Buspar is a prescription medication that can be used to treat anxiety disorders. Buspar can be taken alone or in combination with other medications. It is a group of drugs known as Antianxiety Agents.
BuSpar is used to treat anxiety disorders or the symptoms of anxiety, such as fear, tension, irritability, dizziness, pounding heartbeat, and other physical symptoms.
Is Buspar (Buspirone) a benzodiazepine?
Buspirone hydrochloride tablet is an antianxiety drug that is not chemically nor pharmacologically related to benzodiazepines or barbiturates or any other sedative or anxiolytic medications.
Buspirone hydrochloride is a white crystalline powder and is easily soluble and soluble with water. It has a molecular weight of 422. Chemically, buspirone hydrochloride is 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9- dione monohydrochloride.
Buspirone hydrochloride tablets are intended to be taken orally and contain 5 mg, 10 mg, 15 mg, or 30 mg buspirone. This is equivalent to 4.6, 9.1 mg, 13.7 mg, and 27.4mg buspirone-free base respectively.
Each 5 mg and 10 mg tablet can also be divided into two equal halves of 2.5 mg and 5 mg. Tablets containing 15 and 30 mg can be divided into three. 15 mg tablet can be divided into three with each one-third containing a 5 mg dose. 30 mg tablet can be divided into three with each one-third containing a 10 mg dose.
What is Buspar (Buspirone) Used for?
Buspirone hydrochloride tablets can be used to manage anxiety disorders and short-term relief from symptoms. Treatment with an anxiolytic is not necessary for anxiety or tension caused by everyday stress.
In controlled clinical trials, buspirone hydrochloride tablets were shown to be effective in outpatients with GAD (generalized anxiety disorder). These patients also suffered from co-occurring depressive symptoms. Buspirone hydrochloride tablets were effective in relieving anxiety when these depressive symptoms were present. Patients in these studies experienced symptoms from 1 month to more than a year before the study. The average duration of these symptoms was 6 months.
The American Psychiatric Association’s Diagnostic and Statistical Manual III1 describes Generalized Anxiety Disorder as follows:
Persistent, generalized anxiety lasting at least one month. Symptoms from three of these four categories.
- Shakiness, muscle aches, jitteriness, and trembling or tension, fatigability, twitching of eyes, and the inability to relax.
- Autonomic hyperactivity can manifest as sweating, racing heart, dry, clammy hands, and dizziness or lightheadedness, discomfort in the stomach, cramping, nausea, vomiting, heart pounding, or pallor, fast resting pulse, and high respiration rate.
Symptoms of anxiety
- Anxiety, worry, and fear.
Vigilance and scanning
- Hyperattentiveness can lead to distraction, difficulty in concentration, insomnia, feeling “on edge”, irritability and impatience.
These symptoms are not indicative of schizophrenia or depressive disorders. GAD can also have mild depressive symptoms.
In controlled trials, buspirone hydrochloride tablets’ long-term effectiveness has not been proven. The appropriate length of treatment for GAD is not known.
Buspar Dosage – How to take Buspar (Buspirone):
A recommended starting dose is 15 mg daily (7.5mg b.i.d.). In order to achieve the best therapeutic response, 5 mg may be increased each day at intervals of 2-3 days. The maximum daily intake should not exceed 60 mg per day. Clinical trials that allowed dose titration used divided doses of 20 to 30 mg per day.
Buspirone’s bioavailability is higher when taken with food than it is in a fasted state. Buspirone should be taken consistently by patients, regardless of whether they are taking it with or without food.
Buspirone should not be administered with a potent inhibitor CYP3A4.
Side Effects of Buspar (Buspirone) and Drug Interactions
Buspar may cause serious side effects including:
- chest pain,
- shortness of breath, and
Get medical help right away, if you have any of the symptoms listed above.
Buspar’s most frequent side effects are:
- sleep problems (insomnia),
- upset stomach, and
- feeling nervous or excited
If you experience any side effects that are bothersome or persistent, tell your doctor.
Buspar Drug Interactions:
- MAO Inhibitors
- Buspirone hydrochloride tablets should not be taken in conjunction with MAO inhibitors.
- No statistically significant differences were observed in steady-state pharmacokinetic parameters (Cmax and AUC) of amitriptyline nor its metabolite nortriptyline after adding buspirone.
- The steady-state pharmacokinetic parameters of diazepam (Cmax, CUC, and Cmin) did not show statistically significant changes after adding buspirone. However, increases of around 15% were observed in nordiazepam and there were minor adverse clinical effects such as dizziness, headache, and nausea.
- A study with normal volunteers showed that concomitant administrations of haloperidol and buspirone resulted in higher serum haloperidol levels. This finding is not of clinical significance.
- One report suggests that trazodone Hydrochloride and Buspirone could have caused elevations of SGPT (ALT), ranging from 3- to 6-fold in some patients. Similar studies were done to confirm this finding. However, there was no interaction with hepatic transaminases.
- Buspirone and flurazepam were not shown to increase or prolong the sedative effects of either triazolam or flurazepam.
- Other Psychotropics
- Concomitant administrations of buspirone and most psychotropic drugs are not well-studied. Therefore, it is important to be cautious about concomitant buspirone use with CNS-active drugs.
Inhibitors and Inducers of Cytochrome P450 P450 3A4 (CYP3A4)
In vitro, buspirone was shown to be metabolized in CYP3A4. This is consistent within vivo interactions between buspirone and the following drugs:
- Diltiazem And Verapamil
- A study with nine healthy volunteers showed that buspirone (10mg as a single dose) was co-administered with verapamil (80 mg t.i.d.). or diltiazem (60 mg t.i.d.) Plasma buspirone concentrations increased (verapamil increased Cmax and AUC of buspirone by 3.4-fold, while diltiazem raised Cmax and AUC 5.5-fold and 4-fold respectively.
- Concomitant use of diltiazem and verapamil may increase the likelihood of adverse events caused by buspirone. A subsequent dose adjustment may be required and should be based upon the clinical assessment.
- A study in healthy volunteers showed that coadministration of buspirone (10mg as a single dose) and erythromycin (11.5 g/day) led to an increase in plasma buspirone concentrations (5-fold rise in Cmax, 6-fold increase AUC). These interactions had an associated increase in side effects due to buspirone.
- Combining the drugs should be done with a low dose (e.g. 2.5 mg b.i.d. It is advised to use a low dose of buspirone (e.g., 2.5 mg b.i.d.) when the two drugs are being used together. Clinical assessment should be used to determine the need for subsequent dose adjustments.
- Grapefruit Juice
- A study of healthy volunteers showed that coadministration of buspirone (10mg as a single dose) and grapefruit juice (200mL double-strength t.i.d. For 2 days, plasma buspirone concentrations increased (4.3-fold increase Cmax; 9.2-fold rise in AUC). Buspirone-treated patients should avoid grapefruit juice in excess.
- A study of healthy volunteers showed that coadministration of buspirone (10mg as a single dose) and itraconazole (200mg/day for four days) led to an increase in plasma buspirone concentrations (13-fold rise in Cmax, 19-fold rise in AUC). These interactions had an associated increase in side effects due to buspirone.
- Combining the drugs should be done with a low dose (e.g. 2.5 mg q.d.). It is advised to use a low dose of buspirone (e.g., 2.5 mg q.d.) when the two drugs are being used together. Clinical assessment should be used to determine the need for subsequent dose adjustments.
- A study of steady-state drug kinetics in healthy volunteers showed that buspirone (2.5 mg or 5 mg b.i.d.). was co-administration. With nefazodone, 250 mg b.i.d., coadministration of buspirone (2.5 or 5 mg b.i.d) resulted in significant increases in plasma buspirone levels (up to a 20-fold increase in Cmax and up to 50-fold increase in AUC), and statistically significant decreases in plasma buspirone metabolites 1-PP (about 50%).
- 5 mg per day doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites hydroxy-nefazodone (HO-NEF) (17%) and meta-chlorophenylpiperazine (9%). Cmax values for nefazodone (8%) were slightly higher than those of its metabolite, HO-NEF (11%).
- Buspirone 5 mg was administered to subjects b.i.d. Subjects who received buspirone 5 mg b.i.d. and nefazodone 250mg b.i.d. experienced lightheadedness and asthenia, dizziness, and somnolence. These adverse effects were also seen with the drug alone.
- Low doses of buspirone, such as 2.5 mg per day, are recommended if the drugs are to be combined. It is advised to use a low dose of buspirone (e.g., 2.5 mg q.d.) when the two drugs are being used together. Clinical assessment should be used to determine the need for subsequent dose adjustments.
- A study in healthy volunteers showed that coadministration of buspirone (30mg as a single dose) and rifampin (600mg/day for five days) reduced plasma concentrations (83.7% drop in Cmax; 8.6% decrease in AUC, and pharmacodynamic effects. Buspirone dosage may need to be adjusted if the drugs are combined to maintain their anxiolytic effects.
Other Inhibitors and Inducers of CYP3A4
- Substances that inhibit CYP3A4, like ketoconazole and ritonavir may cause buspirone metabolism to be inhibited and plasma buspirone concentrations to increase. However, substances that induce CYP3A4, like dexamethasone or certain anticonvulsants (phenytoin or phenobarbital), can increase buspirone metabolism.
- Buspirone can cause adverse reactions in patients who have been given a steady dose of buspirone. It is best to use a low dose when buspirone is being administered in combination with a potent inhibitor CYP3A4. To maintain anxiolytic effects, buspirone dosage may need to be adjusted if used with a potent inducer CYP3A4.
Buspar Interactions with Other drugs:
- Buspirone and cimetidine coadministration was shown to increase Cmax (40%) & Tmax (2-fold) while having minimal effect on the AUC.
- Protein Binding
- Buspirone is not able to replace tightly bound drugs such as phenytoin, propranolol, and warfarin in vitro. Buspirone has been reported to prolong prothrombin times in patients who were being treated with warfarin. The patient was also receiving chronic phenytoin and phenobarbital, digoxin, and Synthroid(r).
- Buspirone could displace digoxin, which is less firmly bound in vitro. This property has no clinical significance.
- Aspirin, desipramine, and flurazepam had a minimal effect on the amount of buspirone binding to plasma proteins at therapeutic levels.
Buspar Interactions between Drug and Laboratory Tests
Buspirone hydrochloride may interfere with the urinary metanephrine/catecholamine assay. It was mistakenly misinterpreted as metanephrine in routine assay testing for Pheochromocytoma. This led to a false positive laboratory test result. It is important to stop taking buspirone hydrochloride for 48 hours before you undergo a urine collection to test for catecholamines.
- Controlled Substance Class:
- Buspirone hydrochloride does not belong to any controlled substances
- Dependence on Physical and Psychological Factors
- Buspirone was not found to be addictive or diversionary in animal and human studies. There is also no evidence that it can cause tolerance or psychological dependence.
- Two double-blind clinical studies were conducted on human volunteers who had used recreational drugs or alcohol in the past. The subjects could not distinguish between buspirone hydrochloride tablets or placebo. However, subjects had a statistically significant preference for methaqualone or diazepam.
- Buspirone is not a substance that can be misused, according to studies in rats, mice, and monkeys. Buspirone was not abruptly stopped after prolonged administration in rats. This is in contrast to the common phenomenon of loss of body weight due to physical dependence.
- There is no evidence that buspirone hydrochloride tablets cause physical dependence or drug-seeking behavior. However, it is hard to predict from experimental data the extent to which CNS-active drugs will be misused, diverted, or abused once they are marketed. Therefore, doctors should be careful to check for drug abuse history and monitor patients for signs of abuse or misuse of buspirone hydrochloride tablets (e.g., tolerance, increased dose, drug-seeking behavior).
Buspar (Buspirone) Warnings and Precautions
Buspirone hydrochloride tablets, if administered to patients who are also taking monoamine oxidase inhibitors (MAOI), may cause elevated blood pressure. Therefore, the concomitant use of buspirone hydrochloride tablets and MAOI should be avoided.
Buspirone hydrochloride tablets are not proven to be antipsychotic. They should therefore not be used in place of antipsychotic medication.
Buspar Interference with Cognitive and Motor Performance
Buspirone hydrochloride tablets have been shown to be less sedative than other anxiolytics, and it doesn’t cause significant functional impairment. It is possible that the CNS effects of buspirone hydrochloride tablets may vary from one patient to another. Buspirone treatment can have unpredictable effects on the brain so patients are advised to avoid driving or operating complex machinery until they feel comfortable.
Although buspirone hydrochloride does not cause impairment in motor or mental performance due to alcohol, there are studies that show it does. However, it is wise to avoid the simultaneous use of alcohol with buspirone.
Buspar (Buspirone) Potential For Withdrawal Reactions in patients who are dependent on Sedatives, Hypnotics, and Anxiolytic Drugs:
- Buspirone hydrochloride tablets are not cross-tolerant with benzodiazepines or other common sedatives or hypnotic medications. This will not cause withdrawal symptoms that can often be associated with stopping therapy with these drugs. It is best to slowly withdraw patients from previous treatment before you start therapy with buspirone chloride tablets. Rebound symptoms or withdrawal symptoms can occur at different times depending on the drug and its effective half-life.
- The syndrome of withdrawal from sedatives, hypnotics, and 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 regarding Buspirone’s binding to dopamine receptors
- Buspirone is able to bind to central dopamine receptors. This raises questions about the potential for it to cause chronic and acute changes in dopamine-mediated neurological function. In controlled clinical trials, there has not been any evidence of neuroleptic-like activity.
- However, some patients who received buspirone treatment experienced a temporary feeling of restlessness. There are many explanations for the syndrome. Buspirone, for example, may increase central noradrenergic activation. Or, it may be due to dopaminergic effects, which could explain akathisia.
Buspar (Buspirone) Information For Patients
The following information and instructions are required for patients to ensure safe and effective buspirone hydrochloride tablet use:
- Tell your doctor about all medications, prescription and non-prescription, alcohol, and drugs you take or plan to take while taking buspirone hydrochloride tablets.
- Tell your doctor if you are pregnant or plan to become pregnant, or breastfeeding.
- You should not drive or operate potentially hazardous machinery until you have experienced the effects of this medication.
- Buspirone hydrochloride should be taken regularly, with or without food.
- Avoid grapefruit juice during buspirone hydrochloride tablet treatment.
It is not recommended to perform certain laboratory tests such as urinary metanephrine or catecholamine.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Buspar (Buspirone) has not been observed to have carcinogenic potential. It does not affect fertility either.
Teratogenic Effects have not been observed in animal reproduction studies. However, the data can not be implied to human pregnancies.
Pregnancy Category B
In reproduction studies in rats and rabbits, buspirone doses approximately 30 times the recommended human dose did not cause fertility impairment or fetal harm. However, no well-controlled and adequate studies on pregnant women have been done in humans. This drug should not be used during pregnancy because animal reproduction studies may not always predict human response.
Labor and Delivery
Buspirone hydrochloride has no effect on women’s labor and delivery. In studies on rats, no adverse effects were observed.
It is unknown how much buspirone and its metabolites are excreted in human milk. Buspirone and its metabolites can be excreted in human milk by rats. If it is clinically feasible, buspirone hydrochloride tablets should not be administered to nursing mothers.
Use for children
- Two placebo-controlled 6-week trials that involved 559 children (ranging in age from 6-17 years) were conducted to evaluate the safety and efficacy of buspirone. The doses studied were from 7.5 mg to 30mg b.i.d. (15 to 60 mg/day). Buspirone and placebo did not show any significant differences in the symptoms of GAD when taken at the recommended doses for adults.
- Pharmacokinetic studies showed that plasma exposure to buspirone (1-PP) and its active metabolite (1-PP) is equal or higher in children than it is in adults for the same doses. These studies did not reveal any unexpected safety issues with buspirone. This population does not have any long-term safety or efficacy data.
- One study of 6632 patients receiving buspirone to treat anxiety showed that 605 were over 65 years and 41 were 75 years. The safety and efficacy profiles of these 605 older patients (mean = 70.8 years) were comparable to those of the younger population (mean = 43.3 years).
- Although there are no differences in the incidence of adverse events reported by patients aged 65 and older, it is possible that some older patients may be more sensitive. The pharmacokinetics and toxicity of buspirone were not affected by age.
Use in patients with impaired renal or liver function
Buspirone is metabolized in the liver and excreted through the kidneys. Patients with impaired renal or hepatic function showed increased plasma levels and a longer half-life for buspirone. Buspirone hydrochloride tablets cannot be administered to patients suffering from severe hepatic and renal impairment.
Buspar (Buspirone) Overdosage and Contraindications
DO NOT OVERDOSE
There is no information regarding the overdose of buspirone.
Patients who are hypersensitive to buspirone Hydrochloride Tablets should not take Buspirone Hydrochloride tablets.
Clinical Pharmacology of Buspar (Buspirone):
Buspirone’s mechanism of action is not known. Buspirone is not an anticonvulsant and muscle relaxant, which makes it different from other benzodiazepine anxiolytics. Buspirone also does not have the sedative effects associated with other anxiolytics. Preclinical in vitro studies have demonstrated that buspirone has a high affinity to serotonin (5HT1A) receptors. Buspirone does not have a significant affinity for benzodiazepine and has no effect on GABA binding when tested in preclinical models.
Buspirone shows a moderate affinity for brain D2-dopamine-receptors. Studies have shown that buspirone can also be used to indirectly affect other neurotransmitter systems.
Buspirone hydrochloride can be absorbed quickly by the body and goes through extensive first-pass metabolism. Unchanged buspirone in plasma was only 1% of radioactivity found in a radiolabeled experiment. Plasma concentrations of unchanged buspirone after oral administration are extremely low and vary between subjects. After single oral doses of 20mg, plasma concentrations reached peak levels in the 40- to 90 minute period. Unchanged buspirone tablets have a bioavailability rate of about 90%. However, there are large variations.
In vitro protein binding studies showed that 86% of buspirone was bound to plasma proteins. Aspirin increased plasma levels free buspirone 23% while flurazepam reduced plasma buspirone levels by 20%. It is unknown if these drugs have similar effects on plasma levels free buspirone in vivo or if such changes cause clinically significant differences between treatment outcomes. In vitro studies showed that buspirone didn’t replace highly protein-bound drugs like warfarin and phenytoin from plasma proteins, and that it may even replace digoxin.
Buspirone is metabolized primarily through oxidation. This has been demonstrated in vitro by cytochrome P450 3A4 CYP3A4. Several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP), are produced. 1-PP is about 25% active in animal models that predict anxiolytic potency, but can be present in 20-fold higher amounts. This is not likely to be important for humans.
Blood samples taken from chronically exposed patients to buspirone hydrochloride are not high in 1-PP. The mean levels are about 3 ng/mL. The highest level of 1-PP in human blood was found among 108 patients. It is less than half the 1-PP levels that were observed in animals who received large doses of buspirone.
A single-dose study with 14C-labeled Buspirone showed that 29% to 63% of doses were excreted in urine within 24 hours. This was primarily due to metabolites. Fecal excretion only accounted for 18%-38%. After single doses of 10 to 40 mg, the average elimination half-life for unchanged buspirone is approximately 2 to 3 hours.
Age and gender effects
No significant differences in buspirone’s pharmacokinetics (AUC, Cmax) between older and younger subjects, or between men or women were found after single or multiple doses.
Patients with hepatic impairment were given multiple doses of buspirone. The steady-state AUC of the drug increased 13-fold.
Buspirone was administered in multiple doses to patients with renal impairment (Clcr = 10 – 70 mL/min/1.73m2), and the steady-state AUC increased fourfold when compared to healthy subjects (Clcr >=80 mL/min/1.73m2).
Race and its Effects
It has not been possible to determine the effects of race on buspirone’s pharmacokinetics.
How to use Buspar (Buspirone) tablets:
Buspirone response varies from person to person. To get the right response, your doctor may recommend that you adjust your dose. Each tablet can be scored and broken precisely.
Holding a tablet between your thumbs, index fingers and the correct tablet score (groove) will help you break it accurately and quickly. Next, hold the tablet with your index fingers close to the appropriate tablet score (groove). Press down and tear the sections of the tablet.