Experience
Incidence In Placebo-Controlled
Clinical Studies* |
| (Percent of Patients Reporting) |
| |
Buspirone HCl |
Placebo |
| Adverse Experience |
(n = 477) |
(n = 464) |
| Cardiovascular |
|
|
1 |
1 |
| CNS |
|
|
12 |
3 |
|
|
10 |
9 |
|
|
5 |
1 |
|
|
3 |
3 |
|
|
3 |
- |
|
|
2 |
2 |
|
|
2 |
- |
|
|
2 |
- |
|
|
2 |
- |
|
|
2 |
2 |
| EENT |
|
|
2 |
- |
| Gastrointestinal |
|
|
8 |
5 |
|
|
3 |
4 |
|
|
2 |
2 |
|
|
2 |
- |
|
|
1 |
2 |
|
|
1 |
2 |
| Musculoskeletal |
|
|
1 |
- |
| Neurological |
|
|
2 |
- |
|
|
1 |
- |
|
|
1 |
- |
|
|
1 |
- |
| Skin |
|
|
1 |
- |
| Miscellaneous |
|
|
6 |
3 |
|
|
4 |
4 |
|
|
2 |
- |
|
|
1 |
- |
|
* Events reported by at least 1% of BuSpar patients are
included.
- Incidence less than 1%.
|
Other Events Observed During the Entire Premarketing Evaluation of
Buspirone HCl
During its premarketing assessment, buspirone HCl was evaluated in over
3500 subjects. This section
reports event frequencies for adverse events occurring in approximately
3000 subjects from this group
who took multiple doses of buspirone HCl in the dose
range for which buspirone HCl
is being recommended (i.e., the modal
daily dose of buspirone HCl fell
between 10 and 30 mg for 70% of
the patients studied) and for whom safety data were systematically collected.
The conditions and duration
of exposure to buspirone HCl varied greatly, involving well-controlled
studies as well as experience
in open and uncontrolled clinical
settings. As party
of the total experience
gained in clinical studies,
various adverse events were reported. In
the absence of appropriate
controls in some of the studies, a causal relationship to buspirone HCl
treatment cannot be determined.
The list includes all undesirable events reasonably associated with the
use of the drug.
The following enumeration by organ
system describes events in
terms of their relative frequency of reporting in this data base. Events
of major clinical importance are also described in the PRECAUTIONS
section.
The following definitions of frequency are used: Frequent adverse events
are defined as those occurring in at least 1/100 patients. Infrequent
adverse events are those occurring in 1/100 to 1/1000 patients, while
rare events are those occurring in less than 1/1000 patients.
Cardiovascular: Frequent was nonspecific
chest pain; infrequent were
syncope, hypotension, and hypertension; rare were cerebrovascular accident,
congestive heart failure, myocardial
infarction, cardiomyopathy, and bradycardia.
Central Nervous System: Frequent: were dream
disturbances; Infrequent: were depersonalization, dysphoria, noise
intolerance, euphoria, akathisia, fearfulness, loss
of interest, dissociative reaction, hallucinations, suicidal ideation,
and seizures; Rare: were feelings of claustrophobia, cold
intolerance, stupor, and slurred speech
and psychosis.
EENT: Frequent: were tinnitus, sore
throat, and nasal congestion; Infrequent: were redness and itching
of the eyes, altered taste, altered smell, and conjunctivitis; Rare:
were inner ear abnormality, eye
pain, photophobia, and pressure
on eyes.
Endocrine: Rare: were galactorrhea
and thyroid abnormality.
Gastrointestinal: Infrequent: were flatulence, anorexia,
increased appetite, salivation, irritable
colon, and rectal bleeding;
Rare: was burning of the tongue.
Genitourinary: Infrequent: were urinary frequency,
urinary hesitancy, menstrual irregularity and spotting, and dysuria; Rare:
were amenorrhea, pelvic inflammatory
disease, enuresis, and nocturia.
Musculoskeletal: Infrequent: were muscle
cramps, muscle spasms, rigid/stiff muscles, and arthralgias.
Neurological: Infrequent: were involuntary movements
and slowed reaction time;
Rare: was muscle weakness.
Respiratory: Infrequent: were hyperventilation,
shortness of breath, and chest
congestion; Rare: was epistaxis.
Sexual Function: Infrequent: were decreased or increased
libido; Rare: were delayed ejaculation
and impotence.
Skin: Infrequent: were edema, pruritus, flushing,
easy bruising, hair loss, dry
skin, facial edema, and blisters;
Rare: were acne and thinning
of nails.
Clinical Laboratory: Infrequent: were increases
in hepatic aminotransferases
(SGOT, SGPT); Rare: were eosinophilia, leukopenia, and thrombocytopenia.
Miscellaneous: Infrequent: were weight
gain, fever, roaring sensation
in the head, weight loss, and
malaise; Rare: were alcohol abuse, bleeding
disturbance, loss of voice, and
hiccoughs.
Post-Introduction Clinical Experience
Postmarketing experience
has shown an adverse experience
profile similar to that given
above. Voluntary reports since introduction have included rare occurrences
of allergic reactions, cogwheel
rigidity, dystonic reactions, ecchymosis, emotional lability, tunnel
vision, and urinary retention. Because of the uncontrolled nature of these
spontaneous reports, a
causal relationship to buspirone HCl treatment
has not been determined.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class: Buspirone HCl is not a controlled
substance.
Physical and Psychological Dependence
In human and animal
studies, buspirone has shown no potential
for abuse or diversion and there is no evidence
that it causes tolerance, or either physical or psychological
dependence. Human volunteers with a history of recreational drug
or alcohol usage were studied
in two double-blind clinical investigations. None of the subjects were
able to distinguish between buspirone HCl and placebo. By contrast, subjects
showed a statistically significant preference for methaqualone and diazepam.
Studies in monkeys, mice, and rats have indicated that buspirone lacks
potential for abuse.
Following chronic administration
in the rat, abrupt withdrawal
of buspirone did not result in the loss
of body weight commonly observed
with substances that cause physical
dependency.
Although there is no direct evidence
that buspirone HCl causes physical dependence or drug-seeking behavior,
it is difficult to predict from experiments the extent to which a CNS-active
drug will
be misused, diverted, and/or abused once marketed. Consequently, physicians
should carefully evaluate patients for a history of drug
abuse and follow such patients
closely, observing them for signs of buspirone HCl misuse or abuse
(eg, development of tolerance, incrementation of dose, drug-seeking behavior).
DRUG INTERACTIONS
It is recommended that buspirone hydrochloride
not be used concomitantly with MAO
inhibitors (See WARNINGS.) Because
the effects of concomitant
administration of buspirone
HCl with most other psychotropic drugs have not been studied, the concomitant
use of buspirone HCl with other CNS-active drugs should be approached
with caution.
There is one report suggesting
that the concomitant use
of trazodone hydrochloride (Desyrel) and buspirone HCl may have caused
3- to 6-fold elevations on SGPT
(ALT) in a few patients. In a similar
study, attempting to replicate this finding, no interactive effect
on hepatic transaminases was
identified.
In a study in normal volunteers,
concomitant administration
of buspirone HCl and haloperidol
resulted in increased serum
haloperidol concentrations.
The clinical significance
of this finding is not clear.
In vitro, buspirone does not displace tightly bound
drugs like phenytoin, propranolol, and warfarin from serum
proteins. However, there has been one report
of prolonged prothrombin
time when buspirone was added
to the regimen of a patient
treated with warfarin. The patient
was also chronically receiving phenytoin, phenobarbital, digoxin, and
levothyroxine sodium. In vitro, buspirone may displace less firmly
bound drugs like digoxin. The
clinical significance of
this property is unknown.
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