ere observed. haloperidol in a study in normal volunteers, concomitant administration of buspirone and haloperidol resulted in increased serum haloperidol concentrations. the clinical significance of this finding is not clear. nefazodone (see inhibitors and inducers of cytochrome p450 3a4 [cyp3a4] ) trazodone there is one report suggesting that the concomitant use of desyrel ® (trazodone hydrochloride) and buspirone 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. triazolam/flurazepam coadministration of buspirone with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine. other psychotropics because the effects of concomitant administration of buspirone with most other psychotropic drugs have not been studied, the concomitant use of buspirone with other cns-active drugs should be approached with caution. inhibitors and inducers of cytochrome p450 3a4 (cyp3a4) buspirone has been shown in vitro to be metabolized by cyp3a4. this finding is consistent with the in vivo interactions observed between buspirone and the following: diltiazem and verapamil in a study of nine healthy volunteers, coadministration of buspirone (10 mg as a single dose) with verapamil (80 mg t.i.d.) or diltiazem (60 mg t.i.d.) increased plasma buspirone concentrations (verapamil increased auc and c max of buspirone 3.4-fold while diltiazem increased auc and c max 5.5-fold and 4-fold, respectively). adverse events attributable to buspirone may be more likely during concomitant administration with either diltiazem or verapamil. subsequent dose adjustment may be necessary and should be based on clinical assessment. erythromycin in a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with erythromycin (1.5 g/day for 4 days) increased plasma buspirone concentrations (5-fold increase in c max and 6-fold increase in auc). these pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to buspirone. if the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg b.i.d.) is recommended. subsequent dose adjustment of either drug should be based on clinical assessment. grapefruit juice in a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with grapefruit juice (200 ml double-strength t.i.d. for 2 days) increased plasma buspirone concentrations (4.3-fold increase in c max ; 9.2-fold increase in auc). patients receiving buspirone should be advised to avoid drinking such large amounts of grapefruit juice. itraconazole in a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with itraconazole (200 mg/day for 4 days) increased plasma buspirone concentrations (13-fold increase in c max and 19-fold increase in auc). these pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to buspirone. if the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg q.d.) is recommended. subsequent dose adjustment of either drug should be based on clinical assessment. nefazodone in a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg b.i.d.) with nefazodone (250 mg b.i.d.) resulted in marked increases in plasma buspirone concentrations (increases up to 20-fold in c max and up to 50-fold in auc) and statistically significant decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pp. with 5 mg b.i.d. doses of buspirone, slight increases in auc were observed for nefazodone (23%) and its metabolites hydroxynefazodone (ho-nef) (17%) and meta-chlorophenylpiperazine (9%). slight increases in c max were observed for nefazodone (8%) and its metabolite ho-nef (11%). subjects receiving buspirone 5 mg b.i.d. and nefazodone 250 mg b.i.d. experienced lightheadedness, asthenia, dizziness, and somnolence, adverse events also observed with either drug alone. if the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg q.d.) is recommended. subsequent dose adjustment of either drug should be based on clinical assessment. rifampin in a study in healthy volunteers, coadministration of buspirone (30 mg as a single dose) with rifampin (600 mg/day for 5 days) decreased the plasma concentrations (83.7% decrease in c max ; 89.6% decrease in auc) and pharmacodynamic effects of buspirone. if the two drugs are to be used in combination, the dosage of buspirone may need adjusting to maintain anxiolytic effect. other inhibitors and inducers of cyp3a4 substances that inhibit cyp3a4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce cyp3a4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism. if a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone or diminished anxiolytic activity. consequently, when administered with a potent inhibitor of cyp3a4, a low dose of buspirone used cautiously is recommended. when used in combination with a potent inducer of cyp3a4 the dosage of buspirone may need adjusting to maintain anxiolytic effect. other drugs cimetidine coadministration of buspirone with cimetidine was found to increase c max (40%) and t max (2-fold), but had minimal effects on the auc of buspirone. protein binding 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 synthroid ® (levothyroxine sodium). in vitro , buspirone may displace less firmly bound drugs like digoxin. the clinical significance of this property is unknown. therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of buspirone to plasma proteins (see clinical pharmacology ).

ent anxiety (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 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 for 1 year without ill effect. therefore, the physician who elects to use buspirone hydrochloride tablets for extended periods should periodically reassess the usefulness of the drug for the individual patient.

(e.g., tachycardia, labile 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-hydroxytryptmine 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 tablets has no established antipsychotic activity, it should not be employed in lieu of appropriate antipsychotic treatment.

een with cessation of therapy with these drugs. therefore, before starting therapy with buspirone hydrochloride tablets, it is advisable to withdraw patients gradually, especially patients who have been using a cns-depressant drug chronically, from their prior treatment. rebound or withdrawal symptoms may occur over varying time periods, depending in part on the type of drug, and its effective half-life of elimination. the syndrome of withdrawal from sedative/hypnotic/anxiolytic drugs can appear as any combination of irritability, anxiety, agitation, insomnia, tremor, abdominal cramps, muscle cramps, vomiting, sweating, flu-like symptoms without fever, and occasionally, even as seizures. possible concerns related to buspirone's binding to dopamine receptors because buspirone can bind to central dopamine receptors, a question has been raised about its potential to cause acute and chronic changes in dopamine-mediated neurological function (e.g., dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia). clinical experience in controlled trials has failed to identify any significant neuroleptic-like activity; however, a syndrome of restlessness, appearing shortly after initiation of treatment, has been reported in some small fraction of buspirone-treated patients. the syndrome may be explained in several ways. for example, buspirone may increase central noradrenergic activity; alternatively, the effect may be attributable to dopaminergic effects (i.e., represent akathisia). see adverse reactions: postmarketing experience .

and initiation of therapy with buspirone hydrochloride tablets. conversely, at least 14 days should be allowed after stopping buspirone hydrochloride tablets before starting an maoi antidepressant (see 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 ).

isturbances (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 buspirone hydrochloride patients who participated in 4-week, controlled trials comparing buspirone hydrochloride tablets 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 hydrochloride patients are included. (percent of patients reporting) adverse experience buspirone hydrochloride (n = 477) placebo (n = 464) - incidence less than 1%. 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 - other events observed during the entire premarketing evaluation of buspirone hydrochloride tablets during its premarketing assessment, buspirone hydrochloride tablets were evaluated in over 3,500 subjects. this section reports event frequencies for adverse events occurring in approximately 3,000 subjects from this group who took multiple doses of buspirone hydrochloride tablets in the dose range for which buspirone is being recommended (i.e., the modal daily dose of buspirone hydrochloride tablets 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 tablets 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 1/1,000 patients, while rare events are those occurring in less than 1/1,000 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 tablets treatment has not been determined. to report suspected adverse reactions, contact nivagen pharmaceuticals, inc. at 1-877-977-0687 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

ere observed. haloperidol in a study in normal volunteers, concomitant administration of buspirone and haloperidol resulted in increased serum haloperidol concentrations. the clinical significance of this finding is not clear. nefazodone (see inhibitors and inducers of cytochrome p450 3a4 [cyp3a4] ) trazodone there is one report suggesting that the concomitant use of desyrel ® (trazodone hydrochloride) and buspirone 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. triazolam/flurazepam coadministration of buspirone with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine. other psychotropics because the effects of concomitant administration of buspirone with most other psychotropic drugs have not been studied, the concomitant use of buspirone with other cns-active drugs should be approached with caution. inhibitors and inducers of cytochrome p450 3a4 (cyp3a4) buspirone has been shown in vitro to be metabolized by cyp3a4. this finding is consistent with the in vivo interactions observed between buspirone and the following: diltiazem and verapamil in a study of nine healthy volunteers, coadministration of buspirone (10 mg as a single dose) with verapamil (80 mg t.i.d.) or diltiazem (60 mg t.i.d.) increased plasma buspirone concentrations (verapamil increased auc and c max of buspirone 3.4-fold while diltiazem increased auc and c max 5.5-fold and 4-fold, respectively). adverse events attributable to buspirone may be more likely during concomitant administration with either diltiazem or verapamil. subsequent dose adjustment may be necessary and should be based on clinical assessment. erythromycin in a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with erythromycin (1.5 g/day for 4 days) increased plasma buspirone concentrations (5-fold increase in c max and 6-fold increase in auc). these pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to buspirone. if the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg b.i.d.) is recommended. subsequent dose adjustment of either drug should be based on clinical assessment. grapefruit juice in a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with grapefruit juice (200 ml double-strength t.i.d. for 2 days) increased plasma buspirone concentrations (4.3-fold increase in c max ; 9.2-fold increase in auc). patients receiving buspirone should be advised to avoid drinking such large amounts of grapefruit juice. itraconazole in a study in healthy volunteers, coadministration of buspirone (10 mg as a single dose) with itraconazole (200 mg/day for 4 days) increased plasma buspirone concentrations (13-fold increase in c max and 19-fold increase in auc). these pharmacokinetic interactions were accompanied by an increased incidence of side effects attributable to buspirone. if the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg q.d.) is recommended. subsequent dose adjustment of either drug should be based on clinical assessment. nefazodone in a study of steady-state pharmacokinetics in healthy volunteers, coadministration of buspirone (2.5 or 5 mg b.i.d.) with nefazodone (250 mg b.i.d.) resulted in marked increases in plasma buspirone concentrations (increases up to 20-fold in c max and up to 50-fold in auc) and statistically significant decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pp. with 5 mg b.i.d. doses of buspirone, slight increases in auc were observed for nefazodone (23%) and its metabolites hydroxynefazodone (ho-nef) (17%) and meta-chlorophenylpiperazine (9%). slight increases in c max were observed for nefazodone (8%) and its metabolite ho-nef (11%). subjects receiving buspirone 5 mg b.i.d. and nefazodone 250 mg b.i.d. experienced lightheadedness, asthenia, dizziness, and somnolence, adverse events also observed with either drug alone. if the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg q.d.) is recommended. subsequent dose adjustment of either drug should be based on clinical assessment. rifampin in a study in healthy volunteers, coadministration of buspirone (30 mg as a single dose) with rifampin (600 mg/day for 5 days) decreased the plasma concentrations (83.7% decrease in c max ; 89.6% decrease in auc) and pharmacodynamic effects of buspirone. if the two drugs are to be used in combination, the dosage of buspirone may need adjusting to maintain anxiolytic effect. other inhibitors and inducers of cyp3a4 substances that inhibit cyp3a4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce cyp3a4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism. if a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone or diminished anxiolytic activity. consequently, when administered with a potent inhibitor of cyp3a4, a low dose of buspirone used cautiously is recommended. when used in combination with a potent inducer of cyp3a4 the dosage of buspirone may need adjusting to maintain anxiolytic effect. other drugs cimetidine coadministration of buspirone with cimetidine was found to increase c max (40%) and t max (2-fold), but had minimal effects on the auc of buspirone. protein binding 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 synthroid ® (levothyroxine sodium). in vitro , buspirone may displace less firmly bound drugs like digoxin. the clinical significance of this property is unknown. therapeutic levels of aspirin, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamide had only a limited effect on the extent of binding of buspirone to plasma proteins (see clinical pharmacology ).

tions of unchanged buspirone 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 (c max ) 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 14 c-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 c max ) 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 (cl cr = 10 to 70 ml/min/1.73 m 2 ) patients, steady-state auc of buspirone increased 4-fold compared with healthy (cl cr ≥ 80 ml/min/1.73 m 2 ) subjects (see precautions ). race effects the effects of race on the pharmacokinetics of buspirone have not been studied.

segments, and debossed "5" on each trisect segment, packaged in bottles of 60 tablets (ndc 75834-269-60),100 tablets (ndc 75834-269-01) and 500 tablets (ndc 75834-269-05). buspirone hydrochloride tablets, usp 30 mg are available as white to off white, flat faced, capsule shaped, functionally-scored tablet that can be bisected or trisected, debossed with "1" and "01" on bisect segments, and debossed "10" on each trisect segment, packaged in bottles of 60 tablets (ndc 75834-270-60). store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. dispense in a tight, light-resistant container (usp).

this medication affects you, do not drive a car or operate potentially dangerous machinery. you should take buspirone hydrochloride tablets consistently, either always with or always without food. during your treatment with buspirone hydrochloride tablets, avoid drinking large amounts of grapefruit juice.