iety (of at least 1 month continual duration), manifested by symptoms from three of the four following categories: motor tension: shakiness, jitteriness, jumpiness, trembling, tension, muscle aches, fatigability, inability to relax, eyelid twitch, furrowed brow, strained face, fidgeting, restlessness, easy startle. autonomic hyperactivity: sweating, heart pounding or racing, cold, clammy hands, dry mouth, dizziness, lightheadedness, paresthesias (tingling in hands or feet), upset stomach, hot or cold spells, frequent urination, diarrhea, discomfort in the pit of the stomach, lump in the throat, flushing, pallor, high resting pulse and respiration rate. apprehensive expectation: anxiety, worry, fear, rumination, and anticipation of misfortune to self or others. vigilance and scanning: hyperattentiveness resulting in distractibility, difficulty in concentrating, insomnia, feeling "on edge," irritability, impatience. the above symptoms would not be due to another mental disorder, such as a depressive disorder or schizophrenia. however, mild depressive symptoms are common in gad. the effectiveness of buspirone hydrochloride tablets, usp in long-term use, that is, for more than 3 to 4 weeks, has not been demonstrated in controlled trials. there is no body of evidence available that systematically addresses the appropriate duration of treatment for gad. however, in a study of long-term use, 264 patients were treated with buspirone hydrochloride tablets, usp for 1 year without ill effect. therefore, the physician who elects to use buspirone hydrochloride tablets, usp for extended periods should periodically reassess the usefulness of the drug for the individual patient.

le blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular changes (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). patients should be monitored for emergence of serotonin syndrome. the concomitant use of buspirone with maois intended to treat depression is contraindicated. buspirone should also not be started in a patient who is being treated with reversible maois such as linezolid or intravenous methylene blue. all reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. there have been no reports involving the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. there may be circumstances when it is necessary to initiate treatment with a reversible maoi such as linezolid or intravenous methylene blue in a patient taking buspirone. buspirone should be discontinued before initiating treatment with the reversible maoi (see contraindications, dosage and administration and drug interactions). if concomitant use of buspirone with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. the concomitant use of buspirone with serotonin precursors (such as tryptophan) is not recommended. treatment with buspirone and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. because buspirone hydrochloride has no established antipsychotic activity, it should not be employed in lieu of appropriate antipsychotic treatment.

with buspirone hydrochloride tablets. conversely, at least 14 days should be allowed after stopping buspirone hydrochloride tablets before starting an maoi antidepressant contraindications and drug interactions). use of buspirone hydrochloride tablets with (reversible) maois, such as linezolid or methylene blue do not start buspirone hydrochloride tablets in a patient who is being treated with a reversible maoi such as linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. in a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered (see contraindications and drug interactions). in some cases, a patient already receiving therapy with buspirone hydrochloride tablets may require urgent treatment with linezolid or intravenous methylene blue. if acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, buspirone hydrochloride tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. the patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. therapy with buspirone hydrochloride tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see warnings). the risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg per kg with buspirone hydrochloride tablets is unclear. the clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see contraindications, warnings and drug interactions).

cellaneous 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 buspirone hydrochloride patients who participated in 4-week, controlled trials comparing buspirone hydrochloride 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* * events reported by at least 1% of buspirone patients are included. (percent of patients reporting) buspirone placebo adverse experience (n = 477) (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 - - incidence less than 1%. other events observed during the entire premarketing evaluation of buspirone hydrochloride during its premarketing assessment, buspirone hydrochloride were 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 hydrochloride in the dose range for which buspirone is being recommended (i.e., the modal daily dose of buspirone hydrochloride 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 buspirone hydrochloride 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 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 buspirone hydrochloride treatment has not been determined.

ne are very low and variable between subjects. peak plasma levels of 1 ng/ml to 6 ng/ml have been observed 40 to 90 minutes after single oral doses of 20 mg. the single-dose bioavailability of unchanged buspirone when taken as a tablet is on the average about 90% of an equivalent dose of solution, but there is large variability. the effects of food upon the bioavailability of buspirone hydrochloride tablets have been studied in eight subjects. they were given a 20 mg dose with and without food; the area under the plasma concentration-time curve (auc) and peak plasma concentration (cmax) of unchanged buspirone increased by 84% and 116%, respectively, but the total amount of buspirone immunoreactive material did not change. this suggests that food may decrease the extent of presystemic clearance of buspirone (see dosage and administration). a multiple-dose study conducted in 15 subjects suggests that buspirone has nonlinear pharmacokinetics. thus, dose increases and repeated dosing may lead to somewhat higher blood levels of unchanged buspirone than would be predicted from results of single-dose studies. an in vitro protein binding study indicated that approximately 86% of buspirone is bound to plasma proteins. it was also observed that aspirin increased the plasma levels of free buspirone by 23%, while flurazepam decreased the plasma levels of free buspirone by 20%. however, it is not known whether these drugs cause similar effects on plasma levels of free buspirone in vivo, or whether such changes, if they do occur, cause clinically significant differences in treatment outcome. an in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin, warfarin, and propranolol from plasma protein, and that buspirone may displace digoxin. buspirone is metabolized primarily by oxidation, which in vitro has been shown to be mediated by cytochrome p450 3a4 (cyp3a4) (see precautions, drug interactions). several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-pp), are produced. in animal models predictive of anxiolytic potential, 1-pp has about one quarter of the activity of buspirone, but is present in up to 20-fold greater amounts. however, this is probably not important in humans: blood samples from humans chronically exposed to buspirone hydrochloride tablets do not exhibit high levels of 1-pp; mean values are approximately 3 ng/ml and the highest human blood level recorded among 108 chronically dosed patients was 17 ng/ml, less than 1/200th of 1-pp levels found in animals given large doses of buspirone without signs of toxicity. in a single-dose study using 14c-labeled buspirone, 29% to 63% of the dose was excreted in the urine within 24 hours, primarily as metabolites; fecal excretion accounted for 18% to 38% of the dose. the average elimination half-life of unchanged buspirone after single doses of 10 mg to 40 mg is about 2 to 3 hours. special populations age and gender effects after single or multiple doses in adults, no significant differences in buspirone pharmacokinetics (auc and cmax) were observed between elderly and younger subjects or between men and women. hepatic impairment after multiple-dose administration of buspirone to patients with hepatic impairment, steady-state auc of buspirone increased 13-fold compared with healthy subjects (see precautions). renal impairment after multiple-dose administration of buspirone to renally impaired (clcr = 10 to 70 ml/min/1.73 m2) patients, steady-state auc of buspirone increased 4-fold compared with healthy (clcr > 80 ml/min/1.73 m2) subjects (see precautions). race effects the effects of race on the pharmacokinetics of buspirone have not been studied.

7" on one side of the trisect segments and plain on other side of the trisect segment. bottle of 60: ndc bottle of 100: ndc bottle of 500: ndc store at 200 to 250c (680 to 770f) [see usp controlled room temperature]. dispense in a tight, light-resistant container as defined in the usp, with a child-resistant closure (as required). keep this and all drugs out of reach of children. additional patient information leaflets can be obtained by calling unichem at 1-866-562-4616.