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Risperdal (Risperidone) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

  • Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. Increase the RISPERDAL® dose up to double the patient's usual dose. Titrate slowly. (7.1)
  • Fluoxetine, paroxetine, and other CYP 2D6 enzyme inhibitors increase plasma concentrations of risperidone. Reduce the initial dose. Do not exceed a final dose of 8 mg per day of RISPERDAL®. (7.1)

The dose of RISPERDAL® should be adjusted when used in combination with CYP2D6 enzyme inhibitors (e.g., fluoxetine, and paroxetine) and enzyme inducers (e.g., carbamazepine) [see Table 18 and Dosage and Administration ]. Dose adjustment is not recommended for RISPERDAL® when co-administered with ranitidine, cimetidine, amitriptyline, or erythromycin [see Table 18 ].

Table 18 Summary of Effect of Coadministered Drugs on Exposure to Active Moiety (Risperidone + 9-Hydroxy-Risperidone) in Healthy Subjects or Patients with Schizophrenia
Coadministered Drug Dosing Schedule Effect on Active Moiety (Risperidone + 9-Hydroxy-Risperidone (Ratio *) Risperidone Dose Recommendation
Coadministered Drug Risperidone AUC Cmax
Enzyme (CYP2D6) Inhibitors
Fluoxetine 20 mg/day 2 or 3 mg twice daily 1.4 1.5 Re-evaluate dosing. Do not exceed 8 mg/day
Paroxetine 10 mg/day 4 mg/day 1.3 - Re-evaluate dosing. Do not exceed 8 mg/day
20 mg/day 4 mg/day 1.6 -
40 mg/day 4 mg/day 1.8 -
Enzyme (CYP3A/ PgP inducers) Inducers
Carbamazepine 573 ± 168 mg/day 3 mg twice daily 0.51 0.55 Titrate dose upwards. Do not exceed twice the patient's usual dose
Enzyme (CYP3A) Inhibitors
Ranitidine 150 mg twice daily 1 mg single dose 1.2 1.4 Dose adjustment not needed
Cimetidine 400 mg twice daily 1 mg single dose 1.1 1.3 Dose adjustment not needed
Erythromycin 500 mg four times daily 1 mg single dose 1.1 0.94 Dose adjustment not needed
Other Drugs
Amitriptyline 50 mg twice daily 3 mg twice daily 1.2 1.1 Dose adjustment not needed

[Change relative to reference]

 

Effect of Risperidone on other drugs

 

Lithium

Repeated oral doses of RISPERDAL® (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (Cmax) of lithium (n=13). Dose adjustment for lithium is not recommended.

 

Valproate

Repeated oral doses of RISPERDAL® (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of RISPERDAL®. Dose adjustment for valproate is not recommended.

 

Digoxin

RISPERDAL® (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin. Dose adjustment for digoxin is not recommended.

 

Centrally-Acting Drugs and Alcohol

Given the primary CNS effects of risperidone, caution should be used when RISPERDAL® is taken in combination with other centrally-acting drugs and alcohol.

 

Drugs with Hypotensive Effects

Because of its potential for inducing hypotension, RISPERDAL® may enhance the hypotensive effects of other therapeutic agents with this potential.

 

Levodopa and Dopamine Agonists

RISPERDAL® may antagonize the effects of levodopa and dopamine agonists.

 

Clozapine

Chronic administration of clozapine with RISPERDAL® may decrease the clearance of risperidone.

 

OVERDOSAGE

Premarketing experience included eight reports of acute RISPERDAL® overdosage with estimated doses ranging from 20 to 300 mg and no fatalities. In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. One case, involving an estimated overdose of 240 mg, was associated with hyponatremia, hypokalemia, prolonged QT, and widened QRS. Another case, involving an estimated overdose of 36 mg, was associated with a seizure.

Postmarketing experience includes reports of acute RISPERDAL® overdosage, with estimated doses of up to 360 mg. In general, the most frequently reported signs and symptoms are those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. Other adverse reactions reported since market introduction related to RISPERDAL® overdose include prolonged QT interval and convulsions. Torsade de pointes has been reported in association with combined overdose of RISPERDAL® and paroxetine.

 

For the most up to date information on the management of RISPERDAL® overdosage, contact a certified poison control center (1-800-222-1222 or www.poison.org). Provide supportive care including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures. There is no specific antidote to RISPERDAL®.

 

CONTRAINDICATIONS

RISPERDAL® is contraindicated in patients with a known hypersensitivity to RISPERDAL®. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone.

 

DRUG ABUSE AND DEPENDENCE

RISPERDAL® (risperidone) is not a controlled substance.

 

RISPERDAL® has not been systematically studied in animals or humans for its potential for abuse. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of RISPERDAL® misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).

 

RISPERDAL® has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

 

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