Spitomine, pills 10mg 60pcs

Composition

1 tablet contains:

Active ingredient:

buspirone hydrochloride 10 mg,

excipients:

lactose monohydrate 111.4 mg;

MCC;

sodium carboxymethyl starch;

magnesium stearate;

silicon dioxide colloidal anhydrous

Pharmacological action

Spitomin has an anxiolytic, antidepressant effect.

Pharmacodynamics

An anxiolytic (tranquilizing) agent of the non-benzodiazepine series, it also has an antidepressant effect. Unlike classic anxiolytics, it does not have antiepileptic, sedative, hypnotic and muscle relaxant effects.

The mechanism of action is related to the effect of buspirone on the serotonergic and dopaminergic systems. Selectively blocks presynaptic dopamine receptors and increases the rate of excitation of dopamine neurons in the midbrain. In addition, buspirone is a selective partial agonist of 5-HT1A-serotonin receptors. Buspirone has no significant effect on benzodiazepine receptors and does not affect GABA binding, has no negative effect on psychomotor functions, does not cause tolerance, drug dependence and withdrawal syndrome. Does not potentiate the effect of alcohol. By anxiolytic activity, buspirone is approximately equal to benzodiazepines.

The therapeutic effect develops gradually and is noted in 7-14 days from the start of treatment, the maximum effect is recorded in 4 weeks.

Pharmacokinetics

After oral use, buspirone is rapidly and almost completely absorbed from the gastrointestinal tract.

Buspirone undergoes an intensive first-pass metabolism through the liver. Therefore, the unchanged substance is found in the systemic circulation in a small concentration, which has significant individual differences. Bioavailability is 4%. Cmax in blood plasma is reached 60-90 minutes after taking the drug. In healthy volunteers, buspirone had linear (dose-proportional) pharmacokinetics after use of 10-40 mg. Similar pharmacokinetic parameters were found in elderly patients. After a single oral dose of 20 mg of the drug, its plasma levels range from 1 to 6 ng / ml. Approximately 95% of buspirone binds to plasma proteins (86% to plasma albumin, the remainder to α1-acid glycoprotein).

Buspirone undergoes oxidative metabolism, mainly with the participation of CYP3A4 isoenzymes. Various hydroxylated metabolites are formed. The main metabolite — (5-ONE-buspirone) is inactive. Dealkylated metabolite — (1-(2-pyrimidinyl)-piperazine,1-PP) — active. Its anxiolytic activity is 4-5 times lower than that of the parent substance, but its plasma level is higher, and T1 / 2 is approximately 2 times longer than that of buspirone. After a single use of 14C-labeled buspirone,29-63% of the radioactivity 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 faeces. After a single dose of 10-40 mg, T1 / 2 of the starting substance is approximately 2-3 hours, and T1 / 2 of the active metabolite is 4.8 hours.

Simultaneous food intake slows down the absorption of buspirone, but due to a decrease in pre-systemic clearance (first-pass effect), the bioavailability of buspirone is significantly increased. After ingestion with food, the AUC of buspirone increases by 84%, and its Cmax-by 16%.

Css in blood plasma can be achieved approximately 2 days after the start of regular use.

The apparent Vd is 5.3 l / kg.

Buspirone is excreted in breast milk, but there are no data on placental transmission.

Elevated plasma buspirone levels and AUC values, as well as T1/2 prolongation, can be observed in patients with impaired liver function. Due to the release of unchanged substance in the bile, a second peak of buspirone concentration in blood plasma is possible. Patients with cirrhosis of the liver should be prescribed the drug in lower doses or in the same doses with extended intervals.

In patients with renal insufficiency, the clearance of buspirone may decrease by 50%. In patients with renal insufficiency, buspirone should be administered with caution and in reduced doses.

The pharmacokinetics of buspirone in elderly patients were not changed.

Indications

• generalized anxiety disorder (GAD);
• panic disorder;
• autonomic dysfunction syndrome;
• alcohol withdrawal syndrome (as adjunctive therapy);
• depressive disorders — adjunctive therapy (the drug is not prescribed for monotherapy of depression).

Use during pregnancy and lactation

Due to the lack of properly controlled data from clinical trials, the use of buspirone during pregnancy is possible only if the benefits of the drug justify the possible risks. Women of childbearing age should use adequate contraceptive methods during the course of treatment with buspirone, since the safety of buspirone during pregnancy has not been proven.

Buspirone is excreted in breast milk. There are no sufficient data from clinical studies of the use of buspirone during breastfeeding, so nursing mothers are not recommended to take this drug.

Contraindications

• hypersensitivity to any component of the drug Spitomin;
• severe renal failure (glomerular filtration rate (GFR) — below 10 ml/min);
• severe liver failure (DF — more than 18);
• concurrent use of MAO inhibitors or the 14-day period after the abolition of the irreversible MAO inhibitor, or 1 day after the abolition of the reversible MAO inhibitor;
• glaucoma;
• myasthenia gravis;
• lactation;
• pregnancy or suspected pregnancy;
• age up to 18 years (safety and effectiveness of buspirone for this age group has not been proven).

With caution: cirrhosis of the liver, renal failure.

Side effects

Buspirone is usually well tolerated. Side effects, if observed, usually occur at the beginning of the course of treatment and then disappear, despite continuing to take the drug. In some cases, it is necessary to reduce the dose.

To determine the frequency of side effects of the drug, the following classification is used: often (more than 1/100); infrequently (from 1/100 to 1/1000); rarely (less than 1/1000); very rarely(

From the cardiovascular system: often-chest pain; infrequently-syncope, hypotension, hypertension; rarely-cerebral circulation disorders, decompensation of heart failure, myocardial infarction, myocardiopathy, bradycardia.

From the central nervous system: often — dizziness, headache, increased nervous excitability, sleep disorders; infrequently — dysphoric reactions, depersonalization, dysphoria, hypersensitivity to noise, euphoria, hyperkinesis, fear, apathy, hallucinations, confusion, prolonged reaction time, suicidal thoughts, epileptic seizures, paresthesia, impaired coordination of movements, tremor; rarely — claustrophobia, cold intolerance, stupor, stuttering, extrapyramidal disorders, psychotic disorders.

From the side of the organs of vision and hearing: often-tinnitus, laryngitis, swelling of the nasal mucosa; infrequently-blurred vision, itchy eyes, redness of the eyes, conjunctivitis, impaired taste and olfactory sensations; rarely — inner ear disorders, eye pain, photophobia, increased IOP.

From the endocrine system: rarely-galactorrhea and thyroid damage.

From the gastrointestinal tract: infrequently-nausea, flatulence, anorexia, increased appetite, drooling, intestinal bleeding; rarely-diarrhea, burning in the tongue.

From the genitourinary system: infrequently-dysuric disorders (including frequent urination, urinary retention), menstrual disorders, decreased sexual desire; rarely-amenorrhea, pelvic inflammation, nighttime urinary incontinence, delayed ejaculation, impotence.

From the musculoskeletal system: infrequently-muscle spasms, muscle rigidity, arthralgia; rarely-muscle weakness.

From the respiratory system: infrequently-hyperventilation, lack of air, feeling of heaviness in the chest; rarely-nosebleeds.

Skin disorders: infrequently — swelling, itching, hot flashes, hair loss, dry skin, facial swelling, skin vulnerability, rash.

Others: weight gain, fever, weight loss, muscle and bone pain; rarely-alcohol abuse, loss of voice, tinnitus, hiccups.

Changes in laboratory parameters: infrequently-increased serum ALT and ACT levels; rarely-eosinophilia, leukopenia, thrombocytopenia.

Interaction

Given the pharmacokinetic properties of the drug (low bioavailability, intensive metabolism in the liver, high protein binding), there is a high probability of interaction of buspirone with concomitantly administered drugs; however, since buspirone has a significant therapeutic breadth, pharmacokinetic interactions do not lead to clinically significant pharmacodynamic changes.

MAO inhibitors (MAOIs). An increase in blood pressure and the occurrence of hypertensive crises after simultaneous use of buspirone and drugs acting on MAO (moclobemide, selegiline) are described; therefore, buspirone cannot be combined with MAO. After discontinuation of an irreversible MAOI (such as selegiline), at least 14 days should elapse before the start of Spitomin® use (and vice versa).Similarly, it should be at least 14 days after discontinuation of Spitomin before moclobemide (reversible MAOI) is administered. However, Spitomin® can be given 1 day after moclobemide withdrawal.

Inhibitors and inducers of CYP3A4. In vitro studies have shown that buspirone is mainly metabolized by cytochrome P450 isoenzymes CYP3A4. Concomitant use of buspirone and CYP3A4 inhibitors (erythromycin, itraconazole, nefazodone, diltiazem, verapamil, and grapefruit juice) may lead to drug interactions, and when administered with a strong inhibitor, also increase the level of buspirone in blood plasma; therefore, it is necessary to reduce the dose of buspirone (for example, to 2.5 mg 2 times a day).

Strong inducers of CYP3A4 (e. g. rifampicin) can significantly reduce buspirone plasma levels and reduce its pharmacodynamic effects.

Drugs that bind strongly to proteins. Since buspirone binds strongly to proteins (95%), there is a constant possibility of interaction with other protein-bound active substances. In vitro studies have shown that buspirone cannot displace strongly bound drugs (warfarin, phenytoin, propranolol) from proteins, but it can replace weakly bound drugs, such as digoxin.

When cimetidine is co-administered with buspirone, the Cmax of buspirone increases by 40%, and its AUC does not change. Co-use of these drugs requires careful medical supervision.

When diazepam is co-administered with buspirone, the level of nordiazepam increases slightly, and side effects may occur: systemic dizziness, headache, nausea.

Substances that depress the central nervous system, and alcohol. Co-use of buspirone with triazolam or flurazepam does not increase the duration or strength of the effect of these benzodiazepines. After a single dose of 20 mg of buspirone, its effects on the central nervous system do not increase. Experience with the combined use of buspirone and other anxiolytics or other agents acting on the central nervous system (for example, antipsychotics and antidepressants) is insufficient. Therefore, in such cases, careful medical supervision is necessary.

Other BOS. Due to the lack of relevant clinical data, the combined use of buspirone with antihypertensive drugs, cardiac glycosides, oral contraceptives and antidiabetic agents is possible only under conditions of careful medical supervision.

How to take, course of use and dosage

Inside, always at the same time of day, before or after meals (to avoid significant fluctuations in the concentration of the Active ingredient in the blood plasma throughout the day).

The drug should not be taken occasionally for the treatment of anxiety, since the therapeutic effect of Spitomin develops only after repeated use and manifests itself no earlier than after 7-14 days of treatment.

The dose should be selected for each patient individually. The recommended dose is 15 mg; it can be increased by 5 mg / day every 2 or 3 days. The daily dose should be divided into 2-3 doses. The usual daily dose is 20-30 mg per day. The maximum single dose is 30 mg; the maximum daily dose should not exceed 60 mg.

Special patient groups

Elderly patients. By itself, old age does not require dose adjustment, since the pharmacokinetics of buspirone do not undergo age-related changes.

Impaired renal function. If renal function is impaired, the drug should be used with caution and in reduced doses.

Impaired liver function. If liver function is impaired, the drug should be used with caution and in reduced doses, for which individual doses are reduced or the interval between doses is increased.

Overdose

Symptoms: gastrointestinal disorders, nausea, vomiting, dizziness and drowsiness; depression of consciousness of varying severity (in severe forms).

Treatment: gastric lavage and symptomatic therapy. Dialysis is ineffective.

Experience to date suggests that even extremely high doses (a single oral dose of 375 mg) do not necessarily cause severe symptoms.

Special instructions

Liver failure. Buspirone undergoes intensive metabolism in the liver. A single use of 30 mg to patients with cirrhosis of the liver increases plasma buspirone levels and increases AUC with prolongation of the duration of T1/2 of the drug. Due to the release of unchanged substance in the bile, a second peak of buspirone concentration in blood plasma 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 with extended intervals.

Kidney failure. In moderate or severe renal insufficiency, the clearance of buspirone may decrease by 50%. The drug is contraindicated in patients with severe renal insufficiency with GFR less than 10 ml/min. In mild (GFR greater than 30 ml/min) and moderate (GFR 10-30 ml/min) renal insufficiency, buspirone can be used, but caution should be exercised and reduced doses should be prescribed.

Elderly patients. Elderly age alone does not require dose adjustment, but caution is recommended (for example, due to a possible decrease in kidney and/or liver function and an increased likelihood of side effects). Patients should be given the lowest possible effective dose, and if the dose is increased, the patient should be closely monitored.

The use of the drug requires special care in patients with rectangular glaucoma and myasthenia gravis.

In case of lactose intolerance, the diet should take into account the content of lactose in tablets (55.7 mg — in tablets of 5 mg and 111.4 mg — in tablets of 10 mg).

Patients should be advised not to eat grapefruits or drink significant amounts of grapefruit juice, as these products may increase the level of buspirone in the blood plasma and lead to an increase in the frequency or severity of side effects.

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

Buspirone does not cause addiction to the drug, but its use to patients with an established or suspected predisposition to drug dependence requires careful medical supervision.

Since the anxiolytic effect manifests itself after 7-14 days of taking the drug, and the full therapeutic effect develops in about 4 weeks, patients with severe anxiety need careful medical supervision during the initial period of therapy.

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

Influence on the ability to drive vehicles and manage mechanisms. The results of clinical studies have shown that buspirone monotherapy does not affect the indicators of psychomotor activity of patients. Despite this, temporary undesirable effects may occur at the beginning of the course of treatment, and therefore patients should be warned that driving vehicles and operating mechanisms is possible only if the patient is fully confident in their psychomotor functions. The patient’s ability to drive vehicles and mechanisms should be determined individually, depending on the patient’s response to treatment and the use of concomitant therapy.

Form of production

Tablets

Storage conditions

In a dark place, at a temperature not exceeding 30 °C.

Shelf

life is 5 years.

Active ingredient

Buspirone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets