Buspiron SANDOZ 10mg 20 tablets — Made in Germany — Free Delivery

Pharmacological properties

Pharmacodynamics. Buspirone is an anxiolytic preparation used to treat anxiety conditions of various origins, especially neuroses, which are accompanied by feelings of anxiety, anxiety, tension, irritability. the mechanism of action of buspirone has not been finally established, however, it is known that it differs from the mechanism of action of benzodiazepines and other anxiolytic agents. Buspirone exhibits a high affinity for presynaptic 5NT1a receptors and is a partial agonist of postsynaptic 5NT1a receptors in the central nervous system. in a series of preclinical studies on experimental models, it was established that buspirone has properties characteristic of anxiolytics and antidepressants. buspirone does not have significant activity against benzodiazepine receptors and does not affect gamma binding. unlike benzodiazepines, buspirone does not exhibit anticonvulsant and muscle relaxant effects, does not cause addiction, and after the completion of the course of treatment, there are no withdrawal symptoms. the action of buspirone develops gradually. the therapeutic effect begins to manifest itself between the 7th and 14th days of therapy, and the maximum effect is achieved only approximately 4 weeks after the start of treatment.

Pharmacokinetics. After application, the preparation is rapidly and almost completely absorbed in the gastrointestinal tract. Equilibrium plasma concentration can be reached approximately 2 days after the start of regular use of the preparation.

Buspirone undergoes intensive first pass metabolism through the liver. Systemic bioavailability is 4%. Cmax of the preparation metabolite in blood plasma is also achieved after 60–90 minutes.

About 95% of buspirone binds to blood plasma proteins. T1 / 2 from blood plasma is 2-3 hours. Pharmacological parameters of the preparation do not change with continuous administration of the preparation(no cumulation).

The main pharmacologically active metabolite of buspirone is 1- [2-pyrimidinyl] -piperazine (1-PP).

Its anxiolytic activity is 4–5 times lower than that of the original substance, but the concentration in blood plasma is higher and T½ is 2 times longer than that of buspirone.

About 29–63% of buspirone and its metabolites are excreted in the urine for 24 hours, 18–38% in the feces. In case of impaired renal and liver function, the elimination of buspirone and its metabolites is reduced.

Simultaneous food intake slows down the absorption of buspirone in the gastrointestinal tract.

Buspirone passes into breast milk. There are no data on the penetration of buspirone through the placenta.

Increased concentration of buspirone in blood plasma and the value of AUC, as well as an increase in T½ are possible in case of impaired liver function. As a result of the elimination of the unchanged compound with bile, a second peak may appear in the buspirone concentration curve in the blood plasma. Patients with cirrhosis of the liver should receive the preparation  at lower individual doses or at the same doses, but less frequently.

Renal failure can reduce buspirone clearance by 50%. In patients with renal insufficiency, buspirone should be prescribed with caution and at lower doses.

In the elderly, the pharmacokinetics of buspirone does not change.

Indications

Symptomatic treatment for anxiety states with dominant symptoms: anxiety, inner anxiety, tension.

Application

Doses are determined by the doctor individually for each patient, depending on the condition of the disease. at the beginning of therapy, 5 mg of buspirone hydrochloride is prescribed 3 times a day. to achieve the maximum therapeutic effect, the daily dose is gradually increased to 20-30 mg of buspirone, distributed over several separate doses.

The maximum single dose should not exceed 30 mg.

The maximum daily dose should not exceed 60 mg.

Food increases the bioavailability of buspirone. The tablets should be taken at the same time of day, without chewing, with a small amount of liquid, before or after meals.

If it is necessary to divide the tablet into two halves, place it on a hard surface with a dash up and press it lightly with your thumb.

If buspirone is used in combination with a potent inhibitor of CYP 3A4, the initial dose of buspirone should be reduced and gradually increased only after medical examination of the patient (see INTERACTIONS).

Grapefruit juice increases plasma levels of buspirone. Patients are not advised to consume large quantities of grapefruit juice during treatment.

Special patient groups

Renal failure In renal failure of mild and moderate severity (creatinine clearance - 20–49 ml / min / 1.72 m2), a single use of buspirone causes an increase in its level in blood plasma without an increase in T½. These patients are recommended to use buspirone with caution and in lower doses, take the preparation 2 times a day. It is necessary to carefully monitor the response to treatment and symptoms in the patient before increasing the dose. In patients with anuria, a single use of the preparation leads to an increase in the level of the 1-PP metabolite in the blood, in them dialysis had no effect on the concentration of either buspirone or 1-PP. Buspirone should not be used in persons with a creatinine clearance of 20 ml / min / 1.72 m2, especially in patients with anuria due to the possibility of increasing the concentration of buspirone and its metabolites.

Liver failure. The use of preparations such as buspirone for the treatment of patients with impaired liver function causes a reduced effect of the first passage of preparations through the liver. With cirrhosis of the liver, a single use of buspirone causes an increase in the concentration of its unchanged form in the blood plasma with an increase in T½. These patients are advised to use buspirone with caution and after individual titration of doses to reduce the risk of serious adverse reactions that may occur due to the use of buspirone in high doses. Increasing doses should be considered after careful examination of the patient and only 4–5 days after the previous dose.

Elderly patients. The available data do not indicate the advisability of changing the dosage regimen depending on the age and gender of the patient.

Duration of treatment. Tranquilizers should not be used without medical supervision for a long time. Therefore, the duration of treatment with buspirone 5 mg and / or 10 mg should not exceed 4 months. Doses are determined by the doctor individually for each patient, depending on the condition of the disease. If long-term use of the preparation is necessary (up to 6 months), careful medical monitoring should be carried out.

It should be remembered about psycho- and socio-therapeutic measures combined with treatment with buspirone.

Contraindications

Hypersensitivity to buspirone or to any other component of the preparation. severe liver disease, severe liver failure (prothrombin time 18 s); severe renal failure (glomerular filtration rate (GFR) 10 ml / min); epilepsy; acute intoxication with alcohol, sleeping pills, analgesics and antipsychotics.

Concomitant treatment with MAO inhibitors and within 14 days after discontinuation of an irreversible MAO inhibitor or within 1 day after discontinuation of a reversible MAO inhibitor.

Side effects

Side effects usually occur at the beginning of treatment, and their severity usually decreases with prolonged use. in some cases, a dose reduction is necessary. most often, adverse reactions from the nervous system, such as dizziness, insomnia, nervousness, drowsiness, semi-fainting, were noted, as well as from the digestive tract, such as nausea, as well as other undesirable effects, such as headache and increased fatigue.

Less often, anger and hostility, confusion, blurred vision, diarrhea, pain in muscles and bones, numbness, paresthesia, impaired coordination of movements, tremors and skin rashes, dry mouth, weakness, asthenia, increased sweating, clammy skin were detected.

Frequency of adverse reactions: very often (? 1/10), often (? 1/100, 1/10), infrequently (? 1/1000, 1/100), rarely (? 1/10 000, 1/1000), very rare (1/10 000), unknown (frequency cannot be estimated due to lack of data).

Infections and invasions: frequency unknown - fever.

From the side of the cardiovascular system: often - nonspecific chest pain, tachycardia / palpitations; infrequently - temporary loss of consciousness, arterial hypotension and / or hypertension; rarely - cerebrovascular accident, heart failure, myocardial infarction, cardiomyopathy, bradycardia, cerebrovascular disorders.

From the side of the blood system: rarely - changes in blood parameters (eosinophilia, leukopenia, thrombopenia).

From the side of the psyche: often - nightmares, insomnia, nervousness, decreased concentration, emotional excitement, irritability, hostility, confusion, depression; infrequently - depersonalization, discomfort, pathological increased perception of ordinary sounds, euphoria, hyperkinesia, anxiety, loss of interest, impaired associative perception, hallucinations, suicidal thoughts, dysphoria, fear; rarely - a sharp change in mood, claustrophobia, stupor, slurred speech, psychosis, passing memory problems, serotonin syndrome, affective lability.

From the side of the central nervous system: very often - dizziness, headache, drowsiness; often - numbness, paresthesia (for example, tingling, pain), blurred vision, impaired coordination, tremor; infrequently - numbness, epileptic seizures, dysgeusia, dysosmia, prolonged reaction time; rarely - spontaneous movements, lethargy, extrapyramidal symptoms, including early and tardive dyskinesia, disturbed tone, parkinsonism, akathisia, dystonia, syncope, amnesia, ataxia, serotonin syndrome, toothed muscle stiffness, restless legs syndrome, restlessness.

From the side of the organ of vision: often - blurred vision; infrequently - redness and itching in the eye area, conjunctivitis; rarely - photophobia, a feeling of intraocular pressure, eye pain, narrowed field of vision, increased intraocular pressure.

From the side of the organ of hearing: often - tinnitus; rarely - damage to the inner ear.

From the respiratory system: often - sore throat, nasal congestion, pain in the pharynx and larynx; infrequently - rapid breathing, shortness of breath, feeling of compression in the heart, hyperventilation, feeling of lack of air; rarely - nosebleeds, burning sensation of the tongue.

From the digestive tract: often - nausea, xerostomia, pain in the epigastric region, diarrhea, constipation, vomiting; infrequently - flatulence, lack of appetite, increased appetite, hypersalivation, irritable bowel syndrome, rectal bleeding.

From the urinary system: infrequently - frequent urination, urinary retention; rarely - enuresis, nocturnal urination.

From the side of the skin: often - cold sweat, rash; infrequently - edema, urticaria, hyperemia, hematomas, baldness, dry skin, eczema, facial edema, blisters, increased skin vulnerability, itching; rarely - allergic reactions, ecchymosis, acne, thinning of the nails.

From the musculoskeletal system: often - musculoskeletal pain; infrequently - muscle spasm and stiffness, myalgia, arthralgia; rarely - myasthenia gravis.

From the endocrine system: rarely - galactorrhea, gynecomastia, thyroid dysfunction.

Metabolic disorders: infrequently - anorexia, increased appetite; the frequency is unknown - an increase in body weight, a decrease in body weight.

General disorders: often - asthenia; infrequently - fever, ringing in the head, malaise, increased fatigue, impaired sense of smell and taste, increased sweating, hot flashes, cold hyperesthesia; rarely - a tendency to abuse alcohol, impaired blood coagulation, loss of voice, hiccups, glossalgia.

From the hepatobiliary system: infrequently - increased liver enzymes.

Reproductive system disorders: infrequently - menstrual irregularities, decreased or increased libido; rarely - amenorrhea, inflammation of the genitourinary organs, decreased ejaculation, impotence.

Laboratory tests: increase in the level of transaminases in the blood plasma.

Special instructions

Liver failure. buspirone is extensively metabolized in the liver. in a pharmacokinetic study, the use of buspirone in a single dose of 30 mg in patients with liver cirrhosis increased the concentration of buspirone in the blood plasma, increased the auc value and lengthened t½ buspirone. due to the excretion of the substance into bile, a second peak in the concentration of buspirone in the blood plasma is possible. use of the preparation is contraindicated in patients with severe hepatic impairment. persons with cirrhosis of the liver should be prescribed the preparation in lower doses or in the same doses, but with an increased interval between doses of the preparation.

Renal failure In moderate or severe renal failure, the clearance of buspirone can be reduced by 50%. The preparation  is contraindicated in patients with severe renal impairment (GFR 10 ml / min). With mild (GFR 30 ml / min) and moderate (GFR - 10-30 ml / min) renal failure, buspirone can be prescribed, however, caution should be exercised and used in reduced doses.

Elderly patients. There is no need to clarify the dose, but caution should be exercised when using the preparation (for example, due to a possible decrease in renal and / or liver function and an increased sensitivity to side effects of the preparation). Patients should be prescribed the preparation in the minimum effective dose, and if the dose is increased, the patient's health should be carefully monitored.

Patients should be advised not to consume grapefruits or drink large amounts of grapefruit juice during treatment, as these products can increase plasma levels of buspirone and lead to an increase in the frequency or severity of side effects.

Transfer of patients from benzodiazepines to buspirone. Buspirone cannot eliminate benzodiazepine withdrawal symptoms. If the patient is transferred to buspirone therapy after prolonged therapy with benzodiazepines, buspirone should be prescribed only after the end of the period of gradual dose reduction of benzodiazepines.

Buspirone is not addictive to the preparation, but its use in patients with known or suspected preparation dependence requires careful medical supervision. Since the anxiolytic effect of the preparation appears after 7-14 days of use, and the full therapeutic effect develops after 4 weeks, patients with severe anxiety require careful medical supervision at the initial stage of therapy.

During the course of treatment with buspirone, alcoholic beverages should be avoided.

Buspirone is not intended to treat withdrawal symptoms associated with benzodiazepines or other sedatives / hypnotics. Therefore, before starting treatment with buspirone, the use of these preparations should be gradually discontinued. This is especially true for patients taking preparations that depress the central nervous system. Buspirone should not be used as monotherapy for depression because it may mask the clinical symptoms of depression.

Clinical and experimental studies have not revealed any signs that buspirone causes a risk of addiction or dependence, however, the prescription of the preparation must be justified.

The use of buspirone in patients taking MAO inhibitors can be dangerous. There are reports of an increase in blood pressure with the combined use of these preparations.

Buspirone should be taken with caution in patients with acute angle-closure glaucoma, myasthenia gravis, preparation addiction.

Patients with a history of epileptic seizures should not be prescribed buspirone.

The preparation Buspirone Sandoz contains lactose, so it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Long term toxicity. Since the mechanism of action is not fully understood, long-term toxic effects on the central nervous system or other organ systems may be unpredictable.

Use during pregnancy and lactation. There are no data on the use of buspirone during pregnancy, so the preparation can be prescribed only in cases where the expected benefit to the pregnant woman outweighs the potential risk to the fetus. Buspirone passes into breast milk, so breastfeeding should be discontinued during treatment.

Children. Buspirone is not prescribed for children due to the lack of data on the safety and efficacy of the preparation in this category of patients.

The ability to influence the reaction rate when driving or working with other mechanisms. During treatment, one should refrain from driving vehicles or working with mechanisms, since adverse reactions from the central nervous system and psyche may occur (see SIDE EFFECTS).

Interactions

Due to the lack of relevant clinical data, the combined use of buspirone with antihypertensive, neuroleptic preparations, antidepressants, antidiabetic preparations, anticoagulants, oral contraceptives and cardiac glycosides is possible only under strict medical supervision. buspirone is not used simultaneously with benzodiazepines and other sedatives.

The combination with MAO inhibitors is not recommended due to the risk of hypertensive crisis.

Since buspirone is mainly metabolized by cytochrome P450, potent inhibitors of this enzyme can increase the bioavailability of buspirone.

Nefazodone. The simultaneous use of buspirone (2.5 or 5 mg 2 times a day) and nefazodone (250 mg 2 times a day) led to an increase in Cmax of buspirone in blood plasma by 20 times and AUC - by 50 times and a statistically significant decrease (by about 50 %) of buspirone metabolite, 1-pyrimidinylpiperazine, in blood plasma. In the case of using buspirone at a dose of 5 mg 2 times a day, a slight increase in the AUC of nefazodone (23%) and its metabolites - hydroxynefazodone (HO-NEF) (17%) and mCPP (9%) was noted. A slight increase in Cmax was observed for nefazodone (8%) and its metabolite HO-NEF (11%).

The profile of adverse reactions in patients taking buspirone at a dose of 2.5 mg 2 times a day and nefazodone at a dose of 250 mg 2 times a day did not differ from the profile of adverse reactions in patients who took either of these preparations separately. Adverse reactions in persons who used buspirone at a dose of 5 mg 2 times a day and nefazodone at a dose of 250 mg 2 times a day included light-headedness, asthenia, dizziness and drowsiness. It is recommended to reduce the dose of buspirone while using it with nefazodone.

Erythromycin. The combined use of buspirone (single dose - 10 mg) and erythromycin (1.5 mg 1 time per day for 4 days) led to an increase in buspirone Cmax by 5 times and AUC by 6 times. If the simultaneous use of buspirone and erythromycin is necessary, it is recommended to use buspirone in a low dose (for example, 2.5 mg 2 times a day).

Itraconazole. The simultaneous use of buspirone (single dose - 10 mg) and itraconazole (200 mg 1 time per day for 4 days) led to an increase in buspirone Cmax 13 times and AUC 19 times. If necessary, the simultaneous use of buspirone and itraconazole is recommended to use buspirone in a low dose (for example, 2.5 mg once a day).

Diltiazem. The simultaneous use of buspirone (single dose of 10 mg) and diltiazem (60 mg 3 times a day) led to an increase in buspirone Cmax by 5.3 times and AUC by 4 times. It is possible to enhance the action and increase the toxicity of buspirone if it is necessary to use buspirone and diltiazem at the same time.

Verapamil. The simultaneous use of buspirone and verapamil led to an increase in Cmax and AUC of buspirone by 3.4 times. Possible increased action and increased toxicity of buspirone with the simultaneous use of buspirone and verapamil.

Cimetidine. The combined use of buspirone and cimetidine leads to an increase in the Cmax of buspirone by 40%, Tmax - 2 times, but the AUC practically does not change.

When using buspirone together with the above agents, the therapeutic effect and toxicity of buspirone increase, therefore it is recommended to reduce the dose of the preparation (for example, 2.5 mg 2 times a day). The next dose adjustment should be based on the clinical response to treatment with each of these preparations.

Baclofen, lofexidine, nabilone, antihistamines can increase any sedation.

Rifampicin. The simultaneous use of buspirone (single dose - 30 mg) and rifampicin (600 mg 1 time per day for 5 days) led to a decrease in buspirone Cmax by 83.9% and AUC - by 89.6%.

Inhibitors and inducers of CYP 3A4. Ketoconazole or ritonavir inhibit the metabolism of buspirone and increase its plasma concentration. When using buspirone with a CYP 3A4 inhibitor, its dose should be reduced.

CYP 3A4 inducers, such as dexamethasone, phenytoin, phenobarbital, or carbamazepine, can increase the metabolic rate of buspirone. In this case, it is necessary to increase the dose of buspirone to maintain its anxiolytic efficacy.

Serotonin reuptake inhibitors. Not a single case of dangerous use of buspirone in combination with antidepressants, selective serotonin reuptake inhibitors has been identified. There were isolated reports of the occurrence of seizures during their long-term use with buspirone.

Haloperidol. The simultaneous use of buspirone and haloperidol led to an increase in the concentration of haloperidol in blood plasma.

Trazodone. There were reports that in some patients, with the simultaneous use of trazodone with buspirone, the ALT activity increased by 3 times. However, such an increase in hepatic transaminases has not been confirmed by clinical studies.

Diazepam With the simultaneous use of diazepam and buspirone, the level of the former in the blood plasma increases slightly, and side effects may also occur: dizziness, headache, nausea.

During treatment with buspirone, you should refrain from drinking alcoholic beverages.

Fluvoxamine. Short-term therapy with buspirone simultaneously with taking fluvoxamine led to a double increase in the concentration of buspirone in the blood plasma compared with buspirone monotherapy.

Digoxin. In humans, approximately 95% of buspirone binds to plasma proteins. In vitro, buspirone does not displace preparations that firmly bind proteins (for example, warfarin) in the blood plasma from the sites of protein binding. However, in vitro buspirone can displace preparations from protein binding sites that do not bind proteins strongly enough (for example, digoxin). The clinical significance of this property is unknown.

An increase in prothrombin time has been reported after the addition of buspirone to therapy including warfarin treatment.

During treatment, patients are not recommended to consume large quantities of grapefruit juice (double dose of 200 ml for 2 days), since this can lead to an increase in the concentration of buspirone in the blood plasma and to an increase in the frequency or severity of side effects.

Overdose

Symptoms: nausea, vomiting, dizziness, increased fatigue, drowsiness, loss of consciousness, miosis (pupillary constriction) and gastrointestinal dysfunction. more severe complications in humans were not observed even with the introduction of a daily dose of up to 2400 mg.

Treatment: gastric lavage, monitoring of respiration, pulse, blood pressure. Symptomatic therapy. There is no specific antidote. Buspirone is not excreted by hemodialysis. Based on the experience gained with the use of the preparation, an overdose with high doses (single dose - 375 mg of buspirone orally) does not necessarily cause severe symptoms.

Storage conditions

Does not require special storage conditions.