Side Effects of Buspar (buspirone)

Buspar (buspirone) is used to manage anxiety disorders or for the short-term relief of the symptoms of anxiety. 

Buspar is especially effective in persons with generalized anxiety of a limited or moderate degree. It is not very effective in persons with severe anxiety, panic disorders, or obsessive-compulsive disorders. Buspar also may help improve symptoms of depression in patients with generalized anxiety disorder. 

Its mechanism of action is not clearly understood but may involve effects on neurotransmitters, chemicals that nerves use to communicate with one another. Serotonin and dopamine are two of these neurotransmitters. 

Buspar may work by stimulating serotonin type 1A receptors on nerves, thereby altering the chemical messages that nerves receive. It also has minor effects on dopamine receptors but this does not contribute much to its action. Unlike medications for anxiety of the benzodiazepine class, Buspar does not cause sedation.

Drug interactions of Buspar include monoamine oxidase inhibitors (MAOIs) because the combination with these drugs can cause increased blood pressure. A similar reaction may occur if Buspar is combined with linezolid.

• The combination of Buspar and trazodone may cause abnormal liver enzymes in the blood.
• The combination of Buspar and warfarin may accentuate the effects of warfarin and increase the risk of bleeding.
• Patients taking Buspar should not drink grapefruit juice, since the juice (even well after a dose of Buspar is taken) can increase the amount of Buspar in the blood, possibly leading to side effects.
• Inactivation and removal of Buspar is mediated by liver enzymes.
• Drugs (for example, erythromycin, itraconazole, nefazodone) that inhibit these liver enzymes increase blood concentrations of Buspar, and drugs (for example, rifampin) that enhance these enzymes decrease blood concentrations of Buspar.
• Increased blood concentrations may increase side effects while decreased blood concentrations may reduce efficacy. 

There are no adequate studies of Buspar in pregnant women. 

It is unknown if buspirone is secreted in human breast milk. Because buspirone is secreted in the breast milk of animals, it should not be used by women who are breastfeeding.

What are the common side effects of Buspar?

Common side effects of Buspar include

• dizziness,
• nausea,
• headache,
• nervousness,
• lightheadedness,
• excitement, and
• insomnia.

What are the serious side effects of Buspar?

Other important but less frequent side effects of Buspar include

• unsteady gait,
• diarrhea,
• excitement,
• weakness,
• hostility,
• skin rash, and
• tremors.

Psychotropic Agents

MAO Inhibitors

• It is recommended that buspirone hydrochloride tablets not be used concomitantly with MAO inhibitors.

Amitriptyline

• After addition of buspirone to the amitriptyline dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (Cmax, AUC, and Cmin) of amitriptyline or its metabolite nortriptyline were observed.

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.

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) below.

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 Cmax of buspirone 3.4-fold while diltiazem increased AUC and Cmax 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 Cmax 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 Cmax; 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 Cmax 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 Cmax 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 Cmax 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 Cmax; 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 Cmax (40%) and Tmax (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*. 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.

Drug/Laboratory Test Interactions

• Buspirone hydrochloride may interfere with the urinary metanephrine/catecholamine assay.
• It has been mistakenly read as metanephrine during routine assay testing for pheochromocytoma, resulting in a false positive laboratory result.
• Buspirone hydrochloride should therefore be discontinued for at least 48 hours prior to undergoing a urine collection for catecholamines.

Drug Abuse and Dependencee

Controlled Substance Class

• Buspirone hydrochloride is not a controlled substance.

Physical And Psychological Dependence

• In human and animal studies, buspirone has shown no potential for abuse or diversion and there is no evidence that it causes tolerance, or either physical or psychological dependence.
• Human volunteers with a history of recreational drug or alcohol usage were studied in two doubleblind clinical investigations.
• None of the subjects were able to distinguish between buspirone hydrochloride tablets and placebo.
• By contrast, subjects showed a statistically significant preference for methaqualone and diazepam.
• Studies in monkeys, mice, and rats have indicated that buspirone lacks potential for abuse.
• Following chronic administration in the rat, abrupt withdrawal of buspirone did not result in the loss of body weight commonly observed with substances that cause physical dependency.
• Although there is no direct evidence that buspirone hydrochloride tablets causes physical dependence or drug-seeking behavior, it is difficult to predict from experiments the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed.
• Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of buspirone hydrochloride tablets misuse or abuse (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

Controlled Substance Class

• Buspirone hydrochloride is not a controlled substance.

Physical And Psychological Dependence

• In human and animal studies, buspirone has shown no potential for abuse or diversion and there is no evidence that it causes tolerance, or either physical or psychological dependence.
• Human volunteers with a history of recreational drug or alcohol usage were studied in two doubleblind clinical investigations.
• None of the subjects were able to distinguish between buspirone hydrochloride tablets and placebo.
• By contrast, subjects showed a statistically significant preference for methaqualone and diazepam.
• Studies in monkeys, mice, and rats have indicated that buspirone lacks potential for abuse.
• Following chronic administration in the rat, abrupt withdrawal of buspirone did not result in the loss of body weight commonly observed with substances that cause physical dependency.
• Although there is no direct evidence that buspirone hydrochloride tablets causes physical dependence or drug-seeking behavior, it is difficult to predict from experiments the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed.
• Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of buspirone hydrochloride tablets misuse or abuse (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

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