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A randomised double blind crossover study of domperidone and prochlorperazine suppositories for controlling emesis in outpatients receiving chemotherapy.

Patients receiving outpatient chemotherapy, without cisplatin, were randomised to receive four doses of either domperidone 60 mg or prochlorperazine 25 mg suppositories every 4 h, starting 30 min before the chemotherapy. They were crossed over for the next chemotherapy cycle. To enable analysis of 100 patients who had received identical chemotherapy in each course, 136 patients were randomised. Patients experienced a higher grade of nausea on domperidone (P = 0.05). Only 18% of patients vomited on domperidone and 14% on prochlorperazine, but the number of vomits was higher on domperidone (P = 0.003) and the duration was significantly increased (P = 0.02). Patients experienced significantly more diarrhoea on domperidone (P < 0.0001), although it was predominantly mild. Patients were significantly more sedated on prochlorperazine on the second course (P = 0.006), but not on the first course (P = 0.9). More patients preferred their second course (P < 0.0001), and were significantly less anxious (P = 0.0002). Patients reported tolerating their treatment similarly for both antiemetics, but more patients preferred prochlorperazine (P = 0.003), mainly due to reductions in nausea and vomiting and other side-effects, particularly diarrhoea.

Adult↗

Antibacterial property of the antipsychotic agent prochlorperazine, and its synergism with methdilazine.

The antipsychotic drug prochlorperazine was screened in vitro for possible antimicrobial property against 157 strains of bacteria, belonging to gram positive and gram negative genera. The minimum inhibitory concentration (MIC) of prochlorperazine was determined by agar dilution method, which ranged from 25 to 200 microg/ml with respect to most of the strains. Based on such findings, a further study was undertaken to determine whether the efficacy of this drug could be enhanced in the presence of an antihistaminic agent methdilazine, reported to have remarkable antimicrobial action. Four bacterial strains, sensitive to prochlorperazine as well as to three antibacterial chemotherapeutics, viz., methdilazine, fluphenazine and thioridazine were chosen. Disc diffusion tests with prochlorperazine and methdilazine revealed marked synergism between the combination, compared to their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergism, the checkerboard analysis was performed. The FIC index of this combination turned out to be 0.37, which confirmed synergism. Therefore, this synergistic drug combination might open a new therapeutic approach to combat drug-resistance in bacterial infections.

Antipsychotic Agents↗

Effect of overuse of the antimigraine combination of indomethacin, prochlorperazine and caffeine (IPC) on the disposition of its components in chronic headache patients.

BACKGROUND: The combination of indomethacin, prochlorperazine and caffeine (IPC) is one of the most utilized formulations for the treatment of migraine attacks in Italy. Several patients suffering from chronic headache overuse this symptomatic medication in the attempt to control their headache. OBJECTIVE: To verify whether overuse of IPC combination by chronic headache patients is associated with modified disposition of its components. METHODS: We studied indomethacin, prochlorperazine, and caffeine disposition in 34 female subjects suffering from primary headaches, subdivided into four groups: eight migraine patients occasionally using IPC combination suppositories-group 1; nine patients with chronic headache and probable medication-overuse headache, daily taking one or more suppositories of the IPC combination-group 2; 11 migraine patients occasionally using "mild" suppositories of the IPC combination-group 3; six migraine patients occasionally taking tablets of the IPC combination-group 4. The IPC combination habitually used was administered to each patient. Blood samples were taken at baseline and at fixed intervals up to 6h after administration. Plasma levels of indomethacin and prochlorperazine were assayed by high-pressure liquid chromatographic (HPLC) method; caffeine levels were assayed by enzyme multiplied immunoassay test (EMIT). Pharmacokinetic parameters were calculated by means of a computer software (P K Solutions 2.0. Summit Research Services, Montrose, CO, USA). RESULTS: Half-life of indomethacin was longer, and clearance lower, in group 2 than in the other groups; AUC of indomethacin in group 2 was twice that in group 1 (P<0.05, Newman-Keuls' test). Peak concentrations and AUC(0-->infinity) of caffeine were significantly higher in group 2 than in the other groups (P<0.05, Newman-Keuls' test). We could not define prochlorperazine disposition because it was not detectable in the majority of blood samples. CONCLUSION: Overuse of IPC combination in chronic headache patients is associated with increased plasma levels of indomethacin and caffeine, and with delayed elimination of indomethacin; the high and sustained concentrations of these drugs may cause rebound headache, organ damages, and perpetuate medication-overuse headache.

Anti-Inflammatory Agents, Non-Steroidal↗

Safety and efficacy of rectal prochlorperazine for the treatment of migraine in the emergency department.

STUDY OBJECTIVE: To assess the safety and efficacy of rectal prochlorperazine in the treatment of acute migraines. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: Emergency department of an inner-city university hospital. PARTICIPANTS: ED patients with documented diagnosis of migraines. INTERVENTIONS: Vital signs and level of alertness were monitored immediately before drug administration and 120 minutes after dosing. Pain intensity and adverse events were monitored immediately before drug administration and at 30, 60, and 120 minutes after dosing. RESULTS: A positive outcome was defined as a pain score less than or equal to 5 on a 10-point scale or a 50% reduction in pain intensity from baseline at 120 minutes after dosing. All patients treated with prochlorperazine suppositories experienced a positive treatment outcome; only 50% of patients treated with placebo experienced a positive result at 120 minutes after dosing (P = .016). Pain intensity scores were significantly lower in the prochlorperazine group at 120 minutes (P = .018). There were no adverse reactions in either group, and there were no significant differences in vital signs or levels of alertness between groups. Patients who failed therapy were given rescue medication 120 minutes after dosing. CONCLUSION: Prochlorperazine administered as a 25-mg rectal suppository provides excellent pain relief within 2 hours in patients with acute migraines.

Acute Disease↗

A prospective study of i.v. magnesium and i.v. prochlorperazine in the treatment of headaches.

Previous uncontrolled, nonrandomized trials suggest that magnesium sulfate (MgSO(4)) is effective in the treatment of headache. The objective of this study was to determine the efficacy of MgSO(4) vs. prochlorperazine in emergency department (ED) patients with acute headache. Patients presenting to the ED with a chief complaint of headache who met study criteria were enrolled. Each patient rated pain on a visual analog scale before and 30 min after a randomized study drug infusion. Thirty-six similar patients were enrolled. There was complete or partial pain relief in 90% of the prochlorperazine group and 56% of the MgSO(4) group, a statistically significant difference. Prochlorperazine caused significantly fewer side effects, and none of the patients required additional medication during the study period. It was determined that intravenous prochlorperazine is highly effective in the treatment of headache and magnesium is moderately effective. Response to MgSO(4) was unrelated to serum Mg level.

Adolescent↗

A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy.

In a multicentre, international double-blind trial, patients undergoing courses of five or more daily radiotherapy treatments to the upper abdomen were randomized to receive either oral ondansetron 8 mg t.d.s. or oral prochlorperazine 10 mg t.d.s. throughout their radiation course in order to try to prevent nausea and vomiting. A total of 192 patients were recruited, 135 of whom were included in the efficacy analysis; of these, 70 received ondansetron and 65 prochlorperazine. Forty-three (61%) of the patients prescribed ondansetron and 23 (35%) of those given prochlorperazine had a complete response, with no emetic episodes throughout their treatment course (P = 0.002). There was, however, no significant difference between the two groups with respect to the incidence and severity of nausea. Seventeen (24%) of the patients on ondansetron and 19 (29%) of those given prochlorperazine were treatment failures, experiencing more than five emetic episodes on their worst day during the study. Both drugs were well tolerated, although constipation was seen more commonly with ondansetron.

Adult↗

Indomethacin, caffeine and prochlorperazine alone and combined revert hyperalgesia in in vivo models of migraine.

The combination of indomethacin, caffeine, and prochlorperazine (hereinafter IndoProCaf) represents an effective antimigraine drug available on the Italian market. The aim of this study was to test the efficacy of the three active principles alone and in combination in reverting hyperalgesia. Hyperalgesia was induced by morphine withdrawal in mice treated with morphine for 15 days and then made hyperalgic by morphine substitution with water. This study showed that indomethacin 0.3 mg kg(-1), i.p.; caffeine 0.1 and 0.3 mg kg(-1), i.p.; and prochlorperazine 0.1 mg kg(-1), i.p.; as well as the combination of the three active principles, were able to revert morphine withdrawal induced hyperalgesia, causing a statistically significant increase of pain threshold in hyperalgic mice. In a second model, hyperalgesia was induced by the i.p. injection of a 0.3% solution of acetic acid in mice and was evaluated counting the number of abdominal constrictions. Indomethacin (0.1 mg kg(-1), i.p.), caffeine (0.3 mg kg(-1), i.p.), and prochlorperazine (0.1 mg kg(-1), i.p.) reduced the number of abdominal constrictions, while the combination of the three active principles was able to abolish almost completely the abdominal constrictions, with a significantly higher efficacy compared to the single active principles. In both models, indomethacin, caffeine, and prochlorperazine reverted hyperalgesia at dosages 10 times lower than the corresponding analgesic ones. These data provide the pharmacologic evidence of the efficacy of IndoProCaf in reverting hyperalgesia, a condition of reduction of pain threshold similar to that occurring in migraine.

Acetic Acid↗

Effects of somatostatin, naloxone and prochlorperazine on the control of ventilation in man.

In seven normal subjects the ventilatory responses to progressive isocapnic hypoxia and hyperoxic hypercapnia were measured during rebreathing. During an infusion of somatostatin (10 nmol/min) the mean hypoxic response decreased by 66% (control: -1.6 SD 1.2 litres min-1 %-1 SaO2; somatostatin: -0.6 SD 0.7) but the mean hypercapnic response was unchanged (control: 2.0 SD 0.8 litre min-1 mmHg-1; somatostatin: 2.3 SD 1.2). There was no change in resting VO2 or VCO2 during somatostatin infusion. The opiate antagonist, naloxone (0.1 mg/kg, intravenously), caused little change in either response (mean hypoxic response: -1.7 SD 1.0 litre min-1 %-1 SaO2; mean hypercapnic response: 2.4 SD 0.9 litre min-1 mmHg-1). In five of the subjects the dopamine antagonist, prochlorperazine (10 mg, intravenously), increased the mean hypoxic response by 134% (control: -1.9 SD 1.4 litres min-1 %-1 SaO2; after prochlorperazine: -3.8 SD 1.6; P less than 0.05). The mean hypercapnic response after this drug was also increased (control: 2.1 SD 1.0 litre min-1 mmHg-1; after prochlorperazine: 3.1 SD 1.0) but this change did not achieve significance. The selective effect of somatostatin on the hypoxic response, suggestive of an action on the carotid body, was not inhibited by prior injection of either naloxone or prochlorperazine, and its mode of action remains to be found.

Adult↗

Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial.

OBJECTIVE: To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study. BACKGROUND: A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans. METHODS: One hundred twelve patients with migraine with or without aura according to the diagnostic criteria of the International Headache Society were randomized to treat 2 migraine attacks with a fixed combination of indomethacin, prochlorperazine, and caffeine and 2 migraine attacks with sumatriptan. Both drugs were rectally administered in a single dose for each attack. Patients were asked to take study medication as soon as possible at the onset of a headache. RESULTS: Of the 112 patients, 88 were compliant to the protocol. More attacks became pain-free at 2 hours postdose (primary end point) on the combination than on sumatriptan (49% versus 34%; P<.01), while there was no difference in the relief of headache at 2 hours postdose (71% versus 65%). The combination was statistically superior to sumatriptan in the time to a pain-free response (a higher percentage of attacks became pain-free from 0.5 hours postdose to 5 hours postdose), in alleviation of nausea, and in a sustained pain-free response (pain-free at 2 hours postdose with no use of rescue medication or relapses within 48 hours). Moreover, a significant consistent response was achieved for the combination compared with sumatriptan across (higher percentage of patients pain-free at 2 hours postdose in the first, second, third, and fourth treated attack) and within patients (pain-free in 2 of 2 treated attacks in 35% of patients taking the combination and 20% of patients on sumatriptan). Both drugs were well-tolerated. CONCLUSIONS: This study, analyzed according to the more recent guidelines for controlled trials in migraine, showed that a fixed combination of indomethacin, prochlorperazine, and caffeine is significantly more effective than sumatriptan in the acute treatment of migraine attacks. It is notable that the combination is less expensive than sumatriptan per unit dose.

Acute Disease↗

Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting.

In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic, 41 patients with advanced cancer who were being treated with cisplatin were entered into two double-blind trials. In the first trial patients were randomly assigned to receive either metoclopramide or placebo, and in the second trial they received either metoclopramide or prochlorperazine. Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo (medians, 1.0 vs. 10.5; P = 0.001) or prochlorperazine (medians, 1.5 vs. 12.0; P = 0.005). Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis (P = 0.001 and P = 0.022, respectively) and was more effective than placebo in shortening the duration of nausea (P = 0.042) and vomiting (P = 0.028). Side effects from metoclopramide were minor, with mild sedation frequently observed; one patient had a brief extrapyramidal reaction. We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy.

Adult↗

Prevention of delayed chemotherapy-induced nausea and vomiting after moderately high to highly emetogenic chemotherapy: comparison of ondansetron, prochlorperazine, and dexamethasone.

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.

Adult↗

Breathing during sleep: the responses to asphyxia and prochlorperazine in normal subjects and patients with obstructive sleep apnea.

The effects of sleep and prochlorperazine (12.5 mg intravenous bolus) on the ventilatory and arousal responses to asphyxia were studied in normal subjects and patients with obstructive sleep apnea (OSA). The ventilatory response to asphyxia was reduced during non-rapid eye movement sleep in the six normal subjects studied (1.93 +/- 0.18 l min-1.% SaO2 awake vs. 1.01 +/- 0.10 l min-1.% SaO2 asleep; mean +/- SEM; p less than 0.01) (SaO2 = arterial oxygen saturation). In the two normal subjects studied during sleep following prochlorperazine administration, ventilatory responsiveness was increased (p less than 0.05) but arousal response to asphyxia was depressed (p less than 0.025). Although prochlorperazine increased waking ventilatory responsiveness to asphyxia in five of six patients with OSA (2.26 +/- 0.44 l min-1.% SaO2 vs. 4.77 +/- 1.39 l min-1.% SaO2; mean +/- SEM; p less than 0.01), the drug had no clinically significant effect on upper airway obstruction during sleep; in three patients, apnea frequency was slightly reduced but in four of six patients severity of hypoxemia during apnea was increased with drug administration. We conclude that prochlorperazine administration is unlikely to benefit patients with obstructive sleep apnea despite its ventilatory effects during wakefulness and sleep. This lack of effect may be explained by separate effects of the drug on ventilatory and arousal responses to asphyxia.

Adult↗

Comparative effects of intravenously administered alizapride and prochlorperazine in cisplatin-induced emesis.

A randomized, double blind crossover trial compared the antiemetic effects of alizapride, a benzamide, and prochlorperazine, a phenothiazine, both administered intravenously to 32 patients treated with chemotherapy combinations containing cisplatin. The total dose of alizapride administered to each patient was 14 mg/kg, and of prochlorperazine .56 mg/kg, divided in five doses. Although alizapride resulted in complete protection against emesis in 31% of the patients during their first course of cisplatin therapy, 42% of those who received alizapride had five or more episodes of emesis. Although prochlorperazine was less effective in offering complete protection against emesis, only 15% of the patients receiving this drug vomited more than five times. The duration of emesis during prochlorperazine treatment was also significantly shorter than during alizapride therapy (p less than 0.02). Optimal dosage and pharmacokinetic distribution of both drugs should be investigated further.

Adult↗

Cost-effectiveness analysis of oral ondansetron and prochlorperazine for preventing nausea and vomiting after moderately emetogenic chemotherapy.

The article reports a study comparing the cost-effectiveness of ondansetron tablets and prochlorperazine capsules in preventing nausea and vomiting after moderately emetogenic chemotherapy in an outpatient setting. A decision analysis model was constructed to compare the cost-effectiveness of the two antiemetics from the perspective of third party health care payers. Probability estimates of the model were derived from a reanalysis of data obtained from a clinical trial directly comparing the two antiemetics. Effectiveness was defined as the number of patients with no emetic episodes and no drug-related adverse events during the 3-day period after receiving chemotherapy. Cost-estimates were based on Average Wholesale Price for medications and national average for hospital services adjusted to 1996 U.S. dollars. Cost-effectiveness ratios for ondansetron and prochlorperazine were $261 and $268 per effectively treated patient, respectively. A series of sensitivity analyses were performed to identify the limits of generalizability of study results. Despite the initial price differential between the two antiemetics, ondansetron was more cost effective than prochlorperazine when the duration of therapy was shorter than 3 days, the total cost of rescue therapy per patient was more than $71, the treatment cost of adverse events was less than $24, the complete relief rate for ondansetron was greater than 58.9 percent, and the complete relief rate for prochlorperazine was less than 26.5 percent.

Administration, Oral↗

Synergistic effect of prochlorperazine and dipyridamole on the cellular retention and cytotoxicity of doxorubicin.

Incubation of drug-resistant human tumor cells with a combination of prochlorperazine and dipyridamole has additive/synergistic effect on the cellular retention and cytotoxicity of doxorubicin. In patients administered a fixed dose of doxorubicin and prochlorperazine with escalating doses of dipyridamole, mean plasma levels of dipyridamole and prochlorperazine achieved were as high as 3.01 +/- 0.41 microm and 0.94 +/- 0.09 microm, respectively. Plasma samples from patients were analyzed in an in vitro assay to monitor the effect on the cellular retention of tritium-labeled daunorubicin in MDR1-transfected P388 cells. In 22 of 49 of the plasma samples analyzed, the daunorubicin in efflux blocking activity was one-half or greater than that of cells incubated with 12.5 microM verapamil, a well-known efflux blocker. These observations suggest that a combination of prochlorperazine and dipyridamole may enhance cellular doxorubicin retention by blocking efflux while reducing normal tissue toxicity and unwanted side effects in vivo.

Animals↗

Failure of prevention against postoperative vomiting by ondansetron or prochlorperazine in patients undergoing gynecological laparoscopy.

BACKGROUND: Ondansetron has been approved for the treatment and prevention of postoperative emesis. Since it is presumably considered to possess potent antiemetic effect with fewer side effects, the administration of ondansetron to inhibit emesis in patients following gynecological laparoscopic surgery might be recommendable. Hence, we examined the effects of intravenous ondansetron at dosage of 4 and 8 mg in comparison with intravenous prochlorperazine at 5 mg and placebo. METHODS: A total of 120 patients were allocated randomly into 3 groups. Group 1 patients who served as control were given NaCl 0.9% 4 mL (placebo) intravenously (i.v.); patients in group 2 and group 3 were given ondansetron 4 mg ondansetron 8 mg i.v. respectively; patients in group 4 were given prochlorperazine 5 mg i.v. Premedication was omitted. RESULTS: Logistic regression analysis adjusted for prognostic factors revealed no significant difference between 5 mg prochlorperazine group and 4 mg or 8 mg ondansetron group as compared over the 24 h study period. CONCLUSIONS: The results of this study suggest that i.v. 4 or 8 mg ondansetron and 5 mg prochlorperazine were not effective in prevention of postoperative emesis in patients undergoing gynecological laparoscopy. Since the cost of ondansetron is high, its routine use for prevention against postoperative nausea and vomiting is not be recommended clinically because of its uncertain benefit.

Adult↗

Prochlorperazine-induced cholestasis in a patient with alpha-1 antitrypsin deficiency.

A case of a 58-year-old woman with history of bilateral lung transplant secondary to alpha-1 antitrypsin deficiency (PIZZ), who presented with a severe drug-induced cholestasis secondary to prochlorperazine is reported. After 27 months of prochlorperazine use, she developed liver failure consisting of jaundice with ascites. Computed tomography of the abdomen, abdominal ultrasonography as well as an endoscopic retrograde cholangiopancreatography showed no evidence for biliary obstruction. Liver biopsy demonstrated diffuse ongoing advanced chronic cholestasis, moderate portal and periportal inflammation as well as bridging fibrosis. During her hospitalization, her total bilirubin increased to 38.6 mg/dL; alkaline phosphatase to 362 IU/L, alanine aminotransferase to 71 IU/L and aspartate aminotransferase to 88 IU/L. After several weeks of ursodiol therapy without clinical improvement the prochlorperazine was discontinued and was followed by a rapid improvement in her measures of liver injury. An immediate decline of her serum total bilirubin and alkaline phosphatase to 21.4 mg/dL and 258 IU/L, respectively, occurred strongly suggesting the idea of a prochlorperazine-induced injury.

Antiemetics↗

Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache.

In a prospective, randomized, double-blind clinical trial, intravenous prochlorperazine edisylate (Compazine Edisylate) was compared with a placebo in the treatment of severe headaches. Eighty-two adult patients with vascular or tension-type headaches were identified at the time of presentation to one of three participating emergency departments. After the patient gave informed consent, a 2-mL intravenous injection of sterile saline solution or prochlorperazine edisylate (10 mg) was given to each patient at the time of randomization. The treatment groups were similar with regard to age, sex, and type and duration of headache. Within 60 minutes after injection, 74% (31/42) of those who received prochlorperazine had complete relief; 14% (6/42) of the patients had partial relief. Overall, there was complete or partial relief of pain in 88% (37/42) of the drug group and in 45% (18/40) of the placebo group. This difference was statistically significant using chi 2 analysis. Adverse effects were minimal; one patient experienced asymptomatic orthostatic hypotension. These results suggest that intravenous prochlorperazine is an effective treatment for patients with severe vascular or tension headaches who present to the emergency department.

Acute Disease↗