Spitomin (Buspiron) 10 mg 60 pcs

1 tablet contains:

active substance:

buspyron hydrochloride 10 mg,

excipients:

lactose monohydrate 111.4 mg;

MKC;

sodium carboxymethyl starch;

magnesium stearate;

silicon dioxide colloidal anhydrous

Spitomin has anxiolytic, antidepressant effect.

Pharmacodynamics

Anxiolytic (tranquillizing) non-benzodiazepine-type agent also has an antidepressant effect. Unlike classical anxiolytics, it does not have antiepileptic, sedative, sleeping pills and myorelaxing effects.

The mechanism of action is associated with the influence of buspyron on the serotonergic and dopamineergic systems. Selectively blocks presynaptic dopamine receptors and increases the excitation rate of dopamine neurons of the middle brain. In addition, buspiron is a selective partial agonist of 5-HT1A-serotonin receptors. Buspiron does not have a significant effect on benzodiazepine receptors and does not affect GABA binding, does not have a negative effect on psychomotor functions, does not cause tolerance, drug addiction and withdrawal syndrome. Does not potentiate the effect of alcohol. In terms of anxiolytic activity, buspiron is approximately equal to benzodiazepines.

The therapeutic effect develops gradually and is noted 7-14 days after the beginning of treatment, the maximum effect is registered after 4 weeks.

Pharmacokinetics

After ingestion, the buspiron is quickly and almost completely absorbed from the gastrointestinal tract.

Buspiron is subjected to intensive metabolism of the first passage through the liver. Therefore, the unchanged substance is found in the systemic blood flow in a small concentration, which has significant individual differences. Bioavailability is 4%. Cmax in blood plasma is achieved 60-90 minutes after taking the drug. In healthy volunteers, the buspiron had a linear (proportional dose) pharmacokinetics after taking 10-40 mg. Similar pharmacokinetic parameters have been found in elderly patients. After a single ingestion of 20 mg of the drug, its plasma levels range from 1 to 6 ng/ml. Approximately 95% of buspyron binds to plasma proteins (86% - plasma albumin, the rest with α1-acid glycoprotein).

Buspiron undergoes oxidative metabolism, mainly involving CYP3A4 isoenzymes. Various hydroxylated metabolites are formed. The main metabolite - (5-OH-buspiron) is inactive. Dealkylated metabolite - (1-(2-pyrimidinyl)-piperazine, 1-PP) - is active. Its anxiolytic activity is 4-5 times lower than that of the original substance, but its plasma level is higher, and T1/2 is about 2 times longer than that of buspyron. After a single administration of 14C-labeled buspyron, 29-63% of radioactivity is released with urine for 24 hours, mainly in the form of metabolites. Approximately 18-38% of the administered dose is excreted with feces. After a single intake of 10-40 mg, T1/2 of the original substance is about 2-3 hours, and T1/2 of the active metabolite is 4.8 hours.

Simultaneous meals slow down the absorption of buspyron, but due to a decrease in presystem clearance (first pass effect), the bioavailability of buspyron is significantly increased. After taking with food, the AUC buspyron value increases by 84% and its Cmax by 16%.

Css in blood plasma can be achieved about 2 days after the start of regular administration.

The oming Vd is 5.3 l/kg.

Buspiron is released into breast milk, but there are no data on placental transmission.

Increased plasma buspyron levels and AUC values, as well as T1/2 elongation, can be observed in liver disfunction. Due to the release of unchanged substance into bile, a second peak of buspyron concentration in blood plasma is possible. Patients with liver cirrhosis should prescribe the drug at lower doses or at the same doses at extended intervals.

In case of renal failure, the clearance of busspirone can be reduced by 50%. In case of renal failure, buspiron should be prescribed with caution and in reduced doses.

The pharmacokinetics of buspyron in elderly patients has not been changed.

• generalized anxiety disorder (GTR);
• panic disorder;
• vegetative dysfunction syndrome;
• alcohol withdrawal syndrome (as an auxiliary therapy);
• depressive disorders - auxiliary therapy (the drug is not prescribed for monotherapy of depression).

Due to the lack of properly controlled clinical trial data, the use of buspyron during pregnancy is possible only if the benefits of the drug justifies possible risks. Women of childbearing age should use adequate contraceptive methods during buspiron treatment, as the safety of buspyron during pregnancy has not been proven.

Buspiron is released into breast milk. There are no sufficient data from clinical trials of the use of buspyron during breastfeeding, so nursing mothers are not recommended to take this drug.

• hypersensitivity to any component of Spitomin;
• severe renal failure (glomerular filtration rate (SCF) - below 10 ml/min);
• severe liver failure (PV - more than 18 seconds);
• simultaneous use of MAO inhibitors or a 14-day period after the cancellation of the irreversible MAO inhibitor, or 1 day after the cancellation of the reversible MAO inhibitor;
• glaucoma;
• myasthenia;
• lactation;
• pregnancy or suspicion of pregnancy;
• age up to 18 years (safety and efficacy of buspyron for this age group have not been proven).

Caution: liver cirrhosis, kidney failure.

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

The following classification is used to determine the frequency of side effects of the drug: often (more than 1/100); infrequently (from 1/100 to 1/1000); rarely (less than 1/1000); very rarely (<1/10000) (in many cases, in the absence of a comparison drug, the connection between adverse effects with taking the drug could not be proved).

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

From the CNS side: often - dizziness, headache, increased nervous excitability, sleep disorders; infrequently - dysphoric reactions, depersonalization, dysphoria, hypersensitivity to noise, euphoria, hyperkinesis, fear, apathy, hallucinations, confusion, lengthening reaction time, suicidal thoughts, epileptic seizures, paresthesia, movement coordination disorders, tremors; rarely - claustrophobia, cold intolerance, stupor, stuttering, extrapyramidal disorders, psychotic disorders.

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

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

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

From the genitourinary system: infrequently - dysuric disorders (including frequent urination, delayed urination), menstrual cycle disorders, decreased sex drive; rarely - amenorrhea, inflammation of the pelvic organs, night urinary incontinence, ejaculation delay, impotence.

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

On the respiratory side: infrequently - hyperventilation, lack of air, feeling of heaviness in the chest; rarely - nasal bleeding.

From the skin side: infrequently - swelling, itching, tides, hair loss, dry skin, facial swelling, skin vulnerability, rash.

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

Changes in laboratory indicators: infrequently - increase in blood serum levels of ALT and ACT; rarely - eosinophilia, leukopenia, thrombocytopenia.

Given the pharmacokinetic properties of the drug (low bioavailability, intensive metabolism in the liver, high binding to proteins), there is a high probability of buspyron interaction with simultaneously administered drugs; however, since buspiron has significant therapeutic latitude, pharmacokinetic interactions do not lead to clinically significant pharmacodynamic changes

MAO inhibitors (IMAO). Increased blood pressure and hypertensive crises after simultaneous administration of buspyron and drugs acting on MAO (moclobemide, selegilin) are described; therefore, buspiron cannot be combined with IMAO. After the cancellation of irreversible IMAO (e.g. selegilin), at least 14 days should pass before administration of Spitomin® (and vice versa). Similarly, it should take at least 14 days after the withdrawal of Spitomin® before administration of moclobemid (reversible IMAO). However, Spitomin® can be given 1 day after the abolition of moclobemide.

CYP3A4 inhibitors and inductors. In vitro studies have shown that buxirone is mainly metabolized by CYP3A4 isoenzymes of cytochrome P450. Simultaneous administration of buspyron and CYP3A4 inhibitors (erythromycin, itraconazole, nefazodon, diltiazem, verapamyl and grapefruit juice) can lead to drug interactions, and when administered a strong inhibitor, it is also increased the level of buspyron in blood plasma; therefore, it is necessary to reduce the dose of buspyron (for example, up to 2.5 mg 2 times a day).

Strong CYP3A4 inductors (e.g. rifampicin) can significantly reduce buspyron levels in blood plasma and weaken its pharmacodynamic effects.

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

When cimetidine is administered together with buspiron, the Cmax of the buspyron increases by 40%, and its AUC does not change. Joint administration of these drugs requires careful medical supervision.

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

Substances that oppress the CNS and alcohol. Joint administration of buspyron 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 buspiron, its effects on the CNS do not increase. Experience in the joint use of buspyron and other anxiolytics or other means operating on the CNS (e.g. neuroleptics and antidepressants) is insufficient. Therefore, in such cases, careful medical supervision is necessary.

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

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

The drug should not be taken sporadically to treat anxiety, as the therapeutic effect of Spitomin develops only after repeated administration and manifests itself no earlier than 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 groups of patients

Elderly patients. Older age itself does not require clarification of the dose, as the pharmacokinetics of buspyron does not undergo age-related changes.

Kidney dysfunction. In case of kidney dysfunction, the drug should be used with caution and in reduced doses.

Liver dysfunction. In case of liver function disorders, the drug should be used with caution and in reduced doses, for which individual doses are reduced or the interval between doses is increased.

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

Treatment: stomach rinsing and symptomatic therapy. Dialysis is ineffective.

Experience to date shows that even extremely high doses (one oral administration of 375 mg) do not necessarily cause severe symptoms.

Liver failure. Buspiron undergoes intense metabolism in the liver. A single administration of 30 mg to patients with liver cirrhosis increases plasma buspyron levels and increases AUC with an elongation of the duration of T1/2 of the drug. Due to the release of unchanged substance into bile, a second peak of buspyron concentration in blood plasma is possible. The drug is contraindicated in patients with severe liver failure. Patients with liver cirrhosis should prescribe the drug at lower doses or at the same doses at extended intervals.

Renal failure. In moderate or severe renal failure, the clearance of the buspyron can be reduced by 50%. The drug is contraindicated in patients with severe renal failure in SCF less than 10 ml/min. In case of mild (SCF more than 30 ml/min) and moderate (SCF 10-30 ml/min) renal failure, buxpiron can be used, but caution should be taken and reduced doses should be prescribed.

Elderly patients. Older age alone does not require a dose refinement, 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 prescribed the lowest possible effective doses, and in case of an increase in the dose, careful monitoring of the patient should be established.

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

In case of lactose intolerance, the lactose content in tablets (55.7 mg in tablets 5 mg and 111.4 mg tablets of 10 mg) should be taken into account when making a diet.

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

Transfer of patients from benzodiazepines to buspiron. Buspiron cannot eliminate the symptoms of benzodiazepine withdrawal. If the patient is transferred to buxpiron after prolonged benzodiazepine therapy, buspiron should be prescribed only after the period of gradual reduction of the dose of benzodiazepine is completed.

Buspiron does not cause addiction to the drug, but its administration to patients with an established or suspected predisposition to drug addiction requires careful medical control.

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 strong anxiety need careful medical supervision in the initial period of therapy.

Alcoholic beverages should be avoided throughout the course of buspiron treatment.

Impact on the ability to drive vehicles and control mechanisms. The results of clinical studies have shown that monotherapy with buspiron does not affect the psychomotor activity of patients. Despite this, transient undesirable effects are possible at the beginning of the course of treatment, so patients should be warned that driving and driving 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 reaction to treatment and the use of concomitant therapy.

Tablets