Learning from Incidents: Compatibility Issues with Dexamethasone Injection

Introduction

Earlier this year, we identified an issue where a new brand of dexamethasone injection was causing precipitation when combined with other medications in a syringe. This reaction, which had not been a problem with previous brands, raised concerns, and the first instance was reported to the MHRA. We then obtained a response from the manufacturers.

Manufacturer and MHRA Findings

The manufacturers addressed the incident with the following statement:

“There have been reports of incompatibility between dexamethasone and midazolam in literature references, indicating that cloudiness and precipitation can occur, especially when the concentrations are high. According to its Product Information, Dexamethasone Krka 3.3 mg/mL solution for injection/infusion can be mixed with isotonic saline solution, Ringer’s solution, 5% glucose solution, and 10% glucose solution.”

Conclusion from the Manufacturer:

Based on the information received and the investigation performed, the manufacturers concluded that the observed deviation was not related to the product’s quality.

Use of Low-Dose Dexamethasone in Syringe Drivers

Dexamethasone injections are often added to other drugs in a syringe driver at low doses to reduce injection site reactions, thus prolonging the site’s longevity. Where compatibility allows, adding a low dose of dexamethasone (e.g., 0.66 mg) has shown to extend the life of an infusion site by approximately 50%. However, some sites have remained effective for 2-3 weeks without dexamethasone, so routine addition of dexamethasone is not generally recommended (PCF 8, p. 895).

Dexamethasone is known to interact with several medications commonly prescribed in syringe drivers at end of life, including levomepromazine, midazolam, and cyclizine. Due to its long duration of action and alerting effect, dexamethasone is typically administered as a subcutaneous bolus injection once daily in the morning.

Factors Affecting Drug Stability and Compatibility

Drug stability and compatibility in syringe drivers depend on various complex factors, including:

Drug Concentration and Relative Concentrations

Brand Differences: Variations in preservatives, diluents, and stabilising compounds can differ between brands and even different strengths.

Formulation Differences: Compatibility for drugs like oxycodone can vary based on concentration, such as 10 mg/mL vs. 50 mg/mL.

Diluent Choice: Water for Injection (WFI) is generally preferred unless specific indications exist for Sodium Chloride 0.9%.

Infusion Time: Higher temperatures can increase infusion rates.

Exposure to Light: Some drugs, such as levomepromazine, may discolour (e.g., turn purple, pink, or yellow) when exposed to light, requiring protection of the syringe.

Ambient Temperature: Higher temperatures can accelerate infusion rates.

Order of Mixing: The order in which drugs are combined in the syringe is essential, particularly when compatibility is concentration-dependent. Dexamethasone, for example, should be added last to a diluted and mixed syringe to reduce incompatibility risks.

The Palliative Care Formulary (PCF8) recommends WFI as the preferred diluent for syringe drivers unless Sodium Chloride 0.9% is specifically indicated (e.g., for Furosemide CSCI) or there is a potential for inflammatory reactions at the injection site (PCF 8, p. 890).

References

• Palliative Care Formulary, 8th Edition, 2022 – Wilcox, Howard, and Charlesworth
• Isle of Wight Palliative Care Symptom Control Guidelines, May 2021 – Dr. Paul Howard

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