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Depot Formulation (depot + formulation)
Selected AbstractsPaliperidone palmitate , review of the efficacy, safety and cost of a new second-generation depot antipsychotic medicationINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010L. Citrome Summary Objective:, To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. Data sources:, A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term ,paliperidone palmitate'. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. Study selection:, All available reports of studies were identified. Product labelling provided additional information. Data extraction:, Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose,response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4,7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. Conclusions:, Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use. [source] Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychoticINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2009L. Citrome Summary Objective:, The aim of the study was to describe the efficacy and safety of iloperidone for the treatment of schizophrenia. Data sources:, The pivotal registration trials were accessed by querying http://www.pubmed.gov, http://www.fda.gov and http://www.clinicaltrials.gov for the search term ,iloperidone'. Study selection:, Four published primary reports of phase III studies were identified as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action and pharmacogenomic studies that identify potential genetic biomarkers for efficacy and tolerability. Product labelling provided additional data. Data extraction:, Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Iloperidone is a second-generation antipsychotic agent indicated for the acute treatment of schizophrenia in adults. Iloperidone has been evaluated in several double-blind placebo-controlled clinical trials. The oral formulation has demonstrated efficacy in reducing the symptoms of acute schizophrenia at fixed daily doses ranging from 12 to 24 mg. Data reported for categorical definitions of response using the Positive and Negative Syndrome Scale were limited to one study and specifically to rates of achieving a , 20% decrease in the positive subscale from baseline; significantly more patients receiving iloperidone 24 mg/day (72%) than placebo (52%) met this criterion, yielding a NNT of five. Iloperidone should be titrated slowly to avoid orthostatic hypotension, potentially delaying the achievement of a therapeutic dose level. There appears to be a dose relationship for adverse events such as dizziness, somnolence and dry mouth; for example NNH vs. placebo for somnolence was 25 for iloperidone 10,16 mg/day and 10 for 20,24 mg/day. There is a possibility of a therapeutic dose response as well. Iloperidone is essentially free of extra-pyramidal side effects. Iloperidone is associated with weight gain comparable with risperidone. Long-term double-blind maintenance studies have demonstrated iloperidone's non-inferiority to haloperidol for relapse prevention. Product labelling includes a warning about the potential for QT interval prolongation. At present there are no efficacy studies available that are powered to directly compare iloperidone with other second-generation antipsychotics. The development of a depot formulation of iloperidone as well as efforts to identify genetic biomarkers for prediction of both efficacy and tolerability are in progress. Conclusions:, Aside from paliperidone, iloperidone is the first new second-generation antipsychotic to be commercialised in the USA since 2002. From the limited registration data, iloperidone appears to be relatively well tolerated once titrated to a therapeutic level and can be a useful option to consider. The development of a depot formulation and potential for genetic biomarkers may make this agent compelling. Further comparisons with other available agents among patients with schizophrenia in the ,real world' are needed. [source] Analgesic and antiemetic effect of ketorolac vs. betamethasone or dexamethasone after ambulatory surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2007K. S. Thagaard Background:, Glucocorticoids are known to provide slower onset and more prolonged duration of analgesic effect than ketorolac. In the present study, we wanted to evaluate the effect over time from a single dose of either intravenous (i.v.) dexamethasone or an intramuscular (i.m.) depot formulation of betamethasone compared with i.v. ketorolac. Materials and methods:, One hundred and seventy-nine patients admitted for mixed ambulatory surgery were included in the study. After induction of general i.v. anaesthesia, the patients were randomized to receive double-blindly either dexamethasone 4 mg i.v. (Group D) or betamethasone depot formulation 12 mg i.m. (Group B) or ketorolac 30 mg i.v. (Group K). Fentanyl was used for rescue analgesic medication in the post-operative care unit (PACU) and codeine with paracetamol after discharge, for a study period of 3 days. Results:, There was significantly less post-operative pain in the ketorolac group during the stay in the unit (88% with minor or less pain in Group K vs. 74% and 67% in Groups D and B, respectively, P < 0.05), significantly less need for rescue medication (P < 0.05) and significantly less nausea or vomiting (12% in Group K vs. 30% in the other groups pooled, P < 0.05). The ketorolac patients were significantly faster for ready discharge, median 165 min vs. 192 min and 203 min in Groups D and B, respectively (P < 0.01). There were no differences between the groups in perceived pain, nausea, vomiting or rescue analgesic consumption in the 4- to 72-h period. Conclusion:, Dexamethasone 4 mg or bethamethasone 12 mg did not provide prolonged post-operative analgesic effect compared with ketorolac 30 mg, which was superior for analgesia and antiemesis in the PACU. [source] Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapseTHE PROSTATE, Issue 3 2003David González Barcena Abstract BACKGROUND The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer. METHODS Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48,102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17,91 months). A new remission period with a median duration of 10 months (range 2,29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. RESULTS Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5,±,308.5 to 68.2,±,60.5 ng/ml (mean decline 71,±,8%; P,<,0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62,±,0.48 to 0.37,±,0.69 and an increase in the Karnofsky performance status from 72.3,±,4.21 to 83.6,±,23.2 (P,<,0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. CONCLUSIONS Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy. Prostate 56: 183,191, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||