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Risperdal (Risperidone) - Indications and Dosage

 
 



INDICATIONS AND USAGE

Schizophrenia

RISPERDAL® (risperidone) is indicated for the treatment of schizophrenia.

The efficacy of RISPERDAL® in schizophrenia was established in short-term (6- to 8-weeks) controlled trials of schizophrenic inpatients (see CLINICAL PHARMACOLOGY).

The efficacy of RISPERDAL® in delaying relapse was demonstrated in schizophrenic patients who had been clinically stable for at least 4 weeks before initiation of treatment with RISPERDAL® or an active comparator and who were then observed for relapse during a period of 1 to 2 years (see CLINICAL PHARMACOLOGY - Clinical Trials). Nevertheless, the physician who elects to use RISPERDAL® for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Bipolar Mania

Monotherapy

RISPERDAL® is indicated for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder.

The efficacy of RISPERDAL® was established in two placebo-controlled trials (3-week) with patients meeting DSM-IV criteria for Bipolar I Disorder who currently displayed an acute manic or mixed episode with or without psychotic features (see CLINICAL PHARMACOLOGY).

Combination Therapy

The combination of RISPERDAL® with lithium or valproate is indicated for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder.

The efficacy of RISPERDAL® in combination with lithium or valproate was established in one placebo-controlled (3-week) trial with patients meeting DSM-IV criteria for Bipolar I Disorder who currently displayed an acute manic or mixed episode with or without psychotic features (see CLINICAL PHARMACOLOGY).

The effectiveness of RISPERDAL® for longer-term use, that is, for more than 3 weeks of treatment of an acute episode, and for prophylactic use in mania, has not been systematically evaluated in controlled clinical trials. Therefore, physicians who elect to use RISPERDAL® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Irritability Associated with Autistic Disorder

RISPERDAL® is indicated for the treatment of irritability associated with autistic disorder in children and adolescents, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods.

The efficacy of RISPERDAL® was established in two 8-week, placebo controlled trials in children and adolescents (aged 5 to 16 years) who met the DSM-IV criteria for autistic disorder. The benefit of maintaining patients with irritability associated with autistic disorder on therapy with RISPERDAL® after achieving a responder status for an average duration of about 140 days was demonstrated in a controlled trial (see CLINICAL PHARMACOLOGY - Clinical Trials.) Physicians who elect to use RISPERDAL® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

DOSAGE AND ADMINISTRATION

Schizophrenia

Usual Initial Dose

RISPERDAL® (risperidone) can be administered on either a BID or a QD schedule. In early clinical trials, RISPERDAL® was generally administered at 1 mg BID initially, with increases in increments of 1 mg BID on the second and third day, as tolerated, to a target dose of 3 mg BID by the third day. Subsequent controlled trials have indicated that total daily risperidone doses of up to 8 mg on a QD regimen are also safe and effective. However, regardless of which regimen is employed, in some patients a slower titration may be medically appropriate. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for the active metabolite would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, small dose increments/decrements of 1–2 mg are recommended.

Efficacy in schizophrenia was demonstrated in a dose range of 4 to 16 mg/day in the clinical trials supporting effectiveness of RISPERDAL®; however, maximal effect was generally seen in a range of 4 to 8 mg/day. Doses above 6 mg/day for BID dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are not generally recommended. In a single study supporting QD dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg/day has not been evaluated in clinical trials.

Maintenance Therapy

While there is no body of evidence available to answer the question of how long the schizophrenic patient treated with RISPERDAL® should remain on it, the effectiveness of RISPERDAL® 2 mg/day to 8 mg/day at delaying relapse was demonstrated in a controlled trial in patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years. In this trial, RISPERDAL® was administered on a QD schedule, at 1 mg QD initially, with increases to 2 mg QD on the second day, and to a target dose of 4 mg QD on the third day (see CLINICAL PHARMACOLOGY – Clinical Trials). Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment with an appropriate dose.

Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that when restarting patients who have had an interval off RISPERDAL®, the initial titration schedule should be followed.

Switching From Other Antipsychotics

There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to RISPERDAL®, or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some schizophrenic patients, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching schizophrenic patients from depot antipsychotics, if medically appropriate, initiate RISPERDAL® therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be re-evaluated periodically.

Pediatric Use

The safety and effectiveness of RISPERDAL® in pediatric patients with schizophrenia have not been established.

Bipolar Mania

Usual Dose

Risperidone should be administered on a once daily schedule, starting with 2 mg to 3 mg per day. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments/decrements of 1 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1–6 mg per day (see CLINICAL PHARMACOLOGY – Clinical Trials). RISPERDAL® doses higher than 6 mg per day were not studied.

Maintenance Therapy

There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with risperidone. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of risperidone in such longer-term treatment (i.e., beyond 3 weeks).

Pediatric Use

The safety and effectiveness of RISPERDAL® in pediatric patients with bipolar mania have not been established.

Irritability Associated with Autistic Disorder– Pediatrics (Children and Adolescents)

The safety and effectiveness of RISPERDAL® in pediatric patients with autistic disorder less than 5 years of age have not been established.

The dosage of RISPERDAL® should be individualized according to the response and tolerability of the patient. The total daily dose of RISPERDAL® can be administered once daily, or half the total daily dose can be administered twice daily.

Dosing should be initiated at 0.25 mg per day for patients < 20 kg and 0.5 mg per day for patients ≥ 20 kg. After a minimum of four days from treatment initiation, the dose may be increased to the recommended dose of 0.5 mg per day for patients < 20 kg and 1 mg per day for patients ≥ 20 kg. This dose should be maintained for a minimum of 14 days. In patients not achieving sufficient clinical response, dose increases may be considered at ≥ 2-week intervals in increments of 0.25 mg per day for patients < 20 kg or 0.5 mg per day for patients≥ 20 kg. Caution should be exercised with dosage for smaller children who weigh less than 15 kg.

In clinical trials, 90% of patients who showed a response (based on at least 25% improvement on ABC-I, see CLINICAL PHARMACOLOGY – Clinical Trials) received doses of RISPERDAL® between 0.5 mg and 2.5 mg per day. The maximum daily dose of RISPERDAL® in one of the pivotal trials, when the therapeutic effect reached plateau, was 1.0 mg in patients < 20 kg, 2.5 mg in patients ≥ 20 kg, or 3.0 mg in patients > 45 kg. No dosing data is available for children who weighed less than 15 kg.

Once sufficient clinical response has been achieved and maintained, consideration should be given to gradually lowering the dose to achieve the optimal balance of efficacy and safety.

Patients experiencing persistent somnolence may benefit from a once daily dose administered at bedtime or administering half the daily dose twice daily, or a reduction of the dose.

Dosage in Special Populations

The recommended initial dose is 0.5 mg BID in patients who are elderly or debilitated, patients with severe renal or hepatic impairment, and patients either predisposed to hypotension or for whom hypotension would pose a risk. Dosage increases in these patients should be in increments of no more than 0.5 mg BID. Increases to dosages above 1.5 mg BID should generally occur at intervals of at least 1 week. In some patients, slower titration may be medically appropriate.

Elderly or debilitated patients, and patients with renal impairment, may have less ability to eliminate RISPERDAL® than normal adults. Patients with impaired hepatic function may have increases in the free fraction of risperidone, possibly resulting in an enhanced effect (see CLINICAL PHARMACOLOGY ). Patients with a predisposition to hypotensive reactions or for whom such reactions would pose a particular risk likewise need to be titrated cautiously and carefully monitored (see PRECAUTIONS). If a once-a-day dosing regimen in the elderly or debilitated patient is being considered, it is recommended that the patient be titrated on a twice-a-day regimen for 2–3 days at the target dose. Subsequent switches to a once-a-day dosing regimen can be done thereafter.

Co-Administration of RISPERDAL® with Certain Other Medications

Co-administration of carbamazepine and other enzyme inducers (e.g., phenytoin, rifampin, phenobarbital) with risperidone would be expected to cause decreases in the plasma concentrations of active moiety (the sum of risperidone and 9-hydroxyrisperidone), which could lead to decreased efficacy of risperidone treatment. The dose of risperidone needs to be titrated accordingly for patients receiving these enzyme inducers, especially during initiation or discontinuation of therapy with these inducers (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Fluoxetine and paroxetine have been shown to increase the plasma concentration of risperidone 2.5–2.8 fold and 3–9 fold respectively. Fluoxetine did not affect the plasma concentration of 9-hydroxyrisperidone. Paroxetine lowered the concentration of 9-hydroxyrisperidone by about 10%. The dose of risperidone needs to be titrated accordingly when fluoxetine or paroxetine is co-administered (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Directions for Use of RISPERDAL® M-TAB® Orally Disintegrating Tablets

Tablet Accessing

RISPERDAL® M-TAB ® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg

RISPERDAL® M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are supplied in blister packs of 4 tablet units each.

Do not open the blister until ready to administer. For single tablet removal, separate one of the four blister units by tearing apart at the perforations. Bend the corner where indicated. Peel back foil to expose the tablet. DO NOT push the tablet through the foil because this could damage the tablet.

RISPERDAL® M-TAB ® Orally Disintegrating Tablets 3 mg and 4 mg

RISPERDAL® M-TAB® Orally Disintegrating Tablets 3 mg and 4 mg are supplied in a child-resistent pouch containing a blister with 1 tablet each.

The child-resistant pouch should be torn open at the notch to access the blister. Do not open the blister until ready to administer. Peel back foil from the side to expose the tablet. DO NOT put the tablet through the foil, because this could damage the tablet.

Tablet Administration

Using dry hands, remove the tablet from the blister unit and immediately place the entire RISPERDAL® M-TAB® Orally Disintegrating Tablet on the tongue. The RISPERDAL® M-TAB® Orally Disintegrating Tablet should be consumed immediately, as the tablet cannot be stored once removed from the blister unit. RISPERDAL® M-TAB® Orally Disintegrating Tablets disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid. Patients should not attempt to split or to chew the tablet.

HOW SUPPLIED

RISPERDAL® (risperidone) tablets are imprinted "JANSSEN", and either "Ris" and the strength "0.25", "0.5", or "R" and the strength "1", "2", "3", or "4".

0.25 mg dark yellow tablet: bottles of 60 NDC 50458-301-04, bottles of 500 NDC 50458-301-50, hospital unit dose packs of 100 NDC 50458-301-01.

0.5 mg red-brown tablet: bottles of 60 NDC 50458-302-06, bottles of 500 NDC 50458-302-50, hospital unit dose packs of 100 NDC 50458-302-01.

1 mg white tablet: bottles of 60 NDC 50458-300-06, blister pack of 100 NDC 50458-300-01, bottles of 500 NDC 50458-300-50.

2 mg orange tablet: bottles of 60 NDC 50458-320-06, blister pack of 100 NDC 50458-320-01, bottles of 500 NDC 50458-320-50.

3 mg yellow tablet: bottles of 60 NDC 50458-330-06, blister pack of 100 NDC 50458-330-01, bottles of 500 NDC 50458-330-50.

4 mg green tablet: bottles of 60 NDC 50458-350-06, blister pack of 100 NDC 50458-350-01.

RISPERDAL® (risperidone) 1 mg/mL oral solution (NDC 50458-305-03) is supplied in 30 mL bottles with a calibrated (in milligrams and milliliters) pipette. The minimum calibrated volume is 0.25 mL, while the maximum calibrated volume is 3 mL.

Tests indicate that RISPERDAL® (risperidone) oral solution is compatible in the following beverages: water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea, however.

RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets are etched on one side with "R0.5", "R1", "R2",“R3”, and “R4”, respectively. RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are packaged in blister packs of 4 (2 X 2) tablets. RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets 3 mg and 4 mg are packaged in a child-resistant pouch containing a blister with 1 tablet.

0.5 mg light coral, round, biconvex tablets: 7 blister packages per box, NDC 50458-395-28, long-term care packaging of 30 tablets NDC 50458-395-30.

1 mg light coral, square, biconvex tablets: 7 blister packages per box, NDC 50458-315-28, long-term care packaging of 30 tablets NDC 50458-315-30.

2 mg light coral, round, biconvex tablets: 7 blister packages per box, NDC 50458-325-28.

3 mg coral, round, biconvex tablets: 28 blisters per box, NDC 50458-335-28.

4 mg coral, round, biconvex tablets: 28 blisters per box, NDC 50458-355-28.

Storage and Handling

RISPERDAL® tablets should be stored at controlled room temperature 15°–25°C (59°–77°F). Protect from light and moisture.

Keep out of reach of children.

RISPERDAL® 1 mg/mL oral solution should be stored at controlled room temperature 15°–25°C (59°–77°F). Protect from light and freezing.

Keep out of reach of children.

RISPERDAL® M-TAB® Orally Disintegrating Tablets should be stored at controlled room temperature 15°–25°C (59°–77°F).

Keep out of reach of children.

7503233

December 2006
©Janssen 2003

RISPERDAL® Tablets are manufactured by:
JOLLC, Gurabo, Puerto Rico or
Janssen-Cilag, SpA, Latina, Italy

RISPERDAL® Oral Solution is manufactured by:
Janssen Pharmaceutica N.V.
Beerse, Belgium

RISPERDAL® M-TAB® Orally Disintegrating Tablets are manufactured by:
JOLLC, Gurabo, Puerto Rico

RISPERDAL® Tablets, RISPERDAL® M-TAB® Orally Disintegrating Tablets, and Oral Solution are distributed by:
Janssen, L.P.
Titusville, NJ 08560

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