Compatibility and stability of ternary admixtures of tramadol, haloperidol, and hyoscine N-butyl bromide: retrospective clinical evaluation.
BACKGROUND
Combination of drugs for subcutaneous infusion is common practice in palliative medicine, however, there is no information pertaining to the compatibility and stability of tramadol combined in ternary admixtures and no information exists regarding its clinical performance.


METHODS
Tramadol hydrochloride, haloperidol lactate, and hyoscine N-butyl bromide have been examined for compatibility and stability when combined in solution under conditions mimicking their potential use via subcutaneous infusion in terminal oncology patients. Concentration ranges were 8.8-33.3 mg/mL, 0.208-0.624 mg/mL, and 3.33-6.67 mg/mL for tramadol hydrochloride, haloperidol lactate, and hyoscine N-butyl bromide. With these, 27 different admixtures were prepared and stored at 25 degrees C using 0.9% saline as diluent. Quantification was performed by high-performance liquid chromatography (HPLC). The clinical performance of the admixture was retrospectively assessed in 28 terminal oncology patients exhibiting Karnofsky's indexes of 10%-20%.


RESULTS
All three drugs were very stable (>92%) at 25 degrees C for 15 days. Pain was completely controlled in all patients. Fifty percent of the patients suffered from 3-5 vomiting episodes per day and of these, 75% experienced complete control of the episodes. None of the patients showed local reactions after subcutaneous administration of the admixture.


RESULTS
Our results confirm the compatibility and stability of the ternary admixture and its utility in highly vulnerable patients exhibiting moderate symptoms.
Negro
Sofia
S
Department of Pharmaceutics, School of Pharmacy, University Complutense of Madrid, Spain. soneal@farm.ucm.es
Martín
Alicia
A
Azuara
Luz
L
Sánchez
Yolanda
Y
Barcia
Emilia
E
D000368:Aged; D000369:Aged, 80 and over; D002086:Butylscopolammonium Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004344:Drug Incompatibility; D004355:Drug Stability; D004359:Drug Therapy, Combination; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D002086:Butylscopolammonium Bromide; D014147:Tramadol; D006220:Haloperidol