Risperdal Consta 25mg. 37.5mg. 50mg Injection

RISPERDAL CONSTA is indicated for the treatment of acute and chronic schizophrenia. RISPERDAL CONSTA is also indicated as monotherapy or adjunctive therapy for the maintenance treatment to prevent the recurrence of manic episodes of bipolar I disorder in patients who have previously responded to oral antipsychotics or other anti-manic treatments.

For risperidone naive patients, it is recommended to establish tolerability with oral risperidone prior to initiating treatment with RISPERDAL CONSTA. When starting RISPERDAL CONSTA, the patient must receive an oral antipsychotic medicine simultaneously for at least three weeks, as therapeutic concentrations of RISPERDAL CONSTA are only reached after a three week period. RISPERDAL CONSTA should be administered every two weeks by deep intramuscular deltoid or gluteal injection using the enclosed safety needle. For deltoid administration, use the 2,5 cm needle alternating injections between the two arms. For gluteal administration, use the 5,08 cm needle alternating injections between the two buttocks. Do not administer intravenously (see WARNINGS and SPECIAL PRECAUTIONS and Instructions for use and handling).

Adults (older than 18 years of age) The recommended dose is 25 mg intramuscular every two weeks. Some patients may benefit from the higher doses of 37,5 mg or 50 mg. No additional benefit was observed with 75 mg in clinical trials in patients with schizophrenia. Doses above 50 mg were not studied in patients with bipolar disorder. Sufficient antipychotic coverage should be ensured during the three-week lag period following the first RISPERDAL CONSTA injection. Doses higher than 50 mg every 2 weeks are not recommended. Upward dosage adjustment should not be made more frequently than every 4 weeks. The effect of this dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose.

Special populations Paediatric (18 years of age and younger) RISPERDAL CONSTA has not been studied in children younger than 18 years. Elderly (65 years of age and older) The recommended dose is 25 mg intramuscular every two weeks. Sufficient antipsychotic coverage should be ensured during the three-week lag period following the first RISPERDAL CONSTA injection. Renal and hepatic impairment RISPERDAL CONSTA has not been studied in hepatically and renally impaired patients. If hepatically or renally impaired patients require treatment with RISPERDAL CONSTA, a starting dose of 0,5 mg twice daily oral risperidone is recommended during the first week. The second week 1 mg, twice daily or 2 mg once daily can be given. If an oral total daily dose of at least 2 mg is well tolerated, an injection of 25 mg RISPERDAL CONSTA can be administered every 2 weeks.

RISPERDAL CONSTA is contraindicated in patients with known hypersensitivity to risperidone or any of the components. Not for children under 18 years as efficacy and safety in children under the age of 18 years have not been studied. Hepatic and renal impairment RISPERDAL CONSTA has not been studied in hepatically and renally impaired patients. Parkinsonu2019s disease and Lewy body dementia (see WARNINGS and SPECIAL PRECAUTIONS)

For risperidone naive patients, it is recommended to establish tolerability with oral risperidone prior to initiating treatment with RISPERDAL CONSTA. Elderly Patients with Dementia Overall Mortality Elderly patients with dementia treated with atypical antipsychotic medicines have an increased mortality compared to placebo in a meta-analysis of 17 controlled trials of atypical antipsychotic medicines, including risperidone. In placebo-controlled trials with oral risperidone in this population, the incidence of mortality was 4,0 % for risperidone-treated patients compared to 3,1 % for placebo-treated patients. The mean age (range) of patients who died was 86 years (range 67-100).

Concomitant use with Furosemide In the oral RISPERDAL placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7,3 %; mean age 89 years, range 75-97) when compared to patients treated with risperidone alone (3,1 %; mean age 84 years, range 70-96) or furosemide alone (4,1 %; mean age 80 years, range 67-90). The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant medication 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 (CAE) In placebo-controlled trials in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse events, (cerebrovascular accidents and transient ischemic attacks), including fatalities, in patients treated with oral risperidone compared to patients receiving placebo (mean age 85 years; range 73-97).

Orthostatic Hypotension Due to the alpha-blocking activity of RISPERDAL CONSTA, (orthostatic) hypotension can occur, especially during the initial dose-titration period. (See INTERACTIONS). RISPERDAL CONSTA 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.

Leukopaenia, Neutropaenia, and Agranulocytosis Events of leukopaenia, neutropaenia and agranulocytosis have been reported with RISPERDAL CONSTA. Agranulocytosis has been reported during postmarketing surveillance. Patients with a history of a clinically significant low white blood cell count (WBC) or a medicine-induced leukopaenia/neutropaenia should be monitored during therapy and discontinuation of RISPERDAL CONSTA 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 neutropaenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with significant neutropaenia (absolute neutrophil count < 1 X 10 9 / l) should discontinue RISPERDAL CONSTA and have their WBC followed until recovery.

Venous thromboembolism Cases of venous thromboembolism (VTE) have been reported with RISPERDAL CONSTA. 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 RISPERDAL CONSTA and preventive measures undertaken.

Tardive Dyskinesia/Extrapyramidal Symptoms (TD/EPS) RISPERDAL CONSTA has been associated with the induction of tardive dyskinesia (TD) characterised by potentially irreversible rhythmical involuntary movements, predominantly of the tongue and/or face. It has been reported that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Tardive dyskinesia appears to be more prominent in the elderly especially elderly females. RISPERDAL CONSTA has a potential to induce extrapyramidal symptoms. If signs and symptoms of tardive dyskinesia appear, the discontinuation of RISPERDAL CONSTA should be considered.

Extrapyramidal symptoms and psychostimulants u2013 Caution is warranted in patients receiving both psychostimulants (e.g. methylphenidate) and risperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both medications. Gradual withdrawal of one or both treatments should be considered (See INTERACTIONS).

Neuroleptic Malignant Syndrome (NMS) Neuroleptic Malignant Syndrome is a potentially fatal symptom complex, characterised 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 medicines, including RISPERDAL CONSTA, should be discontinued. After the last administration of RISPERDAL CONSTA, plasma levels of risperidone are present for up to (a minimum) of 6 weeks.

Parkinsonu2019s disease/ Lewy body dementia and NMS Patients with Parkinsonu2019s Disease or Dementia with Lewy bodies (DLB) have an increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotic medications.(see CONTRAINDICATIONS). Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms. In addition, in clinical trials, elderly patients have a higher mortality than placebo-treated patients (see CONTRAINDICATIONS).

Hypersensitivity reactions Although tolerability with oral risperidone should be established prior to initiating treatment with RISPERDAL CONSTA, very rare cases of anaphylactic reaction has been reported during postmarketing experience in patients who have previously tolerated oral risperidone (see DOSAGE AND DIRECTIONS FOR USE and SIDE EFFECTS). If hypersensitivity reactions occur, discontinue use of RIPSERDAL CONSTA, initiate general supportive measures as clinically appropriate and monitor the patient until signs and symptoms resolve. (see CONTRAINDICATIONS and SIDE EFFECTS)

Hyperglycaemia and diabetes mellitus Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with RISPERDAL CONSTA. Patients with an established diagnosis of diabetes mellitus who are started on RISPERDAL CONSTA 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 RISPERDAL CONSTA should be monitored for symptoms of hyperglycaemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycaemia during treatment with RISPERDAL CONSTA should undergo fasting blood glucose testing. In some cases, hyperglycaemia has resolved when RISPERDAL CONSTA was discontinued: however, some patients required continuation of anti-diabetic treatment despite discontinuation of RISPERDAL CONSTA.

Weight gain Significant weight gain has been reported. Monitoring weight gain is advisable when RISPERDAL CONSTA is being used. Patients may be advised to refrain from overeating in view of the possibility of weight gain.

QT Interval Caution should be exercised when RISPERDAL CONSTA is prescribed in patients with a history of cardiac dysrhythmias, in patients with congenital long QT syndrome, and in concomitant use with medicines known to prolong the QT interval.

Priapism Medicines with alpha-adrenergic blocking effects have been reported to induce priapism. Priapism has been reported with risperidone during postmarketing surveillance (see SIDE EFFECTS).

Body Temperature Regulation Disruption of the bodyu2019s ability to reduce core body temperature may occur. Appropriate care is advised when prescribing RISPERDAL CONSTA 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 medication with anticholinergic activity, or being subject to dehydration.

Antiemetic Effect An antiemetic effect was observed in preclinical studies with risperidone. This effect, if it occurs in humans, may mask the signs and symptoms of overdosage with certain medicines or of conditions such as intestinal obstruction, Reyeu2019s syndrome, and brain tumour.

Seizures RISPERDAL CONSTA should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Intraoperative Floppy Iris Syndrome Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients treated with medicines with alpha1a-adrenergic antagonist effect, including RISPERDAL CONSTA. IFIS may increase the risk of eye complications during and after the operation. Current or past use of RISPERDAL CONSTA should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping RISPERDAL CONSTA prior to cataract surgery has not been established and must be weighed against the risk of stopping RISPERDAL CONSTA therapy.

Administration Care must be taken to avoid inadvertent injection of RISPERDAL CONSTA into a blood vessel.

The risk of using RISPERDAL CONSTA in combination with other medicines has not been systematically evaluated. Centrally-Acting Medicines and Alcohol Given the primary CNS depressive effect of RISPERDAL CONSTA, it should be used with caution in combination with other centrally acting medicines or alcohol. Levodopa and Dopamine Agonists RISPERDAL CONSTA may antagonise the effect of levodopa and other dopamine agonists. Psychostimulants The combined use of psychostimulants (e.g. methylphenidate) with risperidone can lead to the emergence of extrapyramidal symptoms upon change of either or both treatments. (See WARNINGS and SPECIAL PRECAUTIONS) Medicines with Hypotensive Effects Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment (see WARNINGS and SPECIAL PRECAUTIONS). Medicines known to prolong the QT interval Caution is advised when prescribing RISPERDAL CONSTA with medicines known to prolong the QT interval. Pharmacokinetic-related Interactions Risperidone is mainly metabolised through CYP2D6, and to a lesser extent through CYP3A4. Both risperidone and its active metabolite 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics of the risperidone active antipsychotic fraction.

Strong CYP2D6 Inhibitors Co-administration of RISPERDAL CONSTA with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active antipsychotic fraction. Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active antipsychotic fraction (e.g., paroxetine, see below). When concomitant paroxetine or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL CONSTA.

CYP3A4 and/or P-gp Inhibitors When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the medical practitioner should re-evaluate the dosing of RISPERDAL CONSTA.

CYP3A4 and/or P-gp Inducers When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the medical practitioner should re-evaluate the dosing of RISPERDAL CONSTA.

Highly Protein-bound Medicines When RISPERDAL CONSTA 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.

Examples Examples of medicines that potentially interact or that were shown not to interact with RISPERDAL CONSTA are listed below: Antibacterials: Erythromycin, a moderate CYP3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction. Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma concentrations of the active antipsychotic fraction. Anticholinesterases: Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction. Antiepileptics: Carbamazepine, a strong CYP3A4 inducer and P-gp inducer, has been shown to decrease the plasma levels of the active antipsychotic fraction of risperidone. Topiramate modestly reduced the bioavailability of risperidone, but not that of the active antipsychotic fraction. Therefore, this interaction is unlikely to be of clinical significance. RISPERDAL CONSTA does not show a clinically relevant effect on the pharmacokinetics of valproate or topiramate. Antifungals: Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of the active antipsychotic fraction, by about 70 % at risperidone doses of 2 to 8 mg/day. Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxyrisperidone. Antipsychotics: Phenothiazines, may increase the plasma concentration of risperidone but not those of the active antipsychotic fraction. Apriprazole, a CYP2D6 and CYP3A4 substrate: Risperidone tablets or injections did not affect the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.

Pregnancy The safety of RISPERDAL CONSTA for use in human pregnancy has not been established. A retrospective observational cohort study based on a US claims database compared the risk of congenital malformations for live births among women with and without antipsychotic use during the first trimester of pregnancy. The risk of congenital malformations with risperidone, after adjusting for confounder variables available in the database, was elevated compared to no antipsychotic exposure (relative risk = 1,26, 95 % Cl: 1,02-1,56). No biological mechanism has been identified to explain these findings and teratogenic effects have not been observed in non-clinical studies. Based on the findings of this single observational study, a causal relationship between in utero exposure to risperidone and congenital malformations has not been established. Although, in experimental animals, risperidone did not show direct reproductive toxicity, some indirect, prolactin- and CNS-mediated effects were observed. Neonates exposed to antipsychotic medicines (including RISPERDAL CONSTA) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms that may vary in severity following delivery. These symptoms in the neonates may include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Therefore, RISPERDAL CONSTA should only be used during pregnancy if the benefits outweigh the risks.

Lactation In animal studies, risperidone and 9-hydroxy-risperidone are excreted in the milk. It has been demonstrated that risperidone and 9-hydroxy-risperidone are also excreted in human breast milk. Therefore, women receiving RISPERDAL CONSTA should not breastfeed.

RISPERDAL CONSTA may interfere with activities requiring mental alertness. Therefore patients should be advised not to drive or operate machinery until their individual susceptibility is known.

The most frequently reported adverse reactions (ARs) in clinical trials (incidence 1/10) are: Insomnia, anxiety, headache, upper respiratory tract infection, parkinsonism, depression, and akathisia. The following are all the ARu2019s that were reported in clinical trials. The following terms and frequencies are applied: very common (u2265 1/10), common (u2265 1/100 to < 1/10), uncommon (u2265 1/1 000 to < 1/100), rare (u2265 1/10 000 to < 1/1 000) and very rare (< 1/10 000) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Investigations Common: Abnormal electrocardiogram, increased blood prolactin, increased blood glucose, increased hepatic enzyme, increased transaminases, increased gamma-glutamyltransferase, increased weight, decreased weight. Uncommon Prolonged electrocardiogram QT. Cardiac disorders Common Atrioventricular block, tachycardia. Uncommon Bundle branch block, bradycardia, sinus bradycardia, palpitations.

Blood and lymphatic system disorders Common Anaemia Uncommon Neutropaenia Nervous system disorders Very common Parkinsonism, akathisia, headache. Common Dizziness, sedation, somnolence, tremor, dystonia, tardive dyskinesia, dyskinesia. Uncommon Convulsion, syncope, dizziness postural, hypoaesthesia, paraesthesia, lethargy, hypersomnia. Eye disorders Common Blurred vision, conjunctivitis. Ear and labyrinth disorders Common Vertigo. Uncommon Ear pain. Respiratory, thoracic and mediastinal disorders Common Dyspnoea, cough, nasal congestion, pharyngolaryngeal pain. Gastrointestinal disorders Common Vomiting, diarrhoea, constipation, nausea, abdominal pain, dyspepsia, toothache, dry mouth, stomach discomfort, gastritis. Renal and urinary disorders Common Urinary incontinence. Uncommon Urinary retention. Skin and subcutaneous tissue disorders Common Rash, eczema. Uncommon Pruritus, acne, dry skin. Musculoskeletal and connective tissue disorders Common Arthralgia, back pain, pain in extremity, myalgia. Uncommon Muscular weakness, neck pain, buttock pain, musculoskeletal chest pain. Metabolism and nutrition disorders Common Hyperglycaemia. Uncommon Increased appetite, decreased appetite. Infections and infestations Very common Upper respiratory tract infection. Common Pneumonia, influenza, lower respiratory tract infection, bronchitis, urinary tract infection, ear infection, sinusitis, viral infection, rhinitis, pharyngitis. Uncommon Cystitis, gastroenteritis, infection, localised infection, subcutaneous abscess. Injury, poisoning and procedural complications Common Fall Uncommon Injection site pain. Vascular disorders Common Hypertension, hypotension. Uncommon Orthostatic hypotension. General disorders and administration site conditions Common Pyrexia, peripheral oedema, chest pain, fatigue, pain, injection site pain, asthenia, influenza-like illness, malaise. Uncommon Injection site induration, induration, chest discomfort, sluggishness, feeling abnormal. Immune system disorders Uncommon Hypersensitivity. Reproductive system and breast disorders Common Amenorrhoea, erectile dysfunction, galactorrhoea, oligomenorrhea, breast discomfort, ejaculation disorder. Uncommon Sexual dysfunction, gynaecomastia. Psychiatric disorders Very common Depression, insomnia, anxiety. Common Agitation, sleep disorder. Uncommon Decreased libido, nervousness.

Symptoms: 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 extrapyramidal symptoms. In overdose, QT-prolongation and convulsions have been reported. Torsades de pointes has been reported in association with combined overdose of oral RISPERDAL and paroxetine. In the case of acute overdosage, the possibility of multiple medicine involvement should be considered.

Treatment: Establish and maintain a clear airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible dysrhythmias. Since there is, no known antidote if accidental poisoning or overdosage is suspected, 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.