Drug Name

Buspar (Buspirone)

Generic Name

Buspirone (byoo-SPY-rone)

Looks like

Buspirone is available with a prescription under the brand name BuSpar. Other brand or generic forms may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

• BuSpar 5 mg white, rounded rectangular, scored tablet
• BuSpar 10 mg white, rounded rectangular, scored tablet
• BuSpar 15 mg two joined, rounded rectangles, forming a white, scored tablet

Dosage Form

Tablets

Route Of Administration

ORAL

Imprint Code

MJ;5;BuSpar / MJ;10;BuSpar / MJ;822;5;5;5

Size

8mm / 10mm / 15mm

Alternatives

Anxiety
Lexapro (Escitalopram), Cymbalta (Duloxetine)

Drug Uses

BuSpar is used to treat symptoms of anxiety, such as fear, tension, irritability, dizziness, pounding heartbeat, and other physical symptoms.

Drug class

BuSpar is an anti-anxiety medicine that affects chemicals in your brain that may become unbalanced and cause anxiety.

Contains

BuSpar is supplied as tablets for oral administration containing 5 mg, 10 mg, 15 mg, or 30 mg of buspirone hydrochloride, USP (equivalent to 4.6 mg, 9.1 mg, 13.7 mg, and 27.4 mg of buspirone free base, respectively). The 5 mg and 10 mg tablets are scored so they can be bisected. Thus, the 5 mg tablet can also provide a 2.5 mg dose, and the 10 mg tablet can provide a 5 mg dose. The 15 mg and 30 mg tablets are provided in the DIVIDOSE tablet design. These tablets are scored so they can be either bisected or trisected. Thus, a single 15 mg tablet can provide the following doses: 15 mg (entire tablet), 10 mg (two thirds of a tablet), 7.5 mg (one half of a tablet), or 5 mg (one third of a tablet). A single 30 mg tablet can provide the following doses: 30 mg (entire tablet), 20 mg (two thirds of a tablet), 15 mg (one half of a tablet), or 10 mg (one third of a tablet). BuSpar Tablets contain the following inactive ingredients: colloidal silicon dioxide, lactose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The 30 mg tablet also contains iron oxide.

Chemical formula

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 empirical formula C21H31N5O2*HCl is represented by the following structural formula:

Mechanism of Action

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. In vitro preclinical studies have shown that buspirone has a high affinity for serotonin (5-HT1A) 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 D2-dopamine receptors. Some studies do suggest that buspirone may have indirect effects on other neurotransmitter systems.

BuSpar is rapidly absorbed in man and undergoes extensive first-pass metabolism. In a radiolabeled 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 1 ng/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 BuSpar 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 (Cmax) 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.

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 in vitro 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 in vivo, or whether such changes, if they do occur, cause clinically significant differences in treatment outcome. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin, warfarin, and propranolol from plasma protein, and that buspirone may displace digoxin.

Buspirone is metabolized primarily by oxidation, which in vitro has been shown to be mediated by cytochrome P450 3A4 (CYP3A4). 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 BuSpar (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 14C-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 mg to 40 mg is about 2 to 3 hours.

How Taken

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

BuSpar is usually taken for only a short time. Do not take this medication for longer than 4 weeks without your doctors advice.

You may take BuSpar with or without food but take it the same way each time.

Some tablet forms of buspirone (Buspar Dividose) may need to be broken before you take the medicine. These tablets have special scored marks on them to make breaking the tablet easy. Do not use the tablet if it has not broken correctly and the piece is too big or too small. Follow your doctors instructions about how much of the tablet to take.
If you have been switched to BuSpar from another anxiety medication, you may need to slowly decrease your dose of the other medication rather than stopping suddenly. Some anxiety medications can cause withdrawal symptoms when you stop taking them suddenly after long-term use.

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. 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.

Missed Dose

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Overdose

Seek emergency medical attention if you think you have used too much of this medicine.
Overdose symptoms may include nausea, vomiting, dizziness, drowsiness, blurred vision, and stomach pain.

Storage

Store BuSpar at room temperature, between 59 and 86 degrees F (15 and 30 degrees C) in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Avoid storing at temperatures above 86 degrees F (30 degrees C). Keep BuSpar out of the reach of children and away from pets.

How Supplied

BuSpar (buspirone hydrochloride tablets, USP) Tablets, 5 mg and 10 mg (white, ovoid-rectangular with score, MJ logo, strength and the name BuSpar embossed) are available in bottles of 100.

5 mg tablets
NDC 0087-0818-41 Bottles of 100

10 mg tablets
NDC 0087-0819-41 Bottles of 100

Tablets, 15 mg white, in the DIVIDOSE tablet design imprinted with the MJ logo, are available in bottles of 60 and 180. Tablets, 30 mg pink, in the DIVIDOSE tablet design imprinted with the MJ logo, are available in bottles of 60. The 15 mg and 30 mg tablets are scored so that they can be either bisected or trisected. The 15 mg tablet has ID number 822 on one side and on the reverse side, the number 5 on each trisect segment. The 30 mg tablet has ID number 824 on one side and on the reverse side, the number 10 on each trisect segment.

15 mg tablets
NDC 0087-0822-32 Bottles of 60
NDC 0087-0822-33 Bottles of 180

30 mg tablets
NDC 0087-0824-81 Bottles of 60

US Patent No. 5,015,646

What is the most important information I should know about Buspar (Buspirone)?

Do not this medication if you are allergic to BuSpar, or if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take BuSpar before the MAO inhibitor has cleared from your body. BuSpar can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It may increase some of the side effects caused by BuSpar.
Grapefruit and grapefruit juice may interact with BuSpar and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

BuSpar is usually taken for only a short time. Do not take this medication for longer than 4 weeks without your doctors advice.

What should I discuss with my doctor before taking Buspar (Buspirone)?

Do not this medication if you are allergic to BuSpar, or if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take BuSpar before the MAO inhibitor has cleared from your body.

Before taking BuSpar, tell your doctor if you are allergic to any drugs, or if you have:

• kidney disease; or
• liver disease.

If you have any of these conditions, you may not be able to use BuSpar, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether BuSpar passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not give this medication to a child younger than 18 years old.

Special Populations

Age and Gender Effects

After single or multiple doses in adults, no significant differences in buspirone pharmacokinetics (AUC and Cmax) were observed between elderly and younger subjects or between men and women.

Hepatic Impairment

After multiple-dose administration of buspirone to patients with hepatic impairment, steady-state AUC of buspirone increased 13-fold compared with healthy subjects

Renal Impairment

After multiple-dose administration of buspirone to renally impaired (Clcr = 10-70 mL/min/1.73 m2) patients, steady-state AUC of buspirone increased 4-fold compared with healthy (Clcr≥80 mL/min/1.73 m2) subjects.

Race Effects

The effects of race on the pharmacokinetics of buspirone have not been studied.

Possible side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• feeling light-headed, fainting;
• fast or uneven heart rate;
• depressed mood, unusual thoughts or behavior; or
• lack of balance or coordination.

Less serious side effects may be more likely to occur, such as:

• drowsiness, dizziness, blurred vision;
• feeling restless;
• nausea, upset stomach;
• sleep problems (insomnia); or
• trouble concentrating.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.

What other drugs will affect Buspar (Buspirone)?

Before taking BuSpar, tell your doctor if you are using any of the following drugs:

• medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), haloperidol (Haldol), mesoridazine (Serentil), pimozide (Orap), or thioridazine (Mellaril);
• dexamethasone (Decadron, Hexadrol);
• erythromycin (E-Mycin, E.E.S., Ery-Tab, Erythrocin);
• itraconazole (Sporanox), ketoconazole (Nizoral);
• ritonavir (Norvir);
• rifampin (Rifadin, Rimactane, Rifater);
• antibiotics such as capreomycin (Capastat), rifampin (Rifadin, Rimactane, Rifater), vancomycin (Vancocin, Vancoled);
• a calcium channel blocker such as diltiazem (Tiazac, Cartia, Cardizem) or verapamil (Calan, Covera, Isoptin, Verelan); or
• seizure medication such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin), phenobarbital (Luminal, Solfoton).

If you are using any of these drugs, you may not be able to use BuSpar, or you may need dosage adjustments or special tests during treatment.

This list is not complete and there may be other drugs that can interact with BuSpar. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

What should I avoid while taking Buspar (Buspirone)?

BuSpar can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It may increase some of the side effects caused by BuSpar.

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, or depression can add to sleepiness caused by BuSpar. Tell your doctor if you regularly use any of these other medicines.

Grapefruit and grapefruit juice may interact with BuSpar and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Contraindications

BuSpar is contraindicated in patients hypersensitive to buspirone hydrochloride.

Warnings

The administration of BuSpar 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 BuSpar (buspirone hydrochloride) has been added to a regimen including an MAOI. Therefore, it is recommended that BuSpar not be used concomitantly with an MAOI.

Because BuSpar has no established antipsychotic activity, it should not be employed in lieu of appropriate antipsychotic treatment.

Precautions

Interference with Cognitive and Motor Performance
Studies indicate that BuSpar is less sedating than other anxiolytics and that it does not produce significant functional impairment. However, its CNS effects in any individual patient may not be predictable. Therefore, patients should be cautioned about operating an automobile or using complex machinery until they are reasonably certain that buspirone treatment does not affect them adversely.

While formal studies of the interaction of BuSpar (buspirone hydrochloride) with alcohol indicate that buspirone does not increase alcohol-induced impairment in motor and mental performance, it is prudent to avoid concomitant use of alcohol and buspirone.

Potential for Withdrawal Reactions in Sedative/Hypnotic/Anxiolytic Drug-Dependent Patients
Because BuSpar does not exhibit cross-tolerance with benzodiazepines and other common sedative/hypnotic drugs, it will not block the withdrawal syndrome often seen with cessation of therapy with these drugs. Therefore, before starting therapy with BuSpar, it is advisable to withdraw patients gradually, especially patients who have been using a CNS-depressant drug chronically, from their prior treatment. 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.

The syndrome of withdrawal from sedative/hypnotic/anxiolytic drugs can appear as any combination of irritability, anxiety, agitation, insomnia, tremor, abdominal cramps, muscle cramps, vomiting, sweating, flu-like symptoms without fever, and occasionally, even as seizures.

Possible Concerns Related to Buspirone's Binding to Dopamine Receptors
Because buspirone can bind to central dopamine receptors, a question has been raised about its potential to cause acute and chronic changes in dopamine-mediated neurological function (eg, dystonia, pseudo-parkinsonism, 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 (ie, represent akathisia).

Information For Patients

Carcinogenesis/ Mutagenesis/ Impairment of Fertility

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 Salmonella typhimurium (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.

Pregnancy

Pregnancy Category B: No fertility impairment or fetal damage was observed in reproduction studies performed in rats and rabbits at buspirone doses of approximately 30 times the maximum recommended human dose. In humans, however, adequate and well-controlled studies during pregnancy have not been performed. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

The extent of the excretion in human milk of buspirone or its metabolites is not known. In rats, however, buspirone and its metabolites are excreted in milk. BuSpar administration to nursing women should be avoided if clinically possible.

Pediatric Use

The safety and effectiveness of buspirone were evaluated in two placebo-controlled 6-week trials involving a total of 559 pediatric patients (ranging from 6 to 17 years of age) with GAD. Doses studied were 7.5 mg to 30 mg b.i.d. (15-60 mg/day). There were no significant differences between buspirone and placebo with regard to the symptoms of GAD following doses recommended for the treatment of GAD in adults. Pharmacokinetic studies have shown that, for identical doses, plasma exposure to buspirone and its active metabolite, 1-PP, are equal to or higher in pediatric patients than adults. No unexpected safety findings were associated with buspirone in these trials. There are no long-term safety or efficacy data in this population.

Geriatric Use

In one study of 6632 patients who received buspirone 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.

Use in Patients With Impaired Hepatic or Renal Function

Buspirone is metabolized by the liver and excreted by the kidneys. A pharmacokinetic study in patients with impaired hepatic or renal function demonstrated increased plasma levels and a lengthened half-life of buspirone. Therefore, the administration of BuSpar to patients with severe hepatic or renal impairment cannot be recommended.

Most important fact about BuSpar

BuSpar should not be used with antidepressant drugs known as monoamine oxidase (MAO) inhibitors. Brands include Nardil and Parnate.

Special warnings about BuSpar

The effects of BuSpar on the central nervous system (brain and spinal cord) are unpredictable. Therefore, you should not drive or operate dangerous machinery or participate in any hazardous activity that requires full mental alertness while you are taking BuSpar.

Special information if you are pregnant or breastfeeding

The effects of BuSpar during pregnancy have not been adequately studied. If you are pregnant or plan to become pregnant, inform your doctor immediately. It is not known whether BuSpar appears in breast milk. If BuSpar is essential to your health, your doctor may advise you to discontinue breastfeeding until your treatment is finished.

References

References and complaints