Risponz/Risponz 1/Risponz 2/Risponz 3

Risponz 1/Risponz 2/Risponz 3: Each film‑coated tablet contains: Risperidone (Risponz 1) 1 mg.
Risperidone (Risponz 2) 2 mg.
Risperidone (Risponz 3) 3 mg.
Risperidone tablet contains Risperidone as an active ingredient which is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives.
The chemical designation is 3‑[2‑[4-(6‑benzisoxazol‑3‑yl)‑1‑piperidinyl]ethyl‑6,7,8,9‑tetrahydro-2‑methyl‑4H‑pyrido(1,2‑a)Pyrimidin‑4-one. Its molecular formula is C₂₂H₂₇FN₄O₂ and its molecular weight is 410.49.
Risperidone is a white to slightly beige powder. It is practically insoluble in water, freely soluble in methylene chloride, and soluble in methanol and 0.1 N HCl.
Risponz: Each mL contains: Risperidone, USP 1 mg.
Risperidone is a clear, colorless solution. Risperidone is a benzisoxazole atypical antipsychotic, reported to be an antagonist at dopamine D2, serotonin (5-HT2), adrenergic (α1 and α2), and histamine (H1) receptors. It is described as an atypical antipsychotic.

Antipsychotic.
Pharmacology: Pharmacodynamics: Risponz 1/Risponz 2/Risponz 3: Risperidone (Risponz) is an antipsychotic of the benzisoxazole derivatives. It is a selective monoaminergic antagonist. Risperidone (Risponz) has affinity for serotonin‑5‑HT2, dopamine‑D2, H1‑histaminic, alpha 1 and alpha 2‑adrenergic receptors. Risperidone (Risponz) has no affinity for cholinergic receptors. It is a potent D2‑antagonist.
Pharmacokinetics: Risponz 1/Risponz 2/Risponz 3: Risperidone (Risponz) is completely absorbed after oral administration. Peak plasma concentrations are attained within 1 to 2 hours. Food does not affect the absorption of Risperidone.
Risperidone is metabolized by cytochrome P‑450 11D6 to 9‑hydroxy‑Risperidone which has a similar pharmacological activity to Risperidone. Risperidone and 9‑hydroxy‑risperidone form the active antipsychotic fraction.
After oral administration to psychotic patients, Risperidone's half‑life is about 3 hours. The elimination half‑life of 9‑hydroxy‑risperidone and the active antipsychotic fraction is 24 hours.
Following 6 mg or 8 mg once daily, peak levels of the active moiety were about 30% higher and trough levels about 30% lower than the peaks and troughs following 3 and 4 mg twice daily.
Steady state is reached within 1 day for Risperidone (Risponz) in most patients and 4‑5 days for 9‑hydroxyrisperidone. Risperidone plasma concentration is dose-proportional within the therapeutic dose‑range. Risperidone (Risponz) is bound to albumin and alpha1‑acid glycoprotein. Plasma protein binding of Risperidone is 88% and 77% for 9‑hydroxy‑risperidone. One week after administration, 70% of the dose is excreted in the urine and 14% in the faeces. In urine, Risperidone and 9‑hydroxy‑risperidone represent 35‑45% of the dose. Risperidone (Risponz) showed higher active plasma concentrations and slower elimination in the elderly and in patients with renal insufficiency. The plasma concentrations of Risperidone (Risponz) were normal in patients with liver insufficiency.
The pharmacokinetics of Risperidone, 9‑hydroxy‑risperidone and the active moiety in children are similar to those in adults.
Risponz: Risperidone is readily absorbed after oral doses, peak plasma concentrations being reached within 1 to 2 hours. It is extensively metabolised in the liver by hydroxylation to its main active metabolite, 9-hydroxyrisperidone; oxidative N-dealkylation is a minor metabolic pathway. Hydroxylation is mediated by the cytochrome P450 isoenzyme CYP2D6 and is the subject of genetic polymorphism. Excretion is mainly in the urine and, to a lesser extent, in the faeces. Risperidone and 9-hydroxyrisperidone are about 90% and 77% bound to plasma proteins, respectively.

Risponz 1/Risponz 2/Risponz 3: For the treatment of schizophrenia and other psychoses and in the short‑term treatment of acute manic or mixed episodes associated with bipolar disorder, and for the treatment of irritability associated with autistic disorder.
Risponz: For the treatment of schizophrenia.
For the treatment of moderate to severe manic episodes associated with bipolar disorder.
For the short-term symptomatic treatment (up to six weeks) of persistent aggression in conduct disorder in children from the age of five years and adolescents with sub-average intellectual functioning or mental retardation diagnosed according to DSM-IV criteria, in whom the severity of aggressive or other disruptive behaviors require pharmacological treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment program, including psychosocial and educational intervention. It is recommended that risperidone 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.

Risponz 1/Risponz 2/Risponz 3: Risperidone (Risponz) is a benzisoxazole antipsychotic reported to be an antagonist at dopamine D2 and serotonin (5‑HT2), adrenergic (α1 and α2), and histamine (H1) receptors. It is described as an atypical antipsychotic. It is given by mouth for the treatment of schizophrenia and other psychoses.
Risperidone (Risponz) may be given in 1 or 2 divided doses daily. The usual initial daily dose of Risperidone (Risponz) is 2 mg on the first day, 4 mg on second day and 6 mg on the third day. Further dosage adjustment may be needed and should generally be made at interval of not less than one week; usual maintenance doses are 4 to 8 mg daily. Extra pyramidal symptoms may be more likely with doses above 10 mg daily. The maximum recommended dose is 16 mg daily.
An initial dose of 0.5 mg twice daily slowly increased in steps of 0.5 mg twice daily to a dose of 1 to 2 mg twice daily suggested for the elderly and for patient with renal or hepatic impairment.
Schizophrenia꞉ The use of Risperidone (Risponz) for the management of schizophrenia has been reviewed. Features for which Risperidone (Risponz) has been promoted have included a relatively low incidence of extra pyramidal effect and efficacy against both positive and negative symptoms of schizophrenia. Most studies have compared Risperidone with haloperidol but, of these, some of the major studies have been criticized for potential methodological flaws and it is difficult to determine any difference in efficacy including effect on negative symptoms. The production of extra pyramidal effects appears to be dose dependent Risperidone (Risponz). Overall the incidence for Risperidone (Risponz) appears to be similar to that for placebo but at doses of more than 10 mg it appears to approach that associated with haloperidol. In the few comparative studies with other atypical antipsychotics Risperidone (Risponz) has appeared to be of similar efficacy to clozapine.
Dementia꞉ Risperidone (Risponz) has been used for the management of behavioural disturbances in patients with dementia. Although there have been anecdotal reports of efficacy in patient with Lewy body dementia other reports suggest that these patients are likely to be just as sensitive to Risperidone (Risponz) as to standard antipsychotic.
Risponz: Schizophrenia: Adults: Risperidone Oral Solution may be given once or twice daily. Patients should start with 2 mg/day risperidone. The dosage may be increased on the second day to 4 mg. Subsequently the dosage can be maintained unchanged, or further individualized, if needed. Most patients will benefit from daily doses between 4 and 8 mg. In some patients, a slower titration phase and a lower starting and maintenance dose may be appropriate. Doses above 10 mg/day have not demonstrated superior efficacy to lower doses and may cause increased incidence of extrapyramidal symptoms. Safety of doses above 16 mg/day has not been evaluated and are therefore not recommended.
Elderly: 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.
Pediatric population: Risperidone is not recommended for the use in children below age 18 with schizophrenia due to a lack of data on efficacy.
Manic episodes in bipolar disorder: Adults: Risperidone should be administered on a once daily schedule, starting with 2 mg risperidone. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments of 1 mg per day. Risperidone 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 have not been investigated in patients with manic episodes. As with all symptomatic treatments, the continued use of risperidone must be evaluated and justified on an on-going basis.
Elderly: 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. Since clinical experience in elderly is limited, caution should be exercised.
Pediatric population: Risperidone is not recommended for use in children below age 18 with bipolar mania due to a lack of data on efficacy.
Persistent aggression in patients with moderate to severe Alzheimer's dementia: A starting dose of 0.25 mg twice daily is recommended. 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 should not be used for more than 6 weeks in patients with persistent aggression in Alzheimer's dementia. During treatment, patients must be evaluated frequently and regularly, and the need for continuing treatment reassessed.
Conduct disorder: Children and adolescents from 5 to 18 years of age: For subjects ≥50 kg, a starting dose of 0.5 mg once daily is recommended. This dosage can be individually adjusted by increments 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 0.5 mg once daily while others may require 1.5 mg once daily. For subjects <50 kg, 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, however, 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 risperidone must be evaluated and justified on an ongoing basis.
Risperidone 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.
Renal and hepatic impairment: Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than in adults with normal renal functions. Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone.
Irrespective of the indication, starting and consecutive dosing should be halved, and dose titration should be slower for patients with renal or hepatic impairment.
Risperidone should be used with caution in these groups of patients.
Method of administration: Risperidone is for oral use. Food does affect the absorption of risperidone.
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 next scheduled injection. The need for continuing existing anti-Parkinson medicines should be re-evaluated periodically.

Risponz 1/Risponz 2/Risponz 3: Reported signs and symptoms have been those resulting from an exaggeration of the medicines known pharmacological effects. Symptoms of acute overdosage include drowsiness, sedation, hypotension tachycardia and extra pyramidal symptoms. In overdose, rare cases of QT‑prolongation have been reported.
In the case of acute overdosage, the possibility of multiple medicine involvement should be considered.

Risponz 1/Risponz 2/Risponz 3: Risperidone (Risponz) is contra‑indicated in patients with known sensitivity to the medicine. Safety of Risperidone (Risponz) in pregnancy or lactating women has not been established. Risperidone (Risponz) and 9‑hydroxy‑risperidone are excreted in human breast milk. Therefore, women receiving Risperidone (Risponz) should not breastfeed.
Conduct and other disruptive behavioural disorders children꞉ Not for children under 5 years as efficacy and safety in children under the age of 5 years have not been demonstrated.
Risponz: Hypersensitivity to the active substance or to any of the excipients.

Risponz 1/Risponz 2/Risponz 3: Risperidone (Risponz) may impair mental alertness. Therefore patients should be advised not to drive or operate machinery until their individual susceptibility is known.
It is recommended to have both the starting dose and the subsequent dose increments in geriatric patients and patients with renal or liver insufficiency.
Due to the alpha‑blocking activity of Risperidone (Risponz), (orthostatic) hypotension can occur, especially during the initial dose-titration period. Risperidone (Risponz) should be used with caution in patients with known cardiovascular disease, and the dosage should be gradually titrated as recommended. A dose reduction should be considered if hypotension occurs.
Caution should be used when prescribing Risperidone (Risponz) to patients with Parkinson disease since, theoretically, it might cause a deterioration of the disease.
Patients may be advised to refrain from excessive eating in view of the possibility of weight gain.
Risponz: Risperidone is not licensed for the treatment of dementia-related behavioral disturbances.
Concomitant use with furosemide: Caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be carefully avoided in elderly patients with dementia.
Cerebrovascular Adverse Events (CVAE): The risk of CVAEs was significantly higher in patients with mixed or vascular type of dementia when compared to Alzheimer's dementia. Therefore, patients with other types of dementias than Alzheimer's should not be treated with risperidone.
Physicians are advised to assess the risks and benefits of the use of risperidone in elderly patients with dementia, taking into account risk predictors for stroke in the individual patient. Patients/caregivers should be cautioned to immediately report signs and symptoms of potential CVAEs such as sudden weakness or numbness in the face, arms or legs, and speech or vision problems. All treatment options should be considered without delay, including discontinuation of risperidone.
Risperidone should only be used short term for persistent aggression in patients with moderate to severe Alzheimer's dementia to supplement non-pharmacological approaches which have limited or no efficacy and when there is potential risk of harm to self or others.
Patients should be reassessed regularly, and the need for continuing treatment reassessed.
Orthostatic hypotension: Due to the alpha-blocking activity of risperidone, (orthostatic) hypotension can occur, especially during the initial dose-titration period. Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment. Risperidone should be used with caution in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolemia, or cerebrovascular disease), and the dosage should be gradually titrated as recommended. A dose reduction should be considered if hypotension occurs.
Tardive Dyskinesia/Extrapyramidal Symptoms (TD/EPS): Medicines with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia, characterized by rhythmical involuntary movements, predominantly of the tongue and/or face. The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all antipsychotic drugs should be considered.
Neuroleptic Malignant Syndrome (NMS): Neuroleptic Malignant Syndrome, characterized by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels has been reported to occur with antipsychotics. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. In this event all antipsychotic drugs, including risperidone, should be discontinued.
Parkinson's disease and dementia with Lewy bodies: Physicians should weigh the risks versus the benefits when prescribing antipsychotics, including risperidone, to patients with Parkinson's disease or Dementia with Lewy Bodies (DLB). Parkinson's disease may worsen with risperidone. Both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotic medicinal products; these patients were excluded from clinical trials. Manifestation of this increased sensitivity can include confusion, obtundation, and postural instability with frequent falls, in addition to extrapyramidal symptoms.
Hyperglycemia: Hyperglycemia or exacerbation of pre-existing diabetes has been reported in very rare cases during treatment with risperidone. Appropriate clinical monitoring is advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus.
Hyperprolactinemia: Tissue culture studies suggest that cell in human breast tumors may be stimulated by prolactin. Although no clear association with the administration of antipsychotics has so far been demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant medical history. Risperidone should be used with caution in patients with pre-existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.
QT prolongation: QT prolongation has very rarely been reported post-marketing. As with other antipsychotics, caution should be exercised when risperidone is prescribed in patients with known cardiovascular disease, family history of QT prolongation, bradycardia, or electrolyte disturbances (hypokalemia, hypomagnesemia), as it may increase the risk of arrhythmogenic effects, and in concomitant use with medicines known to prolong the QT interval.
Seizures: Risperidone should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Priapism: Priapism may occur with risperidone treatment due to its alpha-adrenergic blocking effects.
Body temperature regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic medicines. Appropriate care is advised when prescribing risperidone to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant treatment with anticholinergic activity, or being subject to dehydration.
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Risperidone and preventive measures undertaken.
Use in Children: Children and adolescents: Before risperidone is prescribed to a child or adolescent with conduct disorder they should be fully assessed for physical and social causes of the aggressive behavior such as pain or inappropriate environment demands.
The sedative effect of risperidone should be closely monitored in this population because of possible consequences on learning ability. A change in the time of administration of risperidone could improve the impact of the sedation on attention faculties of children and adolescents.
Risperidone was associated with mean increases in body weight and body mass index (BMI). Changes in height in the long-term open-label extension studies were within expected age-appropriate norms. The effect of long-term risperidone treatment on sexual maturation and height has not been adequately studied.
Because of the potential effects of prolonged hyperprolactinaemia on growth and sexual maturation in children and adolescents, regular clinical evaluation of endocrinological status should be considered, including measurements of height, weight, sexual maturation, monitoring of menstrual functioning, and other potential prolactin-related effects.
During treatment with risperidone regular examination for extrapyramidal symptoms and other movement disorders should also be conducted.

Risponz: Pregnancy: There are no adequate data from the use of risperidone in pregnant women. According to post-marketing data reversible extrapyramidal symptoms in the neonate were observed following the use of risperidone during the last trimester of pregnancy. Consequently newborns should be monitored carefully.
Risperidone was not teratogenic in animal studies but other types of reproductive toxicity were seen. The potential risk for humans is unknown. Therefore, risperidone should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly.
Lactation: In animal studies, risperidone and 9-hydroxyrisperidone are excreted in the milk. It has been demonstrated that risperidone and 9-hydroxyrisperidone are also excreted in human breast milk in small quantities. There are no data available on adverse reactions in breast-feeding infants. Therefore, the advantage of breast-feeding should be weighed against the potential risks for the child.

Risponz 1/Risponz 2/Risponz 3: In some instances it has been difficult to differentiate adverse events from symptoms of the underlying psychosis. The most frequent side-effects observed with Risperidone (Risponz) are꞉ insomnia, agitation, extra pyramidal disorder, anxiety headache. Sedation has been reported more frequently in children and adolescents than in adults.
Less commonly observed are꞉ somnolence, fatigue, dizziness, impaired concentration, constipation, dyspepsia. Nausea, vomiting, abdominal pain, weight gain, blurred vision, priapism, erectile dysfunction, ejaculatory dysfunction. orgastic dysfunction, urinary incontinence, rhinitis, rash and other reactions have been observed.
The following dose dependent extra pyramidal symptoms have been observed꞉ tremor, rigidity, hypersalivation, bradykinesia, oculogyric crisis, akathisia (hyperkinesia) and acute dystonia, hypokinesia. These are usually mild and reversible upon dose reduction and/or administration of anti‑Parkinson medication, if necessary.
Tardive dyskinesia (TD), a syndrome consisting of potentially irreversible, involuntary dyskinetic movements may develop in patients treated with conventional neuroleptics. Although this syndrome of TD appears to be most prevalent in the elderly especially elderly females, it is impossible to predict at the onset of treatment which patients are likely to develop TD.
It has been suggested that the occurrence of Parkinsonian side‑effects is a predictor for the development of TD. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of the antipsychotic administered to the patient increase, however, the syndrome can develop, although less commonly, after relatively brief periods of treatment at low doses. There is no known treatment for an established case of TD. The syndrome may remit partially or completely if the antipsychotic medicine treatment is withdrawn.
The antipsychotic drug treatment itself however, may suppress the signs and symptoms of TD, thereby masking the underlying process. The effect of symptom suppression upon the long‑term course of TD is unknown. In view of these considerations, Risperidone (Risponz) should be prescribed in a manner that is most likely to minimize the risk of TD. As with any antipsychotic medicine, Risperidone (Risponz) should be reserved for patients who appear to be obtaining substantial benefit from the medicine. In such patients the smallest dose and the shortest duration of treatment should be sought. The benefit for continued treatment should be reassessed periodically. If signs and symptoms of TD appear in a patient on antipsychotics, medicine discontinuation should be considered. However, some patients may require treatment despite the presence of this syndrome.
Neuroleptic Malignant Syndrome (NMS) is a potentially fatal symptom complex that has been reported in association with antipsychotic medicines, including Risperidone (Risponz). Clinical manifestations of NMS are hyperthermia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, cardiac arrhythmias and diaphoresis). Additional signs may include elevated creatine phosphokinase (CPK) levels, myoglobinuria (rhabdomyolysis), and acute renal failure.
In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illnesses (e.g. pneumonia, systemic infection, etc.) and untreated or inadequately treated extra pyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, medicine fever and primary central nervous system pathology.
The management of NMS should include: Immediate discontinuation of all antipsychotic medicines 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 medicine treatment after recovery from NMS, the potential reintroduction of medicine therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
Classical neuroleptics are known to lower the seizure threshold. Seizures have been reported alter treatment with Risperidone (Risponz). Caution is recommended when treating patients with epilepsy.
(Orthostatic) hypotension and (reflex) tachycardia or hypertensions have been observed. A mild fall in neutrophil and/or thrombocytes count has been reported.
Risperidone (Risponz) can induce a dose‑dependent increase in plasma prolactin concentration. Possible associated manifestations are꞉ galactorrhoea. gynaecomastia, disturbances of the menstrual cycle and amenorrhoea. Premenopausal women who develop secondary amenorrhea of greater than six months duration should receive appropriate preventative therapy to avoid hypo oestrogenic bone loss.
Cerebrovascular accidents have been observed during treatment with Risperidone (Risponz).
Water intoxication, either due to polydipsia or the syndrome of inappropriate secretion of the antidiuretic hormone (SlADH), and body temperature dysregulation, have been reported.
Risponz: Anxiety, dizziness, dystonic reactions, extrapyramidal reactions, headache, neuroleptic malignant syndrome, tardive dyskinesia; abnormal t-waves with prolonged ventricular repolarization, arrhythmias, orthostatic hypotension, amenorrhea, galactorrhea, gynecomastia, sexual dysfunction; weight gain, constipation, nausea, cholestatic jaundice, agranulocytosis, overflow incontinence, priapism, urinary retention, altered temperature regulation.

Risponz 1/Risponz 2/Risponz 3: The risk of using Risperidone (Risponz) in combination with other medicines has not been systematically evaluated. Risperidone (Risponz) should be used with caution in combination with alcohol and other centrally acting medicines. It 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 (Risponz). Similar effects may be observed with other hepatic enzyme inducers. On discontinuation of carbamazepine or other hepatic enzyme inducers the dosage of Risperidone (Risponz) should be re‑evaluated and, if necessary, decreased. Fluoxetine may increase the plasma concentration of Risperidone but less so of the anti‑psychotic fraction.
Phenothiazines, tricyclic antidepressants and some beta‑blockers may increase the plasma concentration of Risperidone but not that of the antipsychotic fraction.
When Risperidone (Risponz) is taken together with other highly protein‑bound medicines (e.g. diazepam, warfarin, digitoxin, imipramine and propranolol), there is no clinically relevant displacement of either agent from the plasma proteins.
Risponz: 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, disopyramide, 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., chinice and mefloquine), and with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.
Potential for risperidone to affect other medicinal products: Risperidone should be used with caution in combination with other centrally-acting substances notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.
Risperidone may antagonize the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each treatment should be prescribed.
Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment.
Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium, valproate, digoxin or topiramate.
Potential for other medicinal products to affect risperidone: Carbamazepine has been shown to decrease the plasma concentrations of the active antipsychotic fraction of risperidone. Similar effects may be observed with e.g. rifampicin, phenytoin and phenobarbital which also induce CYP3A4 hepatic enzyme as well as P-glycoprotein. When carbamazepine or other CYP3A4 hepatic enzyme/P-glycoprotein (P-gp) inducers are initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
Fluoxetine and paroxetine, CYP2D6 inhibitors, increase the plasma concentration of risperidone, but less so of the active antipsychotic fraction. It is expected that other CYP2D6 inhibitors, such as quinidine, may affect the plasma concentrations of risperidone in a similar way. When concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
Verapamil, an inhibitor of CYP3A4 and P-gp, increases the plasma concentration of risperidone.
Galantamine and donepezil do not show a clinically relevant effect on the pharmacokinetics of risperidone and on the active antipsychotic fraction.
Phenothiazines, tricyclic antidepressants, and some beta-blockers may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction. Cimetidine and ranitidine increase the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction.
Erythromycin, a CYP3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.
The combined use of psychostimulants (e.g methylphenidate) with risperidone in children and adolescents did not alter the pharmacokinetics and efficacy of risperidone.
Regarding increased mortality in elderly patients with dementia concomitantly receiving furosemide.
Concomitant use of oral risperidone with paliperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of two may lead to additive active antipsychotic fraction exposure.

Store at temperatures not exceeding 30°C.

Antipsychotics

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

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