Pharmacology of Risperidone – side effects/ contraindications/ drug interactions

Adverse side effects

Risperidone adverse effects have been accessed via various ways. Through premarketing trials in North America with schizophrenia patients, adverse events such as extrapyrimidal symptoms, dizziness and hyperkinesias, somnolence and Nausea have been associated with discontinuation of treatment with RISPERDAL® (5,7). In the case of bipolar mania other adverse events such as paroniria and involuntary muscle contractions have been associated with discontinuation of RISPERDAL®; in addition to dizziness, somnolence and extrapyrimidal disorder. (5,7).

Adverse effects of RISPERDAL® use have also been observed in controlled clinical trials. Such include anxiety, extrapyrimidal symptoms, constipation, rash and tachycardia in schizophrenia conditions. (5,7). Other adverse events noted for Schizophrenia subjects in clinical controls are somnolence, nausea, rhinitis, rash and dyspepsia. (5,7). Adverse events observed in fixed-dose trials of RISPERDAL® at 2, 6, 10, and 16 mg/day include increased dream activity and sleep duration, diarrhoea, reduced salivation, weight gain and menorrhagia. (5,7). Others were diminished sexual desire, and erectile, ejaculatory and orgastic dysfunction. (5,7). Such adverse effects of RISPERDAL® use in schizophrenics are exemplified in Table 1 below.

Controlled trials with bipolar mania subjects have also suggested other adverse events that could arise with RISPERDAL® use. Such adverse effects include dyspepsia, parkinsonism, abnormal vision, somnolence, akathisia and dystonia. (5,7). A summary of these are presented in table 2 below. Additional adverse effects such as abdominal pain and urinary incontinence have been observed when RISPERDAL® is employed with mood stabilizers as an adjunctive therapy. (5,7). These latter adverse effects of RISPERDAL® use in adjuvant therapy are demonstrated in Table 3 below.

table1

 

 

table2

 

table3

 

Risperidone as a parenteral medication, RISPERDAL® CONSTA®, has also been associated with various adverse events. Such adverse events have been assessed in controlled trials and include. (5,7). A summary of adverse events associated with RISPERDAL® CONSTA® use is as presented in table 4 below.

Table 4:

Incidence of treatment-emergent adverse events in a 3-Week, placebo-controlled trial – adjunctive therapy in bipolar mania.(5, p28; 7, screen3).

table4

 

Drug interactions and their significance

Potential interactions between risperidone and other drugs have been suggested based on various aspects. First due to its principal CNS effects, use of risperidone in combination with alcohol and CNS depressants could lead to additive depressant effects. (5,7,15). Similarly its hypotension inducing property could potentiate effects of antihypertensives. Its blockade of dopamine may also reduce the effects of levodopa and other agents that serve as dopamine agonists. (5,7,15). The use of enzyme inducers such as carbamazepine could reduce risperidone plasma levels thus adversely affecting its efficacy. (5,7,15).

Conversely; cimetidine and ranitidine have been suggested to increase risperidone bioavailability though cimetidine does not additionally increase risperidone AUC as noted for ranitidine. (5,7,15). Chronic use of clozapine in combination with risperidone may retard clearance as would do other inhibitors of CYP2D6 which hinder metabolism of risperidone increasing its plasma concentrations. (5,7,15).Fluoxetine and paroxetine have also been suggested to increase risperidone plasma concentration with only paroxetine being reported to increase such concentrations for 9-OH-risperidone. (5,7,15). Since risperidone is indicated to be a relatively weak CPY2D6-inhibitor, its effects on other drugs utilizing the CPY2D6 metabolism pathway (e.g. galantamine and donepezil) may not be significant. (5,7,15).

Implications of patient conditions

Some factors could put risperidone recipients at a higher treatment risk than benefits derived from treatment. Due to its hypersensitive reactions, risperidone is contraindicated for patients who are shown to develop hypersensitivity to the product. (5,7). It is also not used for treatment of patients with dementia since it increases the risk of stroke. (5,7). For lactating mothers treatment with risperidone could necessitate stoppage of lactation since risperidone is excreted in milk. (5,7). Patients with impaired renal and hepatic function would also require a reduced dosing to avert adverse effects (5,7).

Update to part 7 here.

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