Paliperidone

Registered South African indications:

• Schizophrenia
• Schizoaffective disorder

Contraindications

Prolonged-release tablet

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to risperidone
• Severe renal impairment (CrCl < 10ml/min)
• Decreased gastro-intestinal transit time
• Dementia
• Parkinson’s disease

Prolonged release suspension for intramuscular injection

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to risperidone
• Moderate to severe renal impairment
• Parkinson’s disease
• Dementia with Lewy Bodies

Cautions

• Pregnancy
• Breastfeeding
• Mild renal impairment (inj)
• Mild to moderate renal impairment (PR tab)
• Severe hepatic impairment
• Acutely agitated or severely psychotic patients
• Cardiovascular disease
• Family history of QT prolongation
• History of neutropaenia
• Diabetes mellitus
• Patients with a pre-existing prolactin-dependent tumour
• Cerebrovascular disease 
• History of gastrointestinal narrowing 
• Dysphagia 
• Conditions associated with a shortened gastrointestinal transit time 
• History of seizures or other conditions that potentially lower the seizure threshold
• Parkinson's disease 
• Dementia with Lewy Bodies 
• Elderly patients with dementia
• Children
• Conditions which may contribute to an elevation in core body temperature
• High risk for venous thromboembolism
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail, in SA and covered in this monograph: inj, Prolonged Release (PR) tab

Schizophrenia

• Oral (PR tab): 6mg, dly in morning; Titrate by 3mg/day at intervals of 5 days; Maintenance: 3-12mg/24hrs

Schizoaffective disorder

• Oral (PR tab): 6mg, dly in morning; Titrate by 3mg/day at intervals of 4 days; Maintenance: 6-12mg/24hrs; Treatment duration: 6 weeks

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The patient should be instructed always to take either in the fasting state or always take it together with breakfast and not to alternate between administration in the fasting state or in the fed state

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Do not cut/ crush/ chew/ dissolve

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Schizophrenia

• IM: Initial: 150mg, followed by 100mg, 1 week later, both into deltoid muscle; Maintenance: 25-150mg, monthly in either deltoid or gluteal muscle; Titrate at monthly intervals

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It is recommended to establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with injectable form

Paed. forms avail, in SA and covered in this monograph: Prolonged Release (PR) tab

Schizophrenia

Younger than 12 years

• Not established for use

Between 12-17 years

• Oral (PR tab): 3mg, dly in morning; Titrate by 3mg/day at intervals of 5 days

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Maximum daily dose of 6mg (<51kg) and 12mg (>51kg)

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Safety and effectiveness of paliperidone injection in patients < 18 years of age have not been studied

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Safety and effectiveness of paliperidone tablets for the treatment of schizoaffective disorder in patients < 18 years of age have not been studied

Pregnancy

• Caution; not recommended
• There is no adequate data from the use of paliperidone during pregnancy
• Paliperidone was not teratogenic in animal studies, but other types of reproductive toxicity were observed. Neonates exposed to antipsychotics (including paliperidone) during the third trimester of pregnancy are at risk of adverse reactions including extrapyrimidal and/or withdrawal symptoms that may vary in severity and duration following delivery
• There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully
• Paliperidone should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly

Breastfeeding 

• Caution; not recommended
• Paliperidone is excreted in the breast milk to such an extent that effects on the breast-fed infant are likely if therapeutic doses are administered to breastfeeding women. Paliperidone should not be used while breastfeeding

Renal Impairment

Prolonged-Release tablet

• Mild (CrCl ≥ 50 to < 80ml/min): Caution; dose adjustment recommended
• Moderate (CrCl ≥ 10 to < 50ml/min): Caution; dose adjustment recommended
• Severe (CrCl < 10ml/min): Contraindicated

Prolonged release suspension for intramuscular injection

• Mild: Caution; dose adjustment recommended
• Moderate to severe: Contraindicated

Hepatic Impairment

• Severe: Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Central Nervous System Disorders

• Parkinsonism
• Akathisia
• Sedation
• Somnolence
• Dystonia
• Dizziness
• Dyskinesia
• Tremor
• Headache
• Tardive dyskinesia
• Syncope
• Psychomotor hyperactivity
• Postural dizziness
• Disturbances in attention
• Dysarthria
• Dysgeusia
• Hypoaesthesia
• Paraesthesia
• Neuroleptic malignant syndrome
• Cerebral ischaemia
• Unresponsive to stimuli
• Loss of consciousness
• Depressed level of consciousness
• Convulsions
• Balance disorder
• Abnormal coordination 
• Diabetic coma
• Head titubation
• Insomnia
• Agitation
• Depression
• Anxiety
• Sleep disorder
• Mania
• Decreased libido
• Nervousness
• Nightmare
• Confusional state
• Blunted affect
• Anorgasmia
• Asthenia

Cardiovascular Disorders

• Tachycardia
• Atrioventricular block
• Conduction disorder
• QT interval prolongation
• Postural orthostatic tachycardia syndrome
• Bradycardia
• Palpitations
• Atrial fibrillation
• Sinus arrhythmia
• Hypertension
• Hypotension
• Orthostatic hypotension
• Venous thrombosis
• Flushing
• Pulmonary embolism
• Ischaemia
• Chest pain
• Oedema

Respiratory Disorders

• Cough
• Nasal congestion
• Dyspnoea
• Respiratory tract congestion
• Wheezing
• Pharyngolaryngeal pain
• Epistaxis
• Sleep apnoea syndrome
• Pulmonary congestion
• Rales
• Hyperventilation
• Aspiration pneumonia 
• Dysphonia

Gastrointestinal Disorders

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

Hepatobiliary Disorders

• Increased transaminases 
• Increased gamma-glutamyltransferase 
• Increased hepatic enzyme 
• Jaundice

Genitourinary Disorders

• Urinary incontinence
• Pollakiuria
• Dysuria
• Urinary retention
• Amenorrhoea
• Galactorrhoea
• Erectile dysfunction
• Ejaculation disorder
• Menstrual disorder
• Gynaecomastia
• Sexual dysfunction
• Breast pain
• Breast engorgement
• Breast enlargement
• Vaginal discharge
• Priapism

Endocrine and Metabolic Disorders

• Hyperprolactinaemia
• Inappropriate antidiuretic hormone secretion
• Glucosuria
• Hyperglycaemia
• Increased weight 
• Decreased weight 
• Decreased appetite
• Diabetes mellitus
• Hyperinsulinaemia
• Increased appetite
• Anorexia
• Increased blood triglycerides
• Increased blood cholesterol 
• Diabetic ketoacidosis
• Hypoglycaemia
• Polydipsia
• Water intoxication
• Decreased body temperature
• Hypothermia
• Thirst

Musculoskeletal Disorders

• Musculoskeletal pain
• Back pain
• Arthralgia
• Increased creatine phosphokinase 
• Muscle spasms
• Joint stiffness
• Muscular weakness
• Neck pain
• Rhabdomyolysis
• Joint swelling
• Abnormal posture 
• Abnormal gait

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Pruritus
• Rash
• Alopecia
• Eczema
• Dry skin
• Erythema
• Acne
• Drug eruption
• Hyperkeratosis
• Dandruff
• Angioedema
• Skin discolouration
• Seborrhoeic dermatitis
• Injection site reaction
• Injection site necrosis
• Injection site ulcer
• Injection site abscess
• Injection site cellulitis
• Injection site cyst
• Injection site haematoma

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Anaphylactic reaction
• Decreased white blood cell count
• Thrombocytopenia
• Anaemia
• Neutropenia
• Increased eosinophil count
• Agranulocytosis
• Pyrexia

Sensory Disorders

• Blurred vision
• Conjunctivitis
• Dry eye
• Glaucoma
• Eye movement disorder
• Eye rolling
• Photophobia
• Increased lacrimation
• Ocular hyperaemia
• Floppy iris syndrome
• Vertigo
• Tinnitus
• Ear pain

Others

• Neonatal drug withdrawal syndrome 

• QT interval prolonging agents 
• Central nervous system depressants
• Levodopa 
• Other dopamine agonists
• Agents known to lower the seizure threshold
• Antipsychotics 
• Tricyclic antidepressants
• Benzodiazepines
• Metoclopramide
• Concomitant use with oral risperidone

• Blood pressure 
• Weight 

Specific cases may require

• Electrocardiogram
• Full blood count 
• Renal function 
• Hepatic function 
• Ophthalmic examination 

Switching to other antipsychotic medicinal products

There are no systemically collected data to specifically address switching patients from paliperidone to other antipsychotic medicinal products. Due to different pharmacodynamic and pharmacokinetic profiles among antipsychotic medicinal products, supervision by a clinician is needed when switching to another antipsychotic product is considered medically appropriate

Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone is unknown, but it has been proposed that its therapeutic activity in schizophrenia is mediated through a combination of central dopamine Type 2 and serotonin Type 2 receptor antagonism.

Tablet 3mg

• Invega (Janssen) originator

Tablet 6mg

• Invega (Janssen) originator

Tablet 9mg

• Invega (Janssen) originator

Injection (per 0.5ml) 50mg

• Xeplion pre-filled syringe (Janssen) originator

Injection (per 0.75ml) 75mg

• Xeplion pre-filled syringe (Janssen) originator

Injection (per ml) 100mg

• Xeplion pre-filled syringe (Janssen) originator

Injection (per 1.5ml) 150mg

• Xeplion pre-filled syringe (Janssen) originator

Injection (per 0.875ml) 175mg

• Trevicta 175mg (Janssen) originator

Injection (per 1.315ml) 263mg

• Trevicta 263mg (Janssen) originator

Injection (per 1.75ml) 350mg

• Trevicta 350mg (Janssen) originator

Injection (per 2.625ml) 525mg

• Trevicta 525mg (Janssen) originator