Instructions Buspirone Sandoz tablets 5 mg blister No. 20
Composition
active ingredient: buspirone;
1 tablet contains buspirone hydrochloride 5 mg or 10 mg;
Excipients: lactose monohydrate, corn starch, calcium hydrogen phosphate dihydrate, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), microcrystalline cellulose, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
5 mg and 10 mg tablets: white round tablets with a “snap tab”-like score.
Pharmacotherapeutic group
Agents affecting the nervous system. Anxiolytics. ATX code N05B E01.
Pharmacological properties
Pharmacodynamics
Buspirone is an anxiolytic and is used to treat anxiety states of various origins, especially neuroses accompanied by feelings of anxiety, restlessness, tension, irritability. The mechanism of action of buspirone has not been definitively established, but it is known that it differs from the mechanism of action of benzodiazepines and other anxiolytics. Buspirone exhibits high affinity for presynaptic 5-HT1A receptors and is a partial agonist of postsynaptic 5-HT1A receptors in the central nervous system (CNS). A series of preclinical studies on experimental models have established the presence of buspirone in properties typical of anxiolytics and antidepressants. Buspirone does not exhibit significant activity towards benzodiazepine receptors and does not affect the binding of GABA. Unlike benzodiazepines, buspirone does not have anticonvulsant and muscle relaxant effects, is not addictive, and after the end of the course of treatment, withdrawal symptoms do not develop. The effect of buspirone develops gradually. The therapeutic effect begins to appear between 7 and 14 days of therapy, and the maximum effect is achieved only approximately 4 weeks after the start of treatment.
Pharmacokinetics
After administration, the drug is rapidly and almost completely absorbed from the gastrointestinal tract. Steady-state plasma concentrations can be reached approximately 2 days after the start of regular use of the drug.
Buspirone undergoes extensive first-pass metabolism through the liver. Systemic bioavailability is 4%. Maximum plasma concentration is reached 60–90 minutes after administration. Approximately 95% of buspirone is bound to plasma proteins. The plasma half-life is 2–3 hours. The pharmacological parameters of the drug do not change with continuous use (there is 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 parent compound, but its plasma levels are higher and its half-life is approximately 2 times longer than that of buspirone.
Approximately 29–63% of buspirone and its metabolites are excreted in the urine within 24 hours, 18–38% in the feces. In cases of impaired renal and hepatic function, the elimination of buspirone and its metabolites is somewhat reduced.
Simultaneous food intake slows down the absorption of buspirone from the digestive tract.
Buspirone passes into breast milk. There are no data on the penetration of buspirone through the placenta.
Increased plasma buspirone levels and AUC values, as well as a prolongation of the half-life, may occur in patients with impaired hepatic function. Due to the excretion of unchanged compound in the bile, a second peak in plasma buspirone levels may occur. Patients with cirrhosis of the liver should receive lower individual doses or the same doses but less frequently.
Renal failure may reduce the clearance of buspirone by 50%. Buspirone should be administered with caution and in lower doses to patients with renal failure. The pharmacokinetics of buspirone are not altered in elderly patients.
Indication
Symptomatic treatment of anxiety disorders with dominant symptoms such as anxiety, inner restlessness, and tension.
Contraindication
Hypersensitivity to buspirone or to any of the other ingredients of the drug. Acute congestive glaucoma, severe liver disease, myasthenia gravis, severe hepatic insufficiency (prothrombin time more than 18 seconds); Severe renal insufficiency (creatinine clearance < 20 ml/min/1.72 m2), epilepsy, acute intoxication with alcohol, hypnotics, analgesics and neuroleptics. Concomitant treatment with monoamine oxidase inhibitors (MAO) and a period of 14 days after discontinuation of an irreversible MAO inhibitor or within 1 day after discontinuation of a reversible MAO inhibitor.
Interaction with other medicinal products and other types of interactions
Due to the lack of relevant clinical data, the concomitant use of buspirone with antihypertensives, neuroleptics, antidepressants, antidiabetic agents, anticoagulants, oral contraceptives and cardiac glycosides is possible only under close medical supervision. Buspirone should not be used concomitantly with benzodiazepines and other sedatives.
Combination with MAO inhibitors is not recommended due to the risk of hypertensive crisis.
Nefazodone
Concomitant administration of buspirone (2.5 or 5 mg twice daily) and nefazodone (250 mg twice daily) resulted in a 20-fold increase in the maximum plasma concentration (Cmax) and a 50-fold increase in the area under the concentration-time curve (AUC) of buspirone and a statistically significant decrease (approximately 50%) in the plasma exposure of the buspirone metabolite, 1-pyrimidinylpiperazine. At a dose of 5 mg twice daily, there was a slight increase in the AUC of nefazodone (23%) and its metabolites hydroxynefazodone (HO-NEF) (17%) and mCPP (9%). There was a slight increase in the Cmax of nefazodone (8%) and its metabolite HO-NEF (11%).
The adverse reaction profile in patients receiving buspirone 2.5 mg twice daily and nefazodone 250 mg twice daily was not different from the adverse reaction profile in patients receiving either drug alone. Adverse reactions in patients receiving buspirone 5 mg twice daily and nefazodone 250 mg twice daily included presyncope, asthenia, dizziness, and somnolence. A reduction in the dose of buspirone is recommended when coadministered with nefazodone.
Erythromycin
Concomitant administration of buspirone (single dose of 10 mg) and erythromycin (1.5 g once daily for 4 days) resulted in a 5-fold increase in buspirone Cmax and a 6-fold increase in AUC. If concomitant administration of buspirone and erythromycin is necessary, a low dose of buspirone (e.g. 2.5 mg twice daily) is recommended.
Itraconazole
Concomitant administration of buspirone (single dose of 10 mg) and itraconazole (200 mg once daily for 4 days) resulted in a 13-fold increase in buspirone Cmax and a 19-fold increase in AUC. If concomitant administration of buspirone and itraconazole is necessary, a low dose of buspirone (e.g. 2.5 mg once daily) is recommended.
Diltiazem
Concomitant use of buspirone (single dose of 10 mg) and diltiazem (60 mg 3 times a day) resulted in a 5.3-fold increase in buspirone Cmax and a 4-fold increase in AUC. It is possible to potentiate the action and increase the toxicity of buspirone if it is necessary to use buspirone and diltiazem simultaneously.
Verapamil
Concomitant use of buspirone and verapamil resulted in a 3.4-fold increase in buspirone Cmax and AUC. Increased effects and toxicity of buspirone are possible when buspirone and verapamil are administered concomitantly.
Cimetidine
Simultaneous use of buspirone and cimetidine led to an increase in buspirone Cmax by 40%, tmax by twofold, but AUC remained practically unchanged.
When buspirone is used together with the above-mentioned agents, the therapeutic effect and toxicity of buspirone are increased, therefore it is recommended to reduce the dose of buspirone (for example, 2.5 mg 2 times a day). Subsequent dosage adjustments should be based on the clinical response to treatment for each of these drugs.
Baclofen, lofexidine, nabilone, antihistamines may enhance any sedative effect.
Rifampicin
Concomitant use of buspirone (single dose of 30 mg) and rifampicin (600 mg once daily for 5 days) resulted in a decrease in buspirone Cmax by 83.9% and AUC by 89.6%.
CYP3A4 inhibitors and inducers
Ketoconazole or ritonavir inhibit the metabolism of buspirone and increase its plasma levels. If buspirone is used together with a CYP3A4 inhibitor, its dose should be reduced. CYP3A4 inducers, such as dexamethasone, phenytoin, phenobarbital or carbamazepine, may increase the rate of buspirone metabolism. In such cases, the dose of buspirone should be increased to maintain its anxiolytic efficacy.
Serotonin reuptake inhibitors
There have been no reports of unsafe use of buspirone with antidepressants, selective serotonin reuptake inhibitors. There have been isolated reports of seizures with their long-term use with buspirone.
Haloperidol
Concomitant use of buspirone and haloperidol resulted in increased serum concentrations of haloperidol.
Trazodone
There have been reports that some patients have experienced a 3-fold increase in ALT activity when trazodone was coadministered with buspirone. However, this increase in hepatic transaminases has not been confirmed in clinical studies.
Diazepam
With 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 buspirone therapy with fluvoxamine resulted in a twofold increase in buspirone plasma levels compared to buspirone monotherapy.
Application features
Liver failure.
Renal impairment. In moderate or severe renal impairment, buspirone clearance may be reduced by 50%. The drug is contraindicated in patients with severe renal impairment (creatinine clearance < 20 ml/min/1.72 m2). The drug should be administered with caution to patients with renal impairment (see "Method of administration and dosage").
Elderly patients. No dose adjustment is necessary, but caution should be exercised when using the drug (e.g., due to possible decreased renal and/or hepatic function and increased sensitivity to the side effects of the drug). Patients should be given the lowest effective dose, and in case of increasing the dose, the patient should be closely monitored.
Patients should be advised not to eat grapefruit or drink large amounts of grapefruit juice during treatment, as these products may increase the plasma levels of buspirone and lead to an increase in the frequency or severity of side effects.
Transferring patients from benzodiazepines to buspirone. Buspirone cannot eliminate benzodiazepine withdrawal symptoms. If a patient is transferred to buspirone therapy after long-term benzodiazepine therapy, buspirone should be prescribed only after a period of gradual reduction in the dose of benzodiazepines has been completed.
Buspirone is not habit-forming, but its use in patients with a known or suspected tendency to drug dependence requires careful medical supervision.
Since the anxiolytic effect of the drug appears after 7–14 days of use, and the full therapeutic effect develops after approximately 4 weeks, patients with severe anxiety require careful medical supervision at the initial stage of therapy.
During treatment with buspirone, you should avoid drinking alcoholic beverages.
Buspirone is not indicated for the treatment of withdrawal symptoms caused by the use of benzodiazepines or other sedative/hypnotic drugs. Therefore, before starting treatment with buspirone, these drugs should be gradually discontinued. This is especially true for patients taking drugs that depress the central nervous system. Buspirone should not be used as monotherapy in the treatment of depression, as it may mask the clinical symptoms of depression.
Clinical and experimental studies have not revealed any signs that buspirone poses a risk of addiction or dependence, but the drug should be prescribed with caution.
The use of buspirone in patients taking MAO inhibitors may be dangerous. There have been reports of increased blood pressure with concomitant use of these drugs.
Buspirone should be used with caution in patients with acute angle-closure glaucoma, myasthenia gravis, and drug addiction.
Buspirone should not be prescribed to patients with a history of epileptic seizures.
Buspirone Sandoz contains lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Long-term toxicity: Since the mechanism of action is not fully understood, long-term toxic effects on the CNS or other organ systems cannot be predicted.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, you should refrain from driving or operating other mechanisms, as adverse reactions from the central nervous system and psyche may occur (see the "Adverse Reactions" section).
Use during pregnancy or breastfeeding
There are no data on the use of buspirone during pregnancy, so the drug can be prescribed only if the expected benefit to the pregnant woman outweighs the potential risk to the fetus. Buspirone passes into breast milk, so breastfeeding should be discontinued for the period of treatment.
Method of administration and doses
The doctor determines the doses individually for each patient depending on the condition of the disease.
At the beginning of therapy, prescribe 5 mg of buspirone hydrochloride 3 times a day. To achieve maximum therapeutic effect, the daily dose is gradually increased to 20–30 mg of buspirone, divided into 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 always be taken at the same time of day, without chewing, with a small amount of liquid, after meals or regardless of meals.
If it is necessary to divide the tablet in half, place it on a hard surface with the score facing up and press lightly with your thumb.
If buspirone is used together with a potent CYP3A4 inhibitor, its initial dose should be reduced and gradually increased only after a medical examination of the patient (see section "Interaction with other medicinal products and other types of interactions").
Grapefruit juice increases the plasma levels of buspirone. Patients are advised not to consume large amounts of grapefruit juice during treatment.
Special patient groups.
In mild to moderate renal impairment (creatinine clearance 20–49 mL/min/1.72 m2), a single dose of buspirone causes an increase in its plasma levels without an increase in its half-life. For these patients, it is recommended to use buspirone with caution and in lower doses, taken twice a day. The patient's response to treatment and symptoms should be carefully monitored before increasing the dose. In patients with anuric syndrome, a single dose of the drug causes an increase in the level of the metabolite 1-pyrimidine/piperazine (1-PP) in the blood, in whom dialysis has not shown any effect on the levels of either buspirone or 1-PP. Buspirone should not be used in patients with creatinine clearance less than 20 mL/min/1.72 m2, especially in patients with anuric syndrome, due to the possibility of increasing the level of buspirone and its metabolites.
Liver failure
The use of drugs such as buspirone in patients with reduced liver function demonstrates a reduced first-pass effect. In patients with cirrhosis of the liver, single administration of buspirone results in increased levels of unchanged buspirone in plasma with an increased half-life. In these patients, buspirone is recommended to be used with caution and after individual dose titration to reduce the risk of serious adverse reactions that may occur with high doses of buspirone. Dose increases should be considered after careful patient assessment and only 4–5 days after the previous dose.
Elderly patients
Available data do not indicate the feasibility 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. The doctor determines the doses individually for each patient depending on the condition of the disease. If long-term use of the drug (up to 6 months) is necessary, careful medical monitoring should be carried out.
Psychotherapeutic and sociotherapeutic measures should be considered in parallel with buspirone treatment.
Children
Buspirone should not be prescribed to children due to the lack of data on the safety and effectiveness of the drug in such patients.
Overdose
Symptoms: nausea, vomiting, dizziness, fatigue, drowsiness, loss of consciousness, miosis (narrowing of the pupil) and gastrointestinal dysfunction. No serious complications were observed even when taking a daily dose of up to 2400 mg.
Treatment: gastric lavage, monitoring of breathing, pulse, blood pressure. Symptomatic therapy. There is no specific antidote. Buspirone is not removed by hemodialysis. Based on experience with the drug, overdose with high doses (single dose - 375 mg orally) does not necessarily cause severe symptoms.
Adverse reactions
Side effects occur, as a rule, at the beginning of treatment and usually decrease with prolonged use. In some cases, a dose reduction is necessary. The most common side effects are from the nervous system, such as dizziness, insomnia, nervousness, drowsiness, semi-consciousness, and from the digestive tract, such as nausea, as well as other undesirable effects, such as headache and increased fatigue.
Less commonly observed were anger and hostility, confusion, blurred vision, diarrhea, muscle and bone pain, numbness, paresthesia, impaired coordination of movements, tremor and skin rashes, dry mouth, weakness, asthenia, increased sweating, clammy skin.
Frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated from the available data).
Infections and infestations:
frequency unknown - fever.
From the cardiovascular system:
often - non-specific chest pain, tachycardia/palpitations; infrequently - transient syncope, hypotension and/or hypertension; rarely - cerebrovascular accident, heart failure, myocardial infarction, cardiomyopathy, bradycardia, cerebrovascular disorders.
From the blood system:
rarely - changes in blood parameters (eosinophilia, leukopenia, thrombopenia).
From the psyche:
often - nightmares, insomnia, nervousness, decreased concentration, emotional arousal, irritability, hostility, confusion, depression; infrequently - depersonalization, discomfort, pathologically 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, transient memory problems, serotonin syndrome, affective lability.
very often - dizziness, headache, drowsiness; often - paresthesia (tingling, pain sensation), blurred vision, impaired coordination, tremor; infrequently - numbness, epileptic seizures, dysgeusia, dysosmia, prolonged reaction time; rarely - spontaneous movements, inhibition, extrapyramidal symptoms, including early and tardive dyskinesia, tone disorders, parkinsonism, akathisia, dystonia, syncope, amnesia, ataxia, serotonin syndrome, cogwheel muscle rigidity, restless legs syndrome, excitability.
On the part of the organs of vision:
often - blurred vision; infrequently - redness and itching in the eye area, conjunctivitis; rarely - photophobia, feeling of pressure in the eyes, eye pain, narrowed field of vision, increased intraocular pressure.
On the part of the hearing organs:
often - tinnitus; rarely - inner ear damage.
On the part of the respiratory system:
often - sore throat, nasal congestion, pharyngolaryngeal pain; infrequently - excessively rapid breathing, shortness of breath, tightness in the heart, hyperventilation, feeling of lack of air;
rarely common - nosebleed, burning sensation of the tongue.
From the digestive tract:
often - nausea, dry mouth, epigastric pain, 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, dysuria; rarely - enuresis, nocturia.
On the skin:
often - cold sweat, rash; infrequently - edema, urticaria, hyperemia, hematoma formation, alopecia, dry skin, eczema, facial edema, pemphigus, skin fragility, itching; rarely - allergic reactions, ecchymosis, acne, thinning of nails.
From the musculoskeletal system:
often - musculoskeletal pain; infrequently - muscle spasm and rigidity, myalgia, arthralgia;
rarely - myasthenia gravis.
From the endocrine system:
rarely - galactorrhea, gynecomastia, thyroid dysfunction.
Metabolic disorders:
infrequently - anorexia, increased appetite; frequency unknown - weight gain, weight loss.
General violations:
often - asthenia; infrequently - fever, tinnitus, malaise, increased fatigue, impaired sense of smell and taste, increased sweating, hot flashes, cold hyperesthesia; rarely - tendency to alcohol abuse, blood coagulation disorders, loss of voice, hiccups, glossalgia.
From the hepatobiliary system:
uncommon – increased liver enzymes.
From the reproductive system:
infrequently - menstrual cycle disorders, decreased or increased libido; rarely - amenorrhea, inflammation of the genitourinary organs, decreased ejaculation, impotence.
Laboratory tests: increased serum transaminase levels.
Expiration date
2 years.
Storage conditions
Does not require special storage conditions.
Keep out of reach of children.
Packaging
For 5 mg dosage: 10 or 20 tablets in a blister; 1 (20 × 1) or 2 (10 × 2) blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Salutas Pharma GmbH.
Location of the manufacturer and its business address
Otto-von-Güricke-Allee, 1, 39179 Barleben, Germany.
