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Stallion Laboratories Pvt. Ltd.
Dosage Form, Composition & NAFDAC Registration Number (NRN)
Tablet (NRN: A4-1677): Each film coated tablet contains: Risperidone BP 1 mg. Excipients q.s. Colour: Titanium Dioxide.
Pack Size: Available as Alu-Alu blister pack of 10 tablets in a carton of 3 x 10.
Risperidone is selective monoaminergic antagonist with unique properties. It has a high, affinity for serotonergic 5-HT2 and dopaminergic D2 receptors.
Risperidone bind also to œ,-adrenergic receptors and with lower affinity, to H1-histaminergic and a œ2-adrenergic receptors. Risperidone has no affinity for cholinergic receptors.
Although risperidone is a potent D2 antagonist, which is considered to improve the positive symptoms of schizophrena, it causes less depression of motor activity and induction of catalepsy than classical neuroleptics balanced central serotonin and dopamine antagonism may reduce extrapyramidal side effect liability and extend the therapeutic activity to the negative and affective symptoms of schizophrenia.
Risperidone is completely absorbed after oral administration reaching peak plasma concentration within 1 to 2 hours. The absorption is not affected by food and thus can be given with or without food. Risperidone is metabolized by CYP2D6 to 9-hydroxy-risperidone, which has similar pharmacological activity as risperidone. Risperidone plus 9-hydroxy-risperidone form the active antipsychotic fraction. Another metabolic pathway of risperidone is N-dealkylation.
After oral administration to psychotic patients, risperidone is eliminated with half-life of after 3 hours. The elimination half-life 9-hydroxy-risperidcne and of the active antipsychotic fraction is 24 hours.
Steady state of risperidone is reached within 1 day in most patients.
Steady state of 9-hydroxy-risperidone is reached within 4-5 days of dosing.
Risperidone plasma concentrations are dose-proportional within the therapeutic dose-range.
Risperidone is rapidly distributed. The volume of distributions is 1-2 L/kg in plasma, risperidone is bound to albumin and alpha-1-acid glycoprotein. The plasma protein binding of risperidone is 88% that of the metabolite is 77%. One week after administration,
70% of the dose is excreted in the urine and 14% in the faced. In urine, risperidone plus 9-hydroxy-rispendone represents 35%-45% of dose the remainder is inactive metabolite.
A single-dose study showed higher active plasma concentration and slower elimination of risperidone in the elderly and in patients with renal insufficiency Risperidone plasma concentrations were normal in patients with liver insufficiency.
The pharmacokinetics of risperidone, 9-nydroxy-risperidone and the active moiety in children are similar to those in adults.
AMIDREX is indicated for the treatment of acute and chronic schizophrenic psychoses, and other psychotic conditions, in which positive symptoms (such as hallucinations delusions, thought disturbance, hostility, suspiciousness) and or negative symptoms (such as blunted affect, emotional and social withdrawal, poverty of speech) are prominent.
AMIDREX also alleviates affective symptoms (such as depression, guilt feelings, anxiety) associated with schizophrenia.
AMIDREX is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.
AMIDREX is indicated in the treatment of conduct and other disruptive behaviour disorders in children, adolescents and adults with subaverge intellectual functioning or mental retardation in whom disruptive behaviour (eg. Aggression impulsivity and self-injurious behaviour) are prominent.
AMIDREX is contraindicated in patients with known hypersensitivity to the product.
Due to the alpha-blocking activity of risperidone, (orthostatic) hypotension can occur, especially during the initial dose-titration period. AMIDREX should be used with caution in patients with known cardiovascular disease (e.g. heart failure, myocardial infraction, conduction abnormalities, dehydration, hypovolemia or cerebrovascular disease) and the dosage should be gradually titrated as recommended (see posology and method of administration) a dose reduction should be considered if hypotension occurs.
Drug with dopamine receptor antagonistic properties have been associated with the indication of tardive dyskinesia characterized by rhythmic involuntary movements, predominantly of the tongue or face it has been reported that the occurrence of extrapyramidal symptoms is a risk factors for the development of tardive dyskinesia
Because AMIDREX has a lower potential to induce extrapyramidal, symptoms than classical neuroleptics, it should have a reduced risk of including tardive dyskinesia appear, the discontinuation of all antipsychotic drugs should be considered. The Neuroleptics Malignant syndrome, characterized by hyperthermia, muscle rigidity autonomic instability, altered consciousness and elevated CPK levels has been reported in this event, all antipsychotic drugs, including AMIDREX, should be discontinued.
Physicians should weigh the risk versus the benefits when prescribing antipsychotics, including AMIDREX, to patients with Lewy body dementia or Parkinson’s disease since they may be at the risk of neuroleptic malignant syndrome or a worsening of Parkinson-like symptoms.
For specific posology recommendations for elderly patients and patients with renal and liver disease, refer to posology and method of administration.
In placebo-controlled trials in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse events, including cerebrovascular accidents and transient ischemic attacks, in patients treated with risperidone compared to patients receiving placebo (mean age 85 years, range 79-97).
Classical neuroleptics are known to lower the seizure threshold. Caution is recommended when treating patients with epilepsy.
Patients may be advised to retrain from excessive eating in view of the possibility of weight gain.
Pregnancy and lactation
The safety of Amidrex for use during pregnancy has not been established. Although, in experimental animals, risperidone did not show direct reproductive toxicity, some indirect, prolactin-and CNS-mediated effects were observed. No teratogenic effect of risperidone was noted in any study.
Therefore, AMIDREX should only be used during pregnancy if the benefits outweigh the risks.
In animal studies, risperidone and 9-hydroxy-risperidone are also excreted in milk. It has been demonstrated that risperidone and the 9-hydraxy-risperidone are also excreted in human breast milk. Therefore, women receiving AMIDREX should not breast feed.
Effects on ability to drive and use machine
AMIDREX may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery until their individual susceptibility is shown.
The risk of using AMIDREX in combination with other drugs has not been systematically evaluated. Giving the primary CNS effects of AMIDREX it should be used with caution in combination with other centrally acting drugs.
AMIDREX may antagonize the effect of levodopa and other dopamine agonists.
Carbamazepine has been shown to decrease the plasma levels of the active antipsychotic fraction of risperidone. Similar effects may be observed with other hepatic enzymes inducers. On discontinuation of carbamazepine or other hepatic enzyme inducers, the dosage of AMIDREX should be re-evaluated and if necessary decreased.
Phenothiazines, tricyclic anti-depressants and some beta-blockers may increase the plasma concentrations of risperidone but not hose of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction. Cimetidine and ranitidine increases the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction.
Fluoxetine and paroxetine, CYP2D6 inhibitors, increase the plasma concentration of risperidone, but less so of the active antipsychotic fraction. When concomitant Fluoxetine or paroxetine, CYP is initiated or discontinued, the physician should re-evaluate the dosing of AMIDREX.
Erythromycin, CYP3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction the c’nolinesterase inhibitors, galantamine and donepezil, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
When AMIDREX is taken together with other highly protein bound drugs, there is no clinically relevant displacement of either drug from the plasma proteins.
AMIDREX does not show a clinically relevant effect on the pharmacokinetics of lithium, valproate, or digoxin.
Food does not affect the absorption of AMIDREX.
AMIDREX is generally well tolerated. In many instances it is been difficult to differentiate adverse events from symptom of underlying disease.
Adverse events reported in association with the use of AMIDREX are listed below.
Insomnia, agitation, anxiety, headache Sedation has been reported more frequently in children and adolescents than in adult, it is usually mind and transient.
Somnolence, fatique, dizziness, impaired concentration, constipation, dyspepsia, nausea/vomiting, abdominal pain, priapism, erectile dysfunction, rash and other allergic reaction.
AMIDREX has a lower propensity to induce extrapyramidal symptoms than classical neuroleptics. However, in some cases the following extrapyramidal symptoms may occur. Tremor, rigidity, hyper salivation, bradykinesia, akathisia, acute dystonia. There are usually mild and are reversible upon dose reduction and or administration of antiparkinson medication, if necessary.
Occasionally, (orthostatic) hypotension and (reflex) tachycardia or hypertension, have been reported following administration of AMIDREX (see special warning and special precautions for use). A decrease in neutrophil and or thrombocytes count has been reported.
AMIDREX can induce a dose dependent increase in plasma prolactin concentration. Possible association manifestations are galactorrhea, gynecomastia, disturbance of menstrual cycle and amenorrhea. Weight gain (see special warning and special precautions for use, edema, and increase hepatic enzyme levels have been reported during treatment with AMIDREX.
Cerebrovascular adverse events, including cerebrovascular accidents and transient ischemic attacks, have been reported during treatment with AMIDREX (see special warnings and special precautions for use) hyperglycemia and exacerbation of pre-existing diabetes have been reported in very rear cases during risperidone treatment.
As with classical neuroleptics, the following have occasionally been reported in psychotic patients: water intoxication due to either polydipsia or the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), tardive dyskinesia, neuroleptics malignant syndrome, body temperature deregulation and seizures.
Dosage & Administration
AMIDRX may be given as tablets or oral solution.
The maximum daily dose of risperidone is 5 mg taken twice daily. Check with your doctor if more than this has been prescribed.
AMIDRX cannot be recommended for use in children with schizophrenia under 15 years.
The usual starting dose of AMIDEX is 1 mg twice a day for long term treatment 4 to 6 mg/day is usually sufficient, but your doctor will determine your dose.
AMIDREX may be given once daily or twice daily. Patients should start with 2 mg/day AMIDREX. The dosage may be increased on the second day to 4 mg from then on the dosage can be maintained unchanged further individualized, if needed. Most patients will benefit from daily dose between 4 and 6 mg. In some patients, slower titration phase and a lower starting and Maintaince may be appropriate.
Doses above 10 mg/day have not been shown to be superior in efficacy to lower dose and cause extra pyramidal symptoms. Since the safety of doses above 16 mg/day has not been evaluated, dose above this level should not be used. A benzodiazepine may be added to AMIDREX when additional sedation is required.
A starting dose of 0.5 mg b.i.d is recommended. This dosage can be individually adjusted with 0.5 mg b.i.d increments to 1 to 2 mg b.i.d.
AMIDREX is well tolerated by me elderly.
Renal and liver disease.
A started dose of 0.5 mg b.i.d is recommended. This dosage can be individually adjusted with 0.5 mg b.i.d increments to 1 to 2 mg b.i.d. AMIDREX should be used with caution in this group of patients until further experience is gained.
Conduct and other disruptive behaviour disorders.
Subjects >50 KG
A starting dose of 0.5mg once daily is recommended. The dosage can be individually adjusted by increment of 0.5 mg once daily not more frequently than every other day, if needed. The optimum dose is 1 mg once daily for most patients, some patients, however, may benefit from 0.5mg once daily while others may require 15 mg once daily.
A starting dose of 0.25 mg once daily is recommended, This dosage can be individually adjusted by increments of 0.25 mg once daily not more frequently than every other day, if needed the optimum dose is 0.5 mg once daily for most patients, some patients may benefit from 0.25 mg once daily while others may require 0.75 mg once daily As with all symptomatic treatments, the continued use of AMIDREX must be evaluated and justified on an ongoing basis. Experience is lacking in children aged less than 5 years.
In general, reported signs and symptoms have resulting from an exaggeration of drugs pharmacological effects. These include drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. Over dosages of up to 360 mg have been reported. The available evidence suggests a wide safety margin. In overdose cases of QT-prolongation have been reported.
In cases of acute over dosage, the possibility of multiple drug involvement should be considered.
Establish and maintain a clear airway and ensure adequate oxygenation and ventilation Gastric lavage (after intubations, if the patient is unconscious) and administration of activated charcoal together with a laxative should be considered. Cardiovascular monitoring should commence immediately and should include continuous electrocardiograph monitoring to detect possible arrhythmias.
There is no specific antidote to AMIDREX. Therefore, appropriate supportive measure should be instituted Hypotension and circulatory collapse should be treated with appropriate measure such as intravenous fluid and or sympathomimetic agents. In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.
Store in a cool, dry & dark place.
KEEP MEDICINE OUT OF REACH OF CHILDREN.