Spitomine, tablets 10 mg 60 pcs

Spitomine has an anxiolytic, antidepressant effect.

Pharmacodynamics

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

The mechanism of action is associated with the effect of buspirone on serotonergic and dopaminergic systems. It selectively blocks presynaptic dopamine receptors and increases the rate of excitation of midbrain dopamine neurons. 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. It does not potentiate the effects of alcohol. In terms of anxiolytic activity buspirone is approximately equal to benzodiazepines.

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

Pharmacokinetics

Buspirone is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration.

Buspirone undergoes intensive first-pass metabolism through the liver. Therefore, the unchanged substance is found in the systemic bloodstream at low concentrations, which have significant individual differences. Bioavailability is 4%. Cmax in plasma is reached 60-90 min after drug administration. In healthy volunteers, buspirone had linear (dose-proportional) pharmacokinetics after 10-40 mg administration. Similar pharmacokinetic parameters were found in elderly patients. After a single oral dose of 20 mg of the drug, its plasma levels are 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-ON-buspirone) is inactive. The dealkylated metabolite, (1-(2-pyrimidinyl)-piperazine, 1-PR), is active. Its anxiolytic activity is 4-5 times lower than that of the parent substance, but its plasma levels are higher and the T1/2 is approximately 2 times longer than that of buspirone. After a single administration of 14C-labeled buspirone, 29-63% of the radioactivity is excreted in the urine within 24 hours, mostly in the form of metabolites. Approximately 18-38% of the administered dose is excreted in the feces. After a single dose of 10-40 mg, the T1/2 of the parent substance is approximately 2-3 hours, and the T1/2 of the active metabolite is 4.8 hours.

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

The Css in plasma can be reached about 2 days after starting regular dosing.

The apparent Vd is 5.3 L/kg.

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

Elevated plasma levels of buspirone and AUC values and prolongation of T1/2 may be observed in hepatic dysfunction. Due to excretion of unchanged substance into bile, a second peak in plasma concentration of buspirone is possible. Patients with cirrhosis should prescribe the drug in lower doses or in the same doses with prolonged intervals.

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

The pharmacokinetics of buspirone are not altered in elderly patients.

Indications

Active ingredient

Composition

1 tablet contains:

the active ingredient:

Buspirone hydrochloride 10 mg,

auxiliary substances:

Lactose monohydrate 111.4 mg;

MCC;

Sodium carboxymethyl starch;

magnesium stearate;

colloidal anhydrous silica

How to take, the dosage

Overly, always at the same time of day, before or after meals (to avoid significant fluctuations in plasma concentrations of the active ingredient throughout the day).

The drug must not be taken sporadically to treat anxiety, because the therapeutic effect of Spitomine develops only after repeated administration and does not manifest itself until 7-14 days of treatment.

The dose should be adjusted 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.

Particular patient groups

Elderly patients. Elderly patients alone do not require dose adjustments because the pharmacokinetics of buspirone do not undergo age-related changes.

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

Liver dysfunction. In patients with impaired liver function, the drug should be used with caution and in reduced doses, for which individual doses should be reduced or the interval between doses should be increased.

Interaction

Given the pharmacokinetic properties of the drug (low bioavailability, intensive metabolism in the liver, high protein binding), there is a high possibility of interactions between buspirone and concomitantly administered drugs; however, since buspirone has considerable therapeutic latitude, pharmacokinetic interactions do not result in clinically significant pharmacodynamic changes.

MAO inhibitors (MAOIs). An increase in BP and the occurrence of hypertensive crises after concomitant administration of buspirone and drugs acting on MAOIs (moclobemide, selegiline) has been described; therefore, buspirone should not be combined with IMAOs. A minimum of 14 days should pass before starting Spitomine® (and vice versa) after withdrawing an irreversible MAOI (e.g. selegiline). Similarly, it should be at least 14 days after withdrawal of Spitomine® before starting moclobemide (reversible IBAO). However, Spitomine® can be given 1 day after withdrawal of moclobemide.

CYP3A4 inhibitors and inducers. In vitro studies have shown that buspirone is mainly metabolized by CYP3A4 cytochrome P450 isoenzymes. Simultaneous administration of buspirone and CYP3A4 inhibitors (erythromycin, itraconazole, nefazodone, diltiazem, verapamil and grapefruit juice) may lead to drug interactions, and if a strong inhibitor is given, also increase plasma levels of buspirone; therefore, reduction of buspirone dose (for example, to 2.5 mg twice a day) is necessary.

Powerful CYP3A4 inducers (e.g., rifampicin) can significantly decrease plasma levels of buspirone and impair its pharmacodynamic effects.

Drugs that bind strongly to proteins. Because buspirone binds strongly to proteins (95%), there is always the possibility of interactions with other protein-bound active ingredients. In vitro studies have shown that buspirone cannot displace strongly bound drugs (warfarin, phenytoin, propranololol) from proteins, but can replace weakly bound drugs such as digoxin.

When cimetidine is coadministered with buspirone, the Cmax of buspirone is increased by 40% and its AUC is unchanged. Co-administration of these drugs requires close medical monitoring.

When diazepam is coadministered with buspirone, nordiazepam levels increase slightly and side effects may occur: systemic dizziness, headache, and nausea.

Substances that depress the CNS and alcohol. Co-administration of buspirone with triazolam or flurazepam does not increase the duration or strength of the effects of these benzodiazepines. There is no increase in the CNS effects of buspirone after a single dose of 20 mg. There is insufficient experience with the co-administration of buspirone and other anxiolytics or other CNS-acting drugs (e.g., neuroleptics and antidepressants). Therefore, careful medical monitoring is necessary in such cases.

Other drugs. Due to insufficient relevant clinical data, co-administration of buspirone with antihypertensives, cardiac glycosides, oral contraceptives and antidiabetic agents is possible only under close medical supervision.

Special Instructions

Hepatic insufficiency. Buspirone undergoes intensive metabolism in the liver. A single injection of 30 mg in patients with cirrhosis increases blood plasma levels of buspirone and increases AUC with prolongation of the drug’s T1/2 duration. Due to excretion of unchanged substance into bile, a second peak of plasma concentration of buspirone is possible. The drug is contraindicated in patients with severe hepatic impairment. Patients with cirrhosis should prescribe the drug in lower doses or in the same doses at longer intervals.

Renal insufficiency. In moderate to severe renal failure, the clearance of buspirone may be reduced by 50%. The drug is contraindicated in patients with severe renal insufficiency with a GFR less than 10 ml/min. In mild (GFR over 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 patients do not require dose adjustments per se, but caution is recommended (e.g., due to possible decreased renal and/or hepatic function and increased likelihood of side effects). Patients should be prescribed the lowest possible effective dose, and close patient monitoring should be established if the dose is increased.

The use of the drug requires special caution in patients with rectal glaucoma and myasthenia gravis.

In case of lactose intolerance, the lactose content of the tablets (55.7 mg in 5 mg tablets and 111.4 mg in 10 mg tablets) should be considered when formulating the diet.

Patients should be advised not to eat grapefruit or drink grapefruit juice in significant amounts, as these foods may increase plasma levels of buspirone and lead to increased frequency or severity of side effects.

Transfer patients from benzodiazepines to buspirone. Buspirone cannot eliminate benzodiazepine withdrawal symptoms. If a patient is being transferred to buspirone after long-term benzodiazepine therapy, buspirone should only be administered after a period of gradual benzodiazepine dose reduction is complete.

Buspirone is not addictive, but its administration to patients with an established or suspected predisposition to drug dependence requires careful medical monitoring.

Because the anxiolytic effect occurs after 7-14 days of taking the medication, and full therapeutic effect develops over approximately 4 weeks, patients with severe anxiety require close medical monitoring during the initial period of therapy.

Alcoholic beverages should be avoided during the entire course of treatment with buspirone.

The effect on driving and operating machinery. The results of clinical studies have shown that buspirone monotherapy does not affect the indicators of psychomotor performance of patients. Despite this, transient adverse effects are possible at the beginning of treatment, in connection with which patients should be warned that driving vehicles and operating mechanisms is possible only when the patient is fully confident in his psychomotor functions. Patient’s ability to drive vehicles and operate mechanisms should be determined individually, depending on patient’s reaction to the treatment and application of concomitant therapy.

Contraindications

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 continuation of 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 (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 association of adverse effects with taking the drug could not be proved.)

CRC: frequently – chest pain; infrequently – syncope, hypotension, hypertension; rarely – cerebral circulatory disorders, decompensation of heart failure, myocardial infarction, myocardiopathy, bradycardia.

CNS disorders: frequent – dizziness, headache, increased nervous excitability, sleep disturbances; infrequent – dysphoric reactions, depersonalization, dysphoria, increased sensitivity to noise, euphoria, hyperkinesias, fear, apathy, hallucinations, confusion, prolonged reaction time, suicidal thoughts, epileptic seizures, paresthesias, movement coordination disorders, tremor; Rarely – claustrophobia, cold intolerance, stupor, stuttering, extrapyramidal disorders, psychotic disorders.

Hearing and visual organs: often – tinnitus, laryngitis, nasal mucosal edema; infrequent – blurred vision, itching of the eyes, red eyes, conjunctivitis, disorders of taste and sense of smell; rarely – inner ear disorders, eye pain, photophobia, increased IOP.

Endocrine system disorders: rarely – galactorrhea and thyroid involvement.

Gastrointestinal system disorders: infrequent – nausea, flatulence, anorexia, increased appetite, salivation, intestinal bleeding; rarely – diarrhea, burning of the tongue.

Urogenital system disorders: infrequent – dysuric disorders (including frequent urination, delayed urination), menstrual disorders, decreased sex drive; rare – amenorrhea, pelvic inflammation, nocturnal urinary incontinence, delayed ejaculation, impotence.

Musculoskeletal system disorders: infrequent muscle cramps, muscle stiffness, arthralgia; rarely – muscle weakness.

Respiratory system: infrequent hyperventilation, shortness of breath, feeling of heaviness in the chest; rarely – nasal bleeding.

Skin: infrequent – swelling, itching, hot flashes, hair loss, dry skin, swollen face, skin vulnerability, rash.

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

Laboratory changes: infrequent – increase in serum ALT and ACT levels; rare – eosinophilia, leukopenia, thrombocytopenia.

Overdose

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

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

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

Pregnancy use

In the absence of well-controlled clinical trial data, buspirone may be used during pregnancy only when the benefits of the drug justify the possible risks. Women of childbearing age should use adequate contraception during buspirone treatment because the safety of buspirone in pregnancy has not been proven.

Buspirone is excreted in breast milk. Sufficient data from clinical studies of buspirone use during breastfeeding are not available, so breastfeeding mothers should not take this medication.