Cremophor E.L.


Non ionic surfactant. polyoxyethylated castor oil used to dissolve water insoluble drugs. Greater specific gravity than water, and high viscosity.
 
Incidence
Adverse reactions have been described with numerous drugs.
 
ALTHESIN (alphaxalone), EPONTOL (propanidid): withdrawn from the market,
 
DIPRIVAN (propofol), DAKTARIN (miconazole), KONAKION (vitamin K1), STESOLID MR (diazepam): reformulated without cremophor E.L.
 
SANDIMMUNE (cyclosporine), TAXOL (paclitaxel), VUMON (teniposide), DIDEMNIN B (didemnin B): currently in use.
 
Clinical manifestations
General: anaphylactic shock.
 
Respiratory: bronchospasm.
 
Cutaneous: urticaria, generalized erythema.
 
Diagnostic methods
Cutaneous testing.
 
A few cases with positive intradermal tests with cremophor 0.2 mg/ml to 20 mg/ml.
 
No specific IgE found.
 
Mechanisms
IgE-mediated hypersensitivity (few cases).
 
Non IgE-mediated hypersensitivity (IgG 4).
 
Complement activation (+++).
 
Non specific histamine release.
 
Management
Avoid use as excipient if possible.
 
In the case of intravenous cyclosporine: proper mixing during the preparation of the infusion, and avoidance of polyvinylchlorure in the set-up. This could be extrapolated to other drugs containing cremophor E.L .

References

  1. Volcheck G.W, Van Dellen R.G, "Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine: case report and review", Ann. Allergy. Asthma. Immunol., 1998; 80 (2): 159-63
  2. Michaud L.B, "Methods for preventing reactions secondary to cremophor E.L", Ann. Pharmacother., 1997; 31 (11): 1402-4
  3. Mounier P, Laroche D, Divanon F, Mosquet B, Vergnaud M.C, Esse-Comlan A, Piquet M.A, Bricard H, "Reactions anaphylactoides à une solution polyvitaminée injectable contenant un cremophore", Therapie. , 1995; 50 (6): 571-3
  4. Dorr R.T, "Pharmacology and toxicology of cremophor E.L diluent", Ann. Pharmacother., 1994; 28 (5 s): S11-14
  5. Bowers V.D, Locker S, Ames S, Jennings W, Corry R.J, "The hemodynamic effects of cremophor E.L", Transplantation., 1991; 51 (4): 847-50

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.