Side effects of Buspirone
From the nervous system and sensory organs:
dizziness (12%), drowsiness (10%), headache (6%), nervousness (5%), fatigue (4%), sleep disturbance (3%), decreased ability to concentrate (2%); extrapyramidal disorders (very rare); ≤2% - blurred vision, confusion or depression, weakness, numbness; ≤1% - neurological symptoms (muscle weakness, tingling, pain or weakness in the arms or legs, uncontrolled movements of the torso).
From the cardiovascular system and blood (hematopoiesis, hemostasis):
≤1% - tachycardia/palpitations.
From the gastrointestinal tract:
nausea (8%), dry mouth (3%), diarrhea (2%); ≤1% - vomiting, constipation; decreased appetite.
Other:
≤1% - myalgia, spasms, muscle cramps or stiffness, rash, sweating.
Spitomin tablets 10 mg No. 60
Compound
Active substance: buspirone hydrochloride 10 mg. Excipients: lactose monohydrate - 111.4 mg, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, colloidal anhydrous silicon dioxide.
Pharmacokinetics
Suction
After oral administration, buspirone is quickly and almost completely absorbed from the gastrointestinal tract. Buspirone undergoes extensive first-pass metabolism in 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 achieved 60-90 minutes after taking the drug. In healthy volunteers, buspirone had linear (dose proportional) pharmacokinetics after administration of 10-40 mg. Similar pharmacokinetic parameters were found in elderly patients. After a single oral dose of 20 mg of the drug, its concentration in the blood plasma ranged from 1 to 6 ng/ml.
Concomitant food intake slows down the absorption of buspirone, but due to a decrease in pre-systemic clearance (the “first pass” effect), the bioavailability of buspirone is significantly increased. After administration with food, the AUC value of buspirone increases by 84%, and its Cmax increases by 16%.
Distribution
The binding of buspirone to plasma proteins is approximately 95% (86% to plasma albumin, the rest to α1 acid glycoprotein).
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. There are no data on the penetration of the drug through the placental barrier.
Metabolism
Buspirone undergoes oxidative metabolism mainly with the participation of CYP3A4 isoenzymes. Various hydroxylated metabolites are formed. The main metabolite (5-OH-buspirone) is not active. The dealkylated metabolite (1-(2-pyrimidinyl)-piperazine, 1-PP) is active. Its anxiolytic activity is 4-5 times lower than that of the parent substance, but its level in the blood plasma is higher and T1/2 is approximately 2 times longer than that of buspirone.
Removal
After a single administration 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 feces. After a single dose of 10-40 mg, T1/2 of the original substance is approximately 2-3 hours, and T1/2 of the active metabolite is 4.8 hours.
Pharmacokinetics in special clinical situations
If liver function is impaired, an increase in plasma concentrations of buspirone and AUC values, as well as a prolongation of T1/2, are possible. Due to the release of unchanged substance into the bile, a second peak in the concentration of buspirone in the blood plasma is possible. The drug is contraindicated in patients with severe liver failure. Patients with liver cirrhosis should be prescribed the drug at lower doses or at the same doses at extended intervals.
In renal failure, buspirone clearance may be reduced by 50%. The drug is contraindicated in patients with severe renal failure. In case of renal failure, buspirone should be prescribed with caution and in reduced doses.
The pharmacokinetics of buspirone in elderly patients is not changed.
Indications for use
- Generalized anxiety disorder (GAD);
- panic disorder;
- autonomic dysfunction syndrome;
- alcohol withdrawal syndrome (as an auxiliary therapy);
- auxiliary therapy for depressive disorders (the drug is not prescribed for monotherapy of depression).
Contraindications
- Hypersensitivity to the components of the drug;
- severe renal failure (GFR <10 ml/min);
- severe liver failure (prothrombin time >18 seconds);
- glaucoma;
- myasthenia gravis;
- children and adolescents under 18 years of age (the safety and effectiveness of buspirone for this age group has not been proven);
- simultaneous use of MAO inhibitors or a 14-day period after discontinuation of an irreversible MAO inhibitor or 1 day after discontinuation of a reversible MAO inhibitor;
- lactation period (breastfeeding);
- pregnancy or suspicion of pregnancy.
With caution: liver cirrhosis, renal failure.
Directions for use and doses
The drug should always be taken at the same time of day, before or after meals, to avoid significant fluctuations in the concentration of the active substance 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 doses and appears no earlier than after 7-14 days of treatment.
The dose should be selected individually.
The recommended starting dose is 15 mg, which can be increased by 5 mg/day every 2-3 days. The daily dose should be divided into 2-3 doses. The usual daily dose is 20-30 mg. The maximum single dose is 30 mg. The maximum daily dose is 60 mg.
In elderly patients, dose adjustment is not required, because The pharmacokinetics of buspirone do not depend on age.
If renal function is impaired, the drug should be used with caution and in reduced doses.
If liver function is impaired, the drug should be used with caution and in reduced doses; for this purpose, reduce single doses or increase the interval between doses.
Storage conditions
The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 30°C.
Best before date
5 years. Do not use after the expiration date stated on the packaging.
special instructions
Buspirone undergoes extensive metabolism in the liver. With a single dose of 30 mg in patients with liver cirrhosis, the concentration of buspirone in the blood plasma increases and the AUC increases with prolongation of T1/2 of the drug. Due to the release of unchanged substance into the bile, a second peak in the concentration of buspirone in the blood plasma is possible. The drug is contraindicated in patients with severe liver failure. Patients with liver cirrhosis should be prescribed the drug at lower doses or at the same doses at extended intervals.
In moderate to severe renal impairment, buspirone clearance may be reduced by up to 50%. The drug is contraindicated in patients with severe renal failure and GFR less than 10 ml/min. In case of mild (GFR more than 30 ml/min) and moderate (GFR 10-30 ml/min) renal failure, buspirone can be given, but care should be taken and the drug should be taken in reduced doses.
In elderly patients, no dose adjustment is required, but the drug should be used with caution, for example, due to a possible decrease in renal and/or liver function and an increased likelihood of side effects. For these patients, the drug should be prescribed in the minimum effective doses, and if the dose is increased, the patient should be closely monitored.
The drug should be used with extreme caution in patients with angle-closure glaucoma and myasthenia gravis.
Patients should be advised not to eat grapefruits or drink grapefruit juice in significant quantities, because these products may increase buspirone plasma concentrations and result in an increase in the frequency or severity of side effects.
Switching patients from benzodiazepines to buspirone: Buspirone does not relieve benzodiazepine withdrawal symptoms. If a patient is switched to buspirone after long-term benzodiazepine therapy, buspirone should be given only after the benzodiazepine taper period has been completed.
Buspirone does not cause addiction to the drug, but its administration to patients with an established or suspected predisposition to drug dependence requires careful medical supervision.
Since the anxiolytic effect appears after 7-14 days of taking the drug, and the full therapeutic effect develops in approximately 4 weeks, patients with severe anxiety require careful medical supervision during the initial period of therapy.
Patients should avoid drinking alcohol throughout the course of treatment with buspirone.
In case of lactose intolerance, when preparing a diet, the lactose content in the tablets should be taken into account (55.7 mg in 5 mg tablets and 111.4 mg in 10 mg tablets).
Description
Anxiolytic (tranquilizer).
Use in children
The use of the drug is contraindicated in children and adolescents under 18 years of age (the safety and effectiveness of buspirone for this age group has not been proven).
Pharmacodynamics
Anxiolytic drug (tranquilizer) of the non-benzodiazepine series, also has an antidepressant effect. Unlike classical anxiolytics, it does not have antiepileptic, sedative, hypnotic or muscle relaxant effects.
The mechanism of action is associated with the effect of buspirone on the serotonergic and dopaminergic systems. 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 does not have a significant effect on benzodiazepine receptors and does not affect the binding of GABA, does not have a negative effect on psychomotor functions, does not cause tolerance, drug dependence and withdrawal syndrome. Does not potentiate the effects of alcohol. In terms of anxiolytic activity, buspirone is approximately equal to benzodiazepines.
The therapeutic effect develops gradually and is noted after 7-14 days from the start of treatment, the maximum effect is recorded after 4 weeks.
Side effects
Buspirone is usually well tolerated. Side effects, if observed, usually occur early in the course of treatment and then disappear despite continued use of the drug. In some cases, a dose reduction is necessary.
Determination of the frequency of side effects: often (1/100), infrequently (from 1/100 to 1/1000), rarely (<1/1000). In many cases, in the absence of a comparator drug, the association of adverse effects with the drug could not be proven.
From the cardiovascular system: often - chest pain; infrequently - fainting, arterial hypotension, arterial hypertension; rarely - cerebrovascular accidents, decompensation of heart failure, myocardial infarction, myocardiopathy, bradycardia.
From the nervous system: often - dizziness, headache, increased nervous excitability, sleep disturbances; uncommon - dysphoric reactions, depersonalization, dysphoria, increased sensitivity 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 senses: often - tinnitus; infrequently - blurred vision, itching in the eyes, redness of the eyes, conjunctivitis, impaired taste and olfactory sensations; rarely - inner ear disorders, eye pain, photophobia, increased intraocular pressure.
From the respiratory system: often - laryngitis, swelling of the nasal mucosa; infrequently - hyperventilation, lack of air, feeling of heaviness in the chest; rarely - nosebleeds.
From the endocrine system: rarely - galactorrhea, damage to the thyroid gland.
From the digestive system: infrequently - nausea, flatulence, anorexia, increased appetite, salivation, intestinal bleeding; rarely - diarrhea, burning sensation in the tongue.
From the urinary system: infrequently - dysuria (including frequent urination, urinary retention); rarely - bedwetting.
From the reproductive system: infrequently - menstrual irregularities, decreased libido; rarely - amenorrhea, pelvic inflammation, delayed ejaculation, impotence.
From the musculoskeletal system: infrequently - muscle spasms, muscle rigidity, arthralgia; rarely - muscle weakness, pain in muscles and bones.
From the skin and subcutaneous tissues: uncommon - swelling, itching, hot flashes, hair loss, dry skin, facial swelling, skin tenderness, rash.
Changes in laboratory parameters: infrequently - increased activity of ALT and AST in the serum; rarely - eosinophilia, leukopenia, thrombocytopenia.
Other: weight gain, fever, weight loss; rarely - alcohol abuse, loss of voice, tinnitus, hiccups.
Use during pregnancy and breastfeeding
Due to the lack of properly controlled clinical trial data, the use of buspirone during pregnancy is only possible if the expected benefit of therapy for the mother justifies the possible risk to the fetus.
Women of childbearing potential should use adequate contraception during treatment with buspirone, since the safety of buspirone during pregnancy has not been proven.
Buspirone is excreted in breast milk. There is insufficient data from clinical studies of the use of buspirone during breastfeeding, so the drug should not be prescribed to nursing mothers.
Interaction
Considering the pharmacokinetic properties of the drug (low bioavailability, intensive metabolism in the liver, high protein binding), there is a high probability of interaction between buspirone and drugs when used simultaneously. However, because buspirone has a significant therapeutic breadth, pharmacokinetic interactions do not result in clinically significant pharmacodynamic changes.
MAO inhibitors: an increase in blood pressure and the occurrence of hypertensive crises have been described after the simultaneous administration of buspirone and drugs acting on MAO (moclobemide, selegiline); therefore, buspirone cannot be combined with MAO inhibitors. After discontinuation of an irreversible MAO inhibitor (for example, selegiline), at least 14 days must pass before starting administration of Spitomin® (and vice versa). Likewise, at least 14 days must pass after discontinuation of the drug Spitomin® before starting the administration of moclobemide (a reversible MAO inhibitor). However, Spitomin® can be taken 1 day after discontinuation of moclobemide.
CYP3A4 inhibitors and inducers: In vitro studies have shown that buspirone is primarily metabolized by CYP3A4 isoenzymes. Concomitant administration of buspirone and CYP3A4 inhibitors (erythromycin, itraconazole, nefazodone, diltiazem, verapamil and grapefruit juice) may lead to drug interactions, and with the administration of a strong inhibitor may also increase the plasma concentration of buspirone; therefore, it is necessary to reduce the dose of buspirone (for example, to 2.5 mg 2 times / day). Strong inducers of CYP3A4 (eg, rifampicin) may significantly reduce buspirone plasma concentrations and reduce its pharmacodynamic effects.
Highly protein bound drugs: Since buspirone is highly bound to plasma proteins (95%), there is always the possibility of interaction with other active substances characterized by high plasma protein binding. In vitro studies have shown that buspirone is not able to displace highly binding drugs (warfarin, phenytoin, propranolol) from protein binding sites, but can replace drugs with low binding, such as digoxin.
When cimetidine and buspirone are used together, the Cmax of buspirone increases by 40%, but its AUC does not change. Coadministration of these drugs requires close medical supervision.
When diazepam and buspirone are used together, the concentration of nordiazepam increases slightly, and side effects may occur: systemic dizziness, headache, nausea.
CNS depressants and alcohol: Coadministration 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 are not enhanced. There is insufficient experience with the combined use of buspirone and other anxiolytics or other drugs acting on the central nervous system (for example, antipsychotics and antidepressants). Therefore, in such cases, careful medical supervision is necessary.
Other medicinal products: Due to the lack of relevant clinical data, the combined use of buspirone with antihypertensive drugs, cardiac glycosides, oral contraceptives and hypoglycemic agents is possible only under conditions of careful medical supervision.
Overdose
Symptoms: gastrointestinal disorders, nausea, vomiting, dizziness and drowsiness (also in severe forms), depression of varying degrees of severity.
Treatment: gastric lavage and symptomatic therapy. A specific antidote is unknown, dialysis is ineffective. Experience to date suggests that even extremely high doses (single oral administration of 375 mg) do not necessarily cause severe symptoms.
Impact on the ability to drive vehicles and operate machinery
The results of clinical studies showed that buspirone monotherapy does not affect the psychomotor performance of patients. Despite this, at the beginning of the course of treatment, transient undesirable effects are possible, and therefore patients should be warned that driving vehicles and operating machinery is possible only if the patient is fully confident in his psychomotor functions. The patient's ability to drive vehicles and operate machinery should be determined individually depending on the patient's response to treatment and the use of concomitant therapy.
Precautions for the substance Buspirone
Use with caution simultaneously with neuroleptics, antidepressants, cardiac glycosides, antihypertensive and antidiabetic drugs, and oral contraceptives. For renal and liver failure of mild to moderate severity, liver cirrhosis, it is prescribed in smaller doses and under the strict supervision of a physician. During the treatment period, alcohol consumption should be avoided. At the beginning of treatment, use with caution while working for drivers of vehicles and people whose profession is associated with increased concentration of attention.
