Buspirone Hydrochloride 30mg Information
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Description
Buspirone hydrochloride, USP is an antianxiety agent that is not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative/anxiolytic drugs.
Buspirone hydrochloride is a white crystalline, water soluble compound with a molecular weight of 422.0. Chemically, buspirone hydrochloride is 8-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione monohydrochloride. The molecular formula CHNO • HCl is represented by the following structural formula:
Buspirone hydrochloride is supplied as tablets for oral administration containing 7.5 mg of buspirone hydrochloride USP. Buspirone hydrochloride tablets contain the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Clinical Pharmacology
The mechanism of action 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. preclinical studies have shown that buspirone has a high affinity for serotonin (5-HT) receptors. Buspirone has no significant affinity for benzodiazepine receptors and does not affect GABA binding or when tested in preclinical models.
Buspirone has moderate affinity for brain D2-dopamine receptors. Some studies do suggest that buspirone may have indirect effects on other neurotransmitter systems.
Buspirone hydrochloride is rapidly absorbed in man and undergoes extensive first-pass metabolism. In a radio-labeled study, unchanged buspirone in the plasma accounted for only about 1% of the radioactivity in the plasma. Following oral administration, plasma concentrations of unchanged Buspirone are very low and variable between subjects. Peak plasma levels of 1ng/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 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) 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 ).
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 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 , or whether such changes, if they do occur, cause clinically significant differences in treatment outcome. An study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin, warfarin, and propranolol from plasma proteins, and that buspirone may displace digoxin.
Buspirone is metabolized primarily by oxidation, (which has been shown to be mediated by cytochrome P450 3A4 (CYP3A4). (See .) 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 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 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 to 40 mg is about 2 to 3 hours.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Indications And Usage
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 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 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. Generalized Anxiety Disorder (300.02) is described in the American Psychiatric Association's Diagnostic and Statistical Manual, III as follows:
Generalized, persistent anxiety (of at least 1 month continual duration), manifested by symptoms from three of the four following categories:
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 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 for 1 year without ill effect. Therefore, the physician who elects to use buspirone hydrochloride for extended periods should periodically reassess the usefulness of the drug for the individual patient.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Contraindications
Buspirone hydrochloride is contraindicated in patients hypersensitive to buspirone hydrochloride.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Warnings
Because buspirone hydrochloride has no established antipsychotic activity, it should not be employed in lieu of appropriate antipsychotic treatment.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Precautions
No evidence of carcinogenic potential was observed in rats during a 24-month study at approximately 133 times the maximum recommended human oral dose; or in mice, during an 18-month study at approximately 167 times the maximum recommended human oral dose.
With or without metabolic activation, buspirone did not induce point mutations in five strains of (Ames Test) or mouse lymphoma L5178YTK cell cultures, nor was DNA damage observed with buspirone in Wi-38 human cells. Chromosomal aberrations or abnormalities did not occur in bone marrow cells of mice given one or five daily doses of buspirone.
In one study of 6632 patients who received buspirone hydrochloride tablets for the treatment of anxiety, 605 patients were ≥65 years old and 41 were ≥75 years old; the safety and efficacy profiles for these 605 elderly patients (mean age = 70.8 years) were similar to those in the younger population (mean age = 43.3 years). Review of spontaneously reported adverse clinical events has not identified differences between elderly and younger patients, but greater sensitivity of some older patients cannot be ruled out.
There were no effects of age on the pharmacokinetics of buspirone (see ).
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Adverse Reactions
(See also )
During its premarketing assessment, buspirone hydrochloride was evaluated in over 3500 subjects. This section reports event frequencies for adverse events occurring in approximately 3000 subjects from this group who took multiple doses of buspirone hydrochloride in the dose range for which buspirone hydrochloride is being recommended (i.e., the modal daily dose of buspirone hydrochloride fell between 10 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 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 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 1/1000 patients, while rare events are those occurring in less than 1/1000 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.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Post Marketing 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, and 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 treatment has not been determined.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Drug Abuse And 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 double-blind clinical investigations. None of the subjects were able to distinguish between buspirone hydrochloride 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 causes physical dependence or drugseeking 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 misuse or abuse (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Dosage And Administration
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 (see ). 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 section should be followed.
Buspirone hydrochloride 30mg (Buspirone hydrochloride) How Supplied
Buspirone hydrochloride Tablets, USP, 7.5 mg (off-white, oval shaped tablet debossed with “Par 708” bisected on one side and “10” on the other side.
10 mg tablets
NDC 68788-0469-03 Bottles of 30
NDC 68788-0469-06 Bottles of 60
NDC 68788-0469-09 Bottles of 90
NDC 68788-0469-01 Bottles of 100
Store at 25° C (77° F); excursions permitted between 15° C to 30° C (59° F to 86° F) [see USP controlled room temperature]. Dispense in tight, light-resistant container (USP).
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Reference
1. American Psychiatric Association, Ed.: Diagnostic and Statistical Manual of Mental Disorders-III, American Psychiatric Association, May 1980.
Synthroid® is the registered trademark of Knoll Pharmaceutical Company.
Manufactured by: Spring Valley, NY 10977
Revised: 01/10 OS725-01-1-09
Repackaged By: Anaheim, CA 92807
Buspirone hydrochloride 30mg (Buspirone hydrochloride) Package/label Principal Display Panel
PRINCIPAL DISPLAY PANEL - 10mg
NDC 49884-725-01
Rx only
Dispense in a tight, light-resistantcontainer (USP).
R05/08 LA725-01-1-06
