PROMETHAZINE-INDUCED THROMBOPHLEBITIS IN A NIGERIAN MAN: A CASE REPORT.

Introduction: Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness, allergic conditions, nausea and vomiting, in addition to its use as a sedative. Promethazine has vesicant properties and is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration may result in thrombophlebitis, unintentional intra-arterial administration, perivascular extravasation and tissue necrosis. To the best of our knowledge there is no previous published report of promethazine-induced thrombophlebitis from sub- Saharan Africa. Case Report: A 29-year-old Nigerian male was admitted at our hospital on account of malaria with acute gastroenteritis. Due to persistent vomiting, he was administered 25 mg of promethazine injection via a size 22G intravenous cannula which was inserted the previous day on the anteromedial aspect of his right forearm and maintained with continuous intravenous crystalloid infusion. Upon administration of promethazine, he experienced intense burning and erythema. The cannula was removed immediately, another cannula was inserted on the contralateral arm, and promethazine was replaced with ondansetron. Subsequently, he developed a tender, subcutaneous cord-like swelling extending from the middle-third of the anteromedial aspect of his right forearm, corresponding with the site of previous venous cannulation. Ultrasonography revealed a hypoechoic, non-compressible basilic vein, with no flow on colour Doppler interrogation, in keeping with superficial thrombophlebitis. He was treated with a topical anti-inflammatory agent, and the pain and redness subsided after four weeks. Conclusion: The preferred parenteral route of administration of promethazine is deep intramuscular injection. Recommendations to prevent promethazine-induced thrombophlebitis include: use of large and patent veins, use of lower doses, drug dilution and slow administration, use of alternative therapies, and patient education. Promethazine-induced tissue injury is under-reported in this part of the world. Creating awareness through this case report would help reduce the morbidity following promethazine administration.

Uso de fármacos alertantes para la detecciónde reacciones adversas intrahospitalarias: estudio de farmacovigilancia / Use of tracking drugs for the search of intra-hospital adverse reactions: a pharmacovigilance study

Objetivo: Estimar la incidencia de potenciales reacciones adversasintrahospitalarias con el uso de prescripciones alertantes en un hospitalgeneral del sur de Brasil.Método: Estudio transversal, realizado en un hospital del sur de Brasil.Se evaluaron las historias clínicas electrónicas (TASY®) de los pacienteshospitalizados entre enero y agosto de 2020, a los que se les prescribióuno de los medicamentos destinados al seguimiento de reacciones adversasa medicamentos: los medicamentos incluían flumazenil, clorhidratode fexofenadina, naloxona, prometazina, difenhidramina y loperamida.Resultados: Se revisaron 13.476 historias clínicas y se incluyeron 204 (1,5%)en el estudio en el que se indicó el uso de prescripciones alertantes en elmanejo de reacciones adversas a medicamentos. En este estudio se encontró untotal de 18 signos o síntomas diferentes en las historias clínicas, siendo el prurito,la hiperemia y la urticaria los síntomas más reportados (n = 76). Entre las clasesde fármacos que causaron la mayoría de las reacciones adversas a medicamentos,los opioides fueron los más mencionados (n = 44). Cabe señalar queen 49 historias clínicas no se reportó la información sobre qué fármaco causólos eventos adversos. En cuanto a la causa de hospitalización de los pacientesque utilizaron prescripciones alertantes, el cáncer fue la más frecuente (n = 37). Conclusiones: Este estudio indica que el uso de alertadores puede seruna herramienta para estimar la incidencia de reacciones adversas a medicamentosy establecer eventos adversos relacionados con el uso demedicamentos, los cuales deben ser reportados al servicio de farmacovigilancia,con miras a la seguridad del paciente.

Objective: To estimate the incidence of potential in-hospital adversereactions with the use of alert drugs in a general hospital in southernBrazil.Method: Cross-sectional study, carried out in a hospital in southernBrazil. The electronic medical records (TASY®) of patients hospitalizedbetween January and August 2020, who were prescribed one of thedrugs earmarked for tracking adverse drug reactions, were evaluated:the drugs included flumazenil, fexofenadine hydrochloride, naloxone, promethazine,diphenhydramine and loperamide.Results: A total of 13,476 medical records were reviewed and 204(1.5%) were included in the study in which tracker use was indicated in themanagement of adverse drug reactions. In this study a total of 18 differentsigns or symptoms were found in medical records, with pruritus/hyperemia/urticaria being the most reported symptoms (n = 76). Among the drugclasses that caused most adverse drug reactions, opioids were the mostmentioned (n = 44). It should be noted that in 49 medical records theinformation on which drug caused the adverse events was not reported.Regarding the cause of hospitalization of patients who used screeningdrugs, cancer was the most frequent (n = 37). Conclusions: This study indicates that the use of trackers can be a toolto estimate the occurrence of adverse drug reactions and to establishadverse events related to the use of medications, which should be reportedto the pharmacovigilance service, with a view to patient safety.

Promethazine-induced delirium with perceptual abnormalities: are we thinking broadly when assessing patients?

There is limited information about promethazine-induced delirium with psychotic symptoms. The aim is to highlight the importance of taking a detailed history including medication use/abuse of both prescribed, illicit and over-the-counter preparations. This paper describes a patient who presented with delirium in the context of overuse of promethazine (Phenergan) which was initially missed. The patient was treated successfully, following the diagnosis of promethazine-induced delirium. Clinicians should be aware of assessing patients presenting with delirium to explore the possibility of over-the-counter medication misuse.

Beyond the 'purple drank': Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports.

BACKGROUND: Promethazine is a medicinal product, available on its own or in combination with other ingredients including dextromethorphan, paracetamol and/or expectorants. Anecdotal reports have however indicated that promethazine may have a misuse potential, especially in adolescents. OBJECTIVE: We here aimed at studying how this phenomenon has been reported to the European Monitoring Agency Adverse Drug Reactions database. METHODS: After a formal request to the European Monitoring Agency, the promethazine-specific dataset has been studied, performing a descriptive analysis of misuse/abuse/dependence-related adverse drug reaction reports. The study was approved by the University of Hertfordshire (LMS/PGR/UH/03234). RESULTS: The analysis of promethazine data showed increasing levels of misuse/abuse/ dependence issues over time (2003-2019). Out of a total number of 1543 cases of adverse drug reactions, the abuse/misuse/dependence-related cases reported were 557, with 'drug abuse' (300/557: 53.8%) and 'intentional product misuse' (117/557: 21.0%). being the most represented adverse drug reactions. A high number of fatalities were described (310/557: 55.6%), mostly recorded as 'drug toxicity/drug abuse' cases, with opiates/opioids having been the most commonly reported concomitant drugs used. CONCLUSION: Anecdotal promethazine misuse/abuse reports have been confirmed by European Monitoring Agency data. Promethazine misuse/abuse appears to be an alarming issue, being associated with drug-related fatalities. Thus, healthcare professionals should be warned about a possible misuse of promethazine and be vigilant, as in some countries medicinal products containing promethazine can be purchased over the counter. Since promethazine is often available in association with opioids, its abuse may be considered a public health issue, with huge implications for clinical practice.

Photopatch Testing in New Zealand: A 12-Year Retrospective Review.

BACKGROUND: Little is known about the common photoallergens in New Zealand, where ultraviolet exposure is particularly high. Availability of photopatch testing is limited because of it being performed in very few tertiary referral and contact dermatitis clinics. OBJECTIVE: To review the photopatch testing experience in New Zealand. METHOD: A retrospective review of all patients who underwent photopatch testing at a tertiary referral center in Auckland from 2008 to 2019 was performed. RESULTS: Seventy patients had photopatch testing over the 12-year period. Of the 58 patients tested using the photoallergen series, 6 (10%) patients had a positive photopatch test reaction, of which 4 were to promethazine and 2 were to benzophenone-3. The most common postpatch diagnosis was endogenous dermatitis (54%), followed by allergic contact dermatitis (21%), photoallergic contact dermatitis (9%), and chronic actinic dermatitis (4%). CONCLUSIONS: Both patch and photopatch testing are important investigations in patients with suspected photoallergic contact dermatitis. Promethazine and benzophenone-3 were the most frequent and only photoallergens in our population. Promethazine sensitization was via oral exposure, supporting a mechanism of systematized photoallergy to promethazine.

"Purple Drank" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications.

In the early 1990s, several studies reported the misuse of codeine and promethazine hydrochloride cough syrup. Since then, the combination of this pharmaceutical, together with sprite or alcohol, known on the streets as "purple drank" or "lean", has become a popular drug among rap singers who promote its tranquilizing and euphoric effects through their music and videos. This review examines the "purple drank" phenomenon, taking into consideration its clinical and social implications. The study was conducted using PubMed, Scopus, and Web of Science as search engines, applying several inclusion and exclusion criteria and the string "Purple AND drank", resulting in 138 records. Seven papers that met our criteria were found. The risk of bias assessment, when applicable, was also considered, resulting in a low level of risk. Epidemiological data highlighted a heterogeneous diffusion of the misuse of this mixture, which is not exclusively linked to a specific type of user (African-American teenagers, athletes, and rappers), as previously reported in American newspapers and in the social media. New digital tools should be taken into consideration for further social and medical evaluations of this phenomenon.

Photodermatitis from topical phenothiazines: A case series.

BACKGROUND: In Europe, contact photosensitivity to phenothiazines is well-known, particularly in southern countries. Topical phenothiazines are widely used and sold over-the-counter (OTC) for the treatment of mosquito bites and pruritus in France. OBJECTIVE: To report a series of cases with photodermatitis following use of topical phenothiazines. METHOD: A retrospective study of cases of contact dermatitis from phenothiazines seen in French photodermatology centers was performed. RESULTS: In all, 14 patients with a diagnosis of contact dermatitis from phenothiazines were included. These patients developed eczema on the application sites, and in 13 the eruption spread to photodistributed sites. Topical products containing isothipendyl were the most common cause of photodermatitis. One patient had photoaggravated eczema due to promethazine cream. All patients stopped using topical phenothiazines and were treated successfully with topical corticosteroids. One patient relapsed and developed persistent light eruption. In all of the nine cases tested, photopatch testing to the topical phenothiazine used "as is" was positive. Isothipendyl, chlorproethazine, and the excipients were not tested. Photopatch tests to chlorpromazine and promethazine were positive in 8 of 12 and 7 of 13 tested, respectively. CONCLUSION: Use of isothipendyl and promethazine as OTC (or even prescribed) drugs needs to be limited due to severe reactions and sensitization to other phenothiazines that consequently will have to be avoided.

The risk of fractures, acute myocardial infarction, atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine.

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07-2.63 and OR 3.22; 95% CI 1.69-7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94-5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.

Acute onset of orofacial dystonia from promethazine treatment: A case report.

RATIONALE: Promethazine is an antihistamine agent used commonly for nausea and allergy. Along with its anticholinergic and antidopaminergic functions, promethazine is also used for psychiatric symptoms, such as troubling sleep, anxiety, and agitation. Previous studies have reported that promethazine may occasionally elicit acute dystonia in some individuals, especially for young children and pregnant women. PATIENT CONCERNS: The 68-year-old female patient was admitted to our hospital because of feeling anxious and intermittent palpitation for over 1 year. She developed acute orofacial dystonia following promethazine treatment. DIAGNOSES: Her diagnoses was generalized anxiety disorder. INTERVENTIONS: Discontinuation of the offending agent, promethazine, and injection of Botulinum toxin. OUTCOMES: The acute orofacial dystonia was finally alleviated by local injection of Botulinum toxin. LESSONS: Careful assessment of the risk of developing acute dystonia is also needed in old patients when initiating the promethazine treatment.

Orina verde después de una rectosigmoidoscopia / Green urine after a rectosigmoidoscopy

No disponible

Detecting the diverted use of psychoactive drugs by adolescents and young adults: A pilot study.

PURPOSE: The increasing trend of diversion of nonprescription drugs (NPDs) by adolescents or young adults is worrying. We implemented this pilot study before a national investigation to identify requests for suspected recreational use of psychoactive drugs made by young subjects to community pharmacies. METHODS: Thirty-eight French community pharmacies were asked to complete questionnaire (with age, gender of subjects; name, form, quantity of drugs) for each suspect request formulated by subjects under 26. Besides, pharmacists were asked about the regulatory measures they thought useful to decrease this diverted use by young people. Nineteen pharmacies participated. The study covered from December 12, 2016 to January 23, 2017. RESULTS: Forty-one requests mentioning 51 drugs were reported. They concerned males (85%) aged 20 years old on average, including 6 minors. The most frequent age class was that comprised between 18 and 20 years old. Codeine-containing drugs (29 reports) and promethazine (17 reports), the main components of the popular cocktail "Purple drank," were the most requested, followed by dextromethorphan (3 reports). Fifteen drugs were requested in syrup form. One request concerned the prescription drug ketamine. Pharmacists suggested to schedule the concerned NPDs to prescription-only drugs and to increase the education of students as well as the public. CONCLUSIONS: Codeine and promethazine, the main components of the popular cocktail Purple drank, were the most requested. Suspect requests of psychoactive drugs made by adolescents or young adults in community pharmacies should be carefully surveyed and combined to the monitoring of falsified prescriptions.

Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.

BACKGROUND: Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings. SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence). AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding findings should be interpreted with caution.Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.

Combining evidence from multiple electronic health care databases: performances of one-stage and two-stage meta-analysis in matched case-control studies.

PURPOSE: Clustering of patients in databases is usually ignored in one-stage meta-analysis of multi-database studies using matched case-control data. The aim of this study was to compare bias and efficiency of such a one-stage meta-analysis with a two-stage meta-analysis. METHODS: First, we compared the approaches by generating matched case-control data under 5 simulated scenarios, built by varying: (1) the exposure-outcome association; (2) its variability among databases; (3) the confounding strength of one covariate on this association; (4) its variability; and (5) the (heterogeneous) confounding strength of two covariates. Second, we made the same comparison using empirical data from the ARITMO project, a multiple database study investigating the risk of ventricular arrhythmia following the use of medications with arrhythmogenic potential. In our study, we specifically investigated the effect of current use of promethazine. RESULTS: Bias increased for one-stage meta-analysis with increasing (1) between-database variance of exposure effect and (2) heterogeneous confounding generated by two covariates. The efficiency of one-stage meta-analysis was slightly lower than that of two-stage meta-analysis for the majority of investigated scenarios. Based on ARITMO data, there were no evident differences between one-stage (OR = 1.50, CI = [1.08; 2.08]) and two-stage (OR = 1.55, CI = [1.12; 2.16]) approaches. CONCLUSIONS: When the effect of interest is heterogeneous, a one-stage meta-analysis ignoring clustering gives biased estimates. Two-stage meta-analysis generates estimates at least as accurate and precise as one-stage meta-analysis. However, in a study using small databases and rare exposures and/or outcomes, a correct one-stage meta-analysis becomes essential.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

BACKGROUND: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. AIMS: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). METHODS: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. RESULTS: Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. CONCLUSION: In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients.

A Danish Survey of Antihistamine Use and Poisoning Patterns.

The first-generation antihistamine, promethazine, became a prescription-only drug in Denmark as of December 2014. First-generation antihistamines are known to have a higher toxic potential than second-generation antihistamines. The aim of this study was to provide a nationwide description of the antihistamine use and poisoning pattern from 2007 to 2013 in Denmark based on two independent databases. There were 1049 antihistamine exposures in the national, advisory telephone service specialized in poisonings, the Danish Poison and Information Centre (DPIC), and 456 exposures in the three registers used within the State Serum Institute of Denmark (SSI), a department under the Danish Ministry of Health dealing with research-based health surveillance in Denmark. First-generation antihistamines constitute 61% and 73% of antihistamine registrations in DPIC and SSI, respectively. Antihistamine exposures increased by 7 exposures/10,000 enquiries per year in DPIC and six admissions per year in SSI - this increase is not significant due to a sudden decrease in 2012. Intentional exposures constituted 65% in DPIC of which 82% was due to suicide attempts, and 78% of the involved antihistamines were first-generation antihistamines. Accidental exposures constituted 33% of which 61% were due to play and 29% involved first-generation antihistamines. Single antihistamine exposures constituted 65% of DPIC exposures of which 98% involved only one brand of antihistamine. Multidrug exposures constituted 35% of DPIC exposures with equally distributed coingestants. Hospitalization was recommended in 78% of DPIC exposures. Admissions required only 1-day of treatment in 91% of the SSI exposures. One of the 14 identified deaths in the SSI study population was directly related to antihistamine poisoning. Results support the limited disclosure of promethazine in Denmark and illustrate a generation-specific pattern indicating a suspected replacement of promethazine with other first-generation antihistamines.

A Review of the Ingredients Contained in Over the Counter (OTC) Cough Syrup Formulations in Kenya. Are They Harmful to Infants?

BACKGROUND: Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. METHODS: Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. RESULTS: There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. CONCLUSION: The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy workers and mothers.

Replacement of Promethazine With Ondansetron for Treatment of Opioid- and Trauma-Related Nausea and Vomiting in Tactical Combat Casualty Care.

The current Tactical Combat Casualty Care (TCCC) Guidelines recommend parenteral promethazine as the single agent for the treatment of opioid-induced nausea and/or vomiting and give a secondary indication of "synergistic analgesic effect." Promethazine, however, has a well-documented history of undesired side effects relating to impairment and dysregulation of the central and autonomic nervous systems, such as sedation, extrapyramidal symptoms, dystonia, impairment of psychomotor function, neuroleptic malignant syndrome, and hypotension. These may be particularly worrisome in the combat casualty. Additionally, since 16 September 2009, there has been a US Food and Drug Administration (FDA) black box warning for the injectable form of promethazine, due to "the risk of serious tissue injury when this drug is administered incorrectly." Conversely, ondansetron, which is now available in generic form, has a well-established favorable safety profile and demonstrated efficacy in undifferentiated nausea and vomiting in the emergency department and prehospital settings. It has none of the central and autonomic nervous system side effects noted with promethazine and carries no FDA black box warning. Ondansetron is available in parenteral form and an orally disintegrating tablet, providing multiple safe and effective routes of administration. Despite the fact that it is an off-label use, ondansetron is being increasingly given for acute, undifferentiated nausea and vomiting and is presently being used in the field on combat casualties by some US and Allied Forces. Considering the risks involved with promethazine use, and the efficacy and safety of ondansetron and ondansetron?s availability in a generic form, we recommend removing promethazine from the TCCC Guidelines and replacing it with ondansetron.

[A new approach to the search for vestibuloprotectors].

The results of experimental clinical testing of the antinaupathia action of as new compounds, so motion sickness medications (promethazine, ikaron-1 etc.) are presented. Russian medication mexidol, a derivative of 3-hydroxypyridine (3-HP) demonstrated the ability to control motion sickness in humans and animals; however, unlike reference vestibuloprotector scopolamine, it does not practically produce side-effects. Mexidol acts through ion pathways with the involvement of glutamate and GABA-ergic components. Revealed 9 of new 3-HP derivates with an antimotion sickness effect in rats, three exceeded in efficacy mexidol, and also reference medications (i.e. scopolamine and promethazine). Melatonin achieves a better vestiboloprotective effect in rats than promethazine and melatonin-ergic antidepressant agomelatine through the involvement of melatonin MT1-, MT2- and GABA(A)-receptors. Also, combinations of melatonin with mexidol or promethazine possess a distinct vestibuloprotective effect, as melatonin enhances the action of equally mexidol and promethazine. Analysis of our results and investigations of other authors infer that search for potent vestibuloprotectors should be extended to new 3-HP derivatives and melatoninergic compounds. Individual medications by themselves and in combinations can become a solution to the problem.