Extrapyramidal symptoms following administration of oral perphenazine 4 or 8 mg

Abstract

Background Perphenazine is a treatment option in postoperative nausea and vomiting (PONV) prophylaxis. Chronic administration and high dose are known to cause extrapyramidal system (EPS) dysfunction at a frequency of 8%, but the incidence of acute EPS after a single 4 or 8 mg dose is unknown. Objective A retrospective analysis of patient medication billing data and departmental quality records was performed (January 2001 – 10 July 2012) to identify patients who experienced EPS dysfunction after oral perphenazine. Design Retrospective analysis. Setting Surgical outpatients presenting to any one of ten hospitals in the area of Pittsburgh, PA, USA. Patients, other participants Overall, 45,766 patients received 4 or 8 mg of perphenazine before same-day surgery. Main Outcome Measures EPS dysfunction was defined as acute dystonia, akathisia, or pseudoparkinsonism. Records were reviewed to determine the (i) likely number of reactions to perphenazine, (ii) nature of these reactions, and (iii) impact on patient care. Results There were four “likely” cases of EPS dysfunction, and two “possible” cases. Five reported events were consistent with akathisia, with the sixth being a dystonic reaction. All six patients had resolution of symptoms, with five receiving intravenous diphenhydramine for treatment. The incidence of EPS dysfunction was 1.3 events per 10,000 patients (95% CI: 0.4, 3.0, based on 6 events). All patients who experienced reactions preoperatively were able to proceed to surgery without complications or delay. One patient required unplanned admission and 3-hour observation due to sedation from diphenhydramine. The incidence of EPS dysfunction after oral perphenazine is low. Reactions that did occur were mild and easily treated. Conclusions Given the infrequent side-effects, this single, low-dose of perphenazine should be encouraged as a low-risk adjunct to any multimodal PONV prophylaxis regimen, based on the selection criteria described.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

“…Buprenorphine has been consistently shown to significantly prolong peripheral nerve blocks. However, we recommend that it be used only with multimodal nausea prophylaxis with agents such as perphenazine [ 21 – 23 ], dexamethasone, and a 5-HT3 antagonist [ 21 , 22 ]. Consideration should be given to avoiding use of buprenorphine in patients with a significant history of PONV, pending clinical studies confirming that multimodal antinausea prophylaxis can adequately prevent this side effect in this patient population.…”

Postoperative nausea and vomiting in patients undergoing colorectal surgery within an institutional enhanced recovery after surgery protocol: comparison of two prophylactic antiemetic regimens

“…A systematic review of 11 clinical trials (n = 2,081) has shown that perphenazine significantly reduced the incidence of PONV (RR 0.50; 95% CI: 0.37–0.67) compared to placebo and was equally efficacious compared to other antiemetic drugs [29]. Adverse events such as extrapyramidal symptoms were rare with the use of perphenazine [30]. While aprepitant is a relatively new drug with its efficacy proven from well-conducted clinical trials, perphenazine is an older, underappreciated drug with its studies predominantly conducted before 2000 and no studies have compared the two.…”

Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions

“…202 Besides, the extrapyramidal system (EPS) dysfunction caused by long-term administration and a high dose of 143 should also be kept in mind. 203 Cytotoxic chemotherapy can reduce tumor volume, but owing to the persistence of BCSCs, which are resistant to chemotherapy, it leaves residual disease, which is most likely a critical component of tumor metastasis and tumor recurrence. Regulation of the HIF-1-dependent MAPK signaling pathway is shown to contribute to BCSC enrichment induced by chemotherapy.…”