Buspar
Buspar Medication Information:
Buspar medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Buspar 10 mg
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Buspar 15 mg
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Buspar 30 mg
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Pharmacology
Buspirone is a psychotropic drug with selective anxiolytic properties which belongs chemically to the class of compounds known as the azaspirodecanediones, not chemically or pharmacologically related to benzodiazepines, barbiturates, or other known psychotropic agents.
Buspirone shares some of the properties of the benzodiazepines and the neuroleptics, as well as demonstrating other pharmacological action. Buspirone attenuates punishment suppressed behavior in animals and exerts a taming effect, but is devoid of anticonvulsant and muscle relaxant properties and does not bind to the benzodiazepine/GABA receptor complex. Buspirone affects a variety of dopamine mediated biochemical and behavioral events, but is free of cataleptic activity. Buspirone has an affinity for brain D2-dopamine receptors, where it acts as an antagonist and agonist, and for the 5-HT1A receptors, where it acts as an agonist. Buspirone does not block the neuronal reuptake of monoamines and, on chronic administration, it does not lead to changes in receptor density in the models investigated. However, the mechanism of action of buspirone remains to be fully elucidated.
Buspirone is rapidly absorbed in man and undergoes extensive first pass metabolism. Following oral administration, low peak plasma levels of unchanged drug, of 1 to 6 ng/mL were observed 40 to 90 minutes after a single 20 mg dose. In a number of studies performed in healthy volunteers, the mean half-life of buspirone ranged from 2 to 3 hours up to approximately 11 hours with considerable variation in individual values. Multiple dose studies suggest that steady-state plasma levels were usually achieved within a few days. 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 two pharmacologically active metabolites, 6-hydroxybuspirone (6-OHB) and 1-pyrimidinylpiperazine (1-PP), are produced. In an animal model of anxiolytic potential, 6-OHB has the same activity as buspirone. In healthy subjects administered buspirone orally, plasma concentrations of 6-OHB are approximately 40 times greater than those of buspirone, suggesting this metabolite may be the predominate contributor to clinical anxiolytic effects. In animal models predictive of anxiolytic potential, 1-PP has about 25% or less of the activity of buspirone. Peak plasma levels of 1-PP have been found to be higher than those of its parent drug and its half-life to be approximately double that of unchanged buspirone. 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, while fecal excretion accounted for 18 to 38% of the dose. In man, approximately 95% of buspirone is plasma protein bound. Other highly bound drugs, e.g., phenytoin, propranolol and warfarin, are not displaced by buspirone from plasma protein binding in vitro at clinically relevant concentrations. However, in vitro binding studies show that buspirone does displace digoxin.
The effects of food upon the bioavailability of BuSpar tablets have been studied in 8 subjects. They were given a 20 mg dose with or without food. The AUC and Cmax of unchanged buspirone increased by 84% and 116%, respectively. The total amount of buspirone immunoreactive material did not change. This suggests that food may decrease the extent of presystemic clearance of buspirone.
Buspirone had no effect on hepatic microsomal enzyme activity when administered to rats for 5 days. In man, the effect of buspirone on drug metabolism or concomitant drug disposition has not been studied. Buspirone clearance is reduced in patients with hepatic impairment as well as in patients with impaired renal function. No significant differences in buspirone pharmacokinetics as a function of age and/or sex was found.
Indications
For the short-term symptomatic relief of excessive anxiety in patients with generalized anxiety disorder.
The effectiveness of BuSpar (buspirone hydrochloride) in long-term use (i.e., more than 4 weeks) has not been evaluated in controlled clinical trials.
Eight 3-way short-term, controlled clinical trials involving buspirone, diazepam and placebo are considered central to the evaluation of buspirone as an anxiolytic agent. In 4 of the 8 clinical trials, buspirone demonstrated a significant difference from placebo. In the other 4 trials, there was no significant difference between buspirone and placebo, but a significantly greater improvement was observed with diazepam than with placebo. The adverse effect profiles of buspirone and diazepam in these clinical trials were, however, different.
Precautions
Geriatrics
Buspirone has not been systematically evaluated in older patients. Although it would appear from limited pharmacokinetic and clinical studies that buspirone does not behave differently in the elderly, there is little known about the effects of buspirone in this age group at doses above 30 mg/day. Therefore, it is recommended that buspirone should be used in the elderly at doses not exceeding 30 mg/day for a duration not exceeding 4 weeks.
Drug Interactions
Alcohol: In laboratory studies in healthy volunteers, buspirone in doses up to 20 mg did not potentiate the psychomotor impairment produced by relatively modest doses of alcohol. However, decreased contentedness or dysphoria was observed with a combination of alcohol and a 20 mg single dose of buspirone. Since no data are available on concomitant use of higher doses of buspirone and alcohol, it is prudent to advise patients to avoid alcohol during buspirone therapy.
Food: Food may decrease the extent of presystemic clearance of buspirone.
MAOIs: Concomitant use of MAOIs and buspirone has been reported to cause an increase in blood pressure. Therefore, concomitant use of these medications is not recommended (see Warnings).
Amitriptyline: In a study in normal volunteers, no interaction of buspirone with amitriptyline was seen.
Haloperidol: In another 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.
Trazodone: There is 1 report suggesting that the concomitant use of trazodone and buspirone may have caused 3- to 6-fold elevations in ALT in a few patients. In a similar study, attempting to replicate this finding, no interactive effect on hepatic transaminases was identified.
The concomitant use of buspirone with other CNS active drugs should be approached with caution (see Warnings).
Protein Binding: In vitro, buspirone does not displace from serum protein drugs like phenytoin, propranolol and warfarin that are highly protein-bound. However, there have been rare reports of prolonged prothrombin time when buspirone was added to the regimen of a patient treated with warfarin. In vitro, buspirone may displace less firmly protein-bound drugs like digoxin. The clinical significance of this property is unknown.
Therapeutic levels of ASA, desipramine, diazepam, flurazepam, ibuprofen, propranolol, thioridazine, and tolbutamine had only limited effect on the extent of binding of buspirone to plasma proteins.
SSRI: Overall, there have been no major safety problems reported with the combination of buspirone and selective serotonin reuptake inhibitor antidepressants. Seizures have been reported rarely in patients taking this combination.
Diazepam: After addition of buspirone to the diazepam dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (Cmax, AUC, and Cmin) were observed for diazepam, but increases of about 15% were seen for nordiazepam, and minor adverse clinical effects (dizziness, headache, and nausea) were observed.
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. 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, an adjustment of the dosage of buspirone may be necessary to maintain buspirone's anxiolytic effect.
Cimetidine: Coadministration of buspirone and cimetidine was found to increase Cmax (40%) and Tmax (2-fold) of buspirone, but had minimal effect on AUC of buspirone.
Patients with Impaired Hepatic or Renal Function
Since it is metabolized by the liver and excreted by the kidneys, buspirone should be used with caution in patients with a history of hepatic or renal impairment. It is contraindicated in patients with severe hepatic or renal impairment.
Children
The safety and effectiveness of buspirone in individuals below the age of 18 years have not been established.
Potential Interaction with Drugs That Inhibit Cytochrome P450 3A4 (CYP3A4)
Buspirone has been shown in vitro to be metabolized by CYP3A4. This is consistent with the interaction observed between buspirone and erythromycin, itraconazole, and nefazodone, drugs that inhibit this isozyme. Consequently, when administered with a potent inhibitor of CYP3A4, a low dose of buspirone is recommended. Subsequent dose adjustments of either drug should be based on clinical response.
Nefazodone: The coadministration of buspirone (2.5 or 5 mg b.i.d.) and nefazodone (250 mg b.i.d) to healthy volunteers resulted in marked increases in plasma buspirone concentrations (increases up to 20-fold in Cmax and up to 50-fold in AUC) and statistically significant decreases (about 50%) in plasma concentrations of buspirone metabolite, 1-pyrimidinylpiperazine. 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 mCPP (9%). Slight increases in Cmax were observed for nefazodone (8%) and its metabolite HO-NEF (11%).
The side effect profile for subjects receiving buspirone 2.5 mg b.i.d. and nefazodone 250 mg b.i.d. was similar to that for subjects receiving either drug alone. Subjects receiving buspirone 5 mg b.i.d. and nefazodone 250 mg b.i.d. experienced side effects such as lightheadedness, asthenia, dizziness, and somnolence. It is recommended that the dose of buspirone be lowered when administered with nefazodone. Subsequent dose adjustments of either drug should be based on clinical response.
Erythromycin: The coadministration of buspirone (10 mg as a single dose) and erythromycin (1.5 g/day for 4 days) to healthy volunteers increased plasma buspirone concentrations (5-fold increase in Cmax and a 6-fold increase in AUC). These pharmacokinetic interactions were accompanied by an increased incidence of adverse events attributable to buspirone. If buspirone and erythromycin are to be used in combination, a low dose of buspirone (e.g., 2.5 mg b.i.d.) is recommended. Subsequent dose adjustments of either drug should be based on clinical response.
Itraconazole: The coadministration of buspirone (10 mg as a single dose) and itraconazole (200 mg/day for 4 days) to healthy volunteers increased plasma buspirone concentrations (13-fold increase in Cmax and a 19-fold increase in AUC). These pharmacokinetic interactions were accompanied by an increased incidence of adverse events attributable to buspirone. If buspirone and itraconazole are to be used in combination, a low dose of buspirone (e.g., 2.5 mg q.d.) is recommended. Subsequent dose adjustments of either drug should be based on clinical response.
Diltiazem: In a study of 9 healthy volunteers, administration of buspirone (10 mg as a single dose) with diltiazem (60 mg t.i.d.) increased plasma buspirone concentrations. The AUC and Cmax of buspirone were increased 5.3-fold and 4-fold, respectively. Enhanced effects and increased toxicity of buspirone may be possible when buspirone is administered with diltiazem. Subsequent dose adjustments of either drug should be based on clinical response.
Verapamil: In a study of 9 healthy volunteers, administration of buspirone (10 mg as a single dose) with verapamil (80 mg t.i.d.) increased plasma buspirone concentrations. The AUC and Cmax of buspirone were increased 3.4-fold. Enhanced effects and increased toxicity of buspirone may be possible when buspirone is administered with verapamil. Subsequent dose adjustments of either drug should be based on clinical response.
Rifampicin: In a study in healthy volunteers, coadministration of BuSpar (30 mg as a single dose) with rifampicin (600 mg/day for 5 days) decreased the plasma concentrations (83.7% decrease in Cmax and 89.6% decrease in AUC) and pharmacodynamic effects of buspirone.
Grapefruit juice: In a study in healthy volunteers, coadministration of BuSpar (10 mg as a single dose) with double-strength grapefruit juice (200 mL double-strength t.i.d. for 2 days) increased plasma buspirone concentrations (4.3-fold increase in Cmax and 9.2-fold increase in AUC). Patients receiving buspirone should be advised to avoid consuming large amounts of grapefruit juice.
Occupational Hazards
Until further experience is obtained with buspirone, patients should be warned not to operate an automobile or undertake activities requiring mental alertness, judgment and physical coordination, until they are reasonably certain that buspirone does not affect them adversely.
Laboratory Test
There have been no reports to date of interference of buspirone with commonly employed clinical laboratory tests.
Drug Abuse and Dependence
Preliminary animal and human investigations suggest that buspirone may be significantly devoid of potential for producing physical or psychological dependence, only extensive clinical experience with the drug will provide conclusive evidence. Meanwhile, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of buspirone misuse and abuse.
Effects on Cognitive and Motor Performance
In controlled studies in healthy volunteers, single doses of buspirone up to 20 mg had little effect on most tests of cognitive and psychomotor function, although performance on a vigilance task was impaired in a dose-related manner. The effect of higher single doses of buspirone on psychomotor performance has not been investigated.
Ten mg of buspirone given 3 times daily for 7 days to healthy volunteers produced considerable subjective sedation but no significant effect on psychomotor performance (no vigilance tasks were used in this study). It also caused transient dizziness, especially on standing and walking.
Neuroendocrine Effects
Single doses of 30 mg or higher of buspirone resulted in significantly elevated plasma prolactin and growth hormone concentrations in normal volunteers. No effect was seen at lower doses. In another study, no such increases were observed after buspirone was administered in divided doses (10 mg t.i.d.) for 28 days.
Long-term Toxicity
Buspirone can bind to central serotonin and dopamine receptors. A question has been raised about its potential to cause acute and chronic changes in dopamine mediated neurological function (e.g., dystonia, pseudoparkinsonism, 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). Obviously, the question cannot be totally resolved at this point in time. Because its mechanism of action is not fully elucidated, long-term toxicity in the CNS or other organ systems cannot be predicted.
Supplied
Each white, biconvex, rectangular, pillow-shaped tablet with BuSpar raised on one side and BL logo, bisect score and 10 on the other side, contains: buspirone HCl 10 mg. Nonmedicinal ingredients: lactose anhydrous, magnesium stearate, microcrystalline cellulose, silicon dioxide colloidal and sodium carboxymethyl starch. Bottles of 100. Store at room temperature. Protect from light.
Contraindications
In patients hypersensitive to buspirone or any of the inactive ingredients.
BuSpar is contraindicated in patients with severe hepatic or severe renal impairment.
Warnings
Extrapyramidal Symptoms
Since buspirone can bind to central dopaminergic receptors, the possibility of acute and chronic changes in dopamine mediated neurological function (e.g., dystonia, pseudo-parkinsonism, akathisia and tardive dyskinesia) should be considered (see Precautions).
MAOIs
The occurrence of elevated blood pressure in patients receiving both buspirone and a MAOI has been reported. Therefore, it is recommended that buspirone should not be used concomitantly with a MAOI.
Lactation
See Pregnancy.
Use of Buspirone in Patients Previously Treated with a Benzodiazepine
Patients who have previously taken benzodiazepines may be less likely to respond to buspirone than those who have not. In 2 clinical studies to date, substitution of buspirone did not ameliorate or prevent withdrawal symptoms in either abrupt or gradual withdrawal from various benzodiazepines following long-term use. Therefore, if it is considered desirable to switch a patient who has been receiving benzodiazepine therapy to buspirone, the benzodiazepine should first be withdrawn gradually. A drug-free interval is desirable between withdrawal of the benzodiazepine and initiation of buspirone, in order to increase the likelihood of distinguishing between benzodiazepine withdrawal effects and unrelieved anxiety due to possible failure of buspirone in this category of patients. In patients requiring continued therapy and where a benzodiazepine washout period is not feasible, gradual benzodiazepine taper/withdrawal may be overlapped by buspirone therapy over a few weeks. Buspirone should not, however, be used to detoxify patients addicted to benzodiazepines.
Benzodiazepine 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. These symptoms may appear as any combination of irritability, anxiety, agitation, insomnia, tremor, abdominal cramps, muscle cramps, vomiting, sweating, flu-like symptoms without fever and, occasionally, seizures, and should be treated symptomatically.
Pregnancy
Pregnancy, Lactation, Labor and Delivery: The safety of buspirone during pregnancy and lactation has not been established and, therefore, it should not be used in women of childbearing potential or nursing mothers, unless, in the opinion of the physician, the potential benefits to the patient outweigh the possible hazards to the fetus. Buspirone and its metabolites are excreted in milk in rats. The extent of excretion in human milk has not yet been determined. The effect of buspirone on labor and delivery is unknown.
Convulsive Disorders
BuSpar is not recommended for patients with a history of seizure disorders.
Adverse Effects
Gastrointestinal
Frequent: nausea, gastrointestinal distress, diarrhea, vomiting. Infrequent: flatulence, increased appetite, anorexia, hypersalivation, rectal bleeding, irritable colon. Rare: burning tongue.
Commonly Observed
Side effects of buspirone, if they occur, are generally observed at the beginning of drug therapy and usually subside with use of the medication and/or decreased dosage.
When patients receiving buspirone were compared with patients receiving placebo, dizziness, headache, nervousness, lightheadedness, nausea, excitement, and sweating/clamminess were the only side effects occurring with significantly greater frequency (p<0.10) in the buspirone group than in the placebo group.
Miscellaneous
syncope; tunnel vision; urinary retention; and female galactorrhea.
Endocrine
Infrequent: decreased and increased libido, weight gain, weight loss, menstrual irregularity/breakthrough bleeding. Rare: delayed ejaculation, impotence, galactorrhea, amenorrhea, thyroid abnormality.
Body as a Whole
allergic reactions including urticaria, ecchymosis, angioedema.
Clinical Laboratory
Infrequent: increases in liver enzymes. Rare: eosinophilia, leukopenia, thrombocytopenia.
Respiratory
Frequent: nasal congestion. Infrequent: shortness of breath, chest congestion, hyperventilation. Rare: epistaxis.
Associated with Discontinuation of Treatment
During controlled clinical efficacy trials, approximately 10% of 2200 anxious patients discontinued treatment due to an adverse event. The more common events associated with discontinuation included: CNS 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.
Allergic or Toxic
Frequent: skin rash, sore throat. Infrequent: edema/facial edema, pruritus, chills/fever. Rare: photophobia, erythema, flu-like symptoms.
Neurologic
Frequent: paresthesia, weakness, incoordination, tremor, numbness. Infrequent: muscle cramps and spasms, rigid/stiff muscles, involuntary movements, akathisia, slowed reaction time. Rare: tingling of limbs, stiff neck, rigidity of jaw.
Incidence in Clinical Trials
Adverse reactions reported in approximately 3000 subjects who participated in premarketing trials are listed below by body system. Frequent adverse events are defined as those occurring in at least 1/100 patients. Infrequent adverse events are those occurring in less than 1/100 but at least 1/1000 patients, while rare events are those occurring in less than 1/1000 patients. In the absence of appropriate controls in some of the studies, a causal relationship to BuSpar (buspirone hydrochloride) cannot be determined.
Autonomic
Frequent: dry mouth, sweating/clamminess, blurred vision, constipation. Infrequent: urinary frequency, retention and burning, flushing.
Central Nervous System
Frequent: dizziness, headache, drowsiness, lightheadedness, insomnia, fatigue, nervousness, decreased concentration, abnormal thinking, excitement, depression, confusion, nightmares/vivid dreams, anger/hostility. Infrequent: depersonalization, noise intolerance, euphoria/feeling high, dissociative reaction, fear, loss of interest, dysphoria, hallucinations, seizures, suicidal thoughts. Rare: slurred speech, claustrophobia, cold intolerance, stupor, psychosis.
Cardiovascular
Frequent: tachycardia/palpitations, chest pain. Infrequent: syncope, hypotension, hypertension. Rare: congestive heart failure, cerebrovascular accident, myocardial infarction, cardiomyopathy, bradycardia, ECG change.
Postmarketing Experience
Although treatment conditions and duration vary greatly, and a causal relationship of adverse events to buspirone cannot always be determined, spontaneous adverse event reports have included rare occurrences (less than 1/10 000) of the following adverse events:
CNS/Neurological
extrapyramidal symptoms, including dyskinesias (acute and delayed), dystonic reactions and cogwheel rigidity; depersonalization; emotional lability; hallucinations; psychosis, ataxias, and seizures; transient difficulty with recall; serotonin syndrome, dizziness, parkinsonism, akathisia, restless leg syndrome, restlessness.
Overdose
Symptoms
In clinical pharmacology trials, BuSpar (buspirone hydrochloride) up to 400 mg/day was administered to healthy male volunteers. As this dose was approached, the following symptoms were observed in descending order of frequency: drowsiness, ataxia, nausea and vomiting, dizziness, clammy feeling, difficulty thinking, feeling high, rushing sensation, gastric distress, headache, itching, miosis, hypotension, tremor, incoordination, insomnia and hallucinations. In a dose-ranging study in acute psychotic patients, up to 2400 mg/day was administered. Dizziness, nausea and vomiting were the most common adverse effects. One patient developed extrapyramidal symptoms at 600 mg/day.
Treatment
There is no specific antidote for buspirone. Management should, therefore, be symptomatic and supportive. Any patient suspected of having taken an overdose should be admitted to a hospital as soon as possible, and the stomach emptied by gastric lavage. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage. As with the management of intentional overdosage with any drug, the ingestion of multiple agents should be suspected. In 6 anuric patients, hemodialysis either had no effect on the pharmacokinetics of buspirone or decreased its clearance. The metabolite is partially removed by hemodialysis.
Dosage
Geriatrics
Limited pharmacokinetic and clinical data have shown no difference in the effects of buspirone between elderly patients and healthy adult volunteers. However, until more information has accumulated in the elderly, it is recommended that the maximum daily dose should not exceed 30 mg for a duration not exceeding 4 weeks.
Note: If buspirone is administered to patients with compromised hepatic or renal function, careful monitoring will be required together with appropriate dosage adjustment.
