Safety and Pharmacokinetics of PSD502 in Healthy Chinese Male and Female Volunteers: Two Randomized, Double-Blind, Placebo-Controlled, Phase I Trials.

BACKGROUND AND OBJECTIVE: PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. METHODS: Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. RESULTS: Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. CONCLUSIONS: PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

Metahemoglobinemia secundaria a aplicación de un anestésico tópico (EMLA) / Methemoglobinemia secondary to application of a topical anesthetic (EMLA)

La metahemoglobinemia es un síndrome clínico que se produce por la oxidación del hierro de la hemoglobina impidiendo su adecuada unión al oxígeno, de forma que existe dificultad por parte de los glóbulos rojos tanto para captar el oxígeno, como para cederlo a los tejidos ocasionando hipoxia tisular. Describimos el caso de una paciente que presentó síntomas neurológicos y metahemoglobinemia como reacción adversa por contacto con crema de anestésico tópico (EMLA)

Methemoglobinemia is a clinical syndrome secondary to the oxidation of iron in hemoglobin, preventing its adequate binding to oxygen. Subsequently, red blood cells are unable to appropriately capture oxygen and deliver it to the tissues, causing hypoxia. We describe a case of a patient who presented neurological symptoms in the context of methemoglobinemia as an adverse reaction to the administration of EMLA

Comparison of the efficacy of two different local anesthetics in inferior turbinate reduction.

PURPOSE: The present study compares the local anesthetic efficacy of EMLA® cream and lidocaine injection used in the radiofrequency reduction of the inferior turbinate. METHODS: The study included a total of 124 patients with inferior turbinate hypertrophy and who underwent turbinate reduction under local anesthesia. The operations were performed 15 min after a lidocaine injection and 30 min after EMLA cream application. The respondent patients were asked to interpret such situations as intraoperative pain, discomfort during the procedure, choking sensation and difficulty swallowing using the Visual Analogue Scale (VAS). RESULTS: The EMLA cream patients (Group A) were found to have a lower level of discomfort, choking sensation and difficulty swallowing than the lidocaine patients (Group B), while there was no substantial difference in pain between the two groups. CONCLUSIONS: It is concluded that EMLA® cream is an effective alternative to lidocaine injection during inferior turbinate reduction procedures.

Lidocaine-Propitocain Cream, a Eutectic Mixture of Local Anesthetics, Effectively Relieves Pain Associated With Vascular Access Intervention Therapy in Patients Undergoing Hemodialysis: A Placebo-Controlled, Double-Blind, Crossover Study.

Vascular access intervention therapy (VAIVT) is necessary to maintain vascular access in patients undergoing hemodialysis. VAIVT-associated vasodilatation is painful. However, few reports have focused on effective pain relief at the time of VAIVT. The present study was performed to determine whether lidocaine-propitocain cream, a eutectic mixture of local anesthetics (EMLA), effectively reduces VAIVT-associated pain in patients undergoing hemodialysis. This placebo-controlled, double-blind, crossover study was conducted in a single center. Among 210 patients who underwent a total of 437 VAIVT procedures from August 2017 to June 2018, 30 patients were randomly allocated to either the EMLA-placebo arm or placebo-EMLA arm at the time of VAIVT. EMLA application significantly reduced the visual analog scale score compared with placebo (47.0 ± 21.1 vs. 68.6 ± 20.7 mm, respectively; P < 0.05). EMLA is a safe and effective treatment for relief of VAIVT-associated pain in patients undergoing hemodialysis.

[Intoxication with prilocaine/lidocaine can cause serious methemoglobinemia]. / Överdos av prilokain/lidokain kan ge svår methemoglobinemi - Tre fall där krämen gett toxiska effekter hos spädbarn.

Prilocaine/lidocaine is widely used as local anesthetic in children for cannulation and minor surgical procedures. Usually it is unproblematic but it is important to adhere to recommended dose to avoid serious complications. Excessive amount of prilocaine/lidocaine, large application area, prolonged application time or repeated application can, especially in infants, cause methemoglobinemia with clinical symptoms. In severe cases intensive care and antidote treatment with Methylene blue may be required. We report three infants who were overdosed with prilocaine/lidocaine, two of them due to incorrect use after circumcision and one premature baby where prilocaine/lidocaine was not removed in time. Two of the babies had MetHb levels > 33% and were seriously affected with hypoxia, tachycardia and fatigue. After Methylene blue was given the infants recovered within 15 minutes and MetHb levels returned to normal.

EMLA-induced methemoglobinemia after laser-assisted hair removal procedure.

This is the case of a 23-year-old female with a past medical history of ADHD and Depression who was evaluated in the emergency department for perioral cyanosis and hypoxia after application of the eutectic mixture of lidocaine and prilocaine (EMLA) local anesthetic prior to a laser-assisted hair removal procedure. This report illustrates a case of methemoglobinemia which is a rare but significant complication of topical anesthetic use.

Evaluating different pain lowering medications during intrauterine device insertion: a systematic review and network meta-analysis.

OBJECTIVE: To synthesize the evidence on the most effective medications for the relief of intrauterine device (IUD) insertion-related pain. DESIGN: Systematic review and network meta-analysis of randomized controlled trials (RCTs). SETTING: Not applicable. PATIENT(S): Patients undergoing IUD insertion who received different medications for pain relief versus those who received placebo. INTERVENTION(S): Electronic search in the following bibliographic databases: Medline via PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ScienceDirect. MAIN OUTCOME MEASURE(S): Visual analog scale (VAS) pain score during tenaculum placement, IUD insertion, and 5 to 20 minutes after insertion, the score of easiness of insertion and the need for additional analgesics. RESULT(S): The present review included 38 RCTs (n = 6,314 patients). The network meta-analysis showed that lidocaine-prilocaine cream (genital mucosal application) statistically significantly reduced pain at tenaculum placement compared with placebo (mean difference -2.38; 95% confidence interval, -4.07 to -0.68). In the ranking probability order, lidocaine-prilocaine cream ranked the highest in reducing the pain at tenaculum placement, followed by lidocaine (paracervical). Similarly, lidocaine-prilocaine cream ranked as the highest treatment in pain reduction during IUD insertion, followed by lidocaine (paracervical). CONCLUSION(S): Lidocaine-prilocaine cream is the most effective medication that can be used for IUD insertion-related pain. Other medications are not effective.

Efficacy and Safety of EMLA Cream for Pain Control Due to Venipuncture in Infants: A Meta-analysis.

: media-1vid110.1542/5852339542001PEDS-VA_2018-1173Video Abstract CONTEXT: The eutectic mixture of lidocaine (EMLA) cream has been used to reduce the pain during venipuncture in infants. OBJECTIVE: To determine the efficacy and safety of EMLA in infants <3 months of age requiring venipuncture in comparison with nonpharmacological interventions in terms of pain reduction, change in physiologic variables, and methemoglobinemia. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and gray literature were searched from inception to August 2017, without language restrictions. STUDY SELECTION: We selected randomized controlled trials in which researchers compared EMLA with nonpharmacological interventions. DATA EXTRACTION: Two reviewers independently performed abstract screening and full-text review, and extracted the data and assessed the risk of bias. RESULTS: Ten randomized controlled trials (907 infants) were included. EMLA revealed little or no effect in reduction of pain (standardized mean difference: 0.14; 95% confidence interval [CI]: -0.17 to 0.45; 6 trials, n = 742; moderate-quality evidence) when EMLA was compared with sucrose, breastfeeding, or placebo. In comparison with placebo, EMLA revealed a small-to-moderate effect on increasing methemoglobin levels (mean difference: 0.35; 95% CI: 0.04 to 0.66; 2 trials, n = 134; low-quality evidence). There was an increased risk of blanching of the skin in the EMLA group (relative risk: 2.63; 95% CI: 1.58 to 4.38; 2 trials, n = 123; I2 = 84%, very low-quality evidence). LIMITATIONS: Our results may not be applicable to older infants. CONCLUSIONS: EMLA reveals minimal benefits in terms of reduction of pain due to venipuncture procedure in comparison with placebo and no benefit in comparison with sucrose and/or breastfeeding. Moreover, it produced an elevation in methemoglobin levels and skin blanching.