Is a mixture of 99.1% deionized water and 0.9% benzyl alcohol (BA) compatible with Doxylamine?

Compatibility of 99.1% Deionized Water and 0.9% Benzyl Alcohol with Doxylamine

The mixture of 99.1% deionized water and 0.9% benzyl alcohol (30ml) is likely compatible with doxylamine, but formal compatibility studies are lacking and caution is warranted due to potential chemical interactions.

Compatibility Assessment

Chemical Properties and Considerations

• Benzyl alcohol is commonly used as a preservative and solvent in pharmaceutical preparations at concentrations ranging from 0.9% to 5% 1
• The 0.9% concentration of benzyl alcohol in the proposed mixture is within the lower range of typical pharmaceutical applications, suggesting minimal risk of toxicity
• Doxylamine is an antihistamine that has been studied in various formulations, but specific compatibility data with benzyl alcohol is limited 2

Safety Considerations

• Mixing of medications with parenteral solutions should be avoided unless validated by the manufacturer or an accredited laboratory 3
• Drugs that ionize in aqueous solutions are most likely to cause precipitation, and the pH of the mixture can significantly affect compatibility 3
• The behavior of fluids within infusion tubing, particularly at low flow rates, can lead to "non-circulating fluid spaces" where medications can pool 3

Risk Assessment

Potential Concerns

• Benzyl alcohol has been associated with:

  • Cytotoxicity at higher concentrations 4
  • Rare sensitization reactions (0.21% of patients in patch testing) 5
  • Potential for irritation and non-immunologic contact reactions at concentrations above 2-5% 6

• However, these risks are minimized by:

  • The low concentration (0.9%) in the proposed mixture
  • The established safety profile of benzyl alcohol at this concentration
  • The acceptable daily intake established by WHO at 5 mg/kg for benzyl alcohol 6

Stability Considerations

• Benzyl alcohol is metabolized to benzoic acid in the human body 6
• Long-term toxicology studies have shown no adverse effects of benzyl alcohol in chronic exposure animal studies using rats and mice at appropriate doses 7
• The National Toxicology Program found no evidence of carcinogenic activity of benzyl alcohol in long-term studies 7

Practical Recommendations

1. Prior to mixing:

   • Ensure both components are at compatible pH levels
   • Visually inspect for any immediate signs of incompatibility (precipitation, color change)

2. During preparation:

   • Mix in a clean, appropriate container
   • Observe for any immediate physical changes indicating incompatibility

3. After mixing:

   • Monitor the solution for stability over time
   • Use the mixture promptly if possible to minimize potential degradation

Precautions

• While benzyl alcohol is generally recognized as safe at low concentrations, it should be used with caution in:

  • Patients with known hypersensitivity to benzyl alcohol
  • Neonates and young infants (though this is unlikely to be relevant for doxylamine use)
  • Patients with compromised liver function (as benzyl alcohol is metabolized in the liver)

• Avoid prolonged storage of the mixture unless stability has been established through appropriate testing

The limited evidence available suggests that this mixture should be physically compatible, but without specific compatibility studies, caution is advised and observation for any signs of instability is recommended.