Drug Incompatibilities Research Articles

Application of thermal analysis to the study of anti-tuberculosis drug compatibility. Part 1

Worldwide Brazil is among one of the 22 countries with high rates of tuberculosis placing this disease as a priority for the Government Health Policies in this country. Studies with the main tuberculostatic drugs rifampicin, isoniazid, pyrazinamide, and ethambutol, aiming the development of fixed-dose combination formulations (FDCs) have been performed. The aim of this study was to evaluate the thermal behavior of these drugs by DSC, TG/DTG, and DTA in order to predict possible physical and chemical interactions between tuberculostatics. DSC and DTA curves suggested incompatibility and/or interactions among drug preparations resulting from new thermal events, as well as the disappearance and shift of the melting point of the drugs. TG/DTG curves of drug mixtures presented different profiles from those observed for the individually tested drugs, supporting the evidence of drug incompatibility and indicating that mixtures are less stable when compared to the drugs alone.

Study on words about taboos in ancient literature on materia medica

Words about drug taboos are often used in ancient literature on materia medica. It has been found by analysis of their application that taboo words have their own scope of application. For example, 'fan' and 'wu' are used most in drug incompatibility; 'jin', 'ji' and 'jie' are used in taboos on drugs and food for patients; words such as 'should not be eaten with…', 'wu, wuyu (wufan)…' and 'buyu…and buyi' are primarily used in taboos for food. Adverse incidents could be found in situations described by those words, especially in sections about drug and food taboos.

Errors in the administration of intravenous medications in hospital and the role of correct procedures and nurse experience

BackgroundIntravenous medication administrations have a high incidence of error but there is limited evidence of associated factors or error severity.ObjectiveTo measure the frequency, type and severity of intravenous administration errors...

26 In-Line Filtration Reduces Sirs in Critically Ill Children

Objectives: Sepsis, systemic inflammatory response syndrome (SIRS) or organ failure often complicate the clinical course on intensive care units. Particulate contamination of infusion solution may contribute to clinical deterioration of these patients. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. In-line filtration almost completely prevents particulate infusion. We assessed the effect of in-line filtration on reduction of major complications in critically ill children (Clinical Trials.gov ID NCT 00209768). Patients and Methods: In a randomised, prospective trial children admitted to interdisciplinary PICU of tertiary university hospital were assigned to either control or interventional group, the latter receiving in-line filtration (infusion filter Pall ELD96LLCE/NOE96E, Braun Intrapur Lipid/ Intrapur Neonat Lipid) throughout infusion therapy. Prior to this study, infusion regiment was optimised to prevent precipitation and incompatibilities of solutions and drugs. Primary objectives included a reduction in incidence of sepsis, thrombosis, systemic inflammatory response syndrome (SIRS), organ failure (liver, lung, kidney, circulation) and mortality. Results: 807 children (343 female, 464 male) with heterogeneous background of underlying diagnoses and Gaussian distribution to either control or in-line filtration group were included. According to study criteria a significant reduction in incidence of SIRS for interventional group (95% CI, 145 versus 200 patients, P< 0.001) was evident. No differences were demonstrated for occurrence of sepsis, thrombosis, organ failure (liver, lung, kidney, circulation) or mortality between both groups. Conclusion: SIRS often complicates treatment in intensive care medicine. Inline-filtration is most effective reducing the incidence of SIRS and offers a novel therapeutic option.

A purging procedure for pantoprazole and 4-lumen catheters to prevent IV drug incompatibilities

The purpose of this prospective intervention study was to assess the number of patients with Y-site incompatibilities before and after implementation of quality improvement measures to prevent incompatibilities consisting of a focused instruction for pantoprazole as a drug frequently involved in incompatible drug pairs and of a recommendation to use 4-lumen instead of 3-lumen catheters to increase the number of available central infusion lines. Cardiovascular intensive care unit where several standard operating procedures (SOPs) dealing with compatibility were already in place. In a prospective intervention study, patients' IV medication was assessed for potential incompatibilities using a database containing compatibility information on approximately 60,000 drug pairs. In a first period, routine administration was monitored in 53 consecutive patients (control group). Then, quality improvement measures were implemented recommending a purging procedure before and after bolus administration of pantoprazole as a drug frequently causing incompatibilities in this setting. Additionally, the use of 4-lumen instead of 3-lumen catheters was suggested whenever considered useful by the responsible physicians. The monitoring was repeated during a second period in another 58 patients consecutively admitted to the same unit (intervention group). Overall number of patients with at least one incompatible drug pair and number of patients receiving incompatible pantoprazole combinations. The number of patients receiving incompatible pantoprazole combinations decreased from 15 of the 15 patients receiving pantoprazole (100.0%) in controls to 9/16 (56.2%) in the intervention group (P < 0.01). The overall number of patients with incompatibilities was not influenced by the intervention with 36/58 (62.1%) compared to controls with 38/53 (71.7%, P = 0.28). The fraction of central lines contributed by four lumen central catheters was larger due to the intervention (80/168 lines, 47.6%) compared to controls (16/184, 8.7%, P < 0.001). Only sporadically there were incompatible combinations of drugs governed by the already existing SOPs. In an intensive care setting with good SOP adherence, purging before and after administration decreased the respective incompatibility rate whereas the use of 4-lumen instead of 3- lumen catheters had not the expected benefit on separating drug pairs.

Targeting tacrolimus to deeper layers of skin with improved safety for treatment of atopic dermatitis

Atopic dermatitis (AD) is chronically relapsing eczematous skin disorder having significant impact worldwide. Tacrolimus is the drug-of-choice which inhibits T-cell activation resulting in suppression of inflammation. However, despite being effective, most common adverse events of tacrolimus are low-and-variable bioavailability, burning sensation and pruritus at application site, which prompt for development of novel carrier that could effectively target tacrolimus to site-of-action without producing undesirable side-effects. Tacrolimus-loaded lipid-nanoparticles (T-LN) were prepared and optimized. DSC and FT-IR have been employed to study drug-excipient incompatibility and encapsulation of drug in lipid which was further confirmed by 1H NMR. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to reference Protopic ®. In vitro and in vivo occlusion studies demonstrated similar occlusiveness for T-LN and reference however; T-LN showed significantly higher drug levels penetrating into deeper skin layers where dendritic cells responsible for immunopathogenesis of AD mainly reside. In-vivo skin retention demonstrated 3.36, 30.81 and 28.68-times higher stratum corneum, epidermal and dermal levels respectively compared to reference. Visualization of cutaneous uptake in-vivo using CLSM confirmed targeting to deeper skin layers and Draize test showed no skin irritation with PII 0.00. Thus T-LN displayed superior performance, effective skin targeting and improved safety as compared to reference.

Evaluation of tools to prevent drug incompatibilities in paediatric and neonatal intensive care units

Intravenous drug administration in neonatal (NICU) and paediatric intensive care units (PICU) is critical because of poor venous access, polymedication, fluid restriction and low infusion rate. Risk is further increased by inadequate information on the physicochemical compatibility of drugs. Eight decision-supporting tools were hence evaluated to improve the detection of drug incompatibilities in paediatric wards. NICU and PICU, University hospital. Eight tools (Thériaque 2007, Stabilis 3, Perfysi 2 databases; KIK 3.0 software; Neofax 2007 handbook; King 2008 Guide, CHUV 9.0, pH 2007 cross-tables) were assessed by two pharmacists using 40 drug pairs (20 incompatible; 20 compatible) frequently prescribed in PICUs and NICUs. Trissel's 14th Ed. handbook served as the gold standard. Four criteria were evaluated (each with a maximum of 250 points): accuracy (sensitivity, specificity, positive and negative predictive values), completeness (number of drug pairs documented), comprehensiveness (presence of 16 different items), and applicability (by combining the time needed by 7 pharmacists to classify 5 drug pairs, plus an evaluation of their design, usefulness, reliability and ergonomics, using visual analogy scales). The percentage of non-compliant answers (NCA) was calculated for both the performing pharmacists and the tools. Global score of drug incompatibilities (accuracy + completeness + comprehensiveness + applicability). Thériaque obtained the best global score (840/1000 points), followed by pH (807), CHUV (803), Perfysi (776), Neofax (678), King Guide (642), Stabilis (584) and KIK (523), respectively. The highest scores were reached by Thériaque for accuracy (234/250); Thériaque and pH for completeness (200/250); Thériaque and Perfysi for comprehensiveness (218/250); and pH for applicability (298/250). The range of pharmacists' NCAs was between 9% (4/45 NCAs) and 33% (15/45), whereas that for drug pairs was between 10% (6/63) and 30% (19/63). The range of NCAs for tools was between 6% (2/35, pH) and 49% (18/35, Perfysi). Thériaque proved outstanding as a drug-incompatibility tool. However, all resources showed some shortcomings. The large ranges of pharmacists' NCAs shows that such an assessment is subject to different interpretations. Standard operating procedures for drug-incompatibility assessment should be implemented in drug-information centres. Tools with low NCA percentage, such as the pH or CHUV tables, may be useful for nurses in ICUs.

Crux of drug compatibility and incompatibility

Compatibility and incompatibility of injectable drugs depend on multiple chemical and physical factors of which the crux is classifying organic drugs as either acid cations or base anions according to the three-letter endings of the nondrug ions in the drug salt names, and then avoiding mixtures of

Drug incompatibility in anesthesia - A word of caution

Drug incompatibility in anesthesia - A word of caution

One-year follow-up on procedure to prevent i.v. drug incompatibilities in an intensive care unit

Incompatibility of drug solutions administered through a common line may jeopardize the safety and effectiveness of i.v. drug therapies.[1][1] We recently reported that, in the absence of dedicated preventive strategies, incompatibilities are alarmingly frequent in an intensive care setting.[2][2]

Ceftobiprole: First Cephalosporin with Activity Against Methicillin‐Resistant Staphylococcus aureus

Ceftobiprole medocaril is the first member of a new series of advanced cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). The drug received an approvable letter from the United States Food and Drug Administration (FDA) in March 2008 and from Health Canada in June 2008 for the treatment of complicated skin and skin structure infections including diabetic foot infections. Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin-binding proteins (PBPs) involved in cell wall synthesis. It has an established stability against hydrolysis by many gram-positive beta-lactamases and a higher affinity for various PBPs (such as PBP2a of MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of activity compared with older beta-lactams. Ceftobiprole activity does not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae and some other pathogens, including Enterococcus faecium or Acinetobacter baumanii. Generally well tolerated, with nausea and taste disturbance being the most common adverse events, ceftobiprole appeared noninferior to empiric therapy in several clinical trials. Ceftobiprole is available only for intravenous administration; recommended dosage regimens have not been approved by the FDA as of this writing. However, based on the Canadian package insert, expected dosage recommendations are 500 mg as a 1-hour intravenous infusion every 12 hours for the treatment of complicated skin and skin structure infections caused by certain gram-positive pathogens, and 500 mg as a 2-hour infusion every 8 hours when susceptible gram-negative or both gram-positive and susceptible gram-negative pathogens are involved. Dosage adjustments are indicated for patients with moderate or severe renal impairment, and dosage recommendations are expected to be 500 or 250 mg, respectively, as a 2-hour infusion every 12 hours. Several precautions regarding hypersensitivity and drug incompatibility are reported. Ceftobiprole represents a promising option for the treatment of mono- and polymicrobial infections caused by multidrug-resistant gram-positive and susceptible gram-negative pathogens, but further toxicity and safety studies are warranted.

Calcipotriene plus betamethasone dipropionate gel: a new combination therapy for scalp psoriasis

In 50–80% of patients with plaque psoriasis, the scalp is involved. The scalp may also be the only part of the body affected by plaque psoriasis. Topical steroids and calcipotriene are the mainstay of treatment for scalp psoriasis. They are used as monotherapy or in combination in a morning/evening regimen owing to drug incompatibility. Recently, the US FDA approved a once-daily, stable combination gel containing calcipotriene and betamethasone dipropionate (Taclonex Scalp®). This product has been marketed in other countries under the name Xamiol®. It is convenient, with a faster speed of onset and greater efficacy than its individual active ingredients and also when compared with twice-daily calcipotriene scalp solution. After 2 weeks of therapy, approximately 60% of patients have absent or very mild disease; this number increases to approximately 70% after 8 weeks of therapy. The product is well tolerated with a short-term safety profile similar to betamethasone dipropionate. In clinical trials, approxi...

Drug incompatibility chemistry

The chemical interactions that cause drug incompatibility in solutions, with emphasis on the acid-base and ionized-nonionized forms of organic, weak, electrolyte drugs, are examined. When the dilution or mixing of the salt or ionized forms of organic drugs results in precipitation, the most likely cause is formation of the nonionized drug forms. More than 90% of drugs are organic, weak electrolytes, especially those compounded, manufactured, or reconstituted as injections in predominantly ionized or salt forms. Acid-base reactions are the most common causes of drug incompatibility as precipitation of nonionized drug forms. Precipitation is likely when oppositely charged, organic drug ions that contain aromatic rings are combined in relatively strong concentrations. Salts of polyvalent anions and cations are generally less soluble than salts in which both ions are monovalent or in which one ion is monovalent and its opposite ion is polyvalent. The most clinically important potential precipitates among these ions are dibasic and monohydrogen calcium phosphate. Incompatibility of drug and nutrient injections is clinically hazardous. Knowledge of products' chemical facts, organic acid-base equilibria in relation to ionization and nonionization and aqueous solubility, and ranges of pH and ingredient strength from United States Pharmacopeia monographs and product labeling is the foundation of expertise in drug incompatibility. Precipitation in injectable drug solutions should be suspected, particularly when oppositely charged drug salts are mixed in relatively strong concentrations and when pH values of dilutions create more than 1% of nonionized drug forms.

Prevention of intravenous drug incompatibilities in an intensive care unit

The frequency of drug administration errors and incompatibilities between intravenous drugs before and after an intervention in an intensive care unit (ICU) is discussed. Critically ill adult patients with intoxications, multiorgan failure, and serious infections were included in a retrospective analysis and in a prospective two-period, one-sequence study. In the retrospective analysis, the most frequent brands of i.v. medications used in the ICU of a gastroenterologic department in a teaching hospital were identified. All possible combinations and resulting incompatibilities were defined. Based on the results, a standard operating procedure (SOP) was established to prevent frequent and well-documented incompatibilities among i.v. medications. In the prospective study, trained pharmacy students assessed incompatible coinfusions before and after SOP implementation. In the retrospective analysis of 100 patients, 3617 brands of drug pairs were potentially given concurrently through one i.v. line and 7.2% of the drug pairs were incompatible. Antibiotics, such as piperacillin-tazobactam and imipenem-cilastatin, were the most frequent incompatible drug pairs. The newly developed SOP mandated that administration of these drugs be separated from all other drugs and suggested the use of an idle i.v. line for infusion whenever possible. In the prospective study of 50 patients, the frequency of incompatible drug pairs was reduced by the time of intervention from 5.8% to 2.4%. Incompatible drug pairs that were governed by the new SOP were reduced from 1.9% to 0.5%. Administration of incompatible i.v. drugs in critically ill patients was frequent but significantly reduced by procedural interventions with SOPs.

Drug Incompatibility With Methylprednisolone

Journal of Neurosurgical Anesthesiology: July 2008 - Volume 20 - Issue 3 - p 209-210 doi: 10.1097/ANA.0b013e31817713a1

Drug incompatibility reaction with use of fluorescein during anaesthesia

Drug incompatibility reaction with use of fluorescein during anaesthesia

Possible pharmacologic interactions caused by mixed infusion

It is usual practice in ICUs to infuse several drugs and fluids over a limited number of lines. The danger of drug incompatibility is imminent to this regimen.

Profile of drug interactions in hospitalized children.

The expected therapeutic response may be affected by the presence of drug interactions. With the high number of reports on new drug interactions, it has been difficult for health professionals to keep constantly updated. For this reason, computer systems have helped identify such interactions. To verify the rate and profile of drug interactions in medical prescriptions to hospitalized pediatric patients. A descriptive study investigated prescriptions to hospitalized pediatric patients. The study included patients between 0 and 12 years old, containing 4 or more drugs in their prescriptions. The analysis of interaction and incompatibility possibilities in prescribed drugs used Micromedex / Drug-Reax® program. From 2005 to 2006, 3,170 patients were investigated, and 11,181 prescriptions were analyzed, a mean value of 3.5 prescriptions/patient. In total, 6,857 drug interactions were found, which corresponds to 1.9 interaction/prescription. Among them, relevance to ampicillin and gentamicin, found in 220 (3.2%) prescriptions. In total, 2,411 drug incompatibilities in via y were found, a mean value of 0.5/prescription, with emphasis on vancomycin and cefepime, found in 243 (10.0%) prescriptions. The presence of drug interactions is a permanent risk in hospitals. This way, the utilization of computer programs, pharmacotherapy monitoring of patients and the pharmacist presence in the multidisciplinary team are some manners of contributing to hospitalized patients' treatment.

Integration and verification of semantic constraints in adaptive process management systems

Adaptivity in process management systems is key to their successful applicability in practice. Approaches have been already developed to ensure system correctness after arbitrary process changes at the syntactical level (e.g., avoiding inconsistencies such as deadlocks or missing input parameters after a process change). However, errors may be still caused at the semantical level (e.g., violation of business rules). Therefore, the integration and verification of domain knowledge will flag a milestone in the development of adaptive process management technology. In this paper, we introduce a framework for defining semantic constraints over processes in such a way that they can express real-world domain knowledge on the one hand and are still manageable concerning the effort for maintenance and semantic process verification on the other hand. This can be used to detect semantic conflicts (e.g., drug incompatibilities) when modeling process templates, applying ad hoc changes at process instance level, and propagating process template modifications to already running process instances, even if they have been already individually modified themselves; i.e., we present techniques to ensure semantic correctness for single and concurrent changes which are, in addition, minimal regarding the set of semantic constraints to be checked. Together with further optimizations of the semantic checks based on certain process meta model properties this allows for efficiently verifying processes. Altogether, the framework presented in this paper provides the basis for process management systems which are adaptive and semantic-aware at the same time.

Calcipotriene/betamethasone dipropionate: a new topical ointment for psoriasis

Topical steroids and calcipotriene are the mainstay of treatment for mild-to-moderate psoriasis. They are used as monotherapy or in combination in an a.m./p.m. regimen owing to drug incompatibility. Recently, the US FDA approved a once-daily stable two-compound ointment containing calcipotriene and betamethasone dipropionate (Taclonex®). This product has been marketed in other countries under the names Dovobet® and Daivobet®. It is convenient with a faster speed of onset and greater efficacy than its individual ingredients or tacalcitol. After 4 weeks of therapy, the psoriasis area and severity index is reduced by approximately 70% and half of the patients have absent or very mild disease. Furthermore, more than half of the patients reach PASI-75 after 4 weeks of treatment. The calcipotriene/betamethasone dipropionate ointment is well tolerated with a safety profile similar to betamethasone dipropionate. It is associated with 50 and 75% fewer cutaneous adverse events than calcipotriene and tacalcitol, res...