(See also PRECAUTIONS)
Commonly Observed
The more commonly observed untoward events associated with
the use of BuSpar 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 BuSpar 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 BuSpar 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 enumerates adverse events that
occurred at a frequency of 1% or more among BuSpar (buspirone hydrochloride)
patients who participated in 4-week, controlled trials comparing BuSpar 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.
TREATMENT-EMERGENT ADVERSE EXPERIENCE INCIDENCE IN PLACEBO-CONTROLLED
CLINICAL TRIALS*
| Adverse Experience |
(Percent of Patients Reporting) |
BuSpar
(n=477) |
Placebo
(n=464) |
| Cardiovascular |
| Tachycardia/Palpitations |
1 |
1 |
| CNS |
| Dizziness |
12 |
3 |
| Drowsiness |
10 |
9 |
| Nervousness |
5 |
1 |
| Insomnia |
3 |
3 |
| Lightheadedness |
3 |
— |
| Decreased Concentration |
2 |
2 |
| Excitement |
2 |
— |
| Anger/Hostility |
2 |
— |
| Confusion |
2 |
— |
| Depression |
2 |
2 |
| EENT |
| Blurred Vision |
2 |
— |
| Gastrointestinal |
| Nausea |
8 |
5 |
| Dry Mouth |
3 |
4 |
| Abdominal/Gastric Distress |
2 |
2 |
| Diarrhea |
2 |
— |
| Constipation |
1 |
2 |
| Vomiting |
1 |
2 |
| Musculoskeletal |
| Musculoskeletal Aches/Pains |
1 |
— |
| Neurological |
| Numbness |
2 |
— |
| Paresthesia |
1 |
— |
| Incoordination |
1 |
— |
| Tremor |
1 |
— |
| Skin |
| Skin Rash |
1 |
— |
| Miscellaneous |
| Headache |
6 |
3 |
| Fatigue |
4 |
4 |
| Weakness |
2 |
— |
| Sweating/Clamminess |
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 BuSpar
During its premarketing assessment, BuSpar 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 BuSpar in the dose range for which BuSpar is being recommended (ie,
the modal daily dose of BuSpar fell between 10 mg and 30 mg for 70% of the
patients studied) and for whom safety data were systematically collected. The
conditions and duration of exposure to BuSpar varied greatly, involving well-controlled
studies as well as experience in open and uncontrolled clinical settings. As
part 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 BuSpar (buspirone hydrochloride) 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,
involuntary movements, slowed reaction time, 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; 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.
Postmarketing 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 (including urticaria),
angioedema, cogwheel rigidity, dizziness (rarely reported as vertigo), dystonic
reactions (including dystonia), ataxias, extrapyramidal symptoms, dyskinesias
(acute and tardive), ecchymosis, emotional lability, serotonin syndrome, transient
difficulty with recall, urinary retention, visual changes (including tunnel
vision), parkinsonism, akathisia, restless leg syndrome, and restlessness.
Because of the uncontrolled nature of these spontaneous reports, a causal
relationship to BuSpar treatment has not been determined.
Drug Abuse And Dependence
Controlled Substance Class
BuSpar (buspirone hydrochloride) 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 BuSpar 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 BuSpar 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 BuSpar misuse or abuse (eg, development of tolerance,
incrementation of dose, drug-seeking behavior).