risperidone
Risperdal

Available forms
Available by prescription only
Solution: 1 mg/ml
Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

Indications and dosages
 Short-term (6- to 8-week) treatment of schizophrenia. Adults: Initially, 1 mg P.O. b.i.d. Increase in increments of 1 mg b.i.d. on days 2 and 3 of treatment to a target dose of 3 mg b.i.d. Alternatively, 1 mg P.O. on day 1; increase to 2 mg once daily on day 2, and 4 mg once daily on day 3. Wait at least 1 week before adjusting dosage further. Adjust doses by 1 to 2 mg. Doses above 6 mg/day weren’t more effective than lower doses and were associated with more extrapyramidal reactions. Doses up to 8 mg/day were safe and effective. Safety of doses above 16 mg/day hasn’t been evaluated.
 Delaying relapse in the long-term (1- to 2-year) treatment of schizophrenia. Adults: Initially 1 mg P.O. on day 1; increase to 2 mg once daily on day 2, and 4 mg once daily on day 3. Dosage range is 2 to 8 mg daily.
≡ Dosage adjustment. Geriatric or debilitated patients, hypotensive patients, and patients with severe renal or hepatic impairment should initially receive 0.5 mg P.O. b.i.d. Increase dosage in increments of 0.5 mg b.i.d. Increases in dosages above 1.5 mg b.i.d. should occur at intervals of at least 1 week. Subsequent switches to once-daily dosing may be made after patient is titrated on a twice-daily regimen for 2 to 3 days at the target dose.

Pharmacodynamics
Antipsychotic action: Exact mechanism of action is unknown. Antipsychotic activity may be mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5-HT₂) antagonism. Antagonism at receptors other than D₂ and 5-HT₂ may explain other effects of drug.

Pharmacokinetics
Absorption: Well absorbed after oral administration. Absolute oral bioavailability is 70%. Food doesn’t affect rate or extent of absorption.
Distribution: Plasma protein-binding is about 90% for drug and 77% for its major active metabolite, 9-hydroxyrisperidone.
Metabolism: Extensively metabolized in the liver to 9-hydroxyrisperidone, which is the predominant circulating species and appears about equi-effective with risperidone with respect to receptor binding activity. About 6% to 8% of whites and a low percentage of Asians show little or no receptor binding activity and are called poor metabolizers.
Excretion: Metabolite is excreted by the kidney. Clearance of drug and its metabolite is reduced in patients with renal impairment.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in breast-feeding women. Use cautiously in patients with prolonged QT interval, CV disease, cerebrovascular disease, dehydration, hypovolemia, history of seizures, or exposure to extreme heat or conditions that could affect metabolism or hemodynamic responses.

Interactions
Drug-drug. Antihypertensives: May enhance effects of certain antihypertensives. Monitor blood pressure closely.
Carbamazepine: May increase risperidone clearance, decreasing its effectiveness. Monitor patient closely.
Clozapine: May decrease risperidone clearance, increasing the risk of toxicity. Monitor patient closely.
CNS depressants: May cause additive CNS depression. Give together cautiously.
Dopamine agonists, levodopa: May antagonize effects of these drugs. Avoid use together.
Drug-lifestyle. Alcohol use: Causes additive CNS depression. Discourage alcohol use.
Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: neuroleptic malignant syndrome, somnolence, extrapyramidal reactions, headache, insomnia, agitation, anxiety, tardive dyskinesia, aggressiveness, dizziness.
CV: tachycardia, chest pain, orthostatic hypotension, prolonged QT interval.
EENT: rhinitis, sinusitis, pharyngitis, abnormal vision.
GI: constipation, nausea, vomiting, dyspepsia, abdominal pain, anorexia.
Metabolic: weight gain.
Musculoskeletal: arthralgia, back pain.
Respiratory: cough, upper respiratory infection.
Skin: rash, dry skin, photosensitivity.
Other: fever.

Effects on lab test results
• May increase serum prolactin levels.

Overdose and treatment
Signs and symptoms of overdose reflect exaggeration of risperidone effects, such as drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. Hyponatremia, hypokalemia, prolonged QT interval, widened QRS complex, and seizures also have been reported.
 There’s no specific antidote to risperidone overdose; institute appropriate supportive measures. Consider gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal with a laxative. CV monitoring is essential to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of QT interval-prolonging effects that might be additive to those of risperidone. Similarly, it’s reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of risperidone, resulting in problematic hypotension.

Special considerations
• Risperidone and 9-hydroxyrisperidone appear to lengthen the QT interval in some patients, although there’s no average increase in treated patients, even at 12 to 16 mg daily (well above recommended dose). Other drugs that prolong the QT interval have been linked to torsades de pointes, a life-threatening arrhythmia. Bradycardia, electrolyte imbalance, use with other drugs that prolong the QT interval, or congenital prolongation of the QT interval can increase risk for occurrence of this arrhythmia.
• Drug has an antiemetic effect in animals; this may occur in humans, masking signs and symptoms of overdose or of such conditions as intestinal obstruction, Reye’s syndrome, and brain tumor.
• When restarting drug therapy for patients who have been off drug, follow initial 3-day dose initiation schedule.
• When switching patient from another antipsychotic to risperidone, immediately discontinue other drug at start of risperidone therapy when medically appropriate.
• Tardive dyskinesia may occur after prolonged risperidone therapy. It may not appear until months or years later and may disappear spontaneously or persist for life despite discontinuation of drug.
• Neuroleptic malignant syndrome is rare, but in many cases fatal. It isn’t necessarily related to length of drug use or type of neuroleptic. Monitor patient closely for symptoms, including hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, alteration in blood pressure, and diaphoresis.
Pregnant patients
• Instruct women to report planned, suspected, or known pregnancy.
Breast-feeding patients
• Patient should stop breast-feeding during therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• A lower starting dose is recommended for elderly patients because they have decreased pharmacokinetic clearance; a greater risk of hepatic, renal, or cardiac dysfunction; and a greater tendency toward orthostatic hypotension.

Patient education
• Advise patient to rise slowly from a recumbent or seated position to minimize light-headedness.
• Warn patient not to operate hazardous machinery, including driving a car, until effects of drug are known.
• Tell patient to call before taking new drugs, including OTC drugs, because of potential for interactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use