Spitomin® (Spitomin® )

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceBuspironeBuspirone
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  • Spitomin®
    pills inwards 
    EGIS ZAO Pharmaceutical Plant     Hungary
    • Dosage form: & nbspPills
    Composition:

    5 mg or 10 mg of buspirone hydrochloride in each tablet. Excipients: lactose monohydrate (55.7 mg in tablets of 5 mg and 111.4 mg in tablets of 10 mg), microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, silicon dioxide colloidal anhydrous

    Description:

    Pills 5 mg: White or almost white, round flat tablets with bevel, engraved "E 151" on one side and with the risk - on the other side; odorless or with a weak characteristic odor.
    Tablets 10 mg: White or almost white, round flat tablets with a bevel, with engraving "E 152" on one side and with a risk - on the other side; odorless or with a weak characteristic odor.

    Pharmacotherapeutic group:anxiolytic (tranquilizer)
    ATX: & nbsp

    N.05.B.E   Derivatives of azaspirodekanedione

    N.05.B.E.01   Buspirone

    Pharmacodynamics:

    The anxiolytic (tranquilizing) agent of the non-benzodiazepine series also has an antidepressant effect. Unlike classic anxiolytics, it does not have anti-epileptic, sedative, hypnotic and miorelaxing effects.
    The mechanism of action is associated with the influence 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. Besides, 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 effect of alcohol. By anxiolytic activity buspirone is approximately equal to benzodiazepines.
    The therapeutic effect develops gradually and is observed 7-14 days after the start of treatment, the maximum effect is recorded after 4 weeks.

    Pharmacokinetics:After oral administration buspirone quickly and almost completely absorbed from the gastrointestinal tract. Buspirone is subjected to intensive metabolism of the first passage through the liver. Therefore, unchanged substance is found in the systemic blood stream in a small concentration, which has significant individual differences. Bioavailability is 4%.The maximum concentration in the blood plasma is reached after 60-90 minutes after taking the drug. In healthy volunteers buspirone had a linear (dose-proportional) pharmacokinetics after taking 10-40 mg. Similar pharmacokinetic parameters were found in elderly patients. After a single oral intake of 20 mg of the drug, its plasma levels are from 1 to 6 ng / ml. Approximately 95% of buspirone binds to plasma proteins (86% with plasma albumin, the rest with α1-xylene glycoprotein). Buspirone is subjected to 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 to 5 times lower than that of the starting material, but its plasma level is higher and the half-life is approximately 2 times longer than that of buspirone. After a single injection of 14C-labeled buspirone, 29-63% of radioactivity is excreted in the urine within 24 hours, mainly in the form of metabolites. Approximately 18-38% of the administered dose is excreted with feces.After a single dose of 10-40 mg, the half-life of the starting substance is approximately 2-3 hours, and the half-life of the active metabolite is 4.8 hours. Simultaneous food intake slows the absorption of buspirone, but due to a decrease in the systemic clearance (the effect of the first passage), the bioavailability of buspirone is significantly increased. After eating, Buspirone AUC increases by 84%, and its C max increases by 16%. An equilibrium concentration in the blood plasma can be achieved approximately 2 days after the start of the regular intake. The apparent volume of distribution is 5.3 l / kg.Buspirone is excreted in breast milk, but there is no data on placental transmission. Elevated levels of buspirone in the plasma and AUC values, as well as an elongation of the half-life can be observed with a violation of liver function. In connection with the isolation of an unchanged substance in bile, the second peak of buspirone concentration in the blood plasma is possible. Patients with cirrhosis of the liver should be given a drug in lower doses or in the same doses with longer intervals. In case of renal insufficiency, buspirone clearance can be reduced by 50%.With renal insufficiency buspirone should be administered with caution and in reduced doses. The pharmacokinetics of buspirone in elderly patients is not changed.
    Indications:

    - Generalized anxiety disorder (GAD).

    - Panic disorder.

    - Syndrome of autonomic dysfunction.

    - Alcohol abstinence syndrome (as adjuvant therapy)

    - Auxiliary therapy of depressive disorders (the drug is not prescribed for depression monotherapy).

    Contraindications:

    - Hypersensitivity to any component of the drug.

    - Severe renal failure (GFR below 10 mL / min).

    - Severe hepatic insufficiency (PV more than 18 seconds).

    - Simultaneous application of MAO inhibitors or a 14-day period after the cancellation of the irreversible MAO inhibitor or 1 day after reversal of the reversible MAO inhibitor.

    - Glaucoma

    - Myasthenia gravis

    - Age to 18 years (safety and efficacy of buspirone for this age group are not proven).

    - Lactation

    - Pregnancy or suspicion of pregnancy

    Carefully:cirrhosis of the liver, renal failure (see section "Special instructions")
    Pregnancy and lactation:

    In the absence of properly controlled clinical trials, buspirone during pregnancy is only possible if the benefits of the drug justify the risks. Women of childbearing age during the course of treatment with buspirone should use adequate methods of contraception, since the safety of buspirone during pregnancy is not proven.
    Buspirone is excreted in breast milk. Sufficient data from clinical studies of buspirone use in the period of breastfeeding are not available, therefore it is not recommended for breast-feeding mothers to take this drug.

    Dosing and Administration:

    Tablets should be taken always at the same time of the day, before or after a meal, in order to avoid significant fluctuations in the concentration of active substance in the blood plasma throughout the day.
    The drug should not be taken sporadically for the treatment of anxiety, because the therapeutic effect of the drug 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. Recommended primary a dose of 15 mg; it can be increased by 5 mg per day every 2 or 3 days. The daily dose should be divided into 2 -3 admission. The usual daily dose is 20 to 30 mg per day. The maximum single dose is 30 mg; the maximum daily dose should not exceed 60 mg.
    Special groups:
    Elderly patients: Elder age itself does not require a dose adjustment, since the pharmacokinetics of buspirone does not undergo age-related changes.
    Impaired renal function: If the kidney 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.

    Side effects:

    Buspirone is usually well tolerated. Side effects, if they occur, usually occur at the beginning of the course of treatment and then disappear, despite continued use of the drug. In some cases, a dose reduction is necessary.
    Frequent side effects - at a frequency of 1/100, infrequent at a frequency of 1/100 to 1/1000 and rare at a frequency of less than 1/1000 (in many cases, in the absence of a drug of comparison, the association of undesirable effects with drug administration could not be proved).
    The cardiovascular system:
    Frequent: chest pain.
    Infrequent: fainting, hypotension, hypertension.
    Rare: disorders of cerebral circulation, decompensation of heart failure, myocardial infarction, myocardiopathy, bradycardia.
    Central nervous system:
    Frequent: dizziness, headache, increased nervous excitability, sleep disturbances.
    Infrequent: dysphoric reactions, depersonalization, dysphoria, hypersensitivity to noise, euphoria, hyperkinesia, fear, apathy, hallucinations, confusion, lengthening reaction time, suicidal thoughts, epileptic seizures, paresthesia, impaired coordination of movements, tremor.
    Rare: claustrophobia, cold intolerance, stupor, stuttering, extrapyramidal disorders, psychotic disorders.
    Ophthalmic and otorhinolaryngological:
    Frequent: noises in the ears, laryngitis, swelling of the nasal mucosa.
    Infrequent: blurred vision, itchy eyes, red eyes, conjunctivitis, a violation of taste and olfactory sensations.
    Rare: violations of the inner ear, pain in the eyes, photophobia, increased intraocular pressure.
    Endocrine:
    Rare: galactorrhea and lesion of the thyroid gland.
    Gastrointestinal:
    Infrequent: nausea, flatulence, anorexia, increased appetite, salivation, intestinal bleeding.
    Rare: diarrhea, burning in the tongue.
    Genitourinary system:
    Infrequent: dysuric disorders (including frequent urination, delay urination), menstrual irregularities, decreased sexual desire.
    Rare: amenorrhea, pelvic inflammatory disease, bedwetting, ejaculation delay, impotence.
    Musculoskeletal system:
    Infrequent: muscle spasms, muscle stiffness, arthralgia.
    Rare: muscle weakness.
    On the part of the respiratory system:
    Infrequent: hyperventilation, lack of air, a sense of heaviness in the chest.
    Rare: epistaxis.
    Leather:
    Infrequent: swelling, itching, hot flashes, hair loss, dry skin, face swelling, skin rash, rash.
    Others: weight gain, fever, weight loss, pain in the muscles and bones.
    Rare: alcohol abuse, loss of voice, tinnitus, hiccough.
    Changes in laboratory indicators:
    Infrequent: Increased levels of ALT and ACT serum.
    Rare: eosinophilia, leukopenia, thrombocytopenia.

    Overdose:

    Symptoms: gastrointestinal disturbances, nausea, vomiting, dizziness and drowsiness (also in severe forms), depression of consciousness of varying severity.
    Treatment: Gastric lavage and symptomatic therapy. Specific antidote is not known, dialysis is ineffective.
    The experience to date indicates that even extremely high doses (single ingestion of 375 mg) do not necessarily cause severe symptoms.

    Interaction:

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

    - Inhibitors of monoamine oxidase (MAOI): An increase in blood pressure and the appearance of hypertensive crises after simultaneous administration of buspirone and drugs acting on monoamine oxidase (moclobemide, selegiline); concerning buspirone can not be combined with MAOI. After the cancellation of irreversible MAOI (for example, selegiline) before the introduction of the preparation Spitomin (and vice versa) should pass at least 14 weeks.Similarly, at least 14 days after the discontinuation of the Spitomin preparation before the start of the administration of moclobemide (reversible MAOI) should pass. However, Spitomin can be given 1 day after the abolition of moclobemide.

    - Inhibitors and inducers CYP3A4: Research in vitro showed that buspirone is mainly metabolized by isoenzymes CYP3A4 cytochrome P-450. Simultaneous administration of buspirone and inhibitors CYP3A4 (erythromycin, itraconazole, nefazodone, diltiazem, verapamil and grapefruit juice) can lead to drug interactions, and when a strong inhibitor is introduced, also increase the level of buspirone in the blood plasma; therefore, a decrease in the dose of buspirone (for example, up to 2.5 mg 2 times a day) is necessary. Strong inductors CYP3A4 (e.g., rifampicin) can significantly reduce buspirone levels in blood plasma and weaken its pharmacodynamic effects.

    - Strongly bound protein preparations Because the buspirone strongly binds to the protein (95%), there is always the possibility of interaction with other protein-bound active substances. Research in vitro showed that buspirone can not displace strongly bound proteins from proteins (warfarin, phenytoin, propranolol), but can replace loosely related drugs, for example, digoxin.

    - When co-introduced Cimetidine and buspirone CmOh Buspirone increases by 40%, And his AUC does not change. The joint administration of these drugs requires careful medical supervision.

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

    - Substances depressing the central nervous system, and alcohol: Co-administration 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. The experience of joint application of buspirone and other anxiolytics or other agents acting on the CNS (for example, neuroleptics and antidepressants) is insufficient. Therefore, in such cases careful medical supervision is necessary.

    - Other medicines: Due to the lack of appropriate clinical data, joint use of buspirone with antihypertensive drugs, cardiac glycosides, oral contraceptives and antidiabetics is possible only under conditions of careful medical supervision.

    Special instructions:

    - Renal insufficiency: With moderate or severe renal failure, buspirone clearance can be reduced by 50%. The drug is contraindicated in patients with severe renal failure with GFR less than 10 ml / min. In mild (GFR more than 30 ml / min) and moderate (GFR 10-30 ml / min) renal failure buspirone You can give, but you should be careful and prescribe lower doses.

    - Elderly patients: Elderly age does not in itself require a 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 in case of a dose increase, careful monitoring of the patient should be made.

    - The use of the drug requires extreme caution in patients rectangular glaucoma and myasthenia gravis.

    - When lactose intolerance when preparing a 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 and do not drink grapefruit juice in significant quantities, because. these products can 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 can not eliminate withdrawal symptoms of benzodiazepines. If the patient is transferred to buspirone after prolonged benzodiazepine therapy, buspirone should be given only after the end of the period of a gradual decrease in the dose of benzodiazepines.

    - Buspirone does not cause a predilection for the drug, but its administration to patients with established or suspected predisposition to drug dependence requires careful medical supervision.

    - Since the anxiolytic effect is manifested after 7-14 days reception of the drug, and the full therapeutic effect develops in about 4 weeks, patients with severe anxiety need careful medical observation in the initial period of therapy.

    - Throughout the course of treatment with buspirone, one should avoid eating alcoholic beverages.


    Effect on the ability to drive transp. cf. and fur:

    The results of clinical studies showed that buspirone monotherapy does not affect the parameters of the psychomotor activity 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 and controlling mechanisms is only possible with the patient's complete confidence in their psychomotor functions. The ability of the patient to control vehicles and mechanisms should be determined individually, depending on the patient's response to treatment and the use of concomitant therapy.

    Form release / dosage:

    Tablets 5 and 10 mg.

    Packaging:For 10 tablets are packaged in a blister from PA / Al / PVDC / Al. 6 blisters (60 tablets) in a cardboard pack together with instructions for use.
    Storage conditions:Store in a dark place at a temperature of no higher than 30 ° C, out of the reach of children
    Shelf life:5 years. Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:П N013159 / 01
    Date of registration:27.12.2007
    The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary
    Manufacturer: & nbsp
    Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary
    Information update date: & nbsp25.11.2015
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