Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Laboratorios Farmacéuticos Rovi, S.A., Julián Camarillo, 35, 28037 Madrid., Spain
OKEDI is indicated for the treatment of schizophrenia in adults for whom tolerability and effectiveness has been established with oral risperidone.
OKEDI should be administered every 28 days by intramuscular (IM) injection.
OKEDI should be initiated according to the patient’s clinical context: Patients with history of previous response to Risperidone who are currently stabilised with oral antipsychotics (mild to moderate psychotic symptoms)
Patients stabilised on other oral antipsychotics (different from risperidone) should be titrated with oral risperidone before initiating treatment with OKEDI. The duration of the titration period should be sufficiently long (at least 6 days) to confirm the tolerability and responsiveness to risperidone.
Patients who are candidates to receive OKEDI and have NOT been previously treated with risperidone, the tolerability and responsiveness to risperidone must be confirmed with a period of oral risperidone treatment before initiating treatment with OKEDI. The duration of the titration period is recommended to be at least 14 days.
The recommended doses of oral risperidone and OKEDI needed to maintain a similar active moiety steady-state exposure are as follows:
| Previous oral risperidone dose of 3 mg/day to OKEDI injection 75 mg every 28 days |
| Previous oral risperidone dose of 4 mg/day or higher to OKEDI injection 100 mg every 28 |
OKEDI must be initiated approximately 24 hours after the last oral risperidone dose. Dose adjustments of OKEDI may be made every 28 days. A maintenance dose of OKEDI 75 mg every 28 days is generally recommended. However, some patients may benefit from the 28 days OKEDI dose of 100 mg, according to the patient’s clinical response and tolerability. Neither a loading dose nor any supplemental oral risperidone is recommended when using OKEDI.
When switching from Risperidone bi-weekly long-acting injection, OKEDI should be initiated in place of the next regularly scheduled injection of risperidone bi-weekly long-acting injection (i.e., two weeks after the last risperidone bi-weekly long-acting injection). OKEDI should then be continued at 28 days intervals. No oral concomitant risperidone is recommended.
When switching patients previously stabilised on risperidone bi-weekly long-acting injection to OKEDI, the recommended dose to maintain a similar active moiety steady-state exposure is as follows:
| Risperidone bi-weekly long acting 37.5 mg to OKEDI injection 75 mg every 28 days |
| Risperidone bi-weekly long acting 50 mg to OKEDI injection 100 mg every 28 days |
When switching patients from OKEDI injection back to oral risperidone therapy, the prolonged release characteristics of the OKEDI formulation must be considered. In general, it is recommended to start oral risperidone treatment 28 days after the last OKEDI administration.
To avoid a missed 28 days dose, patients may be given the injection up to 3 days before the 28 days time point. If a dose is delayed by 1 week, the median trough concentration decreases by approximately 50% during that week. The clinical relevance of this is unknown. If the dose is delayed, the next 28 days interval injection should be scheduled according to the last injection date.
Efficacy and safety of OKEDI in elderly > 65 years have not been established for the OKEDI prolonged-release suspension for injection. OKEDI should be used with caution in elderly. Tolerability to ≥3 mg daily oral risperidone should be reliably established prior to administration of OKEDI.
In general, recommended dosing of risperidone for elderly patients with normal renal function is the same as for adult patients with normal renal function. However, if it is considered clinically appropriate, starting with 75 mg OKEDI should be considered (see Renal impairment below for dosing recommendations in patients with renal impairment).
OKEDI has not been systematically studied in patients with renal impairment. For patients with mild renal impairment (creatinine clearance 60 to 89 mL/min) no dose adjustment is required for OKEDI. OKEDI is not recommended in patients with moderate to severe renal impairment (creatinine clearance <60 mL/min).
OKEDI has not been systematically studied in patients with hepatic impairment. Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone. OKEDI should be used with caution in these groups of patients. A careful titration with oral risperidone (halving starting doses and slowing titration) before initiating treatment with OKEDI at a dose of 75 mg is recommended, if tolerability of an oral dose of at least 3 mg is confirmed.
The safety and efficacy of OKEDI in children and adolescents less than 18 years have not been established. No data are available.
OKEDI is only intended for intramuscular use and should not be administered intravenously or subcutaneously (see sections 4.4 and 6.6) or by any other route. It should be administered by a healthcare professional.
OKEDI should be administered by deep intramuscular deltoid or gluteal injection using the appropriate sterile needle. For deltoid administration, the 1-inch needle should be used alternating injections between the two deltoid muscles. For gluteal administration, the 2-inch needle should be used alternating injections between the two gluteal muscles.
The pre-filled syringe of OKEDI powder should be reconstituted with the prefilled syringe of accompanying solvent immediately prior to administration by injection.
The reconstitution process should be done accordingly to the Instructions for Use, see section 6.6. An incorrect reconstitution could affect the correct dissolution of the powder and in case of administration a higher peak of risperidone could appear in the initial hours (overdose) and a lower AUC of the entire dose treatment (underdose).
In general, reported signs and symptoms have been those resulting from an exaggeration of the known pharmacological effects of risperidone. These include drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. In overdose, QT prolongation and convulsions have been reported. Torsade de Pointes has been reported in association with combined overdose of risperidone and paroxetine.
In case of acute overdose, the possibility of multiple medicines involvement should be considered.
A clear airway should be established and maintained, and adequate oxygenation and ventilation should be ensured. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.
There is no specific antidote to OKEDI. Therefore, appropriate supportive measures should be instituted. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. In case of severe extrapyramidal symptoms, an anticholinergic medicinal product should be administered. Close medical supervision and monitoring should continue until the patient recovers.
2 years.
OKEDI should be used immediately after reconstitution.
Store below 30ºC.
Store in the original package in order to protect from moisture.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Powder prefilled syringe:
Cyclic Olefin Polymer syringe with a nozzle cap and plunger stopper composed of chlorobutyl rubber covered with polytetrafluoroethylene.
Solvent prefilled syringe:
Cyclic Olefin Polymer syringe with a tip cap composed of chlorobutyl rubber, and a plunger stopper composed of bromobutyl rubber covered with ethylene-tetrafluoroethylene copolymer. The doses are differentiated by the colour used in the finger flange of the solvent prefilled syringe, 100mg (blue) and 75 mg (red).
Each kit box of OKEDI contains:
IMPORTANT INFORMATION
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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