Levosulpiride Tablets 50mg

1. Name of The Medicinal Product

Levosulpiride 50mg Tablets
Levosulpiride 100mg Tablets

2.Qualitative and Quantitative Composition

a) Each Tablet contains:
Levosulpiride                50mg
Excipients                        q.s.

b) Each Tablet contains:
Levosulpiride                50mg
Excipients                        q.s.

For the full list of excipients, see section 6.1.

3.Pharmaceutical Form

Tablet

4.Clinical Particulars

4.1 Therapeutic indications

Somatic symptom disorders.

Treatment of chronic schizophrenia with negative symptoms.

4.2 Posology and method of administration

Posology

Adults (according to medical prescription)

2-3 tablets of 100 mg per day.

Maintenance therapy: 3 tablets of 50 mg per day.

This dose may be gradually reduced.

Pediatric population

No data are available.

Elderly

In the treatment of elderly patients, the dosage should be decided by the physician which must carefully evaluate a possible reduction of the dosages above mentioned.

Method of administration

Oral use.

4.3 Contraindications

Hypersensitivity to the active substance or any of the excipients listed in section 6.1.

Levosulpiride 50mg and 100mg should be used with caution in epilepsy, manic states, in the manic phase of manic-depressive disorder

Levosulpiride 50 mg and 100 mg is contraindicated in patients with pheochromocytoma because it can cause a hypertensive crisis probably due to the release of catecholamines from the tumor. Such hypertensive crises may be controlled by phentolamine.

Regarding the supposed correlation between the hyperprolactinemic effect of most psychotropic medicines and mammary dysplasia, levosulpiride should not be used in subjects who are already carriers of a malignant mastopathy.

4.4 Special warnings and precautions for use

In randomized clinical trials versus placebo performed in a population of patients with dementia treated with some atypical antipsychotics, an increase of about three times of the risk of the cerebrovascular event was observed. The mechanism for this increased risk is not known. An increased risk for other antipsychotics and other patient populations can not be ruled out. Levosulpiride should be used with caution in patients with risk factors for stroke.

A complex symptoms disorder, potentially fatal, called Neuroleptic Malignant Syndrome has been reported with use of neuroleptics (in general in the course of treatment with antipsychotic drugs).Clinical manifestations of this syndrome are hyperpyrexia, muscle rigidity, akinesia, vegetative disorders (irregular pulse or blood pressure, sweating, tachycardia, arrhythmias), altered state of consciousness that may progress to stupor and coma.The treatment of Neuroleptic Malignant Syndrome consists of immediate discontinuation of the antipsychotic medicines and

other not essential medicinesandsettingof an intensive symptomatic treatment (care must be taken in reducing hyperthermia and in correcting dehydration). In case the resumption of the treatment with antipsychotics is held to be essential, the patient should be carefully monitored. Concomitant therapy with other neuroleptics must be avoided.

Levosulpiride should not be used when the stimulation of gastrointestinal motility can be detrimental, for example in the presence of gastrointestinal bleeding, mechanical obstructions or perforations.

Levosulpiride should be used with caution in patients with cardiovascular disease or with a family history of QT prolongation.

There have been reports of venous thromboembolism (VTE) with antipsychotic medicines use. Since patients treated with antipsychotics often present with acquired risk factors for VTE, these factors need to be identified before and during treatment with levosulpiride, to take appropriate preventive measures.

Simultaneous intake of alcohol must be avoided.

Levosulpiride contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

The association with other medicines requires special caution and vigilance from the physician, to avoid unexpected effects from unwanted interaction.

Concomitant administration of neuroleptics with medicines that prolong the QT interval, increases the risk of cardiac arrhythmias.

Levosulpiride should not be administered concomitantly with medicines that cause electrolyte disturbances.

4.6 Fertility, pregnancy and lactation

Patients should be advised of the need to inform their doctor in case of current or planned pregnancy during treatment with levosulpiride. There are no adequate and well-controlled investigations on pregnant women. Therefore, Levosulpiride should not be used in pregnancy, possible pregnancy and during the breastfeeding period unless the potential benefit justifies a potential risk to the fetus or newborn. Neonates exposed to conventional or atypical antipsychotics included levosulpiride during the third trimester of pregnancy are at risk for side effects including extrapyramidal symptoms or withdrawal symptoms that may vary by severity and duration following delivery. There have been reports of

agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder.

Therefore, newborns should be carefully monitored.

4.7 Effects on ability to drive and use machines

Patients under treatment may experience drowsiness, numbness, dizziness and dyskinesia, therefore they should be advised to avoid driving or operating machinery and to be engaged in activities where a full alertness is required for their possible hazard.

4.8Undesirable effects

Tabulated list of adverse reactions

According to MedDRA system, organ classification, frequency categories are defined as follows: Very common (?1/10), Common (?1/100 to <1/10), Uncommon (?1/1,000 to <1/100), Rare (?1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

SystemVeryCommonUncommonRareVery RareFrequency
Organ Classcommon    not known
       
Metabolism    Weight gain 
and nutrition      
disorders      
       
NervousSomnolenceDizziness,  ParkinsonisNeuroleptic
system, TorporVertigo  m,Malignant
disorders    Dyskinesia,Syndrome
     Tremor,(see section
     Dystonia,4.4)
     Psychomoto 
     r agitation, 
     Disorders 
     of the 
     autonomic 
     nervous 
     system 
       
Reproductive     Amenorrhe
system and     a,
breast     Gynaecoma
       
SystemVeryCommonUncommonRareVery RareFrequency
Organ Classcommon    not known
       
disorders     stia,
      Galactorrhe
      a, Changes
      in libido1
       
Cardiac   QTSudden 
disorders   prolongatiodeath2 
    n,  
    Ventricular  
    arrhythmias  
    such as  
    torsades de  
    pointes,  
    Ventricular  
    tachycardia,  
    Ventricular  
    fibrillation,  
    Cardiac  
    arrest2  
       
Vascular     Thromboem
disorders     bolism
      (including
      cases of
      pulmonary
      embolism
      and deep
      venous
      thrombosis)
      (see section
      4.4)2
       
Pregnancy,     Neonatal
puerperium     withdrawal
and perinatal     syndrome,
conditions     Extrapyram
      idal
       
SystemVeryCommonUncommonRareVery RareFrequency
Organ Classcommon    not known
       
      symptoms
      (see section
      4.6)
       
Investigations     Hyperprola
      ctinaemia1
       

1Observed in special cases, due to prolonged administration and due to a reversible effect of levosulpiride on the functionality of the hypothalamic-pituitary-gonadal axis, similar to that known for many neuroleptics.

2Observed with other drugs of the same therapeutic class.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important.

4.9 Overdose

The medicine can induce extrapyramidal effects and sleep disorders, at higher doses and in patients sensitive to neuroleptics.

In these cases it will be advisable to reduce the dosage or discontinue the treatment, according to the physician decision.

5. Pharmacological Properties

Pharmacotherapeutic group: Psycholeptics, antipsychotics.

5.1 Pharmacodynamic properties

Biochemical, pharmacological and clinical data obtained with the two isomers of sulpiride, indicate that this antidopaminergic activity, both at central and local levels, is due to levorotatory enantiomer.

5.2 Pharmacokinetic properties

When levosulpiride is administered personally at a dose of 50 mg, the peak plasma concentration is reached in 3 hours, in an average of 94.183 ng/ml.

The t? of elimination calculated after administration of 50 mg iv of levosulpiride is 4.305 hours.

The elimination of the medicine occurs mainly via the urine.

5.3 Preclinical safety data

The values expressed as LD50 acute toxicity after oral administration in mice, rats and rabbits were 2450 mg/kg, 2600 mg/kg and greater than 1500 mg/kg. LD 50 values:

in the mouse : 210 mg / kg, via i.p,

in the rat via i.p. and i.v. :to 270 mg / kg and 53 mg / kg, respectively, in the rabbit via i.v.: to 42 mg / kg.

Subacute toxicity tests were conducted by administering the active ingredient in rat, rabbit and dog, daily, for 12-13 weeks. The appearance of any toxic symptoms was not observed at doses of:

25 mg / kg sc and 300 mg / kg p.o. in the rat,

250 mg / kg p.o. and 12.5 mg / kg i.m. in rabbits, 50 and 100 mg / kg p.o. in the dog.

To evidential the chronic toxicity after administration of the drug for 180-190 days, the following doses were well tolerated:

100 mg / kg p.o. and 20 mg / kg s.c. in the rat, 10 mg / kg i.m. in rabbits and

20 mg / kg p.o. in the dog.

Studies performed in rats and mice, administering the medicine at a dose higher than that expected for man, have shown that levosulpiride does not possess carcinogenic properties.

Studies carried out in rats and rabbits have shown that the medicine is not teratogenic.

In vitro tests have ruled out that the medicine possesses mutagenic properties.

6. Pharmaceutical Particulars

6.1 List of excipients

Microcrystalline cellulose, lactose monohydrate, sodium starch glycolate type A&magnesium stearate.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage precautions.

6.5 Nature and contents of container

Packs of 20, 30, 60 and 100 tablets packed in blisters.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. Manufactured in India by:
TAJ LIFE SCIENCES PVT. LTD.
Unit No. 214, Old Bake House,
Bake House Lane, Fort,
Mumbai-400001
at: Ahmedabad- Gujarat, INDIA.
Ho.NO.+91 8448 444 095
Toll Free Phone: (1800-222-434 / 1800-222-825)