Instructions for use Spitomin tablets 10 mg blister No. 60
Composition
active ingredient: buspirone;
1 tablet contains buspirone hydrochloride 5 mg or 10 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate (type A), magnesium stearate, colloidal anhydrous silicon dioxide.
Dosage form
Pills.
Main physicochemical properties:
5 mg tablets: white or almost white, round, flat tablets with a bevel, engraved with the stylistic letter E and the number 151 on one side and a score on the other side, odorless or with a faint characteristic odor;
10 mg tablets: white or almost white, round, flat tablets with a bevel, engraved with the stylistic letter E and the number 152 on one side and a score on the other side, odorless or with a faint characteristic odor.
The score is only used to break the tablet for easier swallowing, not to divide it into equal doses.
Pharmacotherapeutic group
Drugs that affect 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 the anxiolytic effect of buspirone and other azaspirodecanedione derivatives differs from the mechanism of action of benzodiazepines. They do not act on the benzodiazepine-GABA-chloride-ionophore receptor complex; however, since they are partial agonists of 5-HT1A receptors, they act by modulating the serotoninergic system. This effect leads to inhibition of 5-HT renewal and a decrease in the frequency of inflammation of 5-HT neurons in the dorsal raphe nuclei. Buspirone exhibits high affinity for presynaptic 5-HT1A receptors and is a partial agonist of postsynaptic 5-HT1A receptors in the central nervous system. Buspirone has been shown to have properties typical of anxiolytics and antidepressants.
Buspirone does not exhibit significant activity at benzodiazepine receptors and does not affect GABA binding. Unlike benzodiazepines, buspirone does not exhibit muscle relaxant or anticonvulsant properties. Unlike benzodiazepines, buspirone does not cause tolerance or dependence, and withdrawal symptoms do not develop after the end of the course of treatment. The action of buspirone develops gradually. The therapeutic effect begins to appear between 7 and 14 days of therapy, and the maximum effect is achieved only after 4 weeks of treatment.
Pharmacokinetics.
After oral administration, the drug is rapidly and almost completely absorbed from the gastrointestinal tract. Buspirone undergoes extensive first-pass metabolism in the liver. Therefore, the unchanged substance is found in low concentrations in the systemic circulation, which has significant individual differences.
Bioavailability is 4%. Maximum plasma concentration is reached 60-90 minutes after administration. The main metabolite is inactive, the dealkylated metabolite is active. 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 is excreted in the urine within 24 hours, mainly in the form of metabolites. Approximately 18-38% of the administered dose is excreted in the feces. The half-life from plasma is about 2-3 hours.
Simultaneous food intake slows down the absorption of buspirone from the digestive tract.
Steady-state plasma concentrations are reached approximately 2 days after repeated administration of the drug.
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 reduced doses to patients with renal failure. The pharmacokinetics of buspirone are not altered in elderly patients.
Indication
Symptomatic treatment of anxiety states with dominant symptoms: anxiety, inner restlessness, state of tension.
Contraindication
Hypersensitivity to buspirone or to any of the other ingredients of the drug. Acute congestive glaucoma, myasthenia gravis, severe liver disease, severe liver failure (prothrombin time more than 18 seconds); severe renal failure (glomerular filtration rate less than 10 ml/min), epilepsy, acute intoxication with alcohol, hypnotics, analgesics and neuroleptics.
Concomitant treatment with monoamine oxidase inhibitors (MAOIs) and within 14 days of discontinuation of an irreversible MAOI or within 1 day of discontinuation of a reversible MAOI.
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. Since buspirone is mainly metabolized by cytochrome P450, potent inhibitors of this enzyme may increase the bioavailability of buspirone.
Nefazodone.
Concomitant use of buspirone and nefazodone resulted in a 20-fold increase in the maximum plasma concentration of buspirone (Cmax) and a 50-fold increase in the area under the concentration-time curve (AUC).
Erythromycin.
Concomitant use of buspirone and erythromycin resulted in a 5-fold increase in buspirone Cmax and a 6-fold increase in AUC.
Itraconazole.
Concomitant use of buspirone and itraconazole resulted in a 13-fold increase in buspirone Cmax and 19-fold increase in AUC.
Diltiazem.
Concomitant use of buspirone and diltiazem resulted in a 4-fold increase in buspirone Cmax and 5.3-fold increase in AUC.
Verapamil
Concomitant use of buspirone and verapamil resulted in a 3.4-fold increase in Cmax and AUC of buspirone.
Cimetidine.
Simultaneous use of buspirone and cimetidine led to an increase in buspirone Cmax by 40%, tmax - twice, but AUC practically did not change.
When using buspirone together with the above-mentioned agents, the therapeutic effect and toxicity of buspirone increases, therefore it is recommended to reduce the dose of buspirone (for example, 2.5 mg 2 times a day).
Rifampicin.
Concomitant use of buspirone and rifampicin resulted in a decrease in buspirone Cmax by 83.9% and AUC by 89.6%.
CYR3A4 inhibitors and inducers.
Ketoconazole or ritonavir inhibit the metabolism of buspirone and increase its plasma levels.
If buspirone is used together with a CYR3A4 inhibitor, its dose should be reduced.
Inducers of CYR3A4, such as dexamethasone, phenytoin, phenobarbital or carbamazepine, may increase the rate of buspirone metabolism. In this case, the dose of buspirone may need to 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.
Patients are advised not to consume large amounts of grapefruit juice during treatment, as this may lead to increased plasma levels of buspirone and an increase in the frequency or severity of side effects.
Application features
Liver failure.
Buspirone is extensively metabolized in the liver. In a pharmacokinetic study, the use of a single dose of 30 mg of buspirone in patients with cirrhosis of the liver increased buspirone plasma levels, increased AUC, and prolonged the half-life of buspirone. Due to excretion of the substance into the bile, a second peak of buspirone plasma concentration is possible. The drug is contraindicated in patients with severe hepatic insufficiency. Patients with cirrhosis of the liver should be prescribed the drug in lower doses or in the same doses, but with an extended interval.
Renal insufficiency. In moderate or severe renal insufficiency, the clearance of buspirone may be reduced by 50%. The drug is contraindicated in patients with severe renal insufficiency (glomerular filtration rate (GFR) < 10 ml/min). In mild (GFR > 30 ml/min) and moderate (GFR = 10-30 ml/min) renal insufficiency, buspirone can be prescribed, but reduced doses should be observed and prescribed.
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 prescribed the lowest effective dose, and in case of increasing the dose, the patient should be closely monitored.
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.
In patients with lactose intolerance, the lactose content in the tablets (55.7 mg in 5 mg tablets and 111.4 mg in 10 mg tablets) should be taken into account when preparing a diet.
The drug Spitomin® contains lactose, therefore it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
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.
Buspirone is not indicated for the treatment of withdrawal symptoms caused by the use of benzodiazepines or other sedative/hypnotic drugs. Therefore, these drugs should be gradually discontinued before starting treatment with buspirone. This is especially true for patients taking drugs that depress the central nervous system.
The combination of buspirone with MAO inhibitors is not recommended. There have been reports of increased blood pressure with the simultaneous use of these drugs.
Buspirone should not be prescribed to patients with a history of epileptic seizures.
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.
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.
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).
Method of administration and doses
The dose is 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 2-3 times a day. To achieve the maximum therapeutic effect, the daily dose should be 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. Tablets should always 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 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").
Special patient groups.
Available data do not indicate the feasibility of changing the dosage regimen depending on the age or gender of the patient.
Kidney failure
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 2 times 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 did not show 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.
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 drug in plasma with an increased half-life. In these patients, it is recommended to use buspirone with caution and after individual dose titration to reduce the risk of serious adverse reactions that may occur with high doses of buspirone. Increasing the dose should be considered after careful patient assessment and only 4-5 days after the previous dose.
Duration of treatment.
Tranquilizers should not be used without supervision for a long time. Therefore, the duration of treatment with buspirone 5 mg and/or 10 mg should not exceed 4 months. The dose is determined by the doctor 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 safety and efficacy.
Overdose
Symptoms: nausea, vomiting, dizziness, drowsiness, fatigue, miosis, gastrointestinal disorders, loss of consciousness. 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.
Side effects
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 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.
Adverse reactions are classified according to frequency of occurrence: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000); not known (frequency cannot be estimated due to lack of data).
Infections and infestations:
frequency unknown – fever.
From the cardiovascular system:
common – nonspecific chest pain;
uncommon – temporary fainting, hypotension and/or hypertension, tachycardia/palpitations;
Rarely common – cerebrovascular disorders, heart failure, myocardial infarction, cardiomyopathy, bradycardia, cerebrovascular disorders.
From the blood system:
rarely common – changes in blood parameters (eosinophilia, leukopenia, thrombopenia).
Mental disorders:
common – night terrors, drowsiness, insomnia, dizziness, nervousness, decreased concentration, emotional arousal, irritability, hostility, confusion, depression;
uncommon – depersonalization, discomfort, pathologically increased perception of ordinary sounds, euphoria, hyperkinesia, anxiety, loss of interest, impaired associative perception, hallucinations, suicidal thoughts, epileptic seizures, dysphoria, fear;
Rarely common – sudden mood swings, claustrophobia, stupor, slurred speech, transient memory problems, serotonin syndrome, psychosis.
From the nervous system:
uncommon – numbness, paresthesias (e.g. tingling, pain), coordination disorders, tremor, epileptic seizures, dysgeusia, dysosmia, prolonged reaction time;
rarely common – spontaneous movements, inhibition, extrapyramidal symptoms including early and tardive dyskinesia, tonicity disorders, fever, parkinsonism, akathisia, tinnitus.
On the part of the organs of vision:
common – blurred vision;
uncommon – redness and itching in the eye area, conjunctivitis;
rarely common - photophobia, feeling of pressure in the eyes, eye pain, narrowed field of vision, increased intraocular pressure.
On the part of the hearing organs:
common – tinnitus; rare – inner ear disorders.
On the part of the respiratory system:
Common – sore throat, nasal congestion;
uncommon – excessively rapid breathing, shortness of breath, tightness in the heart area, hyperventilation, feeling of lack of air;
rarely common - nosebleed, burning sensation of the tongue.
From the digestive tract:
common – nausea, xerostomia, epigastric pain, diarrhea;
uncommon – flatulence, lack of appetite, increased appetite, hypersalivation, irritable bowel syndrome, rectal bleeding, constipation, vomiting.
From the urinary system:
uncommon – frequent urination, urinary retention, dysuria;
rarely common – enuresis, nighttime urination.
uncommon – edema, urticaria, hyperemia, hematoma formation, alopecia, dry skin, eczema, facial edema, pemphigus, hot flashes, skin fragility, skin rash, itching;
rarely common - allergic reactions, ecchymosis, acne, thinning of nails.
From the musculoskeletal system:
uncommon – muscle spasm and rigidity, myalgia, arthralgia;
Rarely, myasthenia gravis.
From the endocrine system:
Rarely – galactorrhea, gynecomastia, thyroid dysfunction.
Metabolic disorders:
uncommon – anorexia, increased appetite;
frequency unknown - weight gain, weight loss.
General violations:
common – headache, asthenia; uncommon – fever, tinnitus, malaise, fatigue, impaired sense of smell and taste, increased sweating, hot flashes, cold hyperesthesia;
rarely common – tendency to alcohol abuse, blood coagulation disorders, loss of voice, hiccups, glossalgia.
From the hepatobiliary system:
uncommon – increased liver enzymes.
From the reproductive system:
uncommon – menstrual irregularities, decreased or increased libido;
Rarely common – amenorrhea, inflammation of the genitourinary organs, decreased ejaculation, impotence.
Laboratory tests: increased serum transaminase levels.
Expiration date
5 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
Store at a temperature not exceeding 30 °C in a place protected from light.
Keep out of reach of children.
Packaging
10 tablets in a blister, 6 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
CJSC Pharmaceutical Plant EGIS, Hungary.
Address
9900, Kermend, 65 Matyas Kirai Street, Hungary.
1165, Budapest, Bekenfeldi Street, 118-120, Hungary.
