Aspidon/Aspidon OS

Risperidone.

Aspidon: 1 mg: Each film coated tablet contains: Risperidone USP 1 mg.
2 mg: Each film-coated tablet contains: Risperidone 2 mg.
Aspidon OS: Each mL contains: Risperidone 1 mg.

Pharmacology: Aspidon: 1 mg: Risperidone with the precise mechanism of action as other antipsychotic drugs, is known but the antipsychotic activity is mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5HT₂) antagonism.
Risperidone is a selective monoaminergic antagonist with high affinity (Ki of 0.12 to 7.3 nM) for the serotonin type 2 (5HT₂), dopamine type 2 (D₂) a₁ and a₂ adrenergic, and H₁ histaminic receptors. Risperidone has no affinity for cholinergic muscarinic or b₁ and b₂ adrenergic receptors.
The relative oral bioavailability of Risperidone after administration of a single 1 mg tablet was 94%. After oral administration of solution or tablet, mean peak plasma concentrations occurred at about 1 hour. The apparent half-life of Risperidone was three hours. Steady state concentrations of Risperidone are reached in 1 day in extensive metabolizers.
Total plasma protein binding of Risperidone was about 90% over the in vitro concentration range of 0.5 to 200mg/mL and increased with increasing concentrations of a₁ acid glycoprotein. After oral administration, the elimination half-life of the active antipsychotic fraction is 24 hours.
Total recovery of Risperidone at one week was nearly up to 85%, including 70% in the urine and 15% in the feces. Risperidone is extensively metabolized in the liver to a major active metabolite, 9-hydroxyrisperidone that is equi-effective with Risperidone with respect to receptor binding activity and some effects in animals. Plasma concentrations of Risperidone, 9-hydroxyrisperidone, and Risperidone plus 9-hydroxyrisperidone are dose proportional over the dosing range of 1 to 16 mg daily (0.5 to 8 mg b.i.d). Food does not affect either the rate of extent of absorption. Thus, Risperidone can be given with or without meals. The absolute oral bioavailability was 70%.
Pharmacodynamics: Aspidon: 2 mg: The mechanism of action of risperidone, as with other antipsychotic drugs, is unknown. However, it has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) antagonism. Antagonism at receptors other than D2 and 5HT2 may explain some of the other effects of risperidone.
Risperidone is a selective monoaminergic antagonist with high affinity for the serotonin type 2 (5HT2), dopamine type 2 (D2), a1 and a2 adrenergic, and H1 histaminergic receptors. Risperidone antagonizes other receptors, but with lower potency. Risperidone has low to moderate affinity for the serotonin 5HT1C, 5HT1D, and 5HT1A receptors, weak affinity for the dopamine D1 and haloperidol-sensitive, sigma site, and no affinity for cholinergic muscarinic or B1 and B2 adrenergic receptors.
Aspidon OS: Risperidone is a selective monoaminergic antagonist with unique properties. It has a high affinity for serotoninergic 5-HT₂ and dopaminergic D₂ receptors. Risperidone binds also to alpha₁-adrenergic receptors, and, with lower affinity, to H₁-histaminergic and alpha₁-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 schizophrenia, it causes less depression of motor activity and induction of catalepsy than classical antipsychotics. 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.
Pharmacokinetics: Aspidon: 1 mg: Risperidone is readily absorbed after oral doses, peak plasma concentrations being reached within 1 to 2 hours. It is extremely metabolized in the liver to hydroxylation to its main active metabolite, 9-hydroxylation; oxidative N-dealkylation is a minor metabolic pathway. Hydroxylation is mediated by the cytochrome P450 isozyme CYP2D6 and is the subject of genetic polymorphism. Excretion is mainly in the urine and to a lesser extent, in the feces. Risperidone and 9-hydroxyrisperidone are about 88% and 77% bound to plasma proteins, respectively.
2 mg: Absorption: Risperidone is well absorbed. The absolute oral bioavailability of risperidone is 70% (CV=25%). The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) when compared to a solution.
Plasma concentration of risperidone, its major metabolite, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone are dose proportional over the dosing range of 1 to 16 mg daily (0.5 to 8 mg twice daily). Following oral administration of a solution or tablet, mean peak plasma concentrations of risperidone occurred about 1 hour. Peak concentrations of 9-hydroxyrisperidone occurred at about 3 hours in extensive metabolizers, and 17 hours in poor metabolizers. Steady-state concentrations of risperidone are reached in 1 day in extensive metabolizers and would be expected to reach steady-state in about 5 days in poor metabolizers. Steady-state concentrations of 9-hydroxyrisperidone are reached in 5-6 days (measured in extensive metabolizers).
Food Effect: Food does not affect either the rate or extent of absorption of risperidone. Thus, risperidone can be given with or without meals.
Distribution: Risperidone is rapidly distributed. The volume of distribution is 1-2 L/Kg. In plasma, risperidone is bound to albumin and 1-acid glycoprotein. The plasma protein binding of risperidone is 90%, and that of its major metabolite, 9-hydroxyrisperidone, is 77%. Neither risperidone nor 9-hydroxyrisperidone displaces each other from plasma binding sites. High therapeutic concentrations of sulfamethazine (100 mcg/mL), warfarin (10 mcg/mL), and carbamazepine (10 mcg/mL) caused only slight increase in the free fraction of risperidone at 10 ng/mL and 9-hydroxyrisperidone at 50 ng/mL, changes of unknown clinical significance.
Metabolism: Risperidone is extensively metabolized in the liver. The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. A minor metabolic pathway is through N-dealkylation. The main metabolite, 9-hydroxyrisperidone, has similar pharmacological activity as risperidone. Consequently, the clinical effect of the drug results from the combined concentrations of risperidone plus 9-hydroxyrisperidone.
CYP 2D6, also called debrisoquin hydroxylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP 2D6 is subject to genetic polymorphism (about 6%-8% of Caucasians, and a very low percentage of Asians, have little or no activity and are "poor metabolizers") and to inhibition by a variety of substrates and some non-substrates, notably quinidine. Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydoxyrisperidone combined, after single and multiple doses, are similar in extensive and poor metabolizers.
Risperidone could be subject to two kinds of drug-drug interactions. First, inhibitors of CYP 2D6 interfere with conversion of risperidone to 9-hydroxyrisperidone. This occurs with quinidine, giving essentially all recipients a risperidone pharmacokinetic profile typical of poor metabolizers. The therapeutic benefits and adverse effects of risperidone in patients receiving quinidine have not been evaluated, but observations in a modest number (n=70) poor metabolizers given risperidone do not suggest important differences between poor and extensive metabolizers. Second, co-administration of known enzyme inducers (e.g., carbamazepine, phenytoin, rifampin, and phenobarbital) with risperidone may cause a decrease in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone. It would also be possible for risperidone to interfere with metabolism of other drugs metabolized by CYP 2D6. Relatively weak binding of risperidone to the enzyme suggests this is unlikely.
In vitro studies indicate that risperidone is a relatively weak inhibitor of CYP 2D6. Therefore, risperidone is not expected to substantially inhibit the clearance of drugs that are metabolized by this enzymatic pathway. In drug interaction studies, risperidone did not significantly affect the pharmacokinetics of donepezil and galantamine, which are metabolized by CYP 2D6.
In vitro studies demonstrated that drugs metabolized by other CYP isozymes, including 1A1, 1A2, 2C9, 2C19, and 3A4, are only weak inhibitors of risperidone metabolism.
Excretion: Risperidone and its metabolites are eliminated via the urine and, to a much lesser extent, via the feces. As illustrated by a mass balance study of a single 1 mg oral dose of 14C-risperidone administered as solution to three healthy male volunteers, total recovery of radioactivity at 1 week was 84%, including 70% in the urine and 14% in the feces.
The apparent half-life of risperidone was 3 hours (CV=30%) in extensive metabolizers and 20 hours (CV=40%) in poor metabolizers. The apparent half-life of 9-hydroxyrisperidone was about 21 hours (CV=20%) in extensive metabolizers and 30 hours (CV=25%) in poor metabolizers. The pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, were similar in extensive and poor metabolizers, with an overall mean elimination half-life of about 20 hours.
Special Populations: Renal Impairment: In patients with moderate to severe (Clcr 59 to 15 mL/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. Risperidone doses should be reduced in patients with renal disease.
Hepatic Impairment: While the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α1-acid glycoprotein. Risperidone doses should be reduced in patients with liver disease.
Elderly: In healthy elderly subjects renal clearance of both risperidone and 9-hydroxyrisperidone was decreased, and elimination half-lives were prolonged compared to young healthy subjects. Dosing should be modified accordingly in the elderly patients.
Pediatric: The pharmacokinetics of risperidone and 9-hydroxyrisperidone in children were similar to those in adults after correcting for the difference in body weight.
Race and Gender Effects: No specific pharmacokinetic study was conducted to investigate race and gender effects, but a population pharmacokinetic analysis did not identify important differences in the disposition of risperidone due to gender (whether corrected for body weight or not) or race.
Aspidon OS: Risperidone oral solution is bio-equivalent to risperidone film-coated tablets.
Risperidone is metabolized to 9-hydroxy-risperidone, which has a similar pharmacological activity to risperidone.
Risperidone is completely absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. The absolute oral bioavailability of risperidone is 70% (CV=25%). The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) compared with a solution. The absorption is not affected by food and thus risperidone can be given with or without meals. 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 is rapidly distributed. The volume of distribution is 1-2l/kg. In plasma, risperidone is bound to albumin and alpha₁-acid glycoprotein. The plasma protein binding of risperidone is 90%, that of 9-hydroxyrisperidone is 77%.
Risperidone is metabolized by CYP2D6 to 9-hydroxy-risperidone, which has a similar pharmacological activity as risperidone. Risperidone plus 9-hydroxy-risperidone form the active antipsychotic fraction. CYP2D6 is subject to genetic polymorphism. Extensive CYP2D6 metabolizers convert risperidone rapidly into 9-hydroxy-risperidone, whereas poor CYP2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxy-risperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxy-risperidone combined (i.e., the active antipsychotic fraction), after single and multiple doses, are similar in extensive and poor metabolizers of CYP2D6.

Aspidon: 1 mg: Risperidone is indicated for the management of psychotic disorders and nonpsychotic symptoms associated with dementia in the elderly.
2 mg: Risperidone (Aspidon) is indicated for the treatment of schizophrenia, and for the short-term treatment of acute manic or mixed episodes associated with bipolar disorders.
Aspidon OS: Risperidone (Aspidon OS) is indicated for the treatment of schizophrenia, moderate to severe manic episodes associated with bipolar disorders and for short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others.
Risperidone (Aspidon OS) is indicated for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from the age of 5 years and adolescents with subaverage intellectual functioning or mental retardation diagnosed according to DSM-IV criteria, in whom the severity of aggressive or other disruptive behaviors require pharmacologic treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment program, including psychosocial and educational intervention. It is recommended that Risperidone (Aspidon OS) be prescribed by a specialist in child neurology and child and adolescent psychiatry or physicians well familiar with the treatment of conduct disorder of children and adolescents.

Aspidon: 1 mg: Schizophrenia: When switching from other antipsychotics, where medically appropriate, gradual discontinuation of the previous treatment while Risperidone therapy is initiated is recommended.
Adults: Risperidone may be given once or twice daily. Treatment should be started with 2 mg/day, whether for acute or chronic condition. The dosage may be increased to 4 mg/day on the second day.
Some patients, such as first episode patients, may benefit from a slower rate of titration. From then on, the dosage can be maintained unchanged, or further individualized, if needed. Most patients will benefit from daily doses between 4 and 6 mg/day although in some, an optimal response may be obtained at lower doses.
Doses above 10 mg/day generally have not been shown to provide additional efficacy to lower doses and may increase the risk of extrapyramidal symptoms. Doses above 10 mg/day should only be used in individual patients if the benefit is considered to outweigh the risk. Doses above 16 mg/day have not been extensively evaluated for safety and therefore should not be used.
Elderly & Patients with renal and liver disease: A starting dose of 0.5 mg b.d. is recommended. This dosage can be individually adjusted with 0.5 mg b.d. increments to 1 to 2 mg b.d. Risperidone should be used with caution in this group of patients until further experience is gained.
Children: Use of Risperidone for schizophrenia in children aged less than 15 years has not been formally evaluated.
Bipolar Mania: Adults: Risperidone should be administered on a once daily schedule, starting with 2 mg. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments of 1 mg per day. A dosing range between 1 and 6 mg per day is recommended.
As with all symptomatic treatments, the continued use of Risperidone must be evaluated and justified on an ongoing basis.
Elderly & Patients with renal and liver disease: A starting dose of 0.5 mg b.d. is recommended. This dosage can be individually adjusted with 0.5 mg b.d. increments to 1 to 2 mg b.d. Risperidone should be used with caution in this group of patients until further experience is gained.
Combined use with mood stabilisers: There is limited information on the combined use of Risperidone with carbamazepine in bipolar mania. Carbamazepine has been shown to induce the metabolism of risperidone producing lower plasma levels of the antipsychotic fraction of Risperidone. It is therefore not recommended to co-administer Risperidone with carbamazepine in bipolar mania patients until further experience is gained. The combined use with lithium or valproate does not require any adjustment of the dose of Risperidone.
2 mg: Schizophrenia: Adults: Usual Initial Dose: Risperidone (Aspidon) tablets can be administered once or twice daily. Initial dosing is 2 mg per day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to a recommended dose of 4 to 6 mg per day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 10 mg/day have not been shown to be more efficacious than lower doses, and may cause extrapyramidal symptoms and other adverse effects, and are generally not recommended. The safety of doses above 16 mg/day has not been evaluated, doses above this level should not be used.
Adolescents: The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg/day, as tolerated, to a recommended dose of 3 mg/day.
Doses higher than 6 mg per day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
Experience in schizophrenia is lacking in children less than 13 years of age.
Switching From Other Antipsychotics: When switching from other antipsychotics, where medically appropriate, gradual discontinuation of the previous treatment while Risperidone (Aspidon) therapy is initiated is recommended.
Bipolar Mania: Usual Dose: Adults: The initial dose range is 2 mg to 3 mg/ day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg/day.
A dosing range between 1 to 6 mg/day is recommended.
As with all symptomatic treatments, the continued use of Risperidone (Aspidon) must be evaluated and justified on an ongoing basis.
Pediatrics: The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 or 1 mg/day, as tolerated, to the recommended target dose of 1 to 2.5 mg/day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 and 6 mg/day. Doses higher than 6 mg per day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
As with all symptomatic treatments, the continued use of Risperidone (Aspidon) must be evaluated and justified on an ongoing basis.
Experience is lacking in bipolar mania in children less than 10 years of age.
Dosing in Patients with Severe Renal or Hepatic Impairment: For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10-15 points on Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in intervals of one week or greater. Risperidone (Aspidon) should be used with caution in this group of patients.
Dose Adjustments for Specific Drug Interactions: When Risperidone (Aspidon) tablets are co-administered with enzyme inducers (e.g., carbamazepine), the dose of Risperidone (Aspidon) tablets should be increased up to double the patient's usual dose. It may be necessary to decrease the Risperidone (Aspidon) tablets dose when enzyme inducers such as carbamazepine are discontinued. Similar effect may be expected with co-administration of Risperidone (Aspidon) tablets with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).
When fluoxetine or paroxetine is co-administered with Risperidone (Aspidon) tablets, the dose of Risperidone (Aspidon) tablets should be reduced. The Risperidone (Aspidon) tablets dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, Risperidone (Aspidon) tablets should be titrated slowly.
It may be necessary to increase the Risperidone (Aspidon) tablets dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued.
Aspidon OS: Risperidone (Aspidon OS) is for oral use. Food does not affect the absorption of Risperidone (Aspidon OS).
Adult patients with schizophrenia may be given Risperidone (Aspidon OS) once daily or twice daily.
Patients should start with 2 mg/day Risperidone (Aspidon OS). The dosage may be increased on the second day to 4 mg.
In elderly patients with schizophrenia and bipolar disorder, a starting dose of 0.5 mg twice daily is recommended. This dosage can be individually adjusted with 0.5 mg twice daily increments to 1 to 2 mg twice daily.
Risperidone (Aspidon OS) is not recommended for use in children below age 18 with schizophrenia and bipolar mania due to a lack of data on efficacy.
Adult patients with bipolar disorder should be administered with Risperidone (Aspidon OS) on a once daily schedule, starting with 2 mg Risperidone (Aspidon OS). Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments of 1 mg per day. Risperidone (Aspidon OS) can be administered in flexible doses over a range of 1 to 6 mg per day to optimize each patient's level of efficacy and tolerability. Daily doses over 6 mg Risperidone (Aspidon OS) have not been investigated in patients with manic episodes.
A starting dose of 0.25 mg twice daily is recommended in patients with Alzheimer's dementia. This dosage can be individually adjusted by increments of 0.25 mg twice daily, not more frequently than every other day, if needed. The optimum dose is 0.5 mg twice daily for most patients. Some patients, however, may benefit from doses up to 1 mg twice daily. Risperidone (Aspidon OS) should not be used more than 6 weeks in patients with persistent aggression in Alzheimer's dementia.
Risperidone (Aspidon OS) is not recommended in children less than 5 years of age, as there is no experience in children less than 5 years of age with this disorder.
Patients with impaired hepatic function have increases in plasma concentration of the free fraction of Risperidone (Aspidon OS). Irrespective of the indication, starting and consecutive dosing should be halved, and dose titration should be slower for patients with renal or hepatic impairment.
Upon discontinuation, gradual withdrawal is advised. Acute withdrawal symptoms, including nausea, vomiting, sweating, and insomnia have very rarely been described after abrupt cessation of high doses of antipsychotic medicines. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported.
Switching from other antipsychotics: When medically appropriate, gradual discontinuation of the previous treatment while risperidone therapy is initiated is recommended. Also, if medically appropriate, when switching patients from depot antipsychotics, initiate risperidone therapy in place of the next scheduled injection. The need for continuing existing anti-Parkinson medicines should be re-evaluated periodically.
During treatment, patients must be evaluated frequently and regularly, and the need for continuing treatment reassessed.

Aspidon 2 mg/Aspidon OS: In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e. drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. In overdose, QT prolongation and convulsions have been reported. Torsade de pointes has been reported in association with combined overdose of risperidone and paroxetine.
In case of acute overdosage, the possibility of multiple drug involvement should be considered.
Treatment: Establish and maintain clear airway and ensure adequate oxygenation and ventilation. Gastric lavage (after intubation, if the patient is unconscious) and administration of activated charcoal together with laxative should be considered. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.
There is no specific antidote to Risperidone. Therefore appropriate supportive measures should be instituted. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids 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.

Aspidon: Risperidone (Aspidon) is contraindicated in patients with a known hypersensitivity to the product.
2 mg: Hypersensitivity reactions including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone.
Aspidon OS: Hypersensitivity to the active substance or to any of the excipients such as Benzoic acid (E210) water, purified.

Aspidon: 1 mg: Risperidone may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients syncope especially during the initial dose titration period, probably reflecting its alpha-adrenergic antagonistic properties. Risperidone should be used with caution in patients with known cardiovascular disease like myocardial infarction, ischaemia, heart-failure or conduction abnormalities, cerebrovascular diseases and conditions which would pre-dispose patients to hypotension like dehydration, hypovolemia and treatment with anti-hypertensive medicine.
2 mg: Neuroleptic Malignant Syndrome (NMS): Antipsychotic drugs including risperidone can cause a potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS). Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase (CPK), myoglobinuria, rhabdomyolysis, and acute renal failure.
The management of NMS should include: immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
If signs and symptoms of tardive dyskinesia appear in a patient treated with risperidone, consider drug discontinuation.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics including risperidone.
Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics, including risperidone, should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including risperidone, should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including risperidone, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including risperidone should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of risperidone.
Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.
Orthostatic Hypotension: Risperidone may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period, probably reflecting its alpha-adrenergic antagonistic properties. Syncope was reported in 0.2% (6/2607) of risperidone-treated patients in Phase 2 and 3 studies in adults with schizophrenia. The risk of orthostatic hypotension and syncope may be minimized by limiting the initial dose to 2 mg total (either once daily or 1 mg twice daily) in normal adults and 0.5 mg twice daily in the elderly and patients with renal or hepatic impairment (see Dosage & Administration). Monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. A dose reduction should be considered if hypotension occurs. Risperidone should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension, e.g., dehydration and hypovolemia. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medication.
Leukopenia, Neutropenia, and Agranulocytosis: Events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including risperidone. Agranulocytosis has also been reported.
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of risperidone should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue risperidone and have their WBC followed until recovery.
Seizures: Risperidone should be used cautiously in patients with a history of seizures.
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's dementia. Risperidone and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
Priapism: Priapism has been reported. Severe priapism may require surgical intervention.
Body Temperature Regulation: Disruption of body temperature regulation has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Caution is advised when prescribing for patients who will be exposed to temperature extremes.
Potential for Cognitive and Motor Impairment: Somnolence was a commonly reported adverse reaction associated with risperidone treatment. Since risperidone has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that risperidone therapy does not affect them adversely.
Aspidon OS: Risperidone (Aspidon OS) should be used with caution in patients with dementia, cerebrovascular disease, orthostatic hypotension, tardive dyskinesia/ extrapyramidal symptoms (TD/EPS), neuroleptic malignant syndrome (NMS), Parkinson's disease and dementia with lewy bodies, hyperglycemia and diabetes mellitus, hyperprolactinaemia, seizures, priapism, intestinal obstruction, Reye's syndrome, brain tumour, renal and hepatic impairment, venous thromboembolism (VTE), lntraoperative Floppy Iris Syndrome.
Use in the Elderly: Aspidon: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Cerebrovascular adverse reactions (e.g. Stroke, transient ischemic attack), including fatalities were reported in patients (mean age 85 years; range 73 - 97) in trials of risperidone in elderly patients with dementia-related psychosis.
Risperidone (Aspidon) is not approved for the treatment of dementia-related psychosis.

Aspidon: 2 mg: Pregnancy: Adequate and well controlled studies with risperidone have not been conducted in pregnant women.
Neonates exposed to antipsychotic drugs (including risperidone) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There was no increase in the incidence of malformations in embryo-fetal studies in rats and rabbits at 0.4-6 times MHRD. Increased pup mortality was noted at all doses in peripostnatal studies in rats. Risperidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clinical Considerations: Fetal/Neonatal Adverse Reactions: Monitor neonates exhibiting extrapyramidal or withdrawal symptoms. Some neonates recover within hours or days without specific treatment; others may require prolonged hospitalization.
There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in neonates following in utero exposure to antipsychotics in the third trimester. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.
Lactation: Risperidone and 9-hydroxyrisperidone are present in human breast milk. Because of the potential for serious adverse reactions in nursing infants from risperidone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Aspidon OS: Before taking the medicine, tell the doctor if the patient is pregnant, trying to become pregnant or breastfeeding. The doctor will decide if the patient can take it. The following symptoms may occur in newborn babies, of mothers that have used Risperidone (Aspidon OS) in the last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If the baby develops any of these symptoms the patient may need to contact the doctor.

Aspidon: 1 mg: Commonly observed adverse effects are: Insomnia, agitation, anxiety and headache.
Less commonly observed effects are: Somnolence, fatigue, dizziness, impaired concentration, constipation, dyspepsia, nausea, abdominal pain, blurred vision, erectile dysfunction, ejaculatory dysfunction, orgasmic dysfunction, rhinitis, rash. In addition to orthostatic hypotension, hypertension has been reported frequently.
The patient must seek medical attention immediately at the first sign of any adverse drug reaction.
2 mg: The most common adverse reactions in clinical trials (>5% and twice placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.
The most common adverse reactions that were associated with discontinuation from clinical trials (causing discontinuation in >1% of adults and/or >2% of pediatrics) were nausea, somnolence, sedation, vomiting, dizziness, and akathisia.
The patient must seek medical attention immediately at the first sign of any adverse drug reaction shall appear.
Aspidon OS: Very common (affects more than 1 user in 10): Parkinsonism which is a medical term that includes many symptoms. Each individual symptom may occur less frequently than in 1 in 10 people. Parkinsonism includes: increase in saliva secretion or watery mouth, musculoskeletal stiffness, drooling, jerks when bending the limbs, slow, reduced or impaired body movements, no expression on the face, muscle tightness, stiff neck, muscle stiffness, small, shuffling, hurried steps and lack of normal arm movements when walking, persistent blinking in response to tapping of the forehead (an abnormal reflex).
Headache, difficult falling or staying asleep.
Common (affects 1 in 10 users in 100): Drowsiness, fatigue, restlessness, inability to sit still, irritability, anxiety, sleepiness, dizziness, poor attention, feeling exhausted, sleep disorder.
Vomiting, diarrhea, constipation, nausea, increased appetite, abdominal pain or discomfort, sore throat, dry mouth.
Weight increased, increase in body temperature, decreased appetite.
Difficulty breathing, lung infection (pneumonia), flu, infection of the breathing passages, blurred vision, nose congestion, nose bleeding, cough.
Urinary tract infection, bed wetting.
Muscle spasm, involuntary movements of face or arms and legs, joint pain, back pain, swelling of arms and legs, pain in arms and legs.
Rash, skin redness.
Fast beating heart, chest pain.
Blood prolactin hormone level increased.
Uncommon (affects 1 to 10 users in 1000): Excessive drinking of water, stool incontinence, thirsty, very hard faeces, hoarseness or voice disorder.
Lung infection caused by inhaling of food into the breathing passages, bladder infection, 'pink eye', sinus infection, viral infection, ear infection, tonsil infection, infection under the skin, eye infection, stomach infection, eye discharge, yeast infection of nails.
Abnormal electrical conduction of the heart, drop in blood pressure after standing, low blood pressure, feeling dizzy after changing body position, abnormal electric activity tracing of the heart (ECG), abnormal heart rhythm, awareness of heart beating, heart rate increased or decreased.
Urinary incontinence, pain when passing urine, frequent passing of urine.
Confused, disturbance in attention, low level of consciousness, excessive sleep, nervousness, elated mood (mania), lack of energy and interest.
Blood sugar increased, liver enzymes increased, white blood cell count decreased, low hemoglobin or red blood cell count (anemia), increase in eosinophils (special white blood cells), blood creatinine phosphokinase increased, decrease in platelets (blood cells that help you stop bleeding).
Muscle weakness, muscle pain, ear pain, neck pain, joint swelling, abnormal posture, joint stiffness, musculoskeletal chest pain, chest discomfort.
Skin lesion, skin disorder, dry skin, intense itching of skin, acne, hair loss, skin inflammation caused by mites, skin discoloration, thickening of skin, flushing, reduced skin sensitivity to pain or touch, inflammation of oily skin.
No menstruation, sexual dysfunction, erectile dysfunction, ejaculation disorder, breast discharge, enlargement of breast in men, decreased sexual drive, irregular menstruation, vaginal discharge.
Fainting, gait disturbance, sluggishness, decreased appetite resulting in malnutrition and low body weight, feeling 'out of sorts', balance disorder, allergy, edema, speech disorder, chills, abnormal coordination.
Painful oversensitivity to light, increased blood flow to the eye, eye swelling, dry eye, increase in tears.
Breathing passage disorder, lung congestion, crackly lung noise, congestion of breathing passages, trouble speaking, difficulty swallowing, cough with sputum, coarse/whistling sound during breathing, flu-like illness, sinus congestion.
Unresponsive to stimuli, loss of consciousness, sudden swelling of lips and eyes along with difficulty breathing, sudden weakness or numbness of the face, arms, or legs, especially on one side, or instances of slurred speech that last for less than 24 hours (these are called mini-strokes or strokes), involuntary movements of face, arms, or legs, ringing in ears, face edema.
Rare (affects 1 to 10 users in 10,000): Inability to reach orgasm, menstrual disorder.
Dandruff.
Drug allergy, coldness in arms and legs, lip swelling, lip inflammation.
Glaucoma, reduced visual clarity, eyelid margin crusting, eye rolling.
Lack of emotion.
Change in consciousness with increased body temperature and twitching of muscles, edema all over the body, drug withdrawal syndrome, body temperature decreased.
Fast shallow breathing, trouble breathing during sleep, chronic otitis media (ear infection).
Obstruction of intestine.
Reduced blood flow to the brain.
Decrease in white blood cells, inappropriate secretion of a hormone that controls urine volume.
Breakdown of muscle fibers and pain in muscles (rhabdomyolysis), movement disorder.
Coma due to uncontrolled diabetes.
Yellowing of the skin and the eyes (jaundice).
Inflammation of the pancreas.
Very rare (affects less than 1 user in 10,000): Life threatening complications of uncontrolled diabetes.
Unknown frequency of occurrence (frequency cannot be estimated from the available data): Severe allergic reaction resulting in difficulty in breathing and shock.
No granulocytes (a type of white blood cell to help you against infection).
Prolonged and painful erection.
Dangerously excessive intake of water.
Blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If the patient notices any of these symptoms seek medical advice immediately.

Aspidon: 2 mg: Pharmacokinetic-related Interactions: The dose of risperidone should be adjusted when used in combination with CYP2D6 enzyme inhibitors (e.g., fluoxetine, and paroxetine) and enzyme inducers (e.g., carbamazepine). Dose adjustment is not recommended for risperidone when co-administered with ranitidine, cimetidine, amitriptyline, or erythromycin.
Effect of Risperidone on other drugs: Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium, valproate, digoxin or topiramate.
Pharmacodynamic-related Interactions: Centrally-Acting Drugs and Alcohol: Given the primary CNS effects of risperidone, caution should be used when risperidone is taken in combination with other centrally-acting drugs and alcohol.
Drugs with Hypotensive Effects: Because of its potential for inducing hypotension, risperidone may enhance the hypotensive effects of other therapeutic agents with this potential.
Levodopa and Dopamine Agonists: Risperidone may antagonize the effects of levodopa and dopamine agonists.
Clozapine: Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
Aspidon OS: As with other antipsychotics, caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval, e.g., class Ia antiarrhythmics (e.g., quinidine, dysopiramide, procainamide), class III antiarrhythmics (e.g., amiodarone, sotalol), tricyclic antidepressant (i.e., amitriptyline), tetracyclic antidepressants (i.e., maprotiline), some antihistaminics, other antipsychotics, some antimalarials (i.e., quinine and mefloquine), and with medicines causing electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone.

Aspidon: Store at temperatures not exceeding 30°C.
Aspidon OS: Store below 30°C.

Antipsychotics

N05AX08 - risperidone ; Belongs to the class of other antipsychotics.

Rx