Betamaks®

Therapeutic Indications
Acute and chronic schizophrenia.

Posology and Methods of Administration
 BETAMAKSis given by mouth; a whole tablet should be swallowed. Dosage should beadjusted individually based on severity of symptoms and clinicalresponse; the age as well as body weight and individual requirementmust be taken in consideration. Daily dose is usually given in 2-3divided doses.
A usual adult dose is 300-600 mg a day in patientswith predominantly negative symptoms; in patients with mainly positivesymptoms dose may be increased up to 1200 mg.
As the activatingproperties of this medicine may cause sleep disturbance, the last doseof the day is recommended to be take no later than 4 p.m.
Forlong-term treatment lower doses should be used in patients with renalfailure; dose should be adjusted according to creatinine clearance. Ifcreatinine clearance is in the ranges 30 to 60 ml per minute, dailydose should be 70 % the usual regimen; if creatinine clearance 10 to 30ml per minute - 50 % of usual dose; if creatinine  clearance of lessthan 10 ml per minute, daily dose must be reduced to 34 %.

Contraindications
- Hypersensitivity to sulpiride or any other component of the product.
- Phaeochromocytoma (a tumour of the adrenal gland, which causes attacks of raised blood pressure).
- Bone-marrow suppression.
- Porphyria.
- Pregnancy and lactation.
- Children under 14 years.

Special Warnings and Special  Precautions  for  Use
Sulpirideshould be given with caution to maniac or hypomaniac patients. In thepatients with schizophrenia drug may sometimes exacerbate acutepsychotic disturbances should be borne in mind.
Extrapyramidalreactions have been reported in a small number of cases. If warranted,reduction in dosage or antiparkinsonian medication may be necessary.
Aswith other neuroleptics, rare cases of neuroleptic malignant syndromehave been reported. In such an event, all antipsychotic drugs,including BETAMAKS, should be discontinued.
Cases of convulsion, sometimes in patients with no previous history, have been reported.
Medicineshould be used with caution in the patients with cardiovasculardisease, hypotension, impaired renal function, or epilepsy. In thepatients with hypertension phaeochromocitoma should be excluded.
Sulpiridemay induce a prolongation of the QT interval. This effect, known topotentiate  the risk of serious ventricular arrhythmias such as torsadede pointes is enhanced by the pre-existence of bradycardia,hypokalaemia, congenital or acquired long QT interval.
Sulpiride haspronounced dose-dependent effect therefore patients should be advisedto not exceed the recommended dose, particularly treating anxietydisorders or psychosomatic disturbances.
Children and the elderly patients may be more predisposed to adverse effects.
Dueto sulpiride relieves nausea and suppresses vomiting reflex, BETAMAKSmay mask symptoms of overdose with other medicines (includingglycosides) overdose or disorders such as paralytic ileus and cerebralmalignant.
 
BETAMAKS film-coated tablets contain lactose.
Patientswith rare hereditary problems of galactose intolerance, the Lapplactase deficiency or glucose-galactose malabsorption should not takethis medicine.

Interaction with Other Medicinal Products and Other Forms of Interaction
There exists  reciprocal antagonism of effects between dopaminergic antiparkinsonian drugs, e.g. levodopa, and sulpiride.
BETAMAKS potentiates effects of alcohol, CNS depressants and antihypertensives.
Theconcomitant administration of BETAMAKS and digitalis glycosides maymask symptoms of intoxication with cardiac glycosides.Co-administration of antiarrhythmics, which prolong QT interval, mayincrease risk of arrhythmia.
Sulpiride antagonises the effects ofantimuscarinics (e.g. atropine, metylscopolamine) and levodopaneutralising therapeutic action of these drugs. Antacids reduceabsorption of sulpiride from the gastrointestinal tract loweringBETAMAKS bioavailability.

Pregnancy and Lactation
There are no adequate and well-controlled studies in pregnant women as well as nursing mothers.
It is known the medicine is excreted in human breast milk.
 Themedicine should be taken during pregnancy only following doctor’sadvice, if the benefit clearly justifies a potential risk to the fetus.Breast-feeding should be discontinued during treatment.

Effects on ability to drive and use machines
Themedicine may impair the mental and/or physical abilities required forthe performance of hazardous tasks such as operating machinery ordriving a motor vehicle.

Undesirable Effects
Dueto BETAMAKS selective action, undesirable effects are more rarelyobserved during treatment with this drug in contrast to most otherneuroleptics. Agitation, anxiety, sleep disturbances, impairedconcentration occur predominantly because of sulpiride activatingaction; sedative effects are observed in high doses.
Extrapyramidalreactions are occasionally observed: parkinsonian symptoms (tremor,rigidity, loss of balance control and movement disturbances, speechdifficulties, hypersalivation), dyskinesia and dystonia (muscle spasmsor involuntary contractions), oral hyperkinesia (involuntary mouth andjaw movements), akathisia (restlessness or need to keep moving).Extrapyramidal reactions may occurs more commonly the elderly andappear with high doses. The symptoms may be controlled with dosereduction or administration of antiparkinsonian drugs.
Sulpirideadministration may produce elevated prolactin level in serum andendocrine effects such as galactorrhoea, gynaecomastia, menstrualdisturbances, weight gain, that effects are explained with the druginfluence on dopamine receptors in hypophysis. These effects arereversible and improve if drug is stopped.
Because of sulpirideeffects on the autonomic nervous system tachycardia, dizziness,paresthesia, hyperthermia, sweating, urinary disturbances, labile bloodpressure and common weakness may occur in hypersensitive patients.
Drymouth, constipation, blurred vision, anorexia, nausea, elevated bloodliver transaminase activity, skin itching, rash may occasionally occur.
Inseveral case neuroleptics may cause hyperpyrexia, muscle rigidity,altered mental status, cardiac disrhythmias and labile blood pressure,sweating, and impaired kidney function that may be manifestation ofneuroleptic malignant syndrome. If suspicion occurs, the drug may haveto be discontinued and intensive symptomatic therapy is recommended.

Pharmacodynamic properties
Pharmacotherapeutic group: neuroleptic
Code ATC: N05AL01
Sulpiride(BETAMAKS) is an atypical neuroleptic, a member of the group ofsubstituted   benzamide. Drug is characterised with broad-spectrumactions: moderate antipsychotic, minor antidepressant, antiemetic andregulation of the autonomic nervous system. In contrast to otherneuroleptics, which block dopamine D1 and D2 receptors, sulpiride ismore selective and acts primarily as a dopamine D2 antagonist in thecentral nervous system (CNS), particularly blocks D2 autoreceptors. Atlower doses drug activates the dopamine transmission in the limbicsystem, due to inhibition of dopamine reuptake. At higher dosesmedicine inhibits the dopamine transmission in CNS. Thereby drugpharmacological action has dose-dependence. At lower doses sulpirideexerts antidepressive action, it decreases psychotic negative symptomsand relieves inhibition. At higher doses sulpiride exerts antipsychoticaction, it also treats psychotic positive symptoms (hallucination,mare) and decreases aggressiveness, however it does not eliminatepsychomotor reactions.
Practically, sulpiride lacks of catalepsyat doses equivalent to therapeutic doses. Sulpiride has no effect onacetylcholine, gamma-aminobutyric acid (GABA), or adrenaline receptorbinding. Because of selective action extrapyramidal symptoms and otherneuroleptics side effects are rarely observed during sulpiridetreatment.
Sulpiride has property to influence hypothalamus, regulating activity of some higher centres of the autonomic nervous system.
Drughas favourable influence to the gastrointestinal motility; it decreasesthe stomach and intestinal as well as biliary duct spasm. Sulpiride hasprokinetic activity, it improves intestinal peristaltic and inhibitsdopaminergics-induced (apomorphine) vomiting. Sulpiride protects mucousmembrane in gastrointestinal tract and prevents stress-inducedgastroduodenal ulcers genesis as well as promotes healing ulcers up. 

Pharmacokinetic properties
Sulpirideis slowly absorbed from the gastrointestinal tract. The peak plasmaconcentration is reached 3 hours after oral dose. Sulpiridebioavailability is low, approximately 30 %.  Only 40 % sulpiride boundto plasma proteins therefore there is low risk of medicinalinteractions. Sulpiride is rapidly absorbed to the tissues, crosses theplacental barrier and found in breast milk, and limited concentrationsin the cerebrospinal fluid. 
The plasma elimination half-life isup to 7 to 9 hours. Sulpiride is poorly metabolised in the liver thusno active metabolites. Sulpiride is eliminated by glomerular filtrationfrom organism. Unchanged sulpiride are eliminated from organism in thefaeces.
In patients with renal insufficiency elimination of sulpiride is prolonged.

List of excipients
Tablets cores:
Lactose, magnesium aluminometasilicate, carmellose calcium, hydropropylcellulose, magnesium stearate.
Film-coating:
Hydroxypropylmethylcellulose 2910, macrogol 6000, talc, titanium oxide, carnauba wax. 

Incompatibilities
None stated.     

Shelf-life.
5 years

Special precautions for storage
Do not store above 25°C.
Protect from moisture.