Buspirone

Buspirone hydrochloride tablets are indicated for the management of anxiety disorders or the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The efficacy of buspirone hydrochloride tablets has been demonstrated in controlled clinical trials of outpatients whose diagnosis roughly corresponds to Generalized Anxiety Disorder (GAD). Many of the patients enrolled in these studies also had coexisting depressive symptoms and buspirone hydrochloride tablets relieved anxiety in the presence of these coexisting depressive symptoms. The patients evaluated in these studies had experienced symptoms for periods of 1 month to over 1 year prior to the study, with an average symptom duration of 6 months.

of buspirone is unknown. Buspirone differs from typical benzodiazepine anxiolytics in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks the prominent sedative effect that is associated with more typical anxiolytics. In vitro preclinical studies have shown that buspirone has a high affinity for serotonin (5-HT 1A ) receptors. Buspirone has no significant affinity for benzodiazepine receptors and does not affect GABA binding in vitro or in vivo when tested in preclinical models. Buspirone has moderate affinity for brain D 2 -dopamine receptors. Some studies do suggest that buspirone may have indirect effects on other neurotransmitter systems. Buspirone hydrochloride tablets are rapidly absorbed in man and undergoes extensive first-pass metabolism.

The recommended initial dose is 15 mg daily (7.5 mg b.i.d.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day, as needed. The maximum daily dosage should not exceed 60 mg per day. In clinical trials allowing dose titration, divided doses of 20 mg to 30 mg per day were commonly employed. The bioavailability of buspirone is increased when given with food as compared to the fasted state. Consequently, patients should take buspirone in a consistent manner with regard to the timing of dosing, either always with or always without food. When buspirone is to be given with a potent inhibitor of CYP3A4, the dosage recommendations described in the PRECAUTIONS: Drug Interactions section should be followed.

Buspirone hydrochloride tablets are contraindicated in patients hypersensitive to buspirone hydrochloride. The use of monoamine oxidase inhibitors (MAOIs) intended to treat depression with buspirone or within 14 days of stopping treatment with buspirone is contraindicated because of an increased risk of serotonin syndrome and/or elevated blood pressure. The use of buspirone within 14 days of stopping an MAOI intended to treat depression is also contraindicated. Starting buspirone in a patient who is being treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome.

The administration of buspirone hydrochloride tablets to a patient taking a monoamine oxidase inhibitor (MAOI) may pose a hazard. There have been reports of the occurrence of elevated blood pressure when buspirone hydrochloride tablets have been added to a regimen including an MAOI. Therefore, it is recommended that buspirone hydrochloride tablets not be used concomitantly with an MAOI. Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs SSRIs, and other serotonergic drugs, including buspirone, alone but particularly with concomitant use of other serotonergic drugs (including triptans), with drugs that impair metabolism of serotonin (in particular, MAOIs, including reversible MAOIs such as linezolid and intravenous methylene blue), or with antipsychotics or other dopamine antagonists.

Commonly Observed The more commonly observed untoward events associated with the use of buspirone hydrochloride tablets not seen at an equivalent incidence among placebo-treated patients include dizziness, nausea, headache, nervousness, lightheadedness, and excitement. Associated with Discontinuation of Treatment One guide to the relative clinical importance of adverse events associated with buspirone hydrochloride tablets is provided by the frequency with which they caused drug discontinuation during clinical testing. Approximately 10% of the 2200 anxious patients who participated in the buspirone hydrochloride tablets premarketing clinical efficacy trials in anxiety disorders lasting 3 to 4 weeks discontinued treatment due to an adverse event.

Psychotropic Agents MAO inhibitors: The use of monoamine oxidase inhibitors (MAOIs) intended to treat depression with buspirone or within 14 days of stopping treatment with buspirone is contraindicated because of an increased risk of serotonin syndrome and/or elevated blood pressure. The use of buspirone within 14 days of stopping an MAOI intended to treat depression is also contraindicated. Starting buspirone in a patient who is being treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome. Amitriptyline: After addition of buspirone to the amitriptyline dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (C max, AUC, and C min ) of amitriptyline or its metabolite nortriptyline were observed.

Store at 25°C (77°F), excursions permitted between 15° C to 30° C (59° F to 86° F).