Simultaneous quantification of sumatriptan succinate and prochlorperazine maleate in orodispersible films using two validated UV-spectroscopic methods.

The study aimed at simultaneous quantification of sumatriptan succinate (SUM) and prochlorperazine maleate (PCP) in an orodispersible film using two validated spectroscopic methods viz. simultaneous equation (Method I) and the Q-absorption ratio (Method II). The Method I involved measurement of absorbances at λmax of both drugs while in Method II, absorbances were measured at isosbestic wavelength and λmax of one of the two components. Method validation were accomplished as per the ICH guidelines. A 1:1 mixture of the drugs and an orodispersible film (ODF) containing these drugs were assayed by both methods. The absorbance data of SUM and PCP in both methods were linear at respective wavelengths with correlation coefficient values >0.995. Both methods were precise as % RSD in repeatability, interday and intraday precision was less than 2. The estimation of SUM and PCP from the film dosage form by method I was104.74% and 98.34% and by method II was 103.45% and 98.85%, respectively, with a standard deviation <2. The study concluded that both the methods were simple, reliable and robust and can be applied successfully for the simultaneous quantification of SUM and PCP in mixture and orodispersible film dosage form.

A randomized study of IV prochlorperazine plus diphenhydramine versus IV hydromorphone for migraine-associated symptoms: A post hoc analysis.

OBJECTIVE: We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an opioid, versus prochlorperazine, an antidopaminergic antiemetic. METHODS: This was a post hoc analysis of data from a double-blind study registered at http://clinicaltrials.gov (NCT02389829). Patients who met International Classification of Headache Disorders, 3rd edition criteria for migraine without aura or for probable migraine without aura were eligible for participation. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV and could receive a second dose of the same medication 1 h later if needed. The outcomes were sustained relief of nausea, photophobia, and phonophobia. RESULTS: A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15/49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95% CI: 20.5%-57.0%, p < 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13/62 (20.9%) patients treated with hydromorphone (ARR = 20.8%, 95% CI: 4.3%-37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16/59 (27.1%) in the hydromorphone arm (ARR = 17.5%, 95% CI: 0.3%-34.8%, p = 0.049). For adverse events, three patients in the prochlorperazine arm reported anxiety or restlessness, and nine patients in the hydromorphone arm reported dizziness or weakness. CONCLUSIONS: Prochlorperazine plus diphenhydramine is more efficacious than hydromorphone for the treatment of migraine-associated symptoms.

A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department.

OBJECTIVE: To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED). BACKGROUND: Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared. DESIGN: We performed a prospective, randomized, double-blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18-65 years, who presented with migraine, were eligible for recruitment. Sixty-six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post-commencement of the study medicine infusion. RESULTS: Sixty-five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0-4.0) in the chlorpromazine arm versus 2.0 (1.0-4.0) in the prochlorperazine arm (median difference -0.5 (95% confidence interval, -1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277). CONCLUSIONS: Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.

Effectiveness of Standard Combination Therapy in Pediatric Migraine.

BACKGROUND: A combination of parenteral medications (often referred to as standard combination therapy) is frequently used in the treatment of acute migraine in the pediatric emergency department (PED). The primary aim of this study was to evaluate the two-hour, 24-hour, and seven-day impact of one such regimen on pain in children who present to the PED. Standard combination therapy for purposes of our study is defined as a bolus of intravenous saline, and a combination of intravenous ketorolac, prochlorperazine, and diphenhydramine. METHODS: This prospective observational study included 120 children between the ages seven and 18 years who presented to the PED with migraine, whose parents could read and understand the consent form in English, and who were treated with standard combination therapy. The primary outcome measure for this study was the change in severity of pain as noted by the child using the Faces Pain Scale-Revised. We analyzed normally distributed continuous variables by mean and standard deviation, whereas non-normally distributed continuous variables are reported by median and interquartile range. RESULTS: Nonparametric Friedman testing on the entire cohort (n = 120) noted that there was a statistically significant change in the Faces pain scale from before administration of standard combination therapy to the two-hour, 24-hour, and one-week time point with a reduction in pain score of 87.5%, 100%, and 50%, respectively, at the three time points. CONCLUSIONS: This study noted moderate relief of pain after administration of standard combination therapy, which persisted at one-week after administration.

MAGraine: Magnesium compared to conventional therapy for treatment of migraines.

Due to the healthcare burden associated with migraines, prompt and effective treatment is vital to improve patient outcomes and ED workflow. This was a prospective, randomized, double-blind trial. Adults who presented to the ED with a diagnosis of migraine from August of 2019 to March of 2020 were included. Pregnant patients, or with renal impairment were excluded. Patients were randomized to receive intravenous magnesium, prochlorperazine, or metoclopramide. The primary outcome was change in pain from baseline on a numeric rating scale (NRS) evaluated at 30 min after initiation of infusion of study drug. Secondary outcomes included NRS at 60 and 120 min, ED length of stay, necessity for rescue analgesia, and adverse effects. A total of 157 patients were analyzed in this study. Sixty-one patients received magnesium, 52 received prochlorperazine, and 44 received metoclopramide. Most patients were white females, and the median age was 36 years. Hypertension and migraines were the most common comorbidities, with a third of the patients reporting an aura. There was a median decrease in NRS at 30 min of three points across all three treatment arms. The median decrease in NRS (IQR) at 60 min was -4 (2-6) in the magnesium group, -3 (2-5) in the metoclopramide group, and -4.5 (2-7) in the prochlorperazine group (p = 0.27). There were no statistically significant differences in ED length of stay, rescue analgesia, or adverse effects. Reported adverse effects were dizziness, anxiety, and akathisia. No significant difference was observed in NRS at 30 min between magnesium, metoclopramide and prochlorperazine.

I-FiBH trial: intravenous fluids in benign headaches-a randomised, single-blinded clinical trial.

BACKGROUND: Many emergency physicians use an intravenous fluid bolus as part of a 'cocktail' of therapies for patients with headache, but it is unclear if this is beneficial. The objective of this study was to determine if an intravenous fluid bolus helps reduce pain or improve other outcomes in patients who present to the ED with a benign headache. METHODS: This was a randomised, single-blinded, clinical trial performed on patients aged 10-65 years old with benign headaches who presented to a single ED in Las Vegas, Nevada, from May 2017 to February 2019. All patients received prochlorperazine and diphenhydramine, and they were randomised to also receive either 20 mL/kg up to 1000 mL of normal saline (the fluid bolus group) or 5 mL of normal saline (the control group). The primary outcome was the difference between groups in mean pain reduction 60 min after the initiation of treatment. Secondarily, we compared groups with regards to pain reduction at 30 min, nausea scores, the use of rescue medications and disposition. RESULTS: We screened 67 patients for enrolment, and 58 consented. Of those, 35 were randomised to the fluid bolus group and 23 to the control group. The mean pain score dropped by 48.3 mm over 60 min in the fluid bolus group, compared with 48.7 mm in the control group. The between groups difference of 0.4 mm (95% CI -16.5 to 17.3) was not statistically significant (p=0.96). Additionally, no statistically significant difference was found between groups for any secondary outcome. CONCLUSION: Though our study lacked statistical power to detect small but clinically significant differences, ED patients who received an intravenous fluid bolus for their headache had similar improvements in pain and other outcomes compared with those who did not. TRIAL REGISTRATION NUMBER: NCT03185130.

Acute Dystonic Reactions in Children Treated for Headache With Prochlorperazine or Metoclopramide.

BACKGROUND: The incidences of dystonic reactions to metoclopramide and prochlorperazine have not been well characterized in children. METHODS: Medical record data were reviewed for patients at a tertiary care pediatric hospital who received metoclopramide or prochlorperazine for treatment of headache. RESULTS: A total of 4588 clinical encounters were identified, 2542 with prochlorperazine and 2046 with metoclopramide. One patient had a dystonic reaction with metoclopramide (0.049%). Eleven patients had a dystonic reaction with prochlorperazine (0.43%). The relative risk of a dystonic reaction with prochlorperazine over metoclopramide is 8.85 (95% confidence interval 1.15 to 68.5). There were differences between groups of patients who received metoclopramide versus prochlorperazine in terms of age, number of doses, and coadministration of diphenhydramine. In a logistic regression, administration of prochlorperazine over metoclopramide (P = 0.019) and greater number of doses (P < 0.001) remained associated with acute dystonic reactions. CONCLUSIONS: Dystonic reactions are rare events among pediatric patients treated for acute headache, but are more common with prochlorperazine than metoclopramide.

Antimelanoma activity of perphenazine and prochlorperazine in human COLO829 and C32 cell lines.

Cutaneous melanoma is least common (only about 1% of skin cancers) but is the deadliest malignant tumor. Moreover, amelanotic types of melanoma are very difficult for clinical diagnosis. The standard therapy can cause a lot of side effects, e.g., nausea, vomiting, and headaches, which means that novel and effective strategies are required. Interestingly, phenothiazine derivatives possess sedative, antiemetic, and anticancer activity. Our goal was to determine the effect of perphenazine and prochlorperazine on cell viability, motility, microphthalmia-associated transcription factor (MITF) and tyrosinase content in melanotic and amelanotic melanoma cells. The viability of C32 and COLO829 melanoma cells was evaluated by the WST-1 colorimetric assay; impact on motility of human melanoma was performed by wound-healing assay, while tyrosinase and MITF content were determined by Western blot. In the present study, we explore the anticancer effect of perphenazine and prochlorperazine in human melanotic (COLO829) and amelanotic (C32) melanoma cells concluding that prochlorperazine inhibits cell viability in a concentration-dependent manner, impairs motility, and decreases tyrosinase and MITF amounts. Moreover, the analyzed drugs decrease/increase MITF amount depending on the type of melanoma. We demonstrated that the decrease of MITF and tyrosinase protein induces motility inhibition of C32 cells, which suggests the ability of those drugs to restore cancer cell sensitivity to treatment. The ability of prochlorperazine to contain the spread of the amelanotic melanoma in vivo may be helpful in the development of a new and effective antimelanoma therapies.

Buccally absorbed vs intravenous prochlorperazine for treatment of migraines headaches.

OBJECTIVE: To compare the efficacy of buccally absorbed prochlorperazine (BAP) to intravenous prochlorperazine (IVP) for the abortive treatment of migraine headaches. METHODS: Randomized double-blind trial. Eighty subjects aged 18-65 presenting with migraines to the ED of a safety-net, urban hospital. Subjects were randomized to receive either 6 mg BAP plus 2.25 mL saline IV placebo or 10 mg IVP and buccally absorbed saccharine pill placebo. A 100 mm visual analog scale (VAS) was used to assess pain, nausea, and sedation. Comparisons between groups were analyzed by the Mann-Whitney U test or Fisher's exact test. RESULTS: Eighty subjects were recruited from November 2016 to December 2017; 79 completed the study. Demographics: 60 women and 19 men with a mean age of 38 ± 12.2 years. Initial mean VAS pain scores were similar between groups (BAP: 78.5 ± 19.9 mm vs IVP: 76.9 ± 19.5 mm). The improvement in mean VAS pain scores over 60 minutes for the BAP group was not significantly different from the IVP group (-54.9 ± 29.7 mm vs -66.7 ± 23.2 mm, respectively; P = 0.08). No significant differences were found in rates of nausea or sedation. Nine subjects in the BAP group required rescue treatment compared to 1 in the IVP group. Five subjects reported symptoms consistent with akathisia in the IVP group while no adverse effects were reported in the BAP group. CONCLUSION: Buccally absorbed prochlorperazine (BAP) is an effective, non-invasive treatment for migraine headaches when compared to intravenous prochlorperazine (IVP).

The Efficacy and Safety of Prochlorperazine in Patients With Acute Migraine: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED). METHODS: Electronic databases (Medline, Scopus, Web of Science, and Cochrane) were searched for randomized clinical trials that investigated the effect of PCP on headache relief. The outcomes were the number of patients without headache or with reduced headache severity, the number of adverse events, and the need for rescue analgesia. RESULTS: From 450 citations, 11 studies (n = 771) with 15 comparison arms met the inclusion criteria. Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31). The request for rescue analgesia was significantly lower in the PCP group compared with other groups (16% vs 84%; OR = 0.16; 95% CI = 0.09-27). CONCLUSIONS: For adult patients with acute migraine, PCP could effectively abort the acute attack and reduce the request for rescue analgesia in the ED. However, compared with placebo, PCP could increase the risk of adverse events.

Real-world insights on the management of migraine patients: an Italian nationwide study.

Objectives: Understanding migraine management using data from a sample of patients representative of the Italian general adult population.Methods: Retrospective analysis on IQVIA Italian Longitudinal Patient Database. Two cohorts were created. (a) The triptan user cohort included patients with triptan prescriptions between November 2015 and October 2016. Migraine days were estimated counting triptan and indometacin/caffeine/prochlorperazine (ICP) pills prescribed during the 6 months following first triptan prescription. Patients were categorized as having episodic (EM) or chronic (CM) migraine based on the number of migraine days following International Classification of Headache Disorders criteria. (b) The migraine preventive treatment (MPT) user cohort included patients with MPT prescriptions during the period June 2016-May 2017. MPTs considered included beta-blockers, calcium-channel blockers, antiepileptics, antidepressants and antiserotoninergics. Migraine days experienced by MPTs users were estimated counting triptan and ICP pills prescribed during the 6 months following the most recent MPT prescription, while the number of MPT switches was estimated based on MPT prescriptions during the previous two years.Results: There were 9461 patients with triptan prescriptions to treat migraine acute attacks, which accounted yearly for 0.8% of general adult population. CM patients accounted for 3% of triptan users. There were 2004 patients prescribed with MPTs, which accounted for 0.16% of general adult population. Overall, among MPT users, 291 (15%) were still experiencing at least four migraine days/month, with this proportion increasing with the increase in the number of MPT switches.Conclusions: Results from this study suggest an unmet need in the management of migraine: too many patients did not receive MPTs, with this potentially due to several reasons requiring further investigations. Furthermore, even among patients receiving MPTs, disease control level with now available drugs seems to be sub-optimal.

Intravenous Fluid for the Treatment of Emergency Department Patients With Migraine Headache: A Randomized Controlled Trial.

STUDY OBJECTIVE: The objective of this pilot study is to assess the feasibility and necessity of performing a large-scale trial to measure the effect of intravenous fluid therapy on migraine headache pain. METHODS: This was a single-center, pilot randomized controlled trial. We randomized adult emergency department migraine headache patients to receive 1 L of normal saline solution during 1 hour (fluid group) or saline solution at 10 mL/hour for 1 hour (control group). All patients received intravenous prochlorperazine and diphenhydramine at the start of fluid administration. Participants and outcome assessors were blinded; nurses administering the intervention were not. Outcomes were assessed at 60 and 120 minutes, and 48 hours. The primary outcome was the difference in the verbal pain rating (on a scale of 0 to 10) between 0 and 60 minutes. Key secondary outcomes included additional clinical endpoints, the rate of protocol completion, and the effectiveness of blinding. RESULTS: Fifty patients consented to participate; one withdrew, leaving 25 patients randomized to the fluid group and 24 in the no fluid group. The mean improvement in 0- to 60-minute pain score was 4.5 (95% confidence interval 3.7 to 5.3) in the fluid group and 4.9 (95% confidence interval 3.5 to 6.2) in the control group. Primary outcome data were collected for 49 of 50 enrolled patients, and only one participant correctly identified the group assignment. CONCLUSION: This pilot study showed no statistically significant treatment effect from fluid administration, but does not exclude the possibility of a clinically important treatment effect. The study protocol and approach to blinding are both feasible and effective.

Emergency Department Use of Intravenous Prochlorperazine for Acute Migraine.

The Research to Practice Column is designed to improve translational research critique skills of nurse practitioners (NPs). In this issue, the article "Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine" is discussed in the context of a patient with an acute headache presenting to the emergency department (ED). The study was designed to assess the efficacy of intravenous prochlorperazine and diphenhydramine as compared with intravenous hydromorphone for patients with acute migraine in the ED. With the growing trend to avoid the use of opiates to curb potential addiction and increased ED length of stay, NPs need to be aware of efficacious, evidence-based treatments for acute migraines, a common ED presentation.

Opioid-Induced "Likeability" and "Feeling Good" Are Not Associated With Return Visits to an ED Among Migraine Patients Administered IV Hydromorphone.

BACKGROUND: Parenteral opioids are used in more than 50% of emergency department (ED) visits for migraine. Use of opioids for migraine has been associated with subsequent ED visits, perhaps because of opioid-induced euphoria. In this study, we quantify the extent to which nontherapeutic effects of opioids influence migraine outcomes. We hypothesized that "feeling good" and medication likeability would in fact be associated with receipt of opioids (rather than relief of migraine pain) and that receipt of opioids (rather than relief of migraine pain) would be associated with return visits to the ED. METHODS: During an ED-based clinical trial, migraine patients were randomized to receive hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg IV. Thirty minutes after medication administration, we asked, (1) How much did you like the medication you received? and (2) How good did the medication make you feel? Participants were asked to provide answers on a 0-10 scale. We also determined 0-10 pain scores at baseline and 1 hour and number of return visits for headache during the subsequent month. RESULTS: Sixty-three patients received prochlorperazine and 64 hydromorphone. Prochlorperazine pain scores improved by 6.8 (SD: 2.6), hydromorphone by 4.7 (SD: 3.3) (95%CI for difference of 2.1: 1.0, 3.2). On the 0-10 likeability scale, prochlorperazine patients reported a mean of 7.2 (SD: 2.8), hydromorphone 6.9 (SD: 2.9) (95% CI for difference of 0.3: -0.7, 1.3). On the 0-10 feeling good scale, prochlorperazine patients reported a mean of 7.5 (SD: 2.3), hydromorphone 6.8 (SD: 2.8) (95%CI: for difference of 0.7: -0.2, 1.6). In the hydromorphone group, 8/57 (14%, 95%CI: 7, 26%) returned to the ED vs 5/63 (8%, 95%CI: 3,18%) in the prochlorperazine group. In regression modeling, feeling good was independently associated with pain relief (P < .01) but not with medication received (P = .67) or return visits (P = .12). Similarly, medication likeability was independently associated with pain relief (P < .01) but not medication received (P = .12) or return visits (P = .16). CONCLUSION: We did not detect an association between hydromorphone and medication likeability, feeling good, or return visits to the ED. Headache relief was associated with medication likeability and feeling good.

Stability of extemporaneously prepared preservative-free prochlorperazine nasal spray.

PURPOSE: The stability of an extemporaneously prepared preservative-free prochlorperazine 5-mg/mL nasal spray was evaluated. METHODS: The preservative-free prochlorperazine nasal spray was prepared by adding 250 mg of prochlorperazine edisylate to 50 mL of citrate buffer in a low-density polyethylene nasal spray bottle. A stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated using the major degradant prochlorperazine sulfoxide and by performing forced-degradation studies. For chemical stability studies, 3 100-µL samples of the preservative-free prochlorperazine from 5 nasal spray bottles stored at room temperature were collected at days 0, 20, 30, 45, and 60 and were assayed in triplicate using the stability-indicating HPLC method. Microbiological testing involved antimicrobial effectiveness testing based on United States Pharmacopeia (USP) chapter 51 and quantitative microbiological enumeration of aerobic bacteria, yeasts, and mold based on USP chapter 61. Samples for microbiological testing were collected at days 0, 30, and 60. RESULTS: The stability-indicating HPLC method clearly identified the degradation product prochlorperazine sulfoxide without interference from prochlorperazine. All tested solutions retained over 90% of the initial prochlorperazine concentration for the 60-day study period. There were no detectable changes in color, pH, and viscosity in any sample. There was no growth of bacteria, yeast, and mold for 60 days in all samples tested. CONCLUSION: An extemporaneously prepared preservative-free nasal spray solution of prochlorperazine edisylate 5 mg/mL was physically, chemically, and microbiologically stable for 60 days when stored at room temperature in low-density polyethylene bottles.

A Comparison of Headache Treatment in the Emergency Department: Prochlorperazine Versus Ketamine.

STUDY OBJECTIVE: Intravenous subdissociative-dose ketamine has been shown to be effective for pain management, but has not been specifically studied for headaches in the emergency department (ED). For this reason, we designed a study to compare standard treatment (prochlorperazine) with ketamine in patients with benign headaches in the ED. METHODS: This study was a multicenter, double-blind, randomized, controlled trial with a convenience sample of patients presenting to the ED with benign headaches. Patients were randomized to receive either prochlorperazine and diphenhydramine or ketamine and ondansetron. Patients' headache severity was measured on a 100-mm visual analog scale (VAS) at 0, 15, 30, 45, and 60 minutes. Nausea, vomiting, anxiety, and the need for rescue medications were also tracked. Patients were contacted at 24 to 48 hours posttreatment to rate their satisfaction and to determine whether they were still experiencing a headache. RESULTS: There were a total of 54 subjects enrolled. Two patients in the ketamine group and one in the prochlorperazine group withdrew because of adverse effects of the medications. In regard to the primary outcome, at 60 minutes, the prochlorperazine group had a mean improvement in VAS pain scores of 63.5 mm compared with 43.5 mm in the ketamine group, corresponding to a between-groups difference of 20.0 mm (95% confidence interval [CI] 2.8 to 37.2 mm) and a P value of .026. At 45 minutes, the prochlorperazine group had a mean improvement in pain scores of 56.1 mm compared with 38.0 mm in the ketamine group, a difference of 18.1 mm (95% CI 1.0 to 35.2 mm). At 24- to 48-hour follow-up, the mean satisfaction score was 8.3 of 10 for prochlorperazine and 4.9 of 10 for ketamine, a difference of 3.4 (95% CI 1.2 to 5.6). There was not a statistically significant difference in the percentage of patients who had a headache at follow-up or in other secondary outcomes. CONCLUSION: Prochlorperazine appears to be superior to ketamine for the treatment of benign headaches in the ED.

Efficacy of Prophylactic Treatment for Oxycodone-Induced Nausea and Vomiting Among Patients with Cancer Pain (POINT): A Randomized, Placebo-Controlled, Double-Blind Trial.

BACKGROUND: Although opioid-induced nausea and vomiting (OINV) often result in analgesic undertreatment in patients with cancer, no randomized controlled trials have evaluated the efficacy of prophylactic antiemetics for preventing OINV. We conducted this randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of prophylactic treatment with prochlorperazine for preventing OINV. MATERIALS AND METHODS: Cancer patients who started to receive oral oxycodone were randomly assigned in a 1:1 ratio to receive either prochlorperazine 5 mg or placebo prophylactically, given three times daily for 5 days. The primary endpoint was the proportion of patients who had a complete response (CR) during the 120 hours of oxycodone treatment. CR was defined as no emetic episode and no use of rescue medication for nausea and vomiting during 5 days. Key secondary endpoints were the proportion of patients with emetic episodes, proportion of patients with moderate or severe nausea, quality of life, and proportion of treatment withdrawal. RESULTS: From November 2013 through February 2016, a total of 120 patients were assigned to receive prochlorperazine (n = 60) or placebo (n = 60). There was no significant difference in CR rates (69.5% vs. 63.3%; p = .47) or any secondary endpoint between the groups. Patients who received prochlorperazine were more likely to experience severe somnolence (p = .048). CONCLUSION: Routine use of prochlorperazine as a prophylactic antiemetic at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations. IMPLICATIONS FOR PRACTICE: Prophylactic prochlorperazine seems to be ineffective in preventing opioid-induced nausea and vomiting (OINV) and may cause adverse events such as somnolence. Routine use of prophylactic prochlorperazine at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.

Development of Floating Delivery for Solid Self Micro-Emulsifying Drug Delivery System of Prochlorperazine Maleate.

BACKGROUND: Prochlorperazine maleate (PCM) is a phenothiazine antipsychotic used in the treatment of nausea, vomiting and vertigo. It is BCS class II drug with only 12.5% bioavailability. Patents data on PCM had shown work on conjugation and matrix formulation which suggested idea for the present work design. OBJECTIVE: The objective of this study was to enhance solubility of drug and to optimize gastro retentive floating capsule for controlled drug release at the targeted site for stipulated time. METHOD: The solubility of drug was determined in various vehicles like oils, surfactants and cosurfactants. Pseudo ternary phase diagrams were constructed to identify the efficient self emulsifying region. SMEDDS were tested for micro emulsifying properties. The resultant microemulsions were evaluated and were further selected for the floating drug delivery. Magnesium hydroxide was used as carrier to transform SMEDDS into Solid SMEDD (S-SMEDD). Non-effervescent floating capsule containing S-SMEDD were optimized using factorial design with independent variable HPMC K4M and ethyl cellulose. RESULTS: SMEDD consists of PCM, isopropyl myristate, tween 80 and PEG 400 as a drug, oil, surfactant and co-surfactant (1:1 ratio). Optimized formulation F5 showed 10 hrs floating time and percent drug release 91.56±2.7% with controlled drug delivery in stomach. F5 followed Korsmeyer Peppas release kinetics where the drug followed Fickian diffusion transport mechanism due to swelling of polymers in controlled manner. CONCLUSION: It can be concluded that SMEDD enhanced the solubility of drug and floating capsule gave site specific drug release of PCM with the advantages of reduced dosing frequency and better compliance.

Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine.

OBJECTIVE: To determine outcomes among patients with migraine in the emergency department (ED) who receive IV hydromorphone vs IV prochlorperazine + diphenhydramine. METHODS: This study was conducted in 2 EDs in New York City. Patients who met international criteria for migraine were eligible for participation if they had not used an opioid within the previous month. Clinicians, participants, investigators, and research personnel were blinded to treatment. Patients were randomized in blocks of 4. Participants received hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg. Diphenhydramine was administered to prevent akathisia, a common side effect of IV prochlorperazine. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining that level for 48 hours without the requirement of rescue medication. A planned interim analysis was conducted once 48-hour data were available for 120 patients. RESULTS: The trial was halted by the data monitoring committee after 127 patients had been enrolled. The primary outcome was achieved in the prochlorperazine arm by 37 of 62 (60%) participants and in the hydromorphone arm by 20 of 64 (31%) participants (difference 28%, 95% confidence interval 12-45, number needed to treat 4, 95% confidence interval 2-9). CONCLUSIONS: IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the ED and should not be used as first-line therapy. CLINICALTRIALSGOV IDENTIFIER: NCT02389829. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients in the ED with migraine, IV prochlorperazine + diphenhydramine is superior to IV hydromorphone.