Risperidone

Registered South African indications:

• Acute and chronic schizophrenia
• 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
  - As monotherapy or adjunctive therapy

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of  its excipients
• Not for children under 18 years as efficacy and safety in children under the age of 18 years have not been studied
• Renal impairment (has not been studied)
• Hepatic impairment (has not been studied)
• Parkinson’s disease and Lewy body dementia

• Pregnancy 
• Breastfeeding
• Elderly
• Orthostatic hypotension
• Cardiovascular disease
• History of leukopenia and neutropenia
• Diabetes mellitus
• History or family history of QT prolongation
• History of seizures 
• Risk factors for venous thromboembolism  
• Cataract surgery

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

Acute and chronic schizophrenia
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
- As monotherapy or adjunctive therapy

For risperidone naive patients, it is recommended to establish tolerability with oral risperidone prior to initiating treatment with risperidone intramuscular (IM). When starting risperidone IM, the patient must receive an oral antipsychotic medicine simultaneously for at least three weeks, as therapeutic concentrations of risperidone IM are only reached after a three-week period

• IM: 25mg, every 2 weeks; Some patients may benefit from the higher doses: 37.5mg OR 50mg; Titrate at intervals of at least 4 weeks apart; Effects of such dose adjustments should not be anticipated earlier than 3 weeks after the first injection with the higher dose

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No additional benefit was observed with 75mg in clinical trials in patients with schizophrenia; Doses above 50mg were not studied in patients with bipolar disorder

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Sufficient antipsychotic coverage should be ensured during the 3 week lag period following the first injection; Doses higher than 50mg, every 2 weeks are not recommended

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Risperidone IM should be administered every two weeks by deep intramuscular deltoid or gluteal injection using the enclosed safety needle. For deltoid administration, use the 2.5cm needle alternating injections between the two arms. For gluteal administration, use the 5.08cm needle alternating injections between the two buttocks

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Do not administer intravenously

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Caution
• The safety of risperidone IM 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 risperidone IM) 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, risperidone IM should only be used during pregnancy if the benefits outweigh the risks

Breastfeeding

South African recommendations

• Caution; not recommended
• 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 risperidone IM should not breastfeed

Fertility

South African recommendations

• No information available

South African recommendations

• Contraindicated

South African recommendations

• Contraindicated

South African recommendations

• Caution; dose adjustment recommended
  IM: Recommended dose: 25mg, every two weeks; Sufficient antipsychotic coverage should be ensured during the 3-week lag period following the first risperidone IM injection

Central Nervous System Disorders

• Insomnia
• Depression
• Anxiety
• Sleep disorder
• Agitation
• Libido decreased
• Mania
• Confusional state
• Anorgasmia
• Nervousness
• Nightmare
• Blunted affect
• Parkinsonism
• Headache
• Sedation
• Akathisia
• Dystonia
• Dizziness
• Dyskinesia
• Tremor
• Tardive dyskinesia
• Cerebral ischaemia
• Loss of consciousness
• Seizures 
• Syncope
• Psychomotor hyperactivity
• Abnormal coordination
• Dizziness 
• Disturbances in attention
• Dysarthria
• Dysgeusia
• Hypoaesthesia
• Paraesthesia
• Neuroleptic malignant syndrome
• Cerebrovascular disorder
• Head titubation
• Fatigue
• Withdrawal 

Cardiovascular Disorders

• Tachycardia
• Atrial fibrillation
• Atrioventricular block
• Conduction disorder
• QT prolongation
• Bradycardia
• Abnormal ECG
• Palpitations
• Sinus arrhythmia
• Hypotension
• Hypertension
• Orthostatic hypotension
• Pulmonary embolism
• Venous thrombosis
• Flushing
• Oedema
• Chest pain

Respiratory Disorders

• Dyspnoea
• Pharyngolaryngeal pain
• Cough
• Nasal congestion
• Hyperventilation
• Respiratory tract congestion
• Wheezing
• Epistaxis
• Sleep apnoea syndrome
• Pneumonia aspiration
• Pulmonary congestion
• Rales
• Dysphonia
• Respiratory tract infection
• Tonsillitis

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting 
• Constipation
• Gastroenteritis
• Diarrhoea
• Dyspepsia
• Dry mouth
• Toothache
• Faecal incontinence
• Dysphagia
• Flatulence
• Intestinal obstruction
• Swollen tongue
• Faecaloma
• Cheilitis
• Ileus

Hepatobiliary Disorders

• Increased transaminases 
• Increased gamma glutamyltransferase
• Increased hepatic enzymes
• Jaundice
• Pancreatitis

Genitourinary Disorders

• Urinary incontinence
• Pollakiuria
• Urinary retention
• Dysuria
• Erectile dysfunction
• Ejaculation disorder
• Menstrual disorder
• Sexual dysfunction
• Breast pain
• Vaginal discharge
• Priapism
• Breast engorgement
• Breast enlargement
• Breast discharge
• Glycosuria
• Cystitis

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Increased weight
• Increased appetite
• Decreased weight 
• Decreased appetite
• Diabetes mellitus
• Anorexia
• Increased blood triglycerides 
• Increased blood cholesterol 
• Water intoxication
• Hypoglycemia
• Hyperinsulinaemia
• Polydipsia
• Diabetic ketoacidosis
• Diabetic coma 
• Hyperprolactinaemia
• Syndrome of inappropriate antidiuretic hormone secretion
• Amenorrhoea
• Galactorrhoea
• Gynaecomastia

Musculoskeletal Disorders

• Muscle spasms
• Musculoskeletal pain
• Arthralgia
• Increased blood creatine phosphokinase
• Joint stiffness
• Joint swelling
• Muscular weakness
• Rhabdomyolysis
• Posture abnormal
• Gait abnormal

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Alopecia
• Eczema
• Dry skin
• Erythema
• Skin discolouration
• Acne
• Seborrhoeic dermatitis
• Drug eruption
• Urticaria
• Hyperkeratosis
• Dandruff
• Skin disorder
• Skin lesions
• Angioedema
• Cellulitis
• Acrodermatitis
• Subcutaneous abscess
• Onychomycosis
• Face oedema
• Induration

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Decreased white blood cell count
• Thrombocytopenia
• Decreased haematocrit
• Agranulocytosisc
• Neutropenia
• Increased eosinophil count
• Hypersensitivity
• Anaphylactic reaction
• Influenza
• Localised infection
• Viral infection

Sensory Disorders

• Vision blurred
• Conjunctivitis
• Dry eye
• Increased lacrimation 
• Ocular hyperaemia
• Retinal artery occlusion
• Glaucoma
• Eye movement disorder
• Eye rolling
• Photophobia
• Eyelid margin crusting
• Floppy iris syndrome 
• Vertigo
• Tinnitus 
• Pain
• Ear infection
• Eye infection

• QT prolonging agents 
• Centrally-acting agents
• Alcohol
• Levodopa 
• Dopamine agonists
• Drugs with hypotensive effect
• Paliperidone
• CYP2D6 inhibitors
• CYP3A4 inhibitors
• P-glycoprotein inhibitors
• CYP3A4 inducers
• P-glycoprotein inducers 
• Rifampicin
• Carbamazepine
• Itraconazole
• Ketoconazole
• Phenothiazines 
• Ritonavir 
• Beta blockers
• Verapamil
• H2 receptor antagonists
• Fluoxetine
• Paroxetine
• Sertraline
• Fluvoxamine
• Furosemide

None routine. Specific cases may require

• Full blood count
• Blood glucose
• Weight
• Endocrinological status (children, adolescents)
• Vital signs
• Mental status

Risperidone is an antipsychotic of the benzisoxazol derivative class. It has a high affinity for serotoninergic and dopaminergic D2 receptors. Blockade of D2 receptors in the limbic system alleviates positive symptoms of schizophrenia while blockade of the serotonin receptors in the mesocortical tract alleviates negative symptoms. Risperidone also binds at alpha-1 adrenergic receptors and, to a lesser extent, histamine H1 and alpha-2 adrenergic receptors.

Tablet 0.5mg

• Aspen Risperidone (Pharmacare)
• Auroperdal (Aurobindo)
• Mylan Risperidone (Mylan)
• Perida (Unicorn)
• Perizal (Specpharm)
• Risnia (Cipla)
• Rispacor (Accord)
• Risperdal (Janssen) originator
• Risperidone Hexal (Sandoz)
• Risperlet (Janssen) originator
• Rispide fct (Abex)
• Rutra (Aurobindo)
• Schizorol (Akacia)
• Zoxadon (Pharma Dynamics)

Tablet 1mg

• Aspen Risperidone (Pharmacare)
• Auroperdal (Aurobindo)
• Mylan Risperidone (Mylan)
• Perida (Unicorn)
• Perizal (Specpharm)
• Risnia (Cipla)
• Rispacor (Accord)
• Risperdal (Janssen) originator
• Risperidone Hexal (Sandoz)
• Risperlet (Janssen) originator
• Rispevon (Trinity)
• Rispide (Abex)
• Risponz (Zydus)
• Rutra (Aurobindo)
• Schizorol (Akacia)
• Zoxadon (Pharma Dynamics)

Tablet 2mg

• Aspen Risperidone (Pharmacare)
• Auroperdal (Aurobindo)
• Mylan Risperidone (Mylan)
• Perizal (Specpharm)
• Risnia (Cipla)
• Rispacor (Accord)
• Risperdal (Janssen) originator
• Risperidone Hexal (Sandoz)
• Risperlet (Janssen) originator
• Rispevon (Trinity)
• Rispide fct (Abex)
• Risponz (Zydus)
• Rutra (Aurobindo)
• Schizorol (Akacia)
• Zoxadon (Pharma Dynamics)

Tablet 3mg

• Aspen Risperidone (Pharmacare)
• Auroperdal (Aurobindo)
• Perizal (Specpharm)
• Risnia (Cipla)
• Rispacor (Accord)
• Risperdal (Janssen) originator
• Risperidone Hexal (Sandoz)
• Rispevon (Trinity)
• Risponz (Zydus)
• Rutra (Aurobindo)
• Zoxadon (Pharma Dynamics)

Tablet 4mg

• Aspen Risperidone (Pharmacare)
• Auroperdal (Aurobindo)
• Rispacor (Accord)
• Risperdal (Janssen) originator
• Rispevon (Trinity)
• Risponz (Zydus)
• Rutra (Aurobindo)
• Zoxadon (Pharma Dynamics)

Tablet dispersible 0.5mg

• Zoxadon ODT (Pharma Dynamics)

Tablet dispersible 1mg

• Zoxadon ODT (Pharma Dynamics)

Tablet dispersible 2mg

• Zoxadon ODT (Pharma Dynamics)

Injection (per vial) 25mg

• Risperdal Consta (Janssen) originator

Injection (per vial) 37.5mg

• Risperdal Consta (Janssen) originator

Injection (per vial) 50mg

• Risperdal Consta (Janssen) originator

Solution (per ml) 1mg

• Aspen Risperidone Oral Solution (Pharmacare)
• PMI Risperidone 1mg/ml (Unimed Healthcare)
• Risperdal (Janssen) originator