Buspirone Hydrochloride

Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA Class: CN309
Chemical Name: 8-[4-[4-(2-Pyrimidinyl)-1-piperazinyl] butyl]-8-azaspiro[4.5]decane-7,9-dione monohydrochloride
Molecular Formula: C₂₁H₃₁N₅O₂•HCl
CAS Number: 33386-08-2
Brands: BuSpar, BuSpar Dividose

Introduction

Anxiolytic agent;^{2 4 70 89 112 131 132 133} structurally and pharmacologically different than benzodiazepines, barbiturates, and other available anxiolytic agents.^{1 2 4 6 70 78 112 132 133 187}

Uses for Buspirone Hydrochloride

Anxiety Disorders

Management of anxiety disorders (anxiety and phobic neuroses)^{1 2 5 36 37 38 39 40 41 42 45 72 81 83 88 95 107 109 123 189 191} and short-term relief of symptoms of anxiety.^{1 2 47 72 123}

Efficacy generally comparable to that of benzodiazepines (e.g., alprazolam,^{45 83} clorazepate,^{40 42 83 184} diazepam, ^{36 37 38 39 40 41 72 81 83 88 107 109 130 160} lorazepam) in the management of generalized anxiety disorder (GAD).^{45 83}

Preferred by some clinicians for the management of anxiety disorders in patients with a history of aggression or in whom disinhibition has occurred during benzodiazepine therapy.^{154 185 186}

Buspirone Hydrochloride Dosage and Administration

General

• 
  

  Slower onset of action than some anxiolytics (e.g., diazepam).^{36 38 39 80 82 87 112 122 184} Optimum therapeutic effect usually requires at least 3–4 weeks^{39 41 123 193} and occasionally up to 4–6 weeks of therapy.⁸⁷

  
  


• 
  

  Periodically reassess need for continued therapy.^{1 114}

  
  

Administration

Oral Administration

Administer orally in a consistent manner, either always with or always without food.¹ (See Food under Pharmacokinetics.)

The 15- and 30-mg tablets (Dividose tablets) are scored to be broken in 2 halves (each providing a dose of 7.5 and 15 mg, respectively) or in 3 thirds (each providing a dose of 5 and 10 mg, respectively).¹

Dosage

Available as buspirone hydrochloride; dosage is expressed in terms of the salt.¹

Adults

Anxiety Disorders

Oral

Initially, 10–15 mg daily in 2 or 3 divided doses.^{1 2 37 38 41 45 47 49 72 83 123 191 193} Increase dosage in increments of 5 mg daily every 2–4 days according to individual response and tolerance.^{1 2 5 37 38 41 72 83 123} Maintenance, 15–30 mg daily in 2 or 3 divided doses.^{1 37 38 39 40 41 42 45 47 48 51 59 114 123 191}

Reduced dosage recommended in patients receiving concomitant therapy with potent CYP3A4 inhibitor.¹ (See Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Prescribing Limits

Adults

Maximum 60 mg daily.^{1 2 123}

Special Populations

Hepatic Impairment

Prolonged elimination.¹ Consider dosage reduction.^{1 34 110 112} Manufacturer states that use in patients with severe hepatic impairment is not recommended.¹

Renal Impairment

Some clinicians recommend that dosage be reduced by 25–50% in anuric patients.¹⁰⁴ However, other clinicians state that dosage recommendations cannot be made for patients with renal impairment due to variability in plasma buspirone concentrations.^{204 205} (See Absorption under Pharmacokinetics.) Manufacturer states that use in patients with severe renal impairment is not recommended.¹

Cautions for Buspirone Hydrochloride

Contraindications

• 
  

  Known hypersensitivity to buspirone hydrochloride.^{1 2}

  
  

Warnings/Precautions

Warnings

MAO Inhibitors

Avoid concomitant use.^{1 2 63} (See Specific Drugs under Interactions.)

Psychiatric Indications

No established antipsychotic efficacy at usual dosages;^{1 2 51 61 62 70 80 83 84 85 86 87 88 89 90 100 112 122} should not be used in place of appropriate antipsychotic therapy.^{1 2}

General Precautions

CNS Effects

Generally does not produce substantial impairment of cognitive or psychomotor function at usual dosages; however, CNS effects show interindividual variation and may not be predictable.^{1 2}

Prudent to avoid concomitant use with alcohol.^{1 2} (See Specific Drugs under Interactions.)

Benzodiazepine or Sedative/Hypnotic Withdrawal

No cross-tolerance with benzodiazepines or other sedative/hypnotic drugs; will not prevent symptoms of withdrawal following cessation of such therapy.^{1 2 6 39 44 60 70 71 86 124} Withdraw therapy with such drugs gradually in patients being switched to buspirone, particularly following prolonged or relatively high-dose therapy.^{1 2 39 86}

Dopaminergic Effects

Potential for causing changes in dopamine-mediated neurologic function (e.g., dystonia, parkinsonian-like manifestations, akathisia, tardive dyskinesia) not fully elucidated.^{1 186}

Specific Populations

Pregnancy

Category B.¹

Lactation

Buspirone and its metabolites are distributed into milk in rats.¹ Avoid whenever clinically possible.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹ Has been used in pediatric patients 6–17 years of age with GAD without unusual adverse effects; however, dosage of 7.5–30 mg twice daily for 6 weeks was no more effective than placebo.¹

Geriatric Use

No substantial differences in safety, efficacy, or phamacokinetic profile relative to younger adults; however, increased sensitivity cannot be ruled out.¹

Hepatic Impairment

Prolonged elimination.¹ Use with caution.^{1 34 110 112}

Manufacturer states that use in patients with severe hepatic impairment is not recommended.¹

Renal Impairment

Decreased clearance.¹ Use with caution.^{1 34 104 112} Need for dosage adjustment not fully elucidated. (See Renal Impairment under Dosage and Administration.)^{34 104 112}

Manufacturer states that use in patients with severe renal impairment is not recommended.¹

Common Adverse Effects

Dizziness, nausea, headache, nervousness, drowsiness, light-headedness, excitement.^{1 2 5 36 37 38 42 45 58 61 62 89 114 123 130 191}

Interactions for Buspirone Hydrochloride

Metabolized by CYP3A4.^{1 4 5 15 31 32 34 64 112 125}

Drugs Affecting Hepatic Microsomal Enzymes

Possible pharmacokinetic interaction (increased plasma buspirone concentrations) with CYP3A4 inhibitors.¹ Low buspirone dosage (i.e., 2.5 mg once or twice daily) recommended in patients receiving potent CYP3A4 inhibitor; base subsequent adjustments of buspirone and CYP3A4 inhibitor dosage on clinical assessment.¹

Possible pharmacokinetic interaction (decreased plasma buspirone concentrations) with CYP3A4 inducers.¹ May require dosage adjustment to maintain anxiolytic effect.¹

Protein-bound Drugs

Possible displacement from binding sites of buspirone or other protein-bound drugs.^{1 2 34 94}

One report of increased prothrombin time when buspirone was added to a regimen of warfarin, phenytoin, phenobarbital, digoxin, and levothyroxine (Synthroid); clinical importance unknown.¹

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Alcohol	Does not appear to alter blood alcohol concentrations50 51 73 or substantially potentiate alcohol-induced impairment of psychomotor and cognitive performance2 5 10 34 48 50 51 55 73 74 76 90 93 105 112	Prudent to avoid concomitant use1
Amitriptyline	No interaction reported1 2 34 59
Cimetidine	Possible decrease in buspirone clearance 1 119 120 204	Clinical importance not established1
CNS depressants (e.g., analgesics, antihistamines, sedative/hypnotics including benzodiazepines)	Possible CNS depression, although few interactions reported to date2 5 34 48 63 76 81 91 93 112 123 129	Use with caution1 105
Diltiazem	Increased plasma buspirone concentrations1	Buspirone dosage adjustment may be necessary1
Erythromycin	Increased plasma buspirone concentrations1 204 and increased incidence of adverse effects attributable to buspirone1	Decrease buspirone dosage (e.g., 2.5 mg twice daily); base subsequent adjustments of buspirone and erythromycin dosage on clinical assessment1
Grapefruit juice	Increased plasma buspirone concentrations1	Avoid drinking large amounts of grapefruit juice1
Haloperidol	Increased serum haloperidol concentrations2 97	Clinical importance not established1
Itraconazole	Increased plasma buspirone concentrations1 204 and increased incidence of adverse effects attributable to buspirone1	Decrease buspirone dosage (e.g., 2.5 mg daily); base subsequent adjustments of buspirone and itraconazole dosage on clinical assessment1
MAO inhibitors (e.g., tranylcypromine)	Increased blood pressure;1 2 63 196 197 possible contribution to a fatal case of serotonin syndrome when used concomitantly with fluoxetine and tranylcypromine201 202	Do not use concomitantly;1 2 63 196 197 allow 10 days between discontinuance of MAO inhibitor and administration of buspirone196 197
Nefazodone	Marked increase in plasma buspirone concentration; slight increase in concentrations of nefazodone and its metabolite1	Use with caution; decrease buspirone dosage (e.g., 2.5 mg daily); base subsequent adjustments of buspirone and nefazodone dosage on clinical assessment1
Rifampin	Decreased plasma buspirone concentrations1	Adjust buspirone dosage as necessary to maintain anxiolytic effect1
Trazodone	Possible elevation of serum ALT1 2
Verapamil	Increased plasma buspirone concentrations1	Buspirone dosage adjustment may be necessary1

Buspirone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly^{1 2 4 5 29 34 64 88} and almost completely absorbed following oral administration.^{2 34 64 112 116} Undergoes extensive first-pass metabolism in the liver;^{1 2 4 31 34 64 112 116} only about 4% of a dose reaches systemic circulation unchanged.^{2 31 34 104 112 116}

Peak plasma concentrations occur within 40–90 minutes following oral administration.^{1 2 4 29 31 34 64 65 115}

Onset

Anxiolytic activity may be apparent within the first 2 weeks,^{38 123} but optimum therapeutic effect usually requires at least 3–4 weeks^{39 41 123 193} and occasionally up to 4–6 weeks.⁸⁷

Food

Food may delay absorption, thereby decreasing the extent of presystemic clearance^{1 2 34} and increasing the amount of unchanged buspirone reaching systemic circulation.^{1 2 5 30 34}

Distribution

Extent

Extensively distributed into body tissues in animals.^{112 127}

Buspirone and metabolites are distributed into milk in animals;^{1 123} extent of distribution into human milk is unknown.^{1 123 185}

Plasma Protein Binding

Approximately 86–95%^{1 2 34 104 203} (mainly albumin; α₁-acid glycoprotein to a lesser extent).^{34 35}

Elimination

Metabolism

Extensively metabolized in the liver, mainly via oxidation by CYP3A4.^{1 4 5 15 31 32 34 64 112 125}

In animals, the major active metabolite (1-pyrimidinylpiperazine)^{1 5 15 31 32 33 34 112 125} has about 20–25% of the anxiolytic activity of buspirone but is present in the brain in concentrations up to 15-to 30-fold greater than those of unchanged drug.^{1 2 34 112 125 129} Contribution to the drug’s effects in humans is not fully elucidated.^{2 5 15}

Elimination Route

Excreted principally in urine and to a lesser extent in feces;^{1 2 34 112} excreted mainly as metabolites.^{2 5 31 34 64 104 112}

Half-life

2–4 hours.^{1 2 4 15 29 31 34 65 104 110 112 115 116}

Special Populations

Elimination half-life may be prolonged in patients with renal impairment, particularly in those with anuria,^{34 104} and in patients with liver impairment, including those with cirrhosis.^{1 34 110 112}

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at ≤30°C.^{1 185}

ActionsActions

• 
  

  Anxioselective drug;^{4 5 7 9 11 12 13 22 24 48 70 78 79 88 112 133 163} unlike benzodiazepines, has no anticonvulsant^{1 2 6 9 11 12 13 16 18 22 68 70 78 88 112 133 163 176} or muscle relaxant^{1 2 6 9 11 12 13 22 68 70 78 79 88 112 163 176} activity, does not substantially impair psychomotor function,^{11 13 70 73 74 76 78 90 112 133} and has little sedative effect.^{1 2 6 9 11 13 16 18 22 40 41 45 48 61 62 78 112 133 163}

  
  


• 
  

  Mechanism of action is unknown; appears to be complex and distinct from that of benzodiazepines;^{1 2 4 5 6 7 8 11 12 13 15 16 68 70 78 88 112 131 133 163 177 187} probably involves several central neurotransmitter systems.^{1 2 5 6 7 8 9 12 15 68 70 78 88 112 133 187}

  
  


• 
  

  Effects may be mediated by a variety of CNS sites^{1 2 5 6 7 8 9 12 15 68 70 78 101 103 112 133 138 140 141 143 144} including serotonergic, ^{1 2 5 6 7 8 9 10 11 15 68 69 70 78 88 101 102 103 112 133 135 136 137 138 139 140 141 142 143 144 146 147 148 149 163 182 187 190} dopaminergic, ^{1 2 4 5 6 7 8 9 11 12 13 14 15 16 17 18 19 20 24 32 66 68 70 78 79 88 111 112 133 163} cholinergic, ^{12 24 32 78 88} and noradrenergic (α-adrenergic) systems.^{5 7 9 11 12 15 22 23 68 70 78 88 112 133 163 182} No appreciable affinity for the benzodiazepine receptor complex.^{1 2 6 11 14 15 16 66 78 79 112 133}

  
  

Advice to Patients

• 
  

  Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.¹

  
  


• 
  

  Importance of taking buspirone in a consistent manner, either always with or always without food.¹

  
  


• 
  

  Importance of not drinking large quantities of grapefruit juice.¹

  
  


• 
  

  Symptomatic relief may occur within 2 weeks,^{38 123} but optimum effect usually requires at least 3–4 weeks^{39 41 123 193} and occasionally 4–6 weeks of therapy.⁸⁷

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption.¹ Prudent to avoid alcohol-containing beverages or products.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Contraindications and also Warnings/Precautions under Cautions.)¹

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Buspirone Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg*	BuSpar (scored)	Bristol-Myers Squibb
			Buspirone Hydrochloride (scored)	Aegis, Ethex, Mylan, Par, Sandoz, Teva, Watson
		7.5 mg*	Buspirone Hydrochloride (with povidone; scored)	Par
		10 mg*	BuSpar (multi-scored)	Bristol-Myers Squibb
			Buspirone Hydrochloride (scored)	Aegis, Ethex, Mylan, Par, Sandoz, Teva, Watson
		15 mg*	BuSpar Dividose (scored)	Bristol-Myers Squibb
			Buspirone Hydrochloride (multi-scored)	Aegis, Ethex, Mylan, Par, Sandoz, Teva, Watson
		30 mg*	BuSpar Dividose (multi-scored)	Bristol-Myers Squibb
			Buspirone Hydrochloride (multi-scored)	Mylan, Teva

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

BuSpar 30MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$158.07 or 90/$453.94

BusPIRone HCl 10MG Tablets (IVAX PHARMACEUTICALS INC.): 90/$18.99 or 180/$27.98

BusPIRone HCl 15MG Tablets (IVAX PHARMACEUTICALS INC.): 90/$69.31 or 180/$138.62

BusPIRone HCl 30MG Tablets (MYLAN): 30/$50.99 or 90/$133.97

BusPIRone HCl 5MG Tablets (WATSON LABS): 30/$13.99 or 90/$39.99

BusPIRone HCl 7.5MG Tablets (PAR): 60/$99.57 or 180/$282.38

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Bristol-Myers Squibb. BuSpar (buspirone hydrochloride) prescribing information. Princeton, NJ; 2002 Feb.

2. Mead Johnson Pharmaceuticals. BuSpar (buspirone hydrochloride) manufacturer’s information. Evansville, IN; 1986 Dec.

3. Mead Johnson Pharmaceuticals. BuSpar (buspirone hydrochloride) product information. Evansville, IN; (undated).

4. Temple DL Jr, Yevich JP, New JS. Buspirone: chemical profile of a new class of anxioselective agents. J Clin Psychiatry. 1982; 43(12 Part 2):4-10. [IDIS 162637] [PubMed 6185470]

5. Kastenholz KV, Crismon ML. Buspirone, a novel nonbenzodiazepine anxiolytic. Clin Pharm. 1984; 3:600-7. [IDIS 193404] [PubMed 6150781]

6. Riblet LA, Taylor DP, Eison MS et al. Pharmacology and neurochemistry of buspirone. J Clin Psychiatry. 1982; 43(12 Part 2):11-6. [PubMed 6130068]

7. Skolnick P, Weissman BA, Youdim MBH. Monoaminergic involvement in the pharmacological actions of buspirone. Br J Pharmacol. 1985; 86:637-44. [PubMed 2933109]

8. Eison AS, Eison MS, Stanley M et al. Serotonergic mechanisms in the behavioral effects of buspirone and gepirone. Pharmacol Biochem Behav. 1986; 24:701-7. [PubMed 2871564]

9. Hjorth S, Carlsson A. Buspirone: effects on central monoaminergic transmission—possible relevance to animal experimental and clinical findings. Eur J Pharmacol. 1982; 83:299-303. [PubMed 6129148]

10. Glaser T, Traber J. Buspirone: action on serotonin receptors in calf hippocampus. Eur J Pharmacol. 1983; 88:137-8. [PubMed 6133764]

11. Taylor DP, Allen LE, Becker JA et al. Changing concepts of the biochemical action oi the anxioselective drug, buspirone. Drug Dev Res. 1984; 4:95-108.

12. Eison MS, Eison AS. Buspirone as a midbrain modulator: anxiolysis unrelated to traditional benzodiazepine mechanisms. Drug Dev Res. 1984; 4:109-19.

13. Stanton HC, Taylor DP, Riblet LA. Buspirone—an anxioselective drug with dopaminergic action. In: Chronister RB, DeFrance IF, eds. The neurobiology of the nucleus accumbens (proceedings symposium). Brunswick, ME: Haer Institute; 1981:316-21.

14. Cimino M, Ponzio F, Achilli G et al. Dopaminergic effects of buspirone, a novel anxiolytic agent. Biochem Pharmacol. 1983; 32:1069-74. [PubMed 6838654]

15. Leonard BE. Neuropharmacological profile of buspirone: a nonbenzodiazepine anxiolytic with specific mid-brain modulating properties. Br J Clin Pract. 1985; 38(Symp Suppl):74-82.

16. McMillen BA, Matthews RT, Sanghera MK et al. Dopamine receptor antagonism by the novel anti-anxiety drug, buspirone. J Neurosci. 1983; 3:733-8. [PubMed 6131948]

17. Kaulen P, Brüning G, Schneider U et al. Autoradiographic localization of [³H]buspirone binding sites in rat brain. Neurosci Lett. 1985; 53:191-5. [PubMed 3982707]

18. McMillen BA. Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission. J Neural Transm. 1985; 64:1-12. [PubMed 2866230]

19. Wood PL, Nair NPV, Lal S et al. Buspirone: a potential atypical neuroleptic. Life Sci. 1983; 33:269-73. [PubMed 6135133]

20. McMillen BA, Mattiace LA. Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug. J Neural Transm. 1983; 57:255-65. [PubMed 6140299]

21. Oakley NR, Jones BJ. Buspirone enhances [³H]flunitrazepam binding in vivo. Eur J Pharmacol. 1983; 87:499-500. [PubMed 6133760]

22. Sanghera MK, McMillen BA, German DC. Buspirone, a non-benzodiazepine anxiolytic, increases locus coeruleus noradrenergic neuronal activity. Eur J Pharmacol. 1983; 86:107-10.

23. Kozak W, Valzelli L, Garattini S. Anxiolytic activity on locus coeruleus-mediated suppression of muricidal aggression. Eur J Pharmacol. 1984; 105:323-6. [PubMed 6150860]

24. Kolasa K, Fusi R, Garattini S et al. Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system. J Pharm Ph