The Physical Compatibility of Clinically Used Concentrations of Diltiazem Hydrochloride With Heparin Sodium

Background: Acute treatment of atrial fibrillation often requires concomitant intravenous (IV) continuous infusions of unfractionated heparin and diltiazem. Concomitantly infusing these medications through the same IV line minimizes multiple IV sites. Diltiazem and heparin visual compatibility have been previously investigated but with limited drug dwell times and differing drug concentrations leading to inconsistent published results. Objective: To investigate the physical compatibility of diltiazem hydrochloride at concentrations of 5 and 1 mg/mL combined with an equal volume of heparin sodium 100 units/mL. Methods: Using a 0.22-µm filter, 15 mL of heparin sodium were placed into a polyvinyl chloride infusion bag followed by 15 mL of either diltiazem hydrochloride 5 or 1 mg/mL. Admixtures were prepared in triplicate. Each admixture was investigated for visual precipitation, spectrophotometric absorbance, and pH change at baseline and 1, 5, 8, and 24 hours after mixing. Physical incompatibility was determined by visual observation, increased spectrophotometric absorbance, and demonstrative pH changes. Results: Each diltiazem 5 mg/mL admixture exhibited a slight haze and enhanced absorbance readings indicating turbidity while none revealed a demonstrative pH change. None of the diltiazem 1 mg/mL assessments revealed visual precipitation or suggested turbidity. Only one pH reading at 5 hours revealed a demonstrative change from baseline. Conclusions: Our findings indicate that infusing diltiazem hydrochloride 5 mg/mL with heparin sodium 100 units/mL in the same IV line cannot be advocated. In contrast, our findings suggest that heparin sodium 100 units/mL infused with diltiazem hydrochloride 1 mg/mL is physically compatible but chemical stability was not assessed.

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Compatibility and Stability of Paclitaxel Combined with Doxorubicin Hydrochloride in Infusion Solutions

Annals of Pharmacotherapy ◽

10.1345/aph.17400 ◽

1998 ◽

Vol 32 (10) ◽

pp. 1013-1016 ◽

Cited By ~ 6

Author(s):

Lawrence A Trissel ◽

Quanyun A Xu ◽

Doward L Gilbert

Keyword(s):

Chemical Stability ◽

High Intensity ◽

Physical Stability ◽

Visual Observation ◽

Fluorescent Light ◽

Doxorubicin Hydrochloride ◽

Particle Content ◽

Drug Concentrations ◽

Physical And Chemical ◽

Storage Temperatures

OBJECTIVE: To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 300 and 1200 μg/mL with doxorubicin hydrochloride 200 μg/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 °C. DESIGN: The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at 4, 23, and 32 °C for physical and chemical stability. Physical stability was assessed by using visual observation in normal fluorescent light and a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the two drugs was evaluated by using two stability-indicating HPLC analytic techniques. RESULTS: All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred within 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained at more than 97% in all samples throughout the study. Doxorubicin hydrochloride also was stable throughout the study period, remaining above 90% in all samples at all storage temperatures. CONCLUSIONS: Admixtures of paclitaxel 300 and 1200 μg/mL with doxorubicin hydrochloride are limited in their utility time by paclitaxel microcrystalline precipitation. All combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 °C.

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Compatibility and Stability of Paclitaxel Combined with Cisplatin and with Carboplatin in Infusion Solutions

Annals of Pharmacotherapy ◽

10.1177/106002809703101204 ◽

1997 ◽

Vol 31 (12) ◽

pp. 1465-1470 ◽

Cited By ~ 7

Author(s):

Yanping Zhang ◽

Quanyun A Xu ◽

Lawrence A Trissel ◽

Doward L Gilbert ◽

J Frank Martinez

Keyword(s):

Light Beam ◽

Chemical Stability ◽

High Intensity ◽

Physical Stability ◽

Analytical Techniques ◽

Visual Observation ◽

Particle Content ◽

Drug Concentrations ◽

Normal Light ◽

Physical And Chemical

OBJECTIVE: To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 0.3 and 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection and with carboplatin 2 mg/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32°C. DESIGN: The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at temperatures of 4, 23, and 32°C for physical and chemical stability. Physical stability was assessed by using visual observation in normal light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the three drugs was evaluated by using three stability-indicating HPLC analytical techniques. RESULTS: All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred in 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained above 90% in all samples throughout the study. Cisplatin admixtures exhibited paclitaxel concentration-dependent decomposition with cisplatin losses of approximately 5–8% in 4 hours and approximately 20% in 1 day at 23 and 32°C in the paclitaxel 1.2 mg/mL admixtures. With paclitaxel 0.3 mg/mL in the admixtures, cisplatin losses were about 10% in 7 days at these temperatures. Carboplatin in admixtures with both concentrations of paclitaxel was stable for 7 days at 4°C, but sustained losses of about 10% and 12% in 3 days at 23 and 32°C, respectively. CONCLUSIONS: Admixtures of paclitaxel 0.3 and 1.2 mg/mL with cisplatin and carboplatin are limited in their utility time by both paclitaxel microcrystalline precipitation and decomposition of cisplatin and carboplatin. The admixture of paclitaxel 1.2 mg/mL with cisplatin 0.2 mg/mL in NaCl 0.9% injection exhibits unacceptable cisplatin loss in 24 hours. All other combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32°C.

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P984 Nadroparin versus unfractionated heparin for anticoagulation of all cause atrial fibrillation: preliminary results of the NADROPAF trial

European Heart Journal ◽

10.1016/s0195-668x(03)94276-x ◽

2003 ◽

Vol 24 (5) ◽

pp. 167

Author(s):

H GAMRA

Keyword(s):

Atrial Fibrillation ◽

Unfractionated Heparin ◽

Preliminary Results

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Impact of International Normalized Ratio and Activated Clotting Time on Unfractionated Heparin Dosing During Ablation of Atrial Fibrillation

Circulation Arrhythmia and Electrophysiology ◽

10.1161/circep.113.979088 ◽

2013 ◽

Vol 6 (3) ◽

pp. 491-496 ◽

Cited By ~ 14

Author(s):

Ismail Hamam ◽

Emile G. Daoud ◽

Jianying Zhang ◽

Steven J. Kalbfleisch ◽

Ralph Augostini ◽

...

Keyword(s):

Atrial Fibrillation ◽

Unfractionated Heparin ◽

International Normalized Ratio ◽

Clotting Time ◽

Activated Clotting Time

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Safety and timing of resuming dabigatran after major gastrointestinal bleeding reversed by idarucizumab

SAGE Open Medical Case Reports ◽

10.1177/2050313x17753336 ◽

2018 ◽

Vol 6 ◽

pp. 2050313X1775333 ◽

Cited By ~ 1

Author(s):

Gian Galeazzo Riario Sforza ◽

Francesco Gentile ◽

Fabio Stock ◽

Francesco Caggiano ◽

Enrica Chiocca ◽

...

Keyword(s):

Atrial Fibrillation ◽

Case Report ◽

Major Bleeding ◽

Acute Treatment ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Oral Vitamin ◽

Bleeding Events ◽

Massive Rectal Bleeding

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients.

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Extended Stability of Sodium Phosphate Solutions in Polyvinyl Chloride Bags

The Canadian Journal of Hospital Pharmacy ◽

10.4212/cjhp.v70i1.1622 ◽

2017 ◽

Vol 70 (1) ◽

Author(s):

William Perks ◽

John Iazzetta ◽

Pak Cheung Chan ◽

Athina Brouzas ◽

Shirley Law ◽

...

Keyword(s):

United States ◽

Polyvinyl Chloride ◽

Chemical Stability ◽

Sodium Phosphate ◽

United States Pharmacopeia ◽

Moisture Loss ◽

Initial Concentration ◽

Phosphate Injection ◽

Phosphate Solutions ◽

States Pharmacopeia

ABSTRACTBackground: Sodium phosphate injection is used to treat moderate to severe hypophosphatemia. There have been no published reports documenting the physical compatibility or chemical stability of sodium phosphate injection in IV solutions.Objective: To evaluate the physical compatibility and chemical stability of 30 and 150 mmol/L solutions of phosphate, prepared from sodium phosphate injection, in 5% dextrose in water (D5W) and in 0.9% sodium chloride (normal saline [NS]) and stored in polyvinyl chloride (PVC) bags at 23°C or 4°C over 63 days.Methods: On study day 0, solutions of phosphate 30 and 150 mmol/L in D5W or NS were prepared in PVC bags and stored at 4°C and 23°C. On prespecified days during the 63-day study period, the concentrations of sodium and phosphate were determined, and admixture weight was checked to assess moisture loss during storage without a plastic overwrap. Chemical stability was calculated from the intersection of the lower 95% confidence limit of the degradation rate and the lower limit of acceptability (90%) for concentration remaining.Results: The analytical methods for both sodium and phosphate were found to be precise (coefficient of variation averaging less than 1% for pre-study validation samples). Both sodium and phosphate retained more than 94% of the initial concentration over the 63-day study period. With 95% confidence, the time to achieve 90% of the initial concentration of both sodium and phosphate approached or exceeded the 63-day study period, regardless of temperature, concentration, or base solution.Conclusions: Sodium phosphate solutions at a phosphate concentration of 30 or 150 mmol/L in either NS or D5W retained more than 94% of the initial concentration of both sodium and phosphate over 63 days when stored at 23°C or 4°C. In compliance with United States Pharmacopeia General Chapter <797> recommendations, a beyond-use date of 14 days (with refrigeration) or 48 h (room temperature) may be applied. Extending the beyond-use date beyond these limits may be considered, if a validated sterility test is performed.RÉSUMÉContexte : Le phosphate de sodium injectable est employé pour traiter l’hypophosphatémie modérée et grave. À ce jour, aucun rapport portant sur la compatibilité physique ou la stabilité chimique du phosphate de sodium injectable contenu dans les solutions intraveineuses n’a été publié. Objectif : Évaluer la compatibilité physique et la stabilité chimique de solutions de phosphate à des concentrations de 30 et de 150 mmol/L préparées à partir de phosphate de sodium injectable dilué dans du dextrose à 5 % dans l’eau (D5E) ou du chlorure de sodium à 0,9 % (solution physiologique salée [SP]) puis rangées dans des sacs de polychlorure de vinyle (PVC) à des températures de 4 °C ou de 23 °C pendant 63 jours.Méthodes : Au jour 0 de l’étude, les solutions de phosphate à des concentrations de 30 et de 150 mmol/L ont été préparées avec du D5E ou de la SP dans des sacs de PVC, puis entreposées à des températures de 4 °C ou de 23 °C. À des jours donnés pendant la période de 63 jours de l’étude, on a évalué les concentrations de sodium et de phosphate et l’on a pesé les mélanges pour vérifier la perte d’humidité pendant un entreposage n’utilisant pas de suremballage de plastique. La stabilité chimique était calculée au point d’intersection entre la limite inférieure de confiance à 95 % du taux de dégradation et la limite inférieure d’acceptabilité (90 %) de la concentration restante.Résultats : Les méthodes analytiques employées pour évaluer le sodium et le phosphate se sont révélées précises (coefficient de variation moyen inférieur à 1 % pour les échantillons aux fins de validation avant l’étude). Le sodium et le phosphate conservaient chacun plus de 94 % de leurs concentrations initiales pendant la période d’étude de 63 jours. Avec un niveau de confiance de 95 %, le temps nécessaire pour atteindre 90 % de la concentration initiale pour le sodium et pour le phosphate approchait ou dépassait les 63 jours de la période d’étude, peu importe la température, la concentration ou la solution de base.Conclusions : Les solutions de phosphate de sodium dont la concentration en phosphate est de 30 ou de 150 mmol/L, qu’elles soient à base de D5E ou de SP, conservaient plus de 94 % des concentrations initiales de sodium et de phosphate pendant 63 jours, qu’elles soient entreposées à des températures de 4 °C ou de 23 °C. Conformément aux recommandations contenues dans le chapitre <797> de la United States Pharmacopeia, une date limite d’utilisation de 14 jours (sous réfrigération) ou de 48 heures (à température ambiante) peut être utilisée. Allonger la date limite d’utilisation au-delà des bornes fixées par l’organisme américain peut être envisageable si une épreuve validée de stérilité est réalisée.

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Compatibility of treprostinil sodium and dopamine hydrochloride during simulated Y-site administration

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxaa025 ◽

2020 ◽

Vol 77 (8) ◽

pp. 649-657

Author(s):

Anna Bustin ◽

E Zachary Ramsey ◽

Brian D Hanna ◽

Gagan Kaushal

Keyword(s):

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

Chemical Stability ◽

High Performance ◽

Stability Testing ◽

Visual Examination ◽

Stability Indicating ◽

Drug Concentrations ◽

Dopamine Hydrochloride ◽

Physical And Chemical

Abstract Purpose To evaluate the physical and chemical compatibilities of treprostinil sodium and dopamine hydrochloride. Methods Treprostinil sodium (4,000, 76,000, and 500,000 ng/mL) were mixed with dopamine hydrochloride (0.6, 3.2, 6, and 40 mg/mL). Samples were obtained at hours 0, 1, 2, and 4 for physical compatibility and chemical stability testing. Physical compatibility was assessed by visual examination and measurements of turbidity and pH. Drug concentrations were assessed using stability-indicating liquid chromatography mass spectrophotometry (LCMS) for treprostinil sodium and stability-indicating high-performance liquid chromatography (HPLC) for dopamine hydrochloride. Results Treprostinil sodium 4,000 and 76,000 ng/mL, when mixed with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL, were stable for 4 hours. Treprostinil sodium 500,000 ng/mL was stable when mixed with dopamine hydrochloride 0.6 mg/mL for 4 hours, but when mixed with dopamine hydrochloride 3.2, 6, and 40 mg/mL, significant precipitation was seen. Conclusion Treprostinil sodium 4,000 and 76,000 ng/mL were stable for 4 hours during simulated Y-site coadministration with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL. Treprostinil sodium 500,000 ng/mL is stable when mixed with dopamine hydrochloride 0.6 mg/mL.

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Pirmenol: appears effective in the acute treatment of paroxysmal atrial fibrillation

InPharma ◽

10.1007/bf03299015 ◽

1986 ◽

Vol 530 (1) ◽

pp. 5-5

Keyword(s):

Atrial Fibrillation ◽

Paroxysmal Atrial Fibrillation ◽

Acute Treatment

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Drug Stability: Rapid Loss of Fentanyl Citrate Admixed with Fluorouracil in Polyvinyl Chloride Containers

Annals of Pharmacotherapy ◽

10.1177/106002809703100305 ◽

1997 ◽

Vol 31 (3) ◽

pp. 297-302 ◽

Cited By ~ 4

Author(s):

Quanyun A Xu ◽

Lawrence A Trissel ◽

Juan F Martinez

Keyword(s):

Sodium Chloride ◽

Polyvinyl Chloride ◽

Chemical Stability ◽

Drug Stability ◽

Alkaline Ph ◽

Rapid Loss ◽

Fentanyl Citrate ◽

Particle Content ◽

Light Obscuration ◽

Particle Sizer

Objective To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 μg/mL in dextrose 5% and in sodium chloride 0.9% injection. Design Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at −20, 4, 23, and 32 °C. Samples were removed immediately and at various times over 7 days and stored at −70 °C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. Results Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23,32 °C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0–9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time. Conclusions When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 μg/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.

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