A phase II study to evaluate the pharmacokinetics, safety, and tolerability of Risperidone ISM multiple intramuscular injections once every 4 weeks in patients with schizophrenia

• Published in: International clinical psychopharmacology Vol. 33; no. 2; p. 79
• Main Authors: Anta, Lourdes, Llaudó, Jordi, Ayani, Ignacio, Martínez, Javier, Litman, Robert E, Gutierro, Ibón
• Format: Journal Article
• Language: English
• Published: England 01.03.2018
• Subjects: Adult; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacokinetics; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring - methods; Dystonia - chemically induced; Dystonia - diagnosis; Female; Humans; Hyperprolactinemia - chemically induced; Hyperprolactinemia - diagnosis; Injection Site Reaction - diagnosis; Injections, Intramuscular; Male; Middle Aged; Outcome Assessment (Health Care); Pain - diagnosis; Pain - etiology; Psychiatric Status Rating Scales; Risperidone - administration & dosage; Risperidone - adverse effects; Risperidone - pharmacokinetics; Schizophrenia - diagnosis; Schizophrenia - drug therapy
• ISSN: 1473-5857
• DOI: 10.1097/YIC.0000000000000203

This study characterized the pharmacokinetics, safety, and tolerability of Risperidone ISM, a new long-acting intramuscular formulation, for monthly administration without oral supplementation. Patients with schizophrenia received multiple intramuscular injections of 75 mg in the gluteal or deltoid muscle at 28-day intervals. Of the 70 randomized patients, 67 received at least one dose of study medication. The mean Cmax of the active moiety was achieved 24-48 h (tmax) after each administration, regardless of injection site. They ranged over four consecutive doses from 39.6 to 53.2 and 54.1 to 61 ng/ml, when given in gluteal or deltoid muscle, respectively. Active moiety achieved therapeutic levels by 2 h after dose, and the levels were maintained throughout the 4-week dosing period. No significant changes across the study were observed on either Positive and Negative Syndrome Scale or Extrapyramidal Symptoms Scale. Overall, 63 (94%) patients experienced at least one treatment-emergent adverse event (TEAE). One serious TEAE (dystonia) was related to study treatment. The most frequently reported TEAEs were hyperprolactinaemia (57.7%) and injection site pain (32.8%). Risperidone ISM achieved therapeutic levels from the first hours after drug administration and provided a sustained release throughout the 4-week dosing period over multiple intramuscular injections and was found to be safe and well tolerated.